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is the most common arrhythmia in SCD&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">4</span></a> In fact&#44; around 50&#37; of SCD cases are due to VF and&#47;or ventricular tachycardia &#40;VT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">3</span></a> They predominantly occur out-of-hospital&#44; explaining the low survival rates &#40;i&#46;e&#46;&#44; &#60;10&#37;&#41; of patients with VF&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">5</span></a> Conversely&#44; asystole and pulseless electrical activity &#40;PEA&#41; have been emerging in SCD for indefinite reasons&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">3</span></a> Interestingly&#44; in patients with reported out-of-hospital sudden cardiac arrest &#40;SCA&#41;&#44; antipsychotic drugs have shown to be significant predictors of PEA versus VF&#47;VT&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">SCD can be caused by an acquired and&#47;or a genetic background of susceptibility&#44; arising from either electrophysiological &#40;e&#46;g&#46;&#44; inherited channelopathies&#41; or structural cardiac abnormalities &#40;e&#46;g&#46;&#44; CAD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Inherited channelopathies</span><p id="par0020" class="elsevierStylePara elsevierViewall">Long QT syndrome &#40;LQTS&#41;&#44; Brugada syndrome &#40;BrS&#41; and short QT syndrome &#40;SQTS&#41; are rare inherited arrhythmia disorders arising from ion channel abnormalities&#44; which in turn are termed channelopathies&#46; These syndromes are highly concerning&#44; particularly in young people&#44; due to their high propensity to suffer severe ventricular arrhythmias and sudden cardiac death&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Since the overwhelming majority of patients with inherited channelopathies have no structural heart diseases&#44; an electrocardiogram &#40;ECG&#41; is a valuable tool both in detecting features of these syndromes and in early SCD risk stratification&#46;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">1&#44;7</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">QT prolongation&#44; torsades de pointes and congenital long QT syndrome</span><p id="par0030" class="elsevierStylePara elsevierViewall">The QT interval represents the electrocardiographic index of ventricular repolarization and depolarization&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">8</span></a> Because the QT interval varies inversely with heart rate&#44; several correction formulas &#40;e&#46;g&#46;&#44; Bazett&#44; Fridericia&#41; allow us to determine a heart rate-corrected QT &#40;QTc&#41; interval&#46; Fridericia&#39;s formula provides a more accurate assessment at extremes of heart rate than Bazett&#39;s formula and&#44; therefore&#44; it is preferred in such cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The expert group from the American College of Cardiology Foundation and the American Heart Association &#40;ACCF&#47;AHA&#41; gives an upper limit of normal &#40;i&#46;e&#46;&#44; estimated 99th percentile&#41; for abnormally prolonged QTc intervals of 470 ms and 480 ms in otherwise healthy post-pubertal males and females&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">11</span></a> Patients with an absolute QTc interval of &#62;500 ms are considered to be at risk for developing torsades de Pointes &#40;TdP&#41;&#44; a polymorphic ventricular tachycardia that may shift into VF and lead to SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">11&#44;12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Congenital QT prolongation is due to various genetically based LQTSs&#46; 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or detection of at least one unequivocally gene culprit mutation&#44; regardless of QT interval duration&#46; A QTc &#8805;460 ms can also be diagnostic in a scenario of unexplained syncope&#46; In all the above-mentioned criteria&#44; other causes for QT prolongation should previously be ruled out&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Short QT syndrome</span><p id="par0055" class="elsevierStylePara elsevierViewall">A rare inheritable channelopathy&#44; called Short QT Syndrome &#40;SQTS&#41;&#44; was first clinically described in 2000&#44; in three members of one family who presented with abnormally short QT intervals and tall peaked T-waves in the precordial ECG leads&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">18</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Gain-of-function mutations in genes encoding cardiac repolarizing K<span class="elsevierStyleSup">&#43;</span> channels &#40;i&#46;e&#46;&#44; KCNH2&#44; KCNQ1 and KCNJ2&#41; and loss-of-function mutations of calcium channel <span class="elsevierStyleItalic">CACNA1C</span>&#44; <span class="elsevierStyleItalic">CACNB2</span> and <span class="elsevierStyleItalic">CACNA2D1</span> genes have been associated with SQTS&#46;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">1&#44;7&#44;10</span></a> However&#44; the diagnostic yield of genetic testing remains low &#40;i&#46;e&#46;&#44; about 20&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">16</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">SQTS is diagnosed when QTc interval is &#8804;340 ms or&#44; alternatively&#44; should be considered if QTc interval is &#8804;360 ms along with one or more of the following&#58; &#40;1&#41; survival from a VT&#47;VF episode&#44; in the absence of cardiac disease&#59; &#40;2&#41; a confirmed pathogenic mutation&#59; &#40;3&#41; a family history of SQTS&#44; or &#40;4&#41; a family history of sudden death at the age of &#60;40 years&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">1</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Apart from congenital SQTS&#44; other clinical scenarios&#44; such as electrolyte disturbances &#40;e&#46;g&#46;&#44; hypercalcemia&#44; hyperkalemia&#41;&#44; acidosis&#44; increased heart rate and increased levels of acetylcholine or catecholamine can shorten QT interval&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">QT shortening can degenerate into paroxysmal atrial fibrillation &#40;AF&#41; and&#47;or VT and potentially lead to SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">18&#44;19</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Brugada syndrome</span><p id="par0080" class="elsevierStylePara elsevierViewall">Brugada syndrome &#40;BrS&#41; is a relatively recent clinical entity&#44; first described in 1992 by a set of distinctive ECG features&#44; especially right bundle branch block and ST-segment elevation in right precordial leads &#40;i&#46;e&#46;&#44; V<span class="elsevierStyleInf">1</span> to V<span class="elsevierStyleInf">3</span>&#41;&#44; in the absence of other concurrent factors &#40;e&#46;g&#46;&#44; ischemia&#44; structural heart disease or electrolyte imbalance&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">20</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">BrS is inherited through an autosomal dominant mode of transmission&#46; Approximately 20 culprit genes have been reported thus far&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a> The pathogenesis of congenital BrS is more commonly due to loss-of-function mutations in the <span class="elsevierStyleItalic">SCN5A</span> gene&#46; Currently&#44; over 300 <span class="elsevierStyleItalic">SCN5A</span> gene mutations have been described&#44; accounting for the vast majority &#40;i&#46;e&#46;&#44; approximately 75&#37;&#41; of genotype-positive cases&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">22</span></a> Nevertheless&#44; genetic testing identifies such mutations in only about 20-25&#37; of BrS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">16</span></a> The increase in the transient outward potassium current &#40;I<span class="elsevierStyleInf">to</span>&#41; and the decrease in the L-type Ca<span class="elsevierStyleSup">2&#43;</span> current &#40;I<span class="elsevierStyleInf">Ca&#44;L</span>&#41; have also been postulated to contribute to the pathogenesis of BrS&#46;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">15&#44;21</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Patients with a BrS ECG pattern are often clinically concealed at the time of diagnosis&#44; which in turn is often incidental&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a> In fact&#44; patients may persist asymptomatically for life&#44; but a subgroup of BrS patients can experience syncope&#44; nocturnal agonal respiration and palpitations associated with high risk of fatal arrhythmias &#40;e&#46;g&#46;&#44; VT&#47;VF&#41; and SCD&#44; which generally occur in the third or fourth decades of life&#44; mainly at rest or during sleep&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">13&#44;15&#44;21</span></a> Although BrS affects both males and women&#44; the condition appears to be 8 to 10 times more common in males&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">BrS ECG patterns have been categorized as type 1&#44; 2 or 3 according to detailed characteristics of surface ECGs&#46; A coved ST-segment elevation &#8805;2 mm followed by a negative T wave is representative of a type 1 ECG pattern&#46; Type 2 comprises a saddleback ST-segment elevation of &#8805;0&#46;5 mm &#40;i&#46;e&#46;&#44; usually &#8805;2 mm in V<span class="elsevierStyleInf">2</span>&#41; in at least 1 right precordial lead &#40;i&#46;e&#46;&#44; V<span class="elsevierStyleInf">1</span>-V<span class="elsevierStyleInf">3</span>&#41;&#44; followed by a convex shape&#46; T-wave morphology differs in V<span class="elsevierStyleInf">1</span> and it is characteristically positive in V<span class="elsevierStyleInf">2</span>&#46; Type 3 pattern is characterized by either a coved or a saddleback appearance with an ST-segment elevation &#60;1 mm&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">23</span></a> Nonetheless&#44; only type 1 is recognized as diagnostic&#46; Type 2 and type 3 are not specific to BrS and&#44; therefore&#44; it is currently uncertain whether or not they should be considered BrS patterns&#46; However&#44; physicians should be aware and recognize these patterns as they can be an electrocardiographical presentation of some genuine BrS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The diagnostic criteria of BrS were recently updated in the 2016 expert consensus conference on J-wave syndromes&#44;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">23</span></a> since the criteria proposed in the 2015 guidelines<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">1</span></a> and in the previous 2013 consensus statement<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">24</span></a> tend to overdiagnose cases of the type 1 ECG pattern&#46; Overdiagnosis is unmasked after intravenous sodium-channel blocker challenge with ajmaline&#44; flecainide&#44; pilsicainide or procainamide&#46; In such patients&#44; BrS diagnosis should require that the patient also present with at least 1 of the following&#58; &#40;1&#41; nocturnal agonal respiration&#44; &#40;2&#41; syncope of probable arrhythmic cause&#44; &#40;3&#41; family history of SCD at less than 45 years old with negative autopsy&#44; &#40;4&#41; documented polymorphic VT or VF&#44; or &#40;5&#41; coved-type ECGs in family members&#46; A spontaneous type 1 ECG pattern in at least 1 right precordial lead &#40;i&#46;e&#46;&#44; V<span class="elsevierStyleInf">1</span>&#44; V<span class="elsevierStyleInf">2</span> and V<span class="elsevierStyleInf">3</span>&#44; placed in the 2nd&#44; 3rd and 4th intercostal spaces&#44; respectively&#41; is an independent BrS diagnostic criterion&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">23</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Since other acute &#40;e&#46;g&#46;&#44; coronary events&#44; metabolic disorders&#44; electrolyte disturbances&#41; and chronic &#40;e&#46;g&#46;&#44; ventricular hypertrophy&#44; autonomic nervous system disorders&#41; conditions can bring about ST-segment elevation patterns&#44; diagnosis of BrS is feasible only after these scenarios are ruled out&#46;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;23</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Aim</span><p id="par0110" class="elsevierStylePara elsevierViewall">The aim of this article is to comprehensively and critically review the recently published evidence with regard to drug-induced life-threatening arrhythmias and sudden cardiac death&#46; It will take into account the provision of data to physicians that are useful in the identification of the culprit drugs&#44; and thus&#44; contribute to the prompt recognition and management of these serious clinical conditions&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Methods</span><p id="par0115" class="elsevierStylePara elsevierViewall">A comprehensive search was carried out through PubMed to identify human-based studies published in English and&#47;or Portuguese&#44; between January 1&#44; 2011 and January 12&#44; 2017&#46; The following keywords were used in combination&#44; both as Medical Subject Headings &#40;MeSH&#41; terms and text words&#58; &#8220;sudden cardiac death&#8221;&#44; &#8220;cardiac arrhythmias&#8221;&#44; &#8220;long QT syndrome&#8221;&#44; &#8220;torsades de pointes&#8221;&#44; &#8220;Brugada syndrome&#8221;&#44; &#8220;drug-related side effects and adverse reactions&#8221; and &#8220;pharmaceutical preparations&#8221;&#46; Additionally&#44; the text words &#8220;arrhythmias&#8221;&#44; &#8220;proarrhythmia&#8221;&#44; &#8220;torsade de pointes&#8221;&#44; &#8220;short QT syndrome&#8221;&#44; &#8220;adverse effects&#8221;&#44; &#8220;drugs&#8221; and &#8220;drug-induced&#8221; were combined with the abovementioned search terms&#46; The literature search encompassed relevant studies regarding drug-induced proarrhythmia and SCD&#44; especially those which aimed to address the so-called congenital and acquired arrhythmia syndromes LQTS&#44; SQTS or BrS&#46; A clinical perspective was chosen due to the wide range of data within this field&#46; Case reports were excluded&#44; unless they displayed original evidence or were the only source of a causal relationship&#46; Papers that only aimed to address detailed therapeutic strategies were not considered&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">A total of 496 studies were identified&#46; Titles and abstracts were initially screened&#44; and full-text articles were retrieved&#46; The reference list of the identified articles was checked for potentially relevant papers&#46; Two reviewers &#40;i&#46;e&#46;&#44; first and last author&#41; independently analyzed each study to minimize bias&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The final review ended up comprising a total of 90 articles&#46; Two additional websites &#40;i&#46;e&#46;&#44; <a id="intr0025" class="elsevierStyleInterRef" href="http://www.crediblemeds.org/">www&#46;crediblemeds&#46;org</a><a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">25</span></a>&#59; <a id="intr0030" class="elsevierStyleInterRef" href="http://www.brugadadrugs.org/">www&#46;brugadadrugs&#46;org</a><a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">26</span></a>&#41; were included as they provide useful information regarding the aim of this review&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Drug-induced proarrhythmia and SCD</span><p id="par0130" class="elsevierStylePara elsevierViewall">Drug-induced proarrhythmia is the outcome of prior or concomitant use of any drug with life-threatening proarrhythmic effects and SCD risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;27</span></a> Growing evidence suggests the implication of an increasing number of drugs in acquired forms of long QT &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; short QT to a lesser extent &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41; and Brugada syndrome &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Drug-induced LQTS</span><p id="par0135" class="elsevierStylePara elsevierViewall">Acquired LQTS is undoubtedly more common than inherited LQTS&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">9</span></a> Drugs are undeniably the leading cause of acquired LQTS&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">28</span></a> Notably&#44; in the last decade&#44; drug-induced TdP was the single most common cause of the withdrawal or restriction of the use of drugs that have already been marketed&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">12</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The ACCF&#47;AHA scientific statement recognized a QTc interval of &#62;500 ms&#44; or an increase after drug administration of QTc &#62;60 ms from the pre-drug baseline&#44; as alarming signals that should warrant prompt management and correction&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">11</span></a> In fact&#44; the majority of drug-induced TdP cases has been reported with QTc intervals of &#62;500 ms&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">However&#44; data suggests that the magnitude of QTc prolongation does not directly correlate with the risk of developing TdP&#46; Amiodarone and ranolazine are two paradigmatic cases&#44; which undoubtedly cause QT prolongation&#44; but with few reported cases of TdP&#46; Apparently&#44; these agents attenuate the dispersion of ventricular repolarization&#44; which balance out with the QT prolongation effect&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a> Although not yet proven in congenital forms of LQTS&#44; indirect assessment of transmural dispersion of ventricular repolarization using Tpeak-end interval and the Tpeak-Tend&#47;QT ratio &#40;e&#46;g&#46;&#44; significantly increased in cigarette smokers&#41; has been demonstrated to properly predict the risk of potentially life-threatening arrhythmias in drug-induced LQTS&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;10&#44;29&#44;30</span></a> QT dispersion &#40;i&#46;e&#46;&#44; difference between the longest and shortest QT interval in the 12 ECG leads&#41;&#44; is another potential surrogate marker for ventricular repolarization heterogeneity&#44; which was shown to increase with the use of psychotropic drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">31</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Nevertheless&#44; the QT interval is still widely used in clinical practice to assess the risk of TdP and SCD&#44; notwithstanding its poor predictive value&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;32</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Drug interactions with cardiac ion channels are the main mechanisms involved in potentially life-threatening arrhythmias&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a> Theoretically&#44; almost all drugs associated with QT prolongation and TdP block the rapid delayed rectifier potassium current&#44; I<span class="elsevierStyleInf">Kr</span>&#44; but not all I<span class="elsevierStyleInf">Kr</span> inhibitors prolong the QT interval and cause TdP&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">12&#44;14</span></a> However&#44; the use of these channel blockers in the general population has been associated with high risk of SCD&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">33</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Various drugs are metabolized by intestinal or hepatic cytochrome P450 &#40;CYP450&#41; enzymes&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">14&#44;27</span></a> Methadone &#40;i&#46;e&#46;&#44; CYP2C19&#44; notably&#44; the &#42;2 variant that is associated with QTc prolongation&#44;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">34</span></a> CYP3A4 and to a lesser extent the CYP2D6&#44; CYP2B6 and CYP1A2 enzymes<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">35</span></a>&#41;&#44; clarithromycin and erythromycin &#40;CYP3A enzymes&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">36</span></a> domperidone &#40;CYP3A4&#41;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">37</span></a> and clozapine &#40;CYP2D6&#41;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a> are examples of such drugs&#46; If those pathways are more prone to be inhibited by the concurrent use of other drugs or their activity is impaired by certain gene polymorphisms&#44; extremely elevated drug serum levels and fatal outcomes are expected to occur&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Recently&#44; the nitric oxide synthase 1 adaptor protein &#40;NOS1AP&#41; genetic variation has been identified as a new genetic marker in modulating QT prolongation and SCD&#44; both in congenital and drug-induced LQTS&#46;<a class="elsevierStyleCrossRefs" href="#bib0600"><span class="elsevierStyleSup">28&#44;39</span></a> In fact&#44; along with P-glycoprotein&#44; a transmembrane efflux pump &#40;i&#46;e&#46;&#44; domperidone is one of its substrates<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">37</span></a>&#41;&#44; the NOS1AP gene appears to be implicated in the bioavailability of various QT-prolonging drugs&#44; especially calcium channel inhibitors &#40;e&#46;g&#46;&#44; verapamil and diltiazem&#41;&#44; since it is involved in the inhibition of L-type Ca<span class="elsevierStyleSup">2&#43;</span> channels&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">14</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Apart from subclinical congenital LQTS&#44; drug-induced TdP depends on a multitude of risk factors&#44; which comprise female gender&#44; advanced age and common clinical conditions&#44; such as bradycardia&#44; hypertension&#44; structural heart diseases &#40;e&#46;g&#46;&#44; congestive heart failure&#44; hypertrophic cardiomyopathy&#41; and electrolyte imbalances &#40;e&#46;g&#46;&#44; hypokalemia&#44; hypomagnesemia&#44; hypocalcemia&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">11&#44;12&#44;38&#44;40&#44;41</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">An up-to-date list of cardiovascular and non-cardiovascular drugs &#40;i&#46;e&#46;&#44; mainly psychotropics and antimicrobials<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a>&#41; implicated in QT prolongation and&#47;or TdP is currently available at <a id="intr0035" class="elsevierStyleInterRef" href="http://www.crediblemeds.org/">www&#46;crediblemeds&#46;org</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Antiarrhythmic drugs</span><p id="par0180" class="elsevierStylePara elsevierViewall">Antiarrhythmic drugs are among the most harmful regarding their high risk of life-threatening arrhythmias&#46; Vaughan Williams class III drugs &#40;e&#46;g&#46;&#44; sotalol&#44; dofetilide&#44; ibutilide&#41; lead to the greatest concern for TdP within antiarrhythmics&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a> Apart from the well-known QTc prolongation effect&#44; amiodarone exhibits a low risk of TdP&#44; when used alone&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;10&#44;42</span></a> Nevertheless&#44; TdP has already been reported with concomitant use &#40;e&#46;g&#46;&#44; erythromycin and haloperidol&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">40</span></a> Therefore&#44; ECG monitoring is required in all intensive care unit &#40;ICU&#41; patients receiving amiodarone&#44; since this subset of patients has a high incidence of concomitant use of other QT-prolonging drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">42</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Notably&#44; pilsicainide&#44; a class Ic antiarrhythmic drug&#44; triggered TdP in an elderly patient who ended up dying suddenly&#44; two days after receiving it to convert his paroxysmal AF to sinus rhythm&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">43</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Antianginal drugs</span><p id="par0190" class="elsevierStylePara elsevierViewall">In spite of its known QT-prolonging effect&#44; low risk of TdP and SCD have been reported with ranolazine&#44;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;27</span></a> including when it is used to treat non-ST elevation acute coronary syndrome in patients with prolonged baseline QTc intervals&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">44</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Antidepressant and antipsychotic drugs</span><p id="par0195" class="elsevierStylePara elsevierViewall">Tricyclic antidepressants are well-known risk factors for QT prolongation and TdP&#44; especially in overdose cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0595"><span class="elsevierStyleSup">27&#44;45</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Overall&#44; selective serotonin-reuptake inhibitors &#40;SSRIs&#41; increase the QTc interval&#44; but citalopram and escitalopram seem to incite a more pronounced QTc prolongation in a dose-dependent fashion&#46;<a class="elsevierStyleCrossRefs" href="#bib0690"><span class="elsevierStyleSup">46&#8211;48</span></a> Nevertheless&#44; the role of citalopram as a trigger of TdP and SCD remains controversial&#44; as there are no concomitant risk factors for QT prolongation and TdP&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">49</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Although bupropion and venlafaxine prolong the QTc interval almost exclusively in overdose scenarios&#44; generally&#44; newer non-SSRIs pose a low risk of such effect at therapeutic doses&#46; Their shorter market life may explain the limited data&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">50</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">In a cohort study&#44; no considerable differences regarding sudden death and ventricular arrhythmia &#40;SD&#47;VA&#41; risks were detected among 11 antidepressants and paroxetine&#46; High risk of SD&#47;VA was only reported with mirtazapine&#44; but the authors reminded us that such outcome was biased by confounding factors&#46; Therefore&#44; cardiac safety was considered similar among antidepressants&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">51</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Given the numerous adverse effects of antipsychotics&#44; drug-induced LQTS is truly one of the most dangerous&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a> Overall&#44; first-generation antipsychotics are considered to be more likely to prolong QT interval and have higher risks of ventricular arrhythmias &#40;VAs&#41; and SCD than second-generation antipsychotics&#46;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;52</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">The Food and Drug Administration Adverse Event Reporting System &#40;FAERS&#41; database has been systematically analyzed to detect signals of torsadogenicity&#46;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#44;54</span></a> In this regard&#44; detecting new potential signals of torsadogenicity &#40;e&#46;g&#46;&#44; with amisulpride&#44; cyamemazine and olanzapine&#41; provided new insights for pharmacovigilance in antipsychotics&#46; This is because it allowed updating the Arizona Center for Education and Research on Therapeutics &#40;AZCERT<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">25</span></a>&#41; drug list&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">54</span></a> One year later&#44; Fanoe et al&#46; combined pharmacovigilance data from various international databases&#46; Only haloperidol&#44; pimozide&#44; sertindole and ziprasidone were considered to be class B&#42; drugs &#40;i&#46;e&#46;&#44; &#8220;a drug with pronounced QT prolongation&#44; documented cases of TdP&#44; or other serious arrhythmias&#8221;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">55</span></a> Alternatively&#44; the data analysis of three national spontaneous reporting systems &#40;i&#46;e&#46;&#44; France&#44; Germany and Italy&#41; demonstrated that in all of the national databases studied&#44; TdP events were reported only with amisulpride&#44; aripiprazole&#44; haloperidol&#44; olanzapine and risperidone&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">56</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Therefore&#44; available data on haloperidol have consistently favored its marked QT prolongation effect and high risk for TdP and SCD&#44;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#8211;57</span></a> but such outcomes have been disparate for clozapine &#40;low risk of QTc prolongation<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">58</span></a>&#59; &#8220;very strong signals of torsadogenicity&#8221;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#44;54</span></a>&#41; and olanzapine &#40;&#8220;a drug considered to be without any risk of QT prolongation or TdP&#8221;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">55</span></a>&#59; &#8220;potential signal of torsadogenicity&#8221;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">54</span></a>&#59; &#8220;very strong signal of torsadogenicity&#8221;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">53</span></a>&#41;&#46; Despite ziprasidone having QT-prolonging and torsadogenic effects&#44;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#8211;55</span></a> studies have failed to prove an increased risk of SD&#44; SCD or nonsuicide mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0755"><span class="elsevierStyleSup">59&#8211;61</span></a> Aripiprazole has a low risk of TdP and SCD&#44; at least in otherwise healthy patients&#46; However&#44; in patients at risk for TdP&#44; it may represent a safety concern&#44; since few studies have been carried in these vulnerable subsets&#46;<a class="elsevierStyleCrossRefs" href="#bib0770"><span class="elsevierStyleSup">62&#44;63</span></a> Cases of QTc prolongation&#44; TdP and SCD have been reported with quetiapine&#44; but only with concomitant risk factors for QT prolongation or TdP&#46;<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">64</span></a> Increased QTc prolongation and higher risk of SCD have been documented with risperidone during nighttime&#44; when compared to olanzapine users&#46;<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">65</span></a> These perilous effects are likely due to the increased serum levels of risperidone&#39;s active metabolite paliperidone in a dose-dependent manner and not to risperidone alone&#46;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">66</span></a> Two retrospective cohort studies also made a comparison with olanzapine&#44; but both risperidone and quetiapine were not implicated in higher risk of SD or VAs&#46; According to the authors&#44; olanzapine was chosen as the referent&#44; since it is not linked to substantive QT prolongation&#46;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">57</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">Exposure to phenothiazine antipsychotics also carries a risk of QTc prolongation and TdP both in therapeutic and overdose settings&#44; particularly with levomepromazine&#44; chlorpromazine and promethazine&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">45</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Despite increasing safety concerns&#44; widespread use of antipsychotics with torsadogenic potential has been reported in some European countries in recent years&#44; mostly with haloperidol and thioridazine&#46;<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">67</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">ECG monitoring is strongly recommended at hospital admission in patients with acute psychosis &#40;i&#46;e&#46;&#44; recently treated with antipsychotics&#41;&#44; due to the increased risk of QTc prolongation&#46;<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">68</span></a> Conversely&#44; Correll et al&#46; affirmed that&#44; unless other comorbidities are present &#40;e&#46;g&#46;&#44; cardiac diseases&#44; obesity&#44; hypokalemia&#41;&#44; ECG monitoring could potentially be restricted in young people treated with antipsychotics&#44; as significantly prolonged QTc interval was not demonstrated in this subset of patients&#46; Nevertheless&#44; the authors reinforced the idea that larger studies are required in this regard&#46;<a class="elsevierStyleCrossRef" href="#bib0805"><span class="elsevierStyleSup">69</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Antimicrobial drugs</span><p id="par0245" class="elsevierStylePara elsevierViewall">Macrolide antibiotics are one of the most prescribed non-cardiovascular QT-prolonging agents&#44; and exhibit increased risk of fatal ventricular arrhythmias or SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0595"><span class="elsevierStyleSup">27&#44;36</span></a> Azithromycin was once considered to be relatively free of adverse cardiac effects&#46; However&#44; new data has been emerging regarding its cardiac safety&#46;<a class="elsevierStyleCrossRefs" href="#bib0810"><span class="elsevierStyleSup">70&#44;71</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Quinolones are broad-spectrum antimicrobials with known risk of QT prolongation&#46;<a class="elsevierStyleCrossRefs" href="#bib0595"><span class="elsevierStyleSup">27&#44;42</span></a> It is noteworthy that in a United States veterans study&#44;<a class="elsevierStyleCrossRef" href="#bib0815"><span class="elsevierStyleSup">71</span></a> levofloxacin was significantly associated with serious arrhythmias and death&#44; throughout the 10-day course of therapy&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">QT prolongation and TdP have also been reported with antifungal agents&#44; mainly fluconazole&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Anesthetic drugs</span><p id="par0260" class="elsevierStylePara elsevierViewall">Overall&#44; inhaled anesthetics can prolong the QTc interval or increase dispersion of ventricular repolarization to variable degrees&#46; However&#44; only sevoflurane has been associated with TdP risk&#44; though most likely with concomitant risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">An ICU population-based study revealed that a flurane agent had been administered during anesthesia in the overwhelming majority of postoperative patients with QT interval prolongation&#46; Therefore&#44; the authors emphasized the need for QTc interval monitoring in all postoperative ICU patients&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">42</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">A case of SCA following documented QTc interval prolongation &#40;i&#46;e&#46;&#44; 580-600 ms&#41; was reported in a 30-month-old boy during anesthesia induction with sevoflurane and nitric oxide before undergoing plastic surgery for bilateral cutaneous syndactyly&#46; Timothy Syndrome&#44; LQTS type 8 with typical features&#44; including syndactyly&#44; was established by detecting the p&#46;Gly406Arg mutation in the <span class="elsevierStyleItalic">CACNA1C</span> gene encoding Cav1&#46;2 L-type calcium channel&#46;<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">72</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">Anticholinergic drugs &#40;e&#46;g&#46;&#44; atropine&#44; glycopyrronium bromide&#41; can prolong the QT interval when simultaneously used with anticholinesterases in healthy patients&#44; but TdP may occur when used alone in LQTS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Antiemetic drugs</span><p id="par0280" class="elsevierStylePara elsevierViewall">Domperidone can prolong the QTc interval and increase the risk of serious VAs and SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">37&#44;73</span></a> SCD risk seems to be higher in the first two weeks of treatment&#44; in patients older than 60 years and those with doses over 30 mg&#47;day&#46;<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">74</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">Serotonin-receptor antagonists &#40;e&#46;g&#46;&#44; dolasetron&#44; granisetron and ondansetron&#41; are also known QT-prolonging drugs&#44; but their clinical significance remains unclear&#44; due to few reported cases of fatal cardiac arrhythmias and SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">19&#44;75</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Antihistaminic drugs</span><p id="par0290" class="elsevierStylePara elsevierViewall">Apart from not appearing at the forefront of the most common events&#44; adverse cardiac effects are one of the most serious events for patients using first- or second-generation antihistamines&#46;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">The low number of antihistamines on the AZCERT drugs list<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">25</span></a> demonstrates the scarcity of pharmacovigilance data reporting TdP events&#46; An analysis of safety reports from the FAERS database revealed new evidence on torsadogenic activity for loratadine&#44; desloratadine&#44; cetirizine and fexofenadine&#44; in addition to diphenhydramine&#44;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a> which was already on the AZCERT list&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Antineoplastic drugs</span><p id="par0300" class="elsevierStylePara elsevierViewall">High TdP event rates are almost exclusively reported with arsenic trioxide&#46; However&#44; BRAF inhibitor vemurafenib&#44; histone deacetylase inhibitors &#40;e&#46;g&#46;&#44; depsipeptide and vorinostat&#41; and tyrosine kinase inhibitors &#40;e&#46;g&#46;&#44; dasatinib&#44; nilotinib&#44; lapatinib&#44; sunitinib&#44; vandetinib&#41; are also commonly linked to QTc prolongation to varying degrees&#46;<a class="elsevierStyleCrossRefs" href="#bib0845"><span class="elsevierStyleSup">77&#44;78</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Opioid replacement drug therapy</span><p id="par0305" class="elsevierStylePara elsevierViewall">Although more commonly reported at high doses &#40;&#62;200 mg&#47;day&#41;&#44; QT prolongation&#44; TdP and SD can occur even at lower doses of methadone &#40;&#60;100 mg&#47;day&#41;&#46; This is predominantly in early periods of treatment and&#47;or during concomitant use of either QT-prolonging agents or those which impair methadone metabolism&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Attention deficit hyperactivity disorder drug therapy</span><p id="par0310" class="elsevierStylePara elsevierViewall">QT prolongation is associated with atomoxetine use in overdose&#46;<a class="elsevierStyleCrossRef" href="#bib0855"><span class="elsevierStyleSup">79</span></a> Nevertheless&#44; there is scarce evidence regarding the involvement of stimulants in fatal arrhythmias and SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0855"><span class="elsevierStyleSup">79&#44;80</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">In a non-randomized cohort study conducted in adults&#44; the risk of VA or SD was significantly associated with methylphenidate use&#46; However&#44; the authors argued that the lack of a dose-response effect did not suggest a causal relationship&#46;<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">81</span></a></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Non-therapeutic drugs</span><p id="par0320" class="elsevierStylePara elsevierViewall">Data collected from a large sample representative of the general US population revealed that binge drinkers displayed substantially prolonged QT intervals&#44; compared to non-binge drinkers or non-drinkers&#46;<a class="elsevierStyleCrossRef" href="#bib0870"><span class="elsevierStyleSup">82</span></a></p><p id="par0325" class="elsevierStylePara elsevierViewall">TdP was reported in a previously healthy 43-year-old woman who presented with syncope after excessive intake of ginseng for 6 months&#46;<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">83</span></a></p><p id="par0330" class="elsevierStylePara elsevierViewall">Ozturk S et al&#46; described the case of a 59-year-old woman who developed TdP after two days of drinking 5-6 glasses of licorice root tea for constipation&#46; The authors hypothesized that glycyrrhizin was the culprit compound due to its known effects on both cardiac depolarization and repolarization&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">84</span></a></p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Drug-induced SQTS</span><p id="par0335" class="elsevierStylePara elsevierViewall">Drug-induced SQTS is still a rarely reported condition&#46;<a class="elsevierStyleCrossRef" href="#bib0885"><span class="elsevierStyleSup">85</span></a> Therefore&#44; its clinical significance is still unclear&#44; since few fatal arrhythmias and SCD cases have been described thus far&#46;<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">86</span></a></p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Antiepileptic drugs</span><p id="par0340" class="elsevierStylePara elsevierViewall">Rufinamide has been reported as a QT shortening agent&#46; In patients receiving rufinamide&#44; the concomitant use of lamotrigine and valproic acid has been associated with a significant decrease in the QT interval&#46;<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">86</span></a></p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Drug-induced BrS</span><p id="par0345" class="elsevierStylePara elsevierViewall">Evidence suggests that a rising number of drugs universally used in daily clinical practice can reveal the typical ECG pattern of BrS and&#44; thus&#44; potentially lead to fatal arrhythmias&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a></p><p id="par0350" class="elsevierStylePara elsevierViewall">Aside from drugs&#44; other clinical scenarios&#44; including febrile state &#40;e&#46;g&#46;&#44; hyperthermia&#44; hypothermia&#41; and electrolyte disturbances &#40;e&#46;g&#46;&#44; hyperkalemia&#44; hypokalemia&#44; hypercalcemia&#44; hyponatremia&#41;&#44; can trigger a type 1 pattern and modulate the occurrence of potentially life-threatening arrhythmias&#46; Some refer to these modifying factors as &#8220;phenocopies&#8221;&#46; However&#44; at least for now&#44; it is not proper to do so&#44; due to the lack of data regarding genetic predisposition&#46;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;23</span></a> These conditions are actually more suitably designated as acquired forms of Brugada ECG pattern or BrS&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">23</span></a></p><p id="par0355" class="elsevierStylePara elsevierViewall">Psychotropic and anesthetic drugs are the most common non-cardiovascular agents involved in BrS ECG phenotype&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a> Postema et al&#46; founded the website <a id="intr0040" class="elsevierStyleInterRef" href="http://www.brugadadrugs.org/">www&#46;brugadadrugs&#46;org</a> to guarantee the worldwide availability of cardiac safety information regarding drug prescription in BrS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Antiarrhythmic drugs</span><p id="par0360" class="elsevierStylePara elsevierViewall">Type 1 BrS ECG pattern is aggravated by drugs that block the cardiac Na<span class="elsevierStyleSup">&#43;</span> channel&#46; Corroborating this finding&#44; some of them &#40;i&#46;e&#46;&#44; ajmaline&#44; flecainide&#44; pilsicainide and procainamide&#41; are currently used for diagnostic purposes to unmask such a typical pattern in concealed BrS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">15</span></a> Nevertheless&#44; it is noteworthy that flecainide has demonstrated an increased risk of SCD when administered to treat AF&#46;<a class="elsevierStyleCrossRef" href="#bib0900"><span class="elsevierStyleSup">88</span></a></p><p id="par0365" class="elsevierStylePara elsevierViewall">BrS ECG type 1 and type 3 patterns were reported while amiodarone was prophylactically used for AF&#44; following coronary artery bypass grafting&#46;<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">89</span></a></p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Antidepressants and antipsychotic drugs</span><p id="par0370" class="elsevierStylePara elsevierViewall">Some tricyclic and SSRI antidepressants and antipsychotics &#40;e&#46;g&#46;&#44; lithium&#41; can induce a BrS ECG phenotype by blocking I<span class="elsevierStyleInf">Na</span> currents&#46;<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">38&#44;87</span></a></p><p id="par0375" class="elsevierStylePara elsevierViewall">In a population-based study&#44; nortriptyline&#44; an example of such a drug&#44; was associated with a significant 4&#46;5-fold increase in the risk for SCA&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">5</span></a></p><p id="par0380" class="elsevierStylePara elsevierViewall">Although fluvoxamine and paroxetine at therapeutic doses and fluoxetine in overdose can trigger a BrS ECG pattern&#44; no severe VAs have been reported thus far&#46; Similarly&#44; phenothiazine antipsychotics &#40;including cyamemazine&#44; perphenazine and thioridazine&#41; are well-known culprit agents in drug-induced BrS&#44; but without causing fatal VAs&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a></p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Epilepsy and antiepileptic drug therapy</span><p id="par0385" class="elsevierStylePara elsevierViewall">Epilepsy is considered to be an independent risk factor for life-threatening arrhythmias and SCD&#46; In fact&#44; epilepsy has been associated with a two- to three-fold higher risk for SCD than in the general population and with a six-fold higher risk in poorly controlled patients&#46;<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">90</span></a></p><p id="par0390" class="elsevierStylePara elsevierViewall">Recently&#44; Ishizue et al&#46; concluded that the concomitant use of sodium channel-blocking antiepileptic drugs&#44; including carbamazepine&#44; phenytoin and lamotrigine&#44; significantly caused a BrS type 1 pattern&#46; Conversely&#44; the authors admitted the inability to assess the 12-lead ECGs of a large proportion of epilepsy patients&#44; before and after antiepileptic therapy&#46; As a result&#44; epilepsy as a confounding factor cannot be ruled out&#46;<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">91</span></a></p><p id="par0395" class="elsevierStylePara elsevierViewall">Bardai et al&#46; revealed the increased risk of SCD with the use of sodium channel-blocking antiepileptics in epilepsy patients &#40;i&#46;e&#46;&#44; carbamazepine and gabapentin&#41; that was independent from the underlying epileptic condition&#46; In addition&#44; off-label drug use in non-epileptic patients has also been correlated with increased risk for SCD&#44; similarly to epilepsy per se&#46; If we transfer these conclusions to clinical practice&#44; measures involving seizure control with antiepileptic drugs are required&#44; but the risk of SCD must always be taken into account&#46;<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">90</span></a></p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Anesthetic drugs</span><p id="par0400" class="elsevierStylePara elsevierViewall">Despite having one of the safest profiles within modern anesthetics&#44; high doses of propofol can lead to SCD&#44; a condition termed &#8220;propofol infusion syndrome&#8221;&#46; A Brugada ECG pattern is commonly seen before &#8220;propofol infusion syndrome&#8221; occurs&#46; Thus BrS is&#44; until proven otherwise&#44; an underlying mechanism for potentially life-threatening arrhythmias and SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;87</span></a></p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Antiemetic drugs</span><p id="par0405" class="elsevierStylePara elsevierViewall">Metoclopramide has been reported to trigger typical BrS ECG features at therapeutic doses&#44; without being involved in serious arrhythmias&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a></p><p id="par0410" class="elsevierStylePara elsevierViewall">In a population-based nested case-control study&#44; oral exposure to metoclopramide demonstrated higher risk for developing SCD than oral exposure to domperidone&#46; However&#44; the authors alleged that this was an unexpected outcome and thus recommended further research in this regard&#46;<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">74</span></a></p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Antihistaminic drugs</span><p id="par0415" class="elsevierStylePara elsevierViewall">Both first- and second-generation antihistamines &#40;e&#46;g&#46;&#44; diphenhydramine almost exclusively in overdose and terfenadine&#41; have been involved in drug-induced BrS&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a></p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Non-therapeutic drugs</span><p id="par0420" class="elsevierStylePara elsevierViewall">Type 1 Brugada ECG pattern was documented in a woman with a family history of SCD&#44; who used topical nicotine patches for smoking cessation at high doses&#46;<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">92</span></a></p><p id="par0425" class="elsevierStylePara elsevierViewall">Cocaine and alcohol are two well-known triggers of BrS-like ECG pattern and VF&#44; both alone or with cocaethylene&#44; the ensuing metabolite of their combined use&#46;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">15&#44;87</span></a></p></span></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Discussion and conclusions</span><p id="par0430" class="elsevierStylePara elsevierViewall">An increasing number of cardiovascular and non-cardiovascular drugs have been broadly associated with proarrhythmia and SCD&#46; In fact&#44; drug-induced proarrhythmia should always be viewed as a prelude to SCD&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a> Hence&#44; it has been a growing challenge for physicians&#44; the regulatory agencies responsible for assessing drug safety and the pharmaceutical industry due to the pressure to create newer and safer agents&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a></p><p id="par0435" class="elsevierStylePara elsevierViewall">Physicians should weigh the risks of potentially fatal outcomes against therapeutic benefits when making decisions about drug prescriptions&#46; In the event of a suspicious drug-induced proarrhythmia&#44; withdrawal of the offending drugs is recommended&#44; but only after ruling out other concomitant risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">12</span></a></p><p id="par0440" class="elsevierStylePara elsevierViewall">Physicians who are aware of inherited arrhythmia syndrome should provide a letter or a similar useful tool to their patients and family members&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">15</span></a> Postema et al&#46; provide an example of such a letter&#44; available in various languages on their website&#44; which contains drugs that should be avoided or contraindicated in BrS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">26</span></a></p><p id="par0445" class="elsevierStylePara elsevierViewall">The uncertainty regarding the correlation between the magnitude of QT interval prolongation and the risk of TdP events should lead to a search for more knowledge on risk stratification of drug-induced TdP&#44; given the possible devastating consequences&#46;</p><p id="par0450" class="elsevierStylePara elsevierViewall">Post-approval safety studies provide reliable data for physicians about drug safety&#46; Given the tremendous significance in clinical practice&#44; this review highlights the need for synergy among physicians&#44; regulatory agencies and drug manufacturers&#44; and the need for routine spontaneous reporting and drug utilization analyses&#46;</p><p id="par0455" class="elsevierStylePara elsevierViewall">Future studies to obtain further knowledge and a better understanding of genetic variants related to pharmacokinetics and pharmacodynamics are crucial to more accurately predict drug-induced fatal outcomes for at-risk patients and to clarify which drugs can be administrated more safely&#46; This may avoid the inappropriate withdrawal of certain drugs from the market&#46; Undoubtedly&#44; the field of genetics is growing faster than expected&#44; and it will surely play a key role in this major health concern&#46;</p></span></span>"
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          "titulo" => "Introduction"
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              "identificador" => "sec0010"
              "titulo" => "Sudden cardiac death"
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            1 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Inherited channelopathies"
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            2 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "QT prolongation&#44; torsades de pointes and congenital long QT syndrome"
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              "titulo" => "Short QT syndrome"
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          "titulo" => "Drug-induced proarrhythmia and SCD"
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            0 => "Sudden cardiac death"
            1 => "Long QT syndrome"
            2 => "Torsades de pointes"
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            4 => "Brugada syndrome"
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            0 => "Morte s&#250;bita card&#237;aca"
            1 => "S&#237;ndrome do QT longo"
            2 => "<span class="elsevierStyleItalic">Torsades de pointes</span>"
            3 => "S&#237;ndrome do QT curto"
            4 => "S&#237;ndrome de Brugada"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Sudden cardiac death is a major public health challenge&#44; which can be caused by genetic or acquired structural or electrophysiological abnormalities&#46; These abnormalities include hereditary channelopathies&#58; long QT&#44; short QT and Brugada syndromes&#46; These syndromes are a notable concern&#44; particularly in young people&#44; due to their high propensity for severe ventricular arrhythmias and sudden cardiac death&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Current evidence suggests the involvement of an increasing number of drugs in acquired forms of long QT and Brugada syndromes&#46; However&#44; drug-induced short QT syndrome is still a rarely reported condition&#46; Therefore&#44; there has been speculation on its clinical significance&#44; since few fatal arrhythmias and sudden cardiac death cases have been described so far&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Drug-induced proarrhythmia is a growing challenge for physicians&#44; regulatory agencies and the pharmaceutical industry&#46; Physicians should weigh the risks of potentially fatal outcomes against the therapeutic benefits&#44; when making decisions about drug prescriptions&#46; Growing concerns about its safety and the need for more accurate predictive models for drug-induced fatal outcomes justify further research in these fields&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The aim of this article is to comprehensively and critically review the recently published evidence with regard to drug-induced life-threatening arrhythmias and sudden cardiac death&#46; This article will take into account the provision of data to physicians that are useful in the identification of the culprit drugs&#44; and thus&#44; contribute to the prompt recognition and management of these serious clinical conditions&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A morte s&#250;bita card&#237;aca &#233; um desafio significativo para a sa&#250;de p&#250;blica&#44; pode desencadear-se de anormalidades estruturais ou eletrofisiol&#243;gicas&#44; tanto gen&#233;ticas como adquiridas&#44; e abranger as assim chamadas canalopatias heredit&#225;rias&#58; s&#237;ndromes do QT longo&#44; QT curto e Brugada&#46; Essas s&#237;ndromes s&#227;o um problema consider&#225;vel&#44; particularmente para os jovens&#44; pela sua elevada propens&#227;o para arritmias ventriculares graves e morte s&#250;bita card&#237;aca&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A evid&#234;ncia atual sugere o envolvimento de um n&#250;mero crescente de f&#225;rmacos nas formas adquiridas das s&#237;ndromes do QT longo e Brugada&#46; No entanto&#44; a s&#237;ndrome do QT curto induzida por f&#225;rmacos &#233; ainda uma condi&#231;&#227;o raramente reportada&#46; Consequentemente&#44; especula&#231;&#227;o tem surgido sobre o seu significado cl&#237;nico&#44; uma vez que poucos casos de arritmias fatais e de morte s&#250;bita card&#237;aca foram descritos at&#233; ao momento&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A pr&#243;-arritmia induzida por f&#225;rmacos &#233; um desafio crescente tanto para m&#233;dicos como para entidades reguladoras e ind&#250;stria farmac&#234;utica&#46; Os m&#233;dicos devem pesar o risco de desfechos potencialmente fatais com os benef&#237;cios terap&#234;uticos&#44; aquando da tomada de decis&#245;es na prescri&#231;&#227;o de f&#225;rmacos&#46; As preocupa&#231;&#245;es crescentes sobre a sua seguran&#231;a e a necessidade de modelos preditivos mais precisos para desfechos fatais induzidos por f&#225;rmacos justificam pesquisas adicionais nesses dom&#237;nios&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">O objetivo deste artigo foi rever&#44; de forma abrangente e cr&#237;tica&#44; a evid&#234;ncia publicada recentemente&#44; no que diz respeito &#224;s arritmias potencialmente fatais e morte s&#250;bita card&#237;aca induzidas por f&#225;rmacos&#44; tendo em considera&#231;&#227;o o fornecimento de dados &#250;teis para m&#233;dicos na identifica&#231;&#227;o dos f&#225;rmacos respons&#225;veis e&#44; assim&#44; contribuir para o pronto reconhecimento e gest&#227;o desses quadros cl&#237;nicos graves&#46;</p></span>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Adapted from the website <a class="elsevierStyleInterRef" target="_blank" id="intr0005" href="http://www.crediblemeds.org/">www&#46;crediblemeds&#46;org</a><a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">25</span></a> &#40;accessed January 12&#44; 2017&#41;&#46; For an extensive and systematically updated list of all available evidence about the offending drugs and corresponding TdP risk categories&#44; please visit <a class="elsevierStyleInterRef" target="_blank" id="intr0010" href="http://www.crediblemeds.org/">www&#46;crediblemeds&#46;org</a>&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; GI&#58; gastrointestinal&#59; SNRI&#58; serotonin and norepinephrine reuptake inhibitors&#59; SSRI&#58; selective serotonin reuptake inhibitors&#59; TdP&#58; torsades de pointes&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug Class&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Risk category<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">&#42;&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Generic name&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antianginals</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bepridil<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ranolazine<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiarrhythmics&#44; class Ia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Disopyramide&#44;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">19&#44;38</span></a> Procainamide&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Quinidine<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">13&#44;14&#44;19&#44;27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiarrhythmics&#44; class III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amiodarone&#44;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">1&#44;10&#44;14&#44;19&#44;27&#44;38&#44;40&#44;42</span></a><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#8225;</span></a> Dofetilide&#44;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">14&#44;19&#44;27</span></a> Ibutilide<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">19&#44;27&#44;38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiarrhythmics&#47;Beta blockers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sotalol<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">1&#44;10&#44;13&#44;14&#44;19&#44;27&#44;38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antibiotics&#44; macrolides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Azithromycin&#44;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">36&#44;42&#44;71</span></a> Clarithromycin&#44;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">1&#44;27&#44;36</span></a> Erythromycin<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">1&#44;27&#44;36&#44;38&#44;40</span></a><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antibiotics&#44; quinolones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ciprofloxacin&#44;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">42</span></a> Grepafloxacin&#44;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a> Levofloxacin&#44;<a class="elsevierStyleCrossRefs" href="#bib0670"><span class="elsevierStyleSup">42&#44;71</span></a> Moxifloxacin&#44;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">14</span></a> Sparfloxacin<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antiemetics</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Domperidone&#44;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">37&#44;73</span></a> Ondansetron<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">19&#44;42&#44;75</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dolasetron&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Granisetron<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antifungals</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fluconazole&#44;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a> Pentamidine<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Voriconazole<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antihistamines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diphenhydramine<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antimania&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lithium<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;38&#44;55&#44;87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antimalarials</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Halofantrine<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Quinine sulfate<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antineoplastics</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Arsenic trioxide&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a> Vandetanib<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dasatinib&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a> Lapatinib&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a> Nilotinib&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a> Sunitinib&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a> Vemurafenib&#44;<a class="elsevierStyleCrossRefs" href="#bib0845"><span class="elsevierStyleSup">77&#44;78</span></a> Vorinostat<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antipsychotics</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Haloperidol&#44;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;9&#44;14&#44;27&#44;38&#44;40&#44;41&#44;48&#44;53&#8211;56&#44;63&#44;67</span></a> Levomepromazine&#44;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;45&#44;48&#44;53&#44;55&#44;63</span></a> Mesoridazine&#44;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a> Pimozide&#44;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">55</span></a> Thioridazine<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;9&#44;14&#44;38&#44;41&#44;67</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cyamemazine &#40;cyamepromazine&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#44;54&#44;63</span></a> Flupentixol&#44;<a class="elsevierStyleCrossRefs" href="#bib0735"><span class="elsevierStyleSup">55&#44;56</span></a> Perphenazine<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">Antipsychotics&#44; atypical</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sulpiride<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Aripiprazole&#44;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">56</span></a> Clozapine&#44;<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">38&#44;41&#44;53&#8211;55&#44;63</span></a> Iloperidone&#44;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">14</span></a> Paliperidone&#44;<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">38&#44;55&#44;66</span></a> Risperidone&#44;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">14&#44;38&#44;41&#44;53&#8211;56&#44;63&#44;65</span></a> Sertindole&#44;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;38&#44;63</span></a> Tiapride<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">56</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amisulpride&#44;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#8211;56&#44;63</span></a> Olanzapine&#44;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">14&#44;41&#44;53&#44;54&#44;56&#44;63</span></a> Quetiapine&#44;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">14&#44;27&#44;38&#44;39&#44;41&#44;53&#8211;55&#44;63&#44;64</span></a> Ziprasidone<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;9&#44;14&#44;38&#44;41&#44;53&#8211;55&#44;63</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antipsychotics&#47;antiemetics</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Chlorpromazine&#44;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;38&#44;45&#44;53&#44;54&#44;63</span></a> Droperidol<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">19&#44;53&#44;54</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Promethazine<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GI stimulants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cisapride&#44;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">General anesthetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sevoflurane<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">19&#44;72</span></a><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Opioid agonists&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Levomethadyl acetate&#44;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Methadone<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;14&#44;19&#44;34&#44;35&#44;55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Opioid receptor modulator&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Buprenorphine<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Psychostimulants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Atomoxetine<a class="elsevierStyleCrossRef" href="#bib0855"><span class="elsevierStyleSup">79</span></a><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SNRI antidepressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Venlafaxine<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">38&#44;41&#44;50&#44;55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">SSRI antidepressants</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Citalopram&#44;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;27&#44;41&#44;46&#8211;48&#44;55</span></a> Escitalopram<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;27&#44;38&#44;41&#44;46&#44;48&#44;55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fluoxetine&#44;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">41</span></a> Sertraline<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Tricyclic antidepressants</td><td class="td" title="table-entry  " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clomipramine&#44;<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">45&#44;55</span></a> Desipramine&#44;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">45</span></a> Imipramine &#40;melipramine&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0665"><span class="elsevierStyleSup">41&#44;45&#44;55</span></a> Nortriptyline<a class="elsevierStyleCrossRefs" href="#bib0665"><span class="elsevierStyleSup">41&#44;45&#44;55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amitriptyline&#44;<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">45&#44;55</span></a> Doxepin<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other therapeutic drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not applicable<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amoxapine&#44;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">45</span></a> Atropine&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Bromperidol&#44;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">53</span></a> Bupropion&#44;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">50</span></a><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#8224;</span></a> Cetirizine&#44;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a> Chlorprothixene&#44;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#44;55&#44;63</span></a> Clotiapine&#44;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">48</span></a> Depsipeptide&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a> Desflurane&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Desloratadine&#44;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a> Enflurane&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Fexofenadine&#44;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a> Fluphenazine&#44;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#44;63</span></a> Ganciclovir&#44;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">56</span></a> Glycopyrrolate&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Halothane&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Hydroquinidine&#44;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a> Isoflurane&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Levocetirizine&#44;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">56</span></a> Loratadine&#44;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a> Mizolastine&#44;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a> Moclobemide&#44;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">55</span></a> Nitric oxide&#44;<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">72</span></a><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#8225;</span></a> Oxatomide&#44;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">56</span></a> Oxycodone&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Pentobarbital&#44;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a> Pilsicainide&#44;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">43</span></a> Promazine&#44;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">48</span></a> Propericiazine&#44;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">45</span></a> Propoxyphene&#44;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Prothipendyl&#44;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">53</span></a> Succinylcholine&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Verapamil&#44;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">39</span></a> Zuclopenthixol<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">53</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Non-therapeutic drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not applicable<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Alcohol&#44;<a class="elsevierStyleCrossRef" href="#bib0870"><span class="elsevierStyleSup">82</span></a><a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">&#42;&#42;</span></a> Ginseng&#44;<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">83</span></a><br>Licorice root compounds &#40;glycyrrhizin&#44; flavones&#41;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">84</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Not included in the original drug list of CredibleMeds&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Only in Overdose&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Concomitant use of QT-prolonging drugs&#46;</p>"
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            3 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "&#167;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Removed from market&#46;</p>"
            ]
            4 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "&#42;&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Only in binge drinking &#40;i&#46;e&#46;&#44; &#8805;5 alcoholic beverages in one day&#44; during the previous 12 months&#41;&#46;</p>"
            ]
            5 => array:3 [
              "identificador" => "tblfn0030"
              "etiqueta" => "&#42;&#42;&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">TdP risk categories&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Agents implicated in drug-induced QT prolongation and&#47;or torsades de pointes&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
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        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug class&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Generic name&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiarrhythmics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Digitalis<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiepileptics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rufinamide&#44;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;86</span></a> Lamotrigine&#44;<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">86</span></a><a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">&#42;</span></a> Valproic acid<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">86</span></a><a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1752732.png"
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          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0035"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Combined with rufinamide&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Agents implicated in drug-induced QT shortening and&#47;or life-threatening arrhythmias&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Adapted from the website <a class="elsevierStyleInterRef" target="_blank" id="intr0015" href="http://www.brugadadrugs.org/">www&#46;brugadadrugs&#46;org</a><a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">26</span></a> &#40;accessed January 12&#44; 2017&#41;&#46; For an extensive and systematically updated list of all available evidence about the offending drugs&#44; corresponding risk categories and classes of recommendation&#44; please visit <a class="elsevierStyleInterRef" target="_blank" id="intr0020" href="http://www.brugadadrugs.org/">www&#46;brugadadrugs&#46;org</a>&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; SSRI&#58; selective serotonin reuptake inhibitors&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug class&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Risk category<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Generic name&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Class&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Anesthetics&#47;analgesics</td><td class="td" title="table-entry  " align="left" valign="top">To be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine&#44;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;21&#44;23&#44;87</span></a> Procaine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;23&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Propofol<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;21&#44;23&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ketamine<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Tramadol<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antianginals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not to be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diltiazem&#44;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a> Nicorandil&#44;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a> Nifedipine&#44;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a> Nitroglycerine<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antiarrhythmics&#44; class Ia</td><td class="td" title="table-entry  " align="left" valign="top">To be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ajmaline&#44;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">7&#44;10&#44;15&#44;21&#44;23&#44;63&#44;87</span></a> Procainamide<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">7&#44;10&#44;15&#44;21&#44;23&#44;87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cibenzoline&#44;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a> Disopyramide<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antiarrhythmics&#44; class Ic</td><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">To be avoided</td><td class="td" title="table-entry  " align="left" valign="top">Flecainide&#44;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">7&#44;10&#44;15&#44;21&#44;23&#44;63&#44;87</span></a> Pilsicainide<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">7&#44;10&#44;15&#44;21&#44;23&#44;87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Propafenone<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiarrhythmics&#44; class III &#40;also Ia&#44; II and IV effects&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amiodarone<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">89</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiarrhythmics&#44; class IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verapamil<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiemetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dimenhydrinate&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a> Metoclopramide<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antiepileptics</td><td class="td" title="table-entry  " align="left" valign="top">To be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oxcarbazepine<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Carbamazepine&#44;<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">91</span></a><a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">&#8225;</span></a> Lamotrigine&#44;<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">91</span></a><a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">&#8225;</span></a> Phenytoin<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">91</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antihistamines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diphenhydramine&#44;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Terfenadine&#47;Fexofenadine<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antipsychotics</td><td class="td" title="table-entry  " align="left" valign="top">To be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Loxapine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a> Trifluoperazine<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cyamemazine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;38&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Perphenazine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Thioridazine<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SSRI antidepressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fluoxetine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;38&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Fluvoxamine&#44;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a> Paroxetine<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tetracyclic Antidepressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Maprotiline<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;38&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Tricyclic Antidepressants</td><td class="td" title="table-entry  " align="left" valign="top">To be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amytriptiline&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Clomipramine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;38&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Desipramine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Nortriptyline<a class="elsevierStyleCrossRefs" href="#bib0485"><span class="elsevierStyleSup">5&#44;21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dosulepin&#44;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Doxepin&#44;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Imipramine<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">To be avoided&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Edrophonium<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a>&nbsp;\t\t\t\t\t\t\n
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      "titulo" => "References"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death&#58; The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology &#40;ESC&#41; Endorsed by&#58; Association for European Paediatric and Congenital Cardiology &#40;AEPC&#41;"
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                          "etal" => true
                          "autores" => array:3 [ …3]
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                    0 => array:2 [
                      "doi" => "10.1093/europace/euv319"
                      "Revista" => array:6 [
                        "tituloSerie" => "Europace"
                        "fecha" => "2015"
                        "volumen" => "17"
                        "paginaInicial" => "1601"
                        "paginaFinal" => "1687"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
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              "identificador" => "bib0470"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sudden cardiac death in young adult"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12012-014-9255-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cardiovasc Toxicol"
                        "fecha" => "2014"
                        "volumen" => "14"
                        "paginaInicial" => "379"
                        "paginaFinal" => "386"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0475"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ventricular arrhythmias and sudden cardiac death"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(12)61413-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2012"
                        "volumen" => "380"
                        "paginaInicial" => "1520"
                        "paginaFinal" => "1529"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pathophysiology and prevention of sudden cardiac death"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1139/cjpp-2015-0366"
                      "Revista" => array:6 [
                        "tituloSerie" => "Can J Physiol Pharmacol"
                        "fecha" => "2016"
                        "volumen" => "94"
                        "paginaInicial" => "237"
                        "paginaFinal" => "244"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sudden cardiac arrest associated with use of a non-cardiac drug that reduces cardiac excitability&#58; evidence from bench&#44; bedside&#44; and community"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/eht054"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2013"
                        "volumen" => "34"
                        "paginaInicial" => "1506"
                        "paginaFinal" => "1516"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0490"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antipsychotic drugs are associated with pulseless electrical activity&#58; the Oregon Sudden Unexpected Death Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.hrthm.2012.12.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart Rhythm"
                        "fecha" => "2013"
                        "volumen" => "10"
                        "paginaInicial" => "526"
                        "paginaFinal" => "530"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0495"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ventricular arrhythmias in the absence of structural heart disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2012.01.036"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2012"
                        "volumen" => "59"
                        "paginaInicial" => "1733"
                        "paginaFinal" => "1744"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antipsychotic medication and QT prolongation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.12669/pjms.315.8998"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pak J Med Sci"
                        "fecha" => "2015"
                        "volumen" => "31"
                        "paginaInicial" => "1269"
                        "paginaFinal" => "1271"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Assessing QT interval prolongation and its associated risks with antipsychotics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2165/11587800-000000000-00000"
                      "Revista" => array:6 [
                        "tituloSerie" => "CNS Drugs"
                        "fecha" => "2011"
                        "volumen" => "25"
                        "paginaInicial" => "473"
                        "paginaFinal" => "490"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanisms of drug-induced proarrhythmia in clinical practice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4330/wjc.v5.i6.175"
                      "Revista" => array:6 [
                        "tituloSerie" => "World J Cardiol"
                        "fecha" => "2013"
                        "volumen" => "5"
                        "paginaInicial" => "175"
                        "paginaFinal" => "185"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            10 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevention of torsade de pointes in hospital settings&#58; a scientific statement from the American Heart Association and the American College of Cardiology Foundation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2010.01.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2010"
                        "volumen" => "55"
                        "paginaInicial" => "934"
                        "paginaFinal" => "947"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
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              ]
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              "identificador" => "bib0520"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced prolongation of the QT interval"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra032426"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2004"
                        "volumen" => "350"
                        "paginaInicial" => "1013"
                        "paginaFinal" => "1022"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Unveiling specific triggers and precipitating factors for fatal cardiac events in inherited arrhythmia syndromes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1253/circj.CJ-15-0322"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circ J"
                        "fecha" => "2015"
                        "volumen" => "79"
                        "paginaInicial" => "1185"
                        "paginaFinal" => "1192"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacogenetics of drug-induced QT interval prolongation&#58; an update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40264-015-0316-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Drug Saf"
                        "fecha" => "2015"
                        "volumen" => "38"
                        "paginaInicial" => "855"
                        "paginaFinal" => "867"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
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              "identificador" => "bib0535"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiac sodium channels and inherited electrophysiological disorders&#58; an update on the pharmacotherapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1517/14656566.2014.936380"
                      "Revista" => array:6 [
                        "tituloSerie" => "Expert Opin Pharmacother"
                        "fecha" => "2014"
                        "volumen" => "15"
                        "paginaInicial" => "1875"
                        "paginaFinal" => "1887"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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              "identificador" => "bib0540"
              "etiqueta" => "16"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HRS&#47;EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies&#58; this document was developed as a partnership between the Heart Rhythm Society &#40;HRS&#41; and the European Heart Rhythm Association &#40;EHRA&#41;"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/europace/eur245"
                      "Revista" => array:6 [
                        "tituloSerie" => "Europace"
                        "fecha" => "2011"
                        "volumen" => "13"
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                        "paginaFinal" => "1109"
                        "link" => array:1 [
                          0 => array:2 [ …2]
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                    ]
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              "identificador" => "bib0545"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "QTc behavior during exercise and genetic testing for the long-QT syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
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                    ]
                  ]
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                      "doi" => "10.1161/CIRCULATIONAHA.111.062182"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2011"
                        "volumen" => "124"
                        "paginaInicial" => "2181"
                        "paginaFinal" => "2184"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            17 => array:3 [
              "identificador" => "bib0550"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Idiopathic short QT interval&#58; a new clinical syndrome&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000047299"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cardiology"
                        "fecha" => "2000"
                        "volumen" => "94"
                        "paginaInicial" => "99"
                        "paginaFinal" => "102"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0555"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sudden cardiac death and disorders of the QT interval&#58; anesthetic implications and focus on perioperative management"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.jvca.2015.07.026"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cardiothorac Vasc Anesth"
                        "fecha" => "2015"
                        "volumen" => "29"
                        "paginaInicial" => "1723"
                        "paginaFinal" => "1733"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0560"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Right bundle branch block&#44; persistent ST segment elevation and sudden cardiac death&#58; a distinct clinical and electrocardiographic syndrome&#46; A multicenter report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "1992"
                        "volumen" => "20"
                        "paginaInicial" => "1391"
                        "paginaFinal" => "1396"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            20 => array:3 [
              "identificador" => "bib0565"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brugada syndrome&#58; clinical&#44; genetic&#44; molecular&#44; cellular&#44; and ionic aspects"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cpcardiol.2015.06.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Probl Cardiol"
                        "fecha" => "2016"
                        "volumen" => "41"
                        "paginaInicial" => "7"
                        "paginaFinal" => "57"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            21 => array:3 [
              "identificador" => "bib0570"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetics of Brugada syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.joa.2016.07.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Arrhythm"
                        "fecha" => "2016"
                        "volumen" => "32"
                        "paginaInicial" => "418"
                        "paginaFinal" => "425"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            22 => array:3 [
              "identificador" => "bib0575"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "J-Wave syndromes expert consensus conference report&#58; emerging concepts and gaps in knowledge&#58; endorsed by the Asia Pacific Heart Rhythm Society &#40;APHRS&#41;&#44; the European Heart Rhythm Association &#40;EHRA&#41;&#44; the Heart Rhythm Society &#40;HRS&#41;&#44; and the Latin American Society of Cardiac Pacing and Electrophysiology &#40;Sociedad Latinoamericana de Estimulaci&#243;n Card&#237;aca y Electrofisiolog&#237;a &#91;SOLAECE&#93;&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Europace"
                        "fecha" => "2016"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0580"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HRS&#47;EHRA&#47;APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes&#58; document endorsed by HRS&#44; EHRA&#44; and APHRS in May 2013 and by ACCF&#44; AHA&#44; PACES&#44; and AEPC in June 2013"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.hrthm.2013.05.014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart Rhythm"
                        "fecha" => "2013"
                        "volumen" => "10"
                        "paginaInicial" => "1932"
                        "paginaFinal" => "1963"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            24 => array:3 [
              "identificador" => "bib0585"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Woosley R&#44; Heise CW&#44; Romero KA&#46; QTdrugs List&#46; AZCERT&#44; Inc&#46;&#44; 1822 Innovation Park Dr&#46;&#44; Oro Valley&#44; AZ 85755&#46; <a id="intr0045" class="elsevierStyleInterRef" href="http://www.crediblemeds.org/">www&#46;CredibleMeds&#46;org</a> &#91;accessed 12&#46;01&#46;17&#93;&#46;"
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              ]
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            25 => array:3 [
              "identificador" => "bib0590"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safe drug use in long QT syndrome and Brugada syndrome&#58; comparison of website statistics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/europace/eut018"
                      "Revista" => array:6 [
                        "tituloSerie" => "Europace"
                        "fecha" => "2013"
                        "volumen" => "15"
                        "paginaInicial" => "1042"
                        "paginaFinal" => "1049"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            26 => array:3 [
              "identificador" => "bib0595"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced proarrhythmia&#58; risk factors and electrophysiological mechanisms"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrcardio.2015.110"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Cardiol"
                        "fecha" => "2016"
                        "volumen" => "13"
                        "paginaInicial" => "36"
                        "paginaFinal" => "47"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            27 => array:3 [
              "identificador" => "bib0600"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetics of congenital and drug-induced long QT syndromes&#58; current evidence and future research perspectives"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10840-013-9779-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Interv Card Electrophysiol"
                        "fecha" => "2013"
                        "volumen" => "37"
                        "paginaInicial" => "9"
                        "paginaFinal" => "19"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            28 => array:3 [
              "identificador" => "bib0605"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of smoking on Tp-e interval&#44; Tp-e&#47;QT and Tp-e&#47;QTc ratios as indices of ventricular arrhythmogenesis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.hlc.2014.03.016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart Lung Circ"
                        "fecha" => "2014"
                        "volumen" => "23"
                        "paginaInicial" => "827"
                        "paginaFinal" => "832"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            29 => array:3 [
              "identificador" => "bib0610"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effects of cigarette smoking on the Tp-e interval&#44; Tp-e&#47;QT ratio and Tp-e&#47;QTc ratio"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Adv Clin Exp Med"
                        "fecha" => "2015"
                        "volumen" => "24"
                        "paginaInicial" => "973"
                        "paginaFinal" => "978"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            30 => array:3 [
              "identificador" => "bib0615"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of psychotropic drugs on QT interval dispersion in adult patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arq Bras Cardiol"
                        "fecha" => "2014"
                        "volumen" => "102"
                        "paginaInicial" => "465"
                        "paginaFinal" => "472"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            31 => array:3 [
              "identificador" => "bib0620"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Psychiatric medications and sudden cardiac death&#58; putting the risk in perspective"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3928/02793695-20150527-55"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Psychosoc Nurs Ment Health Serv"
                        "fecha" => "2015"
                        "volumen" => "53"
                        "paginaInicial" => "23"
                        "paginaFinal" => "25"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            32 => array:3 [
              "identificador" => "bib0625"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Non-cardiovascular drugs that inhibit hERG-encoded potassium channels and risk of sudden cardiac death"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/hrt.2009.188367"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart"
                        "fecha" => "2011"
                        "volumen" => "97"
                        "paginaInicial" => "215"
                        "paginaFinal" => "220"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            33 => array:3 [
              "identificador" => "bib0630"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A possible mechanistic link between the CYP2C19 genotype&#44; the methadone metabolite ethylidene-1&#44;5-dimethyl-3&#44;3-diphenylpyrrolidene &#40;EDDP&#41;&#44; and methadone-induced corrected QT interval prolongation in a pilot study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40291-015-0137-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Diagn Ther"
                        "fecha" => "2015"
                        "volumen" => "19"
                        "paginaInicial" => "131"
                        "paginaFinal" => "138"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            34 => array:3 [
              "identificador" => "bib0635"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "QT interval prolongation&#58; prevalence&#44; risk factors and pharmacovigilance data among methadone-treated patients in France"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1472-8206.2010.00871.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Fundam Clin Pharmacol"
                        "fecha" => "2011"
                        "volumen" => "25"
                        "paginaInicial" => "503"
                        "paginaFinal" => "510"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            35 => array:3 [
              "identificador" => "bib0640"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of macrolide antibiotics in increasing cardiovascular risk"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2015.09.029"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2015"
                        "volumen" => "66"
                        "paginaInicial" => "2173"
                        "paginaFinal" => "2184"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
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            36 => array:3 [
              "identificador" => "bib0645"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Domperidone in Parkinson&#39;s disease&#58; a perilous arrhythmogenic or the gold standard&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Drug Saf"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "paginaInicial" => "63"
                        "paginaFinal" => "68"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            37 => array:3 [
              "identificador" => "bib0650"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sudden death of cardiac origin and psychotropic drugs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fphar.2012.00076"
                      "Revista" => array:5 [
                        "tituloSerie" => "Front Pharmacol"
                        "fecha" => "2012"
                        "volumen" => "3"
                        "paginaInicial" => "76"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            38 => array:3 [
              "identificador" => "bib0655"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nitric oxide synthase 1 adaptor protein&#44; an emerging new genetic marker for QT prolongation and sudden cardiac death"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Cardiol Sin"
                        "fecha" => "2013"
                        "volumen" => "29"
                        "paginaInicial" => "217"
                        "paginaFinal" => "225"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            39 => array:3 [
              "identificador" => "bib0660"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced long QT syndrome and fatal arrhythmias in the intensive care unit"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/aas.12257"
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                        "tituloSerie" => "Acta Anaesthesiol Scand"
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                        "volumen" => "58"
                        "paginaInicial" => "266"
                        "paginaFinal" => "272"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            40 => array:3 [
              "identificador" => "bib0665"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of age and sex on QT prolongation in patients receiving psychotropics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/070674371506000502"
                      "Revista" => array:6 [
                        "tituloSerie" => "Can J Psychiatry"
                        "fecha" => "2015"
                        "volumen" => "60"
                        "paginaInicial" => "206"
                        "paginaFinal" => "214"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
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            ]
            41 => array:3 [
              "identificador" => "bib0670"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acquired long QT syndrome&#58; frequency&#44; onset&#44; and risk factors in intensive care patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4037/ccn2012900"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Nurse"
                        "fecha" => "2012"
                        "volumen" => "32"
                        "paginaInicial" => "32"
                        "paginaFinal" => "41"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0675"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A case of sudden cardiac death due to pilsicainide-induced torsades de pointes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4070/kcj.2014.44.2.122"
                      "Revista" => array:6 [
                        "tituloSerie" => "Korean Circ J"
                        "fecha" => "2014"
                        "volumen" => "44"
                        "paginaInicial" => "122"
                        "paginaFinal" => "124"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0680"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The risk of sudden cardiac death in patients with non-ST elevation acute coronary syndrome and prolonged QTc interval&#58; effect of ranolazine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/europace/eus400"
                      "Revista" => array:6 [
                        "tituloSerie" => "Europace"
                        "fecha" => "2013"
                        "volumen" => "15"
                        "paginaInicial" => "429"
                        "paginaFinal" => "436"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0685"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk factors for QT prolongation associated with acute psychotropic drug overdose"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ajem.2014.09.048"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Emerg Med"
                        "fecha" => "2015"
                        "volumen" => "33"
                        "paginaInicial" => "142"
                        "paginaFinal" => "149"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0690"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiac toxicity in selective serotonin reuptake inhibitor users"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/PAF.0000000000000205"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Forensic Med Pathol"
                        "fecha" => "2015"
                        "volumen" => "36"
                        "paginaInicial" => "293"
                        "paginaFinal" => "297"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0695"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Meta-analysis of selective serotonin reuptake inhibitor-associated QTc prolongation"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4088/JCP.13r08672"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Psychiatry"
                        "fecha" => "2014"
                        "volumen" => "75"
                        "paginaInicial" => "e441"
                        "paginaFinal" => "e449"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0700"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced long QT in adult psychiatric inpatients&#58; the 5-year cross-sectional ECG Screening Outcome in Psychiatry study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1176/appi.ajp.2013.12060860"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Psychiatry"
                        "fecha" => "2013"
                        "volumen" => "170"
                        "paginaInicial" => "1468"
                        "paginaFinal" => "1476"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0705"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Citalopram&#44; QTc interval prolongation&#44; and torsade de pointes&#46; How should we apply the recent FDA ruling&#63;"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.amjmed.2011.12.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med"
                        "fecha" => "2012"
                        "volumen" => "125"
                        "paginaInicial" => "859"
                        "paginaFinal" => "868"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0710"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of QT&#47;QTc prolongation among newer non-SSRI antidepressants"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/1060028014550645"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Pharmacother"
                        "fecha" => "2014"
                        "volumen" => "48"
                        "paginaInicial" => "1620"
                        "paginaFinal" => "1628"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0715"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antidepressants and the risk of sudden cardiac death and ventricular arrhythmia"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/pds.2181"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacoepidemiol Drug Saf"
                        "fecha" => "2011"
                        "volumen" => "20"
                        "paginaInicial" => "903"
                        "paginaFinal" => "913"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0720"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antipsychotic drugs and the risk of ventricular arrhythmia and&#47;or sudden cardiac death&#58; a nation-wide case-crossover study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "J Am Heart Assoc"
                        "fecha" => "2015"
                        "volumen" => "4"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0725"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Torsadogenic risk of antipsychotics&#58; combining adverse event reports with drug utilization data across Europe"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0081208"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS ONE"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "paginaInicial" => "e81208"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0730"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antipsychotics and torsadogenic risk&#58; signals emerging from the US FDA Adverse Event Reporting System database"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40264-013-0032-z"
                      "Revista" => array:6 [
                        "tituloSerie" => "Drug Saf"
                        "fecha" => "2013"
                        "volumen" => "36"
                        "paginaInicial" => "467"
                        "paginaFinal" => "479"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0735"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of arrhythmia induced by psychotropic medications&#58; a proposal for clinical management"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehu100"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2014"
                        "volumen" => "35"
                        "paginaInicial" => "1306"
                        "paginaFinal" => "1315"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0740"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The contribution of national spontaneous reporting systems to detect signals of torsadogenicity&#58; issues emerging from the ARITMO project"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40264-015-0353-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Drug Saf"
                        "fecha" => "2016"
                        "volumen" => "39"
                        "paginaInicial" => "59"
                        "paginaFinal" => "68"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0745"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antipsychotics and the risks of sudden cardiac death and all-cause death&#58; cohort studies in Medicaid and dually-eligible Medicaid-Medicare beneficiaries of five states"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4172/2155-9880.S10-006"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Exp Cardiolog"
                        "fecha" => "2013"
                        "volumen" => "10"
                        "numero" => "Suppl"
                        "paginaInicial" => "1"
                        "paginaFinal" => "9"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0750"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "QTc prolongation&#58; is clozapine safe&#63; Study of 82 cases before and after clozapine treatment"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hup.1221"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hum Psychopharmacol"
                        "fecha" => "2011"
                        "volumen" => "26"
                        "paginaInicial" => "397"
                        "paginaFinal" => "403"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0755"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparative mortality associated with ziprasidone and olanzapine in real-world use among 18&#44;154 patients with schizophrenia&#58; The Ziprasidone Observational Study of Cardiac Outcomes &#40;ZODIAC&#41;"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1176/appi.ajp.2010.08040484"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Psychiatry"
                        "fecha" => "2011"
                        "volumen" => "168"
                        "paginaInicial" => "193"
                        "paginaFinal" => "201"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0760"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Methodological challenges in the coding and adjudication of sudden deaths in a large simple trial with observational follow-up&#58; the ziprasidone observational study of cardiac outcomes &#40;ZODIAC&#41;"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/pds.2185"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacoepidemiol Drug Saf"
                        "fecha" => "2011"
                        "volumen" => "20"
                        "paginaInicial" => "1192"
                        "paginaFinal" => "1198"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0765"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug safety evaluation of ziprasidone"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1517/14740338.2011.560114"
                      "Revista" => array:6 [
                        "tituloSerie" => "Expert Opin Drug Saf"
                        "fecha" => "2011"
                        "volumen" => "10"
                        "paginaInicial" => "437"
                        "paginaFinal" => "448"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0770"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The cardiac safety of aripiprazole treatment in patients at high risk for torsade&#58; a systematic review with a meta-analytic approach"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Psychopharmacology &#40;Berl&#41;"
                        "fecha" => "2015"
                        "volumen" => "232"
                        "paginaInicial" => "3297"
                        "paginaFinal" => "3308"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0775"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiovascular safety of antipsychotics&#58; a clinical overview"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1517/14740338.2016.1161021"
                      "Revista" => array:6 [
                        "tituloSerie" => "Expert Opin Drug Saf"
                        "fecha" => "2016"
                        "volumen" => "15"
                        "paginaInicial" => "679"
                        "paginaFinal" => "688"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0780"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Quetiapine&#44; QTc interval prolongation&#44; and torsade de pointes&#58; a review of case reports"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/2045125313510194"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ther Adv Psychopharmacol"
                        "fecha" => "2014"
                        "volumen" => "4"
                        "paginaInicial" => "130"
                        "paginaFinal" => "138"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0785"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased risk of antipsychotic-related QT prolongation during nighttime&#58; a 24-hour holter electrocardiogram recording study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/JCP.0b013e31823f6f21"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Psychopharmacol"
                        "fecha" => "2012"
                        "volumen" => "32"
                        "paginaInicial" => "18"
                        "paginaFinal" => "22"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0790"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "QT prolongation of the antipsychotic risperidone is predominantly related to its 9-hydroxy metabolite paliperidone"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hup.1258"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hum Psychopharmacol"
                        "fecha" => "2012"
                        "volumen" => "27"
                        "paginaInicial" => "39"
                        "paginaFinal" => "42"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0795"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prescribing pattern of antipsychotic drugs during the years 1996&#8211;2010&#58; a population-based database study in Europe with a focus on torsadogenic drugs"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/bcp.12955"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Clin Pharmacol"
                        "fecha" => "2016"
                        "volumen" => "82"
                        "paginaInicial" => "487"
                        "paginaFinal" => "497"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0800"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "QTc prolongation in patients acutely admitted to hospital for psychosis and treated with second generation antipsychotics"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1155/2013/375020"
                      "Revista" => array:5 [
                        "tituloSerie" => "Schizophr Res Treatment"
                        "fecha" => "2013"
                        "volumen" => "2013"
                        "paginaInicial" => "375020"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0805"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antipsychotic drug administration does not correlate with prolonged rate-corrected QT interval in children and adolescents&#58; results from a nested case-control study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1089/cap.2011.0024"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Child Adolesc Psychopharmacol"
                        "fecha" => "2011"
                        "volumen" => "21"
                        "paginaInicial" => "365"
                        "paginaFinal" => "368"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0810"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Azithromycin and the risk of cardiovascular death"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1003833"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2012"
                        "volumen" => "366"
                        "paginaInicial" => "1881"
                        "paginaFinal" => "1890"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0815"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Azithromycin and levofloxacin use and increased risk of cardiac arrhythmia and death"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1370/afm.1601"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Fam Med"
                        "fecha" => "2014"
                        "volumen" => "12"
                        "paginaInicial" => "121"
                        "paginaFinal" => "127"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0820"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sudden cardiac arrest during anesthesia in a 30-month-old boy with syndactyly&#58; a case of genetically proven Timothy syndrome"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3346/jkms.2013.28.5.788"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Korean Med Sci"
                        "fecha" => "2013"
                        "volumen" => "28"
                        "paginaInicial" => "788"
                        "paginaFinal" => "791"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0825"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Domperidone and risk of ventricular arrhythmia and cardiac death&#58; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40261-015-0360-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Drug Investig"
                        "fecha" => "2016"
                        "volumen" => "36"
                        "paginaInicial" => "97"
                        "paginaFinal" => "107"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0830"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of out-of-hospital sudden cardiac death in users of domperidonem proton pump inhibitors&#44; or metoclopramide&#58; a population-based nested case-control study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40264-015-0338-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Drug Saf"
                        "fecha" => "2015"
                        "volumen" => "38"
                        "paginaInicial" => "1187"
                        "paginaFinal" => "1199"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0835"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intravenous ondansetron and the QT interval in adult emergency department patients&#58; an observational study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/acem.12836"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acad Emerg Med"
                        "fecha" => "2016"
                        "volumen" => "23"
                        "paginaInicial" => "102"
                        "paginaFinal" => "105"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0840"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pro-arrhythmic potential of oral antihistamines &#40;H1&#41;&#58; combining adverse event reports with drug utilization data across Europe"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0119551"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLOS ONE"
                        "fecha" => "2015"
                        "volumen" => "10"
                        "paginaInicial" => "e0119551"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib0845"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chemotherapy and QT prolongation&#58; overview with clinical perspective"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s11936-014-0303-8"
                      "Revista" => array:5 [
                        "tituloSerie" => "Curr Treat Options Cardiovasc Med"
                        "fecha" => "2014"
                        "volumen" => "16"
                        "paginaInicial" => "303"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib0850"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "What links BRAF to the heart function&#63; New insights from the cardiotoxicity of BRAF inhibitors in cancer treatment"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.18632/oncotarget.5853"
                      "Revista" => array:6 [
                        "tituloSerie" => "Oncotarget"
                        "fecha" => "2015"
                        "volumen" => "6"
                        "paginaInicial" => "35589"
                        "paginaFinal" => "35601"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            78 => array:3 [
              "identificador" => "bib0855"
              "etiqueta" => "79"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of serious cardiovascular problems with medications for attention-deficit hyperactivity disorder"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40263-012-0019-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "CNS Drugs"
                        "fecha" => "2013"
                        "volumen" => "27"
                        "paginaInicial" => "15"
                        "paginaFinal" => "30"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            79 => array:3 [
              "identificador" => "bib0860"
              "etiqueta" => "80"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Do prescription stimulants increase the risk of adverse cardiovascular events&#63;&#58; A systematic review"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2261-12-41"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Cardiovasc Disord"
                        "fecha" => "2012"
                        "volumen" => "12"
                        "paginaInicial" => "41"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            80 => array:3 [
              "identificador" => "bib0865"
              "etiqueta" => "81"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Methylphenidate and risk of serious cardiovascular events in adults"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1176/appi.ajp.2011.11010125"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Psychiatry"
                        "fecha" => "2012"
                        "volumen" => "169"
                        "paginaInicial" => "178"
                        "paginaFinal" => "185"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            81 => array:3 [
              "identificador" => "bib0870"
              "etiqueta" => "82"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Coffee&#44; alcohol&#44; smoking&#44; physical activity and QT interval duration&#58; results from the Third National Health and Nutrition Examination Survey"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0017584"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS ONE"
                        "fecha" => "2011"
                        "volumen" => "6"
                        "paginaInicial" => "e17584"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            82 => array:3 [
              "identificador" => "bib0875"
              "etiqueta" => "83"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ginseng&#58; a potential cause of long QT"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jelectrocard.2010.08.007"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Electrocardiol"
                        "fecha" => "2011"
                        "volumen" => "44"
                        "paginaInicial" => "357"
                        "paginaFinal" => "358"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            83 => array:3 [
              "identificador" => "bib0880"
              "etiqueta" => "84"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Polymorphic ventricular tachycardia &#40;Torsades de pointes&#41; due to licorice root tea"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Turk Kardiyol Dern Ars"
                        "fecha" => "2013"
                        "volumen" => "41"
                        "paginaInicial" => "241"
                        "paginaFinal" => "244"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            84 => array:3 [
              "identificador" => "bib0885"
              "etiqueta" => "85"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced QT interval shortening&#58; potential harbinger of proarrhythmia and regulatory perspectives"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1476-5381.2009.00191.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Pharmacol"
                        "fecha" => "2010"
                        "volumen" => "159"
                        "paginaInicial" => "58"
                        "paginaFinal" => "69"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            85 => array:3 [
              "identificador" => "bib0890"
              "etiqueta" => "86"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.hrthm.2012.01.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart Rhythm"
                        "fecha" => "2012"
                        "volumen" => "9"
                        "paginaInicial" => "776"
                        "paginaFinal" => "781"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            86 => array:3 [
              "identificador" => "bib0895"
              "etiqueta" => "87"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced Brugada syndrome by noncardiac agents"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/pace.12234"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pacing Clin Electrophysiol"
                        "fecha" => "2013"
                        "volumen" => "36"
                        "paginaInicial" => "1570"
                        "paginaFinal" => "1577"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            87 => array:3 [
              "identificador" => "bib0900"
              "etiqueta" => "88"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The safety of flecainide treatment of atrial fibrillation&#58; long-term incidence of sudden cardiac death and proarrhythmic events"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2796.2011.02395.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Intern Med"
                        "fecha" => "2011"
                        "volumen" => "270"
                        "paginaInicial" => "281"
                        "paginaFinal" => "290"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            88 => array:3 [
              "identificador" => "bib0905"
              "etiqueta" => "89"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brugada electrocardiogram pattern &#8220;unmasked&#8221; by amiodarone infusion"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.mjt.0000433948.16654.91"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Ther"
                        "fecha" => "2014"
                        "volumen" => "21"
                        "paginaInicial" => "540"
                        "paginaFinal" => "541"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            89 => array:3 [
              "identificador" => "bib0910"
              "etiqueta" => "90"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sudden cardiac death is associated both with epilepsy and with use of antiepileptic medications"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/heartjnl-2014-305664"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart"
                        "fecha" => "2015"
                        "volumen" => "101"
                        "paginaInicial" => "17"
                        "paginaFinal" => "22"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            90 => array:3 [
              "identificador" => "bib0915"
              "etiqueta" => "91"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Polytherapy with sodium channel-blocking antiepileptic drugs is associated with arrhythmogenic ST-T abnormality in patients with epilepsy"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.seizure.2016.06.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Seizure"
                        "fecha" => "2016"
                        "volumen" => "40"
                        "paginaInicial" => "81"
                        "paginaFinal" => "87"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            91 => array:3 [
              "identificador" => "bib0920"
              "etiqueta" => "92"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Type 1 Brugada pattern associated with nicotine toxicity"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jemermed.2015.08.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Emerg Med"
                        "fecha" => "2015"
                        "volumen" => "49"
                        "paginaInicial" => "e183"
                        "paginaFinal" => "e186"
                        "link" => array:1 [ …1]
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                ]
              ]
            ]
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Review Article
Drug-induced life-threatening arrhythmias and sudden cardiac death: A clinical perspective of long QT, short QT and Brugada syndromes
Arritmias potencialmente fatais e morte súbita cardíaca induzidas por fármacos: uma perspetiva clínica das síndromes do QT longo, QT curto e Brugada
Diogo Ramalhoa,
Autor para correspondência
silva.josediogo@gmail.com

Corresponding author.
, João Freitasb
a Departamento de Medicina, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
b Serviço de Cardiologia, Centro Hospitalar de São João EPE, Porto, Portugal
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therefore&#44; it is preferred in such cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The expert group from the American College of Cardiology Foundation and the American Heart Association &#40;ACCF&#47;AHA&#41; gives an upper limit of normal &#40;i&#46;e&#46;&#44; estimated 99th percentile&#41; for abnormally prolonged QTc intervals of 470 ms and 480 ms in otherwise healthy post-pubertal males and females&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">11</span></a> Patients with an absolute QTc interval of &#62;500 ms are considered to be at risk for developing torsades de Pointes &#40;TdP&#41;&#44; a polymorphic ventricular tachycardia that may shift into VF and lead to SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">11&#44;12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Congenital QT prolongation is due to various genetically based LQTSs&#46; 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KCNH2&#44; KCNQ1 and KCNJ2&#41; and loss-of-function mutations of calcium channel <span class="elsevierStyleItalic">CACNA1C</span>&#44; <span class="elsevierStyleItalic">CACNB2</span> and <span class="elsevierStyleItalic">CACNA2D1</span> genes have been associated with SQTS&#46;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">1&#44;7&#44;10</span></a> However&#44; the diagnostic yield of genetic testing remains low &#40;i&#46;e&#46;&#44; about 20&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">16</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">SQTS is diagnosed when QTc interval is &#8804;340 ms or&#44; alternatively&#44; should be considered if QTc interval is &#8804;360 ms along with one or more of the following&#58; &#40;1&#41; survival from a VT&#47;VF episode&#44; in the absence of cardiac disease&#59; &#40;2&#41; a confirmed pathogenic mutation&#59; &#40;3&#41; a family history of SQTS&#44; or &#40;4&#41; a family history of sudden death at the age of &#60;40 years&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">1</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Apart from congenital SQTS&#44; other clinical scenarios&#44; such as electrolyte disturbances &#40;e&#46;g&#46;&#44; hypercalcemia&#44; hyperkalemia&#41;&#44; acidosis&#44; increased heart rate and increased levels of acetylcholine or catecholamine can shorten QT interval&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">QT shortening can degenerate into paroxysmal atrial fibrillation &#40;AF&#41; and&#47;or VT and potentially lead to SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">18&#44;19</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Brugada syndrome</span><p id="par0080" class="elsevierStylePara elsevierViewall">Brugada syndrome &#40;BrS&#41; is a relatively recent clinical entity&#44; first described in 1992 by a set of distinctive ECG features&#44; especially right bundle branch block and ST-segment elevation in right precordial leads &#40;i&#46;e&#46;&#44; V<span class="elsevierStyleInf">1</span> to V<span class="elsevierStyleInf">3</span>&#41;&#44; in the absence of other concurrent factors &#40;e&#46;g&#46;&#44; ischemia&#44; structural heart disease or electrolyte imbalance&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">20</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">BrS is inherited through an autosomal dominant mode of transmission&#46; Approximately 20 culprit genes have been reported thus far&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a> The pathogenesis of congenital BrS is more commonly due to loss-of-function mutations in the <span class="elsevierStyleItalic">SCN5A</span> gene&#46; Currently&#44; over 300 <span class="elsevierStyleItalic">SCN5A</span> gene mutations have been described&#44; accounting for the vast majority &#40;i&#46;e&#46;&#44; approximately 75&#37;&#41; of genotype-positive cases&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">22</span></a> Nevertheless&#44; genetic testing identifies such mutations in only about 20-25&#37; of BrS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">16</span></a> The increase in the transient outward potassium current &#40;I<span class="elsevierStyleInf">to</span>&#41; and the decrease in the L-type Ca<span class="elsevierStyleSup">2&#43;</span> current &#40;I<span class="elsevierStyleInf">Ca&#44;L</span>&#41; have also been postulated to contribute to the pathogenesis of BrS&#46;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">15&#44;21</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Patients with a BrS ECG pattern are often clinically concealed at the time of diagnosis&#44; which in turn is often incidental&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a> In fact&#44; patients may persist asymptomatically for life&#44; but a subgroup of BrS patients can experience syncope&#44; nocturnal agonal respiration and palpitations associated with high risk of fatal arrhythmias &#40;e&#46;g&#46;&#44; VT&#47;VF&#41; and SCD&#44; which generally occur in the third or fourth decades of life&#44; mainly at rest or during sleep&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">13&#44;15&#44;21</span></a> Although BrS affects both males and women&#44; the condition appears to be 8 to 10 times more common in males&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">BrS ECG patterns have been categorized as type 1&#44; 2 or 3 according to detailed characteristics of surface ECGs&#46; A coved ST-segment elevation &#8805;2 mm followed by a negative T wave is representative of a type 1 ECG pattern&#46; Type 2 comprises a saddleback ST-segment elevation of &#8805;0&#46;5 mm &#40;i&#46;e&#46;&#44; usually &#8805;2 mm in V<span class="elsevierStyleInf">2</span>&#41; in at least 1 right precordial lead &#40;i&#46;e&#46;&#44; V<span class="elsevierStyleInf">1</span>-V<span class="elsevierStyleInf">3</span>&#41;&#44; followed by a convex shape&#46; T-wave morphology differs in V<span class="elsevierStyleInf">1</span> and it is characteristically positive in V<span class="elsevierStyleInf">2</span>&#46; Type 3 pattern is characterized by either a coved or a saddleback appearance with an ST-segment elevation &#60;1 mm&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">23</span></a> Nonetheless&#44; only type 1 is recognized as diagnostic&#46; Type 2 and type 3 are not specific to BrS and&#44; therefore&#44; it is currently uncertain whether or not they should be considered BrS patterns&#46; However&#44; physicians should be aware and recognize these patterns as they can be an electrocardiographical presentation of some genuine BrS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The diagnostic criteria of BrS were recently updated in the 2016 expert consensus conference on J-wave syndromes&#44;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">23</span></a> since the criteria proposed in the 2015 guidelines<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">1</span></a> and in the previous 2013 consensus statement<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">24</span></a> tend to overdiagnose cases of the type 1 ECG pattern&#46; Overdiagnosis is unmasked after intravenous sodium-channel blocker challenge with ajmaline&#44; flecainide&#44; pilsicainide or procainamide&#46; In such patients&#44; BrS diagnosis should require that the patient also present with at least 1 of the following&#58; &#40;1&#41; nocturnal agonal respiration&#44; &#40;2&#41; syncope of probable arrhythmic cause&#44; &#40;3&#41; family history of SCD at less than 45 years old with negative autopsy&#44; &#40;4&#41; documented polymorphic VT or VF&#44; or &#40;5&#41; coved-type ECGs in family members&#46; A spontaneous type 1 ECG pattern in at least 1 right precordial lead &#40;i&#46;e&#46;&#44; V<span class="elsevierStyleInf">1</span>&#44; V<span class="elsevierStyleInf">2</span> and V<span class="elsevierStyleInf">3</span>&#44; placed in the 2nd&#44; 3rd and 4th intercostal spaces&#44; respectively&#41; is an independent BrS diagnostic criterion&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">23</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Since other acute &#40;e&#46;g&#46;&#44; coronary events&#44; metabolic disorders&#44; electrolyte disturbances&#41; and chronic &#40;e&#46;g&#46;&#44; ventricular hypertrophy&#44; autonomic nervous system disorders&#41; conditions can bring about ST-segment elevation patterns&#44; diagnosis of BrS is feasible only after these scenarios are ruled out&#46;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;23</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Aim</span><p id="par0110" class="elsevierStylePara elsevierViewall">The aim of this article is to comprehensively and critically review the recently published evidence with regard to drug-induced life-threatening arrhythmias and sudden cardiac death&#46; It will take into account the provision of data to physicians that are useful in the identification of the culprit drugs&#44; and thus&#44; contribute to the prompt recognition and management of these serious clinical conditions&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Methods</span><p id="par0115" class="elsevierStylePara elsevierViewall">A comprehensive search was carried out through PubMed to identify human-based studies published in English and&#47;or Portuguese&#44; between January 1&#44; 2011 and January 12&#44; 2017&#46; The following keywords were used in combination&#44; both as Medical Subject Headings &#40;MeSH&#41; terms and text words&#58; &#8220;sudden cardiac death&#8221;&#44; &#8220;cardiac arrhythmias&#8221;&#44; &#8220;long QT syndrome&#8221;&#44; &#8220;torsades de pointes&#8221;&#44; &#8220;Brugada syndrome&#8221;&#44; &#8220;drug-related side effects and adverse reactions&#8221; and &#8220;pharmaceutical preparations&#8221;&#46; Additionally&#44; the text words &#8220;arrhythmias&#8221;&#44; &#8220;proarrhythmia&#8221;&#44; &#8220;torsade de pointes&#8221;&#44; &#8220;short QT syndrome&#8221;&#44; &#8220;adverse effects&#8221;&#44; &#8220;drugs&#8221; and &#8220;drug-induced&#8221; were combined with the abovementioned search terms&#46; The literature search encompassed relevant studies regarding drug-induced proarrhythmia and SCD&#44; especially those which aimed to address the so-called congenital and acquired arrhythmia syndromes LQTS&#44; SQTS or BrS&#46; A clinical perspective was chosen due to the wide range of data within this field&#46; Case reports were excluded&#44; unless they displayed original evidence or were the only source of a causal relationship&#46; Papers that only aimed to address detailed therapeutic strategies were not considered&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">A total of 496 studies were identified&#46; Titles and abstracts were initially screened&#44; and full-text articles were retrieved&#46; The reference list of the identified articles was checked for potentially relevant papers&#46; Two reviewers &#40;i&#46;e&#46;&#44; first and last author&#41; independently analyzed each study to minimize bias&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The final review ended up comprising a total of 90 articles&#46; Two additional websites &#40;i&#46;e&#46;&#44; <a id="intr0025" class="elsevierStyleInterRef" href="http://www.crediblemeds.org/">www&#46;crediblemeds&#46;org</a><a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">25</span></a>&#59; <a id="intr0030" class="elsevierStyleInterRef" href="http://www.brugadadrugs.org/">www&#46;brugadadrugs&#46;org</a><a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">26</span></a>&#41; were included as they provide useful information regarding the aim of this review&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Drug-induced proarrhythmia and SCD</span><p id="par0130" class="elsevierStylePara elsevierViewall">Drug-induced proarrhythmia is the outcome of prior or concomitant use of any drug with life-threatening proarrhythmic effects and SCD risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;27</span></a> Growing evidence suggests the implication of an increasing number of drugs in acquired forms of long QT &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; short QT to a lesser extent &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41; and Brugada syndrome &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Drug-induced LQTS</span><p id="par0135" class="elsevierStylePara elsevierViewall">Acquired LQTS is undoubtedly more common than inherited LQTS&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">9</span></a> Drugs are undeniably the leading cause of acquired LQTS&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">28</span></a> Notably&#44; in the last decade&#44; drug-induced TdP was the single most common cause of the withdrawal or restriction of the use of drugs that have already been marketed&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">12</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The ACCF&#47;AHA scientific statement recognized a QTc interval of &#62;500 ms&#44; or an increase after drug administration of QTc &#62;60 ms from the pre-drug baseline&#44; as alarming signals that should warrant prompt management and correction&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">11</span></a> In fact&#44; the majority of drug-induced TdP cases has been reported with QTc intervals of &#62;500 ms&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">However&#44; data suggests that the magnitude of QTc prolongation does not directly correlate with the risk of developing TdP&#46; Amiodarone and ranolazine are two paradigmatic cases&#44; which undoubtedly cause QT prolongation&#44; but with few reported cases of TdP&#46; Apparently&#44; these agents attenuate the dispersion of ventricular repolarization&#44; which balance out with the QT prolongation effect&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a> Although not yet proven in congenital forms of LQTS&#44; indirect assessment of transmural dispersion of ventricular repolarization using Tpeak-end interval and the Tpeak-Tend&#47;QT ratio &#40;e&#46;g&#46;&#44; significantly increased in cigarette smokers&#41; has been demonstrated to properly predict the risk of potentially life-threatening arrhythmias in drug-induced LQTS&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;10&#44;29&#44;30</span></a> QT dispersion &#40;i&#46;e&#46;&#44; difference between the longest and shortest QT interval in the 12 ECG leads&#41;&#44; is another potential surrogate marker for ventricular repolarization heterogeneity&#44; which was shown to increase with the use of psychotropic drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">31</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Nevertheless&#44; the QT interval is still widely used in clinical practice to assess the risk of TdP and SCD&#44; notwithstanding its poor predictive value&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;32</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Drug interactions with cardiac ion channels are the main mechanisms involved in potentially life-threatening arrhythmias&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a> Theoretically&#44; almost all drugs associated with QT prolongation and TdP block the rapid delayed rectifier potassium current&#44; I<span class="elsevierStyleInf">Kr</span>&#44; but not all I<span class="elsevierStyleInf">Kr</span> inhibitors prolong the QT interval and cause TdP&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">12&#44;14</span></a> However&#44; the use of these channel blockers in the general population has been associated with high risk of SCD&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">33</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Various drugs are metabolized by intestinal or hepatic cytochrome P450 &#40;CYP450&#41; enzymes&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">14&#44;27</span></a> Methadone &#40;i&#46;e&#46;&#44; CYP2C19&#44; notably&#44; the &#42;2 variant that is associated with QTc prolongation&#44;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">34</span></a> CYP3A4 and to a lesser extent the CYP2D6&#44; CYP2B6 and CYP1A2 enzymes<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">35</span></a>&#41;&#44; clarithromycin and erythromycin &#40;CYP3A enzymes&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">36</span></a> domperidone &#40;CYP3A4&#41;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">37</span></a> and clozapine &#40;CYP2D6&#41;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a> are examples of such drugs&#46; If those pathways are more prone to be inhibited by the concurrent use of other drugs or their activity is impaired by certain gene polymorphisms&#44; extremely elevated drug serum levels and fatal outcomes are expected to occur&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Recently&#44; the nitric oxide synthase 1 adaptor protein &#40;NOS1AP&#41; genetic variation has been identified as a new genetic marker in modulating QT prolongation and SCD&#44; both in congenital and drug-induced LQTS&#46;<a class="elsevierStyleCrossRefs" href="#bib0600"><span class="elsevierStyleSup">28&#44;39</span></a> In fact&#44; along with P-glycoprotein&#44; a transmembrane efflux pump &#40;i&#46;e&#46;&#44; domperidone is one of its substrates<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">37</span></a>&#41;&#44; the NOS1AP gene appears to be implicated in the bioavailability of various QT-prolonging drugs&#44; especially calcium channel inhibitors &#40;e&#46;g&#46;&#44; verapamil and diltiazem&#41;&#44; since it is involved in the inhibition of L-type Ca<span class="elsevierStyleSup">2&#43;</span> channels&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">14</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Apart from subclinical congenital LQTS&#44; drug-induced TdP depends on a multitude of risk factors&#44; which comprise female gender&#44; advanced age and common clinical conditions&#44; such as bradycardia&#44; hypertension&#44; structural heart diseases &#40;e&#46;g&#46;&#44; congestive heart failure&#44; hypertrophic cardiomyopathy&#41; and electrolyte imbalances &#40;e&#46;g&#46;&#44; hypokalemia&#44; hypomagnesemia&#44; hypocalcemia&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">11&#44;12&#44;38&#44;40&#44;41</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">An up-to-date list of cardiovascular and non-cardiovascular drugs &#40;i&#46;e&#46;&#44; mainly psychotropics and antimicrobials<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a>&#41; implicated in QT prolongation and&#47;or TdP is currently available at <a id="intr0035" class="elsevierStyleInterRef" href="http://www.crediblemeds.org/">www&#46;crediblemeds&#46;org</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Antiarrhythmic drugs</span><p id="par0180" class="elsevierStylePara elsevierViewall">Antiarrhythmic drugs are among the most harmful regarding their high risk of life-threatening arrhythmias&#46; Vaughan Williams class III drugs &#40;e&#46;g&#46;&#44; sotalol&#44; dofetilide&#44; ibutilide&#41; lead to the greatest concern for TdP within antiarrhythmics&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a> Apart from the well-known QTc prolongation effect&#44; amiodarone exhibits a low risk of TdP&#44; when used alone&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;10&#44;42</span></a> Nevertheless&#44; TdP has already been reported with concomitant use &#40;e&#46;g&#46;&#44; erythromycin and haloperidol&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">40</span></a> Therefore&#44; ECG monitoring is required in all intensive care unit &#40;ICU&#41; patients receiving amiodarone&#44; since this subset of patients has a high incidence of concomitant use of other QT-prolonging drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">42</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Notably&#44; pilsicainide&#44; a class Ic antiarrhythmic drug&#44; triggered TdP in an elderly patient who ended up dying suddenly&#44; two days after receiving it to convert his paroxysmal AF to sinus rhythm&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">43</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Antianginal drugs</span><p id="par0190" class="elsevierStylePara elsevierViewall">In spite of its known QT-prolonging effect&#44; low risk of TdP and SCD have been reported with ranolazine&#44;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;27</span></a> including when it is used to treat non-ST elevation acute coronary syndrome in patients with prolonged baseline QTc intervals&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">44</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Antidepressant and antipsychotic drugs</span><p id="par0195" class="elsevierStylePara elsevierViewall">Tricyclic antidepressants are well-known risk factors for QT prolongation and TdP&#44; especially in overdose cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0595"><span class="elsevierStyleSup">27&#44;45</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Overall&#44; selective serotonin-reuptake inhibitors &#40;SSRIs&#41; increase the QTc interval&#44; but citalopram and escitalopram seem to incite a more pronounced QTc prolongation in a dose-dependent fashion&#46;<a class="elsevierStyleCrossRefs" href="#bib0690"><span class="elsevierStyleSup">46&#8211;48</span></a> Nevertheless&#44; the role of citalopram as a trigger of TdP and SCD remains controversial&#44; as there are no concomitant risk factors for QT prolongation and TdP&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">49</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Although bupropion and venlafaxine prolong the QTc interval almost exclusively in overdose scenarios&#44; generally&#44; newer non-SSRIs pose a low risk of such effect at therapeutic doses&#46; Their shorter market life may explain the limited data&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">50</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">In a cohort study&#44; no considerable differences regarding sudden death and ventricular arrhythmia &#40;SD&#47;VA&#41; risks were detected among 11 antidepressants and paroxetine&#46; High risk of SD&#47;VA was only reported with mirtazapine&#44; but the authors reminded us that such outcome was biased by confounding factors&#46; Therefore&#44; cardiac safety was considered similar among antidepressants&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">51</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Given the numerous adverse effects of antipsychotics&#44; drug-induced LQTS is truly one of the most dangerous&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a> Overall&#44; first-generation antipsychotics are considered to be more likely to prolong QT interval and have higher risks of ventricular arrhythmias &#40;VAs&#41; and SCD than second-generation antipsychotics&#46;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;52</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">The Food and Drug Administration Adverse Event Reporting System &#40;FAERS&#41; database has been systematically analyzed to detect signals of torsadogenicity&#46;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#44;54</span></a> In this regard&#44; detecting new potential signals of torsadogenicity &#40;e&#46;g&#46;&#44; with amisulpride&#44; cyamemazine and olanzapine&#41; provided new insights for pharmacovigilance in antipsychotics&#46; This is because it allowed updating the Arizona Center for Education and Research on Therapeutics &#40;AZCERT<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">25</span></a>&#41; drug list&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">54</span></a> One year later&#44; Fanoe et al&#46; combined pharmacovigilance data from various international databases&#46; Only haloperidol&#44; pimozide&#44; sertindole and ziprasidone were considered to be class B&#42; drugs &#40;i&#46;e&#46;&#44; &#8220;a drug with pronounced QT prolongation&#44; documented cases of TdP&#44; or other serious arrhythmias&#8221;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">55</span></a> Alternatively&#44; the data analysis of three national spontaneous reporting systems &#40;i&#46;e&#46;&#44; France&#44; Germany and Italy&#41; demonstrated that in all of the national databases studied&#44; TdP events were reported only with amisulpride&#44; aripiprazole&#44; haloperidol&#44; olanzapine and risperidone&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">56</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Therefore&#44; available data on haloperidol have consistently favored its marked QT prolongation effect and high risk for TdP and SCD&#44;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#8211;57</span></a> but such outcomes have been disparate for clozapine &#40;low risk of QTc prolongation<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">58</span></a>&#59; &#8220;very strong signals of torsadogenicity&#8221;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#44;54</span></a>&#41; and olanzapine &#40;&#8220;a drug considered to be without any risk of QT prolongation or TdP&#8221;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">55</span></a>&#59; &#8220;potential signal of torsadogenicity&#8221;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">54</span></a>&#59; &#8220;very strong signal of torsadogenicity&#8221;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">53</span></a>&#41;&#46; Despite ziprasidone having QT-prolonging and torsadogenic effects&#44;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#8211;55</span></a> studies have failed to prove an increased risk of SD&#44; SCD or nonsuicide mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0755"><span class="elsevierStyleSup">59&#8211;61</span></a> Aripiprazole has a low risk of TdP and SCD&#44; at least in otherwise healthy patients&#46; However&#44; in patients at risk for TdP&#44; it may represent a safety concern&#44; since few studies have been carried in these vulnerable subsets&#46;<a class="elsevierStyleCrossRefs" href="#bib0770"><span class="elsevierStyleSup">62&#44;63</span></a> Cases of QTc prolongation&#44; TdP and SCD have been reported with quetiapine&#44; but only with concomitant risk factors for QT prolongation or TdP&#46;<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">64</span></a> Increased QTc prolongation and higher risk of SCD have been documented with risperidone during nighttime&#44; when compared to olanzapine users&#46;<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">65</span></a> These perilous effects are likely due to the increased serum levels of risperidone&#39;s active metabolite paliperidone in a dose-dependent manner and not to risperidone alone&#46;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">66</span></a> Two retrospective cohort studies also made a comparison with olanzapine&#44; but both risperidone and quetiapine were not implicated in higher risk of SD or VAs&#46; According to the authors&#44; olanzapine was chosen as the referent&#44; since it is not linked to substantive QT prolongation&#46;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">57</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">Exposure to phenothiazine antipsychotics also carries a risk of QTc prolongation and TdP both in therapeutic and overdose settings&#44; particularly with levomepromazine&#44; chlorpromazine and promethazine&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">45</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Despite increasing safety concerns&#44; widespread use of antipsychotics with torsadogenic potential has been reported in some European countries in recent years&#44; mostly with haloperidol and thioridazine&#46;<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">67</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">ECG monitoring is strongly recommended at hospital admission in patients with acute psychosis &#40;i&#46;e&#46;&#44; recently treated with antipsychotics&#41;&#44; due to the increased risk of QTc prolongation&#46;<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">68</span></a> Conversely&#44; Correll et al&#46; affirmed that&#44; unless other comorbidities are present &#40;e&#46;g&#46;&#44; cardiac diseases&#44; obesity&#44; hypokalemia&#41;&#44; ECG monitoring could potentially be restricted in young people treated with antipsychotics&#44; as significantly prolonged QTc interval was not demonstrated in this subset of patients&#46; Nevertheless&#44; the authors reinforced the idea that larger studies are required in this regard&#46;<a class="elsevierStyleCrossRef" href="#bib0805"><span class="elsevierStyleSup">69</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Antimicrobial drugs</span><p id="par0245" class="elsevierStylePara elsevierViewall">Macrolide antibiotics are one of the most prescribed non-cardiovascular QT-prolonging agents&#44; and exhibit increased risk of fatal ventricular arrhythmias or SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0595"><span class="elsevierStyleSup">27&#44;36</span></a> Azithromycin was once considered to be relatively free of adverse cardiac effects&#46; However&#44; new data has been emerging regarding its cardiac safety&#46;<a class="elsevierStyleCrossRefs" href="#bib0810"><span class="elsevierStyleSup">70&#44;71</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Quinolones are broad-spectrum antimicrobials with known risk of QT prolongation&#46;<a class="elsevierStyleCrossRefs" href="#bib0595"><span class="elsevierStyleSup">27&#44;42</span></a> It is noteworthy that in a United States veterans study&#44;<a class="elsevierStyleCrossRef" href="#bib0815"><span class="elsevierStyleSup">71</span></a> levofloxacin was significantly associated with serious arrhythmias and death&#44; throughout the 10-day course of therapy&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">QT prolongation and TdP have also been reported with antifungal agents&#44; mainly fluconazole&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Anesthetic drugs</span><p id="par0260" class="elsevierStylePara elsevierViewall">Overall&#44; inhaled anesthetics can prolong the QTc interval or increase dispersion of ventricular repolarization to variable degrees&#46; However&#44; only sevoflurane has been associated with TdP risk&#44; though most likely with concomitant risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">An ICU population-based study revealed that a flurane agent had been administered during anesthesia in the overwhelming majority of postoperative patients with QT interval prolongation&#46; Therefore&#44; the authors emphasized the need for QTc interval monitoring in all postoperative ICU patients&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">42</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">A case of SCA following documented QTc interval prolongation &#40;i&#46;e&#46;&#44; 580-600 ms&#41; was reported in a 30-month-old boy during anesthesia induction with sevoflurane and nitric oxide before undergoing plastic surgery for bilateral cutaneous syndactyly&#46; Timothy Syndrome&#44; LQTS type 8 with typical features&#44; including syndactyly&#44; was established by detecting the p&#46;Gly406Arg mutation in the <span class="elsevierStyleItalic">CACNA1C</span> gene encoding Cav1&#46;2 L-type calcium channel&#46;<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">72</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">Anticholinergic drugs &#40;e&#46;g&#46;&#44; atropine&#44; glycopyrronium bromide&#41; can prolong the QT interval when simultaneously used with anticholinesterases in healthy patients&#44; but TdP may occur when used alone in LQTS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Antiemetic drugs</span><p id="par0280" class="elsevierStylePara elsevierViewall">Domperidone can prolong the QTc interval and increase the risk of serious VAs and SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">37&#44;73</span></a> SCD risk seems to be higher in the first two weeks of treatment&#44; in patients older than 60 years and those with doses over 30 mg&#47;day&#46;<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">74</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">Serotonin-receptor antagonists &#40;e&#46;g&#46;&#44; dolasetron&#44; granisetron and ondansetron&#41; are also known QT-prolonging drugs&#44; but their clinical significance remains unclear&#44; due to few reported cases of fatal cardiac arrhythmias and SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">19&#44;75</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Antihistaminic drugs</span><p id="par0290" class="elsevierStylePara elsevierViewall">Apart from not appearing at the forefront of the most common events&#44; adverse cardiac effects are one of the most serious events for patients using first- or second-generation antihistamines&#46;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">The low number of antihistamines on the AZCERT drugs list<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">25</span></a> demonstrates the scarcity of pharmacovigilance data reporting TdP events&#46; An analysis of safety reports from the FAERS database revealed new evidence on torsadogenic activity for loratadine&#44; desloratadine&#44; cetirizine and fexofenadine&#44; in addition to diphenhydramine&#44;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a> which was already on the AZCERT list&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Antineoplastic drugs</span><p id="par0300" class="elsevierStylePara elsevierViewall">High TdP event rates are almost exclusively reported with arsenic trioxide&#46; However&#44; BRAF inhibitor vemurafenib&#44; histone deacetylase inhibitors &#40;e&#46;g&#46;&#44; depsipeptide and vorinostat&#41; and tyrosine kinase inhibitors &#40;e&#46;g&#46;&#44; dasatinib&#44; nilotinib&#44; lapatinib&#44; sunitinib&#44; vandetinib&#41; are also commonly linked to QTc prolongation to varying degrees&#46;<a class="elsevierStyleCrossRefs" href="#bib0845"><span class="elsevierStyleSup">77&#44;78</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Opioid replacement drug therapy</span><p id="par0305" class="elsevierStylePara elsevierViewall">Although more commonly reported at high doses &#40;&#62;200 mg&#47;day&#41;&#44; QT prolongation&#44; TdP and SD can occur even at lower doses of methadone &#40;&#60;100 mg&#47;day&#41;&#46; This is predominantly in early periods of treatment and&#47;or during concomitant use of either QT-prolonging agents or those which impair methadone metabolism&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Attention deficit hyperactivity disorder drug therapy</span><p id="par0310" class="elsevierStylePara elsevierViewall">QT prolongation is associated with atomoxetine use in overdose&#46;<a class="elsevierStyleCrossRef" href="#bib0855"><span class="elsevierStyleSup">79</span></a> Nevertheless&#44; there is scarce evidence regarding the involvement of stimulants in fatal arrhythmias and SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0855"><span class="elsevierStyleSup">79&#44;80</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">In a non-randomized cohort study conducted in adults&#44; the risk of VA or SD was significantly associated with methylphenidate use&#46; However&#44; the authors argued that the lack of a dose-response effect did not suggest a causal relationship&#46;<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">81</span></a></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Non-therapeutic drugs</span><p id="par0320" class="elsevierStylePara elsevierViewall">Data collected from a large sample representative of the general US population revealed that binge drinkers displayed substantially prolonged QT intervals&#44; compared to non-binge drinkers or non-drinkers&#46;<a class="elsevierStyleCrossRef" href="#bib0870"><span class="elsevierStyleSup">82</span></a></p><p id="par0325" class="elsevierStylePara elsevierViewall">TdP was reported in a previously healthy 43-year-old woman who presented with syncope after excessive intake of ginseng for 6 months&#46;<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">83</span></a></p><p id="par0330" class="elsevierStylePara elsevierViewall">Ozturk S et al&#46; described the case of a 59-year-old woman who developed TdP after two days of drinking 5-6 glasses of licorice root tea for constipation&#46; The authors hypothesized that glycyrrhizin was the culprit compound due to its known effects on both cardiac depolarization and repolarization&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">84</span></a></p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Drug-induced SQTS</span><p id="par0335" class="elsevierStylePara elsevierViewall">Drug-induced SQTS is still a rarely reported condition&#46;<a class="elsevierStyleCrossRef" href="#bib0885"><span class="elsevierStyleSup">85</span></a> Therefore&#44; its clinical significance is still unclear&#44; since few fatal arrhythmias and SCD cases have been described thus far&#46;<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">86</span></a></p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Antiepileptic drugs</span><p id="par0340" class="elsevierStylePara elsevierViewall">Rufinamide has been reported as a QT shortening agent&#46; In patients receiving rufinamide&#44; the concomitant use of lamotrigine and valproic acid has been associated with a significant decrease in the QT interval&#46;<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">86</span></a></p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Drug-induced BrS</span><p id="par0345" class="elsevierStylePara elsevierViewall">Evidence suggests that a rising number of drugs universally used in daily clinical practice can reveal the typical ECG pattern of BrS and&#44; thus&#44; potentially lead to fatal arrhythmias&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a></p><p id="par0350" class="elsevierStylePara elsevierViewall">Aside from drugs&#44; other clinical scenarios&#44; including febrile state &#40;e&#46;g&#46;&#44; hyperthermia&#44; hypothermia&#41; and electrolyte disturbances &#40;e&#46;g&#46;&#44; hyperkalemia&#44; hypokalemia&#44; hypercalcemia&#44; hyponatremia&#41;&#44; can trigger a type 1 pattern and modulate the occurrence of potentially life-threatening arrhythmias&#46; Some refer to these modifying factors as &#8220;phenocopies&#8221;&#46; However&#44; at least for now&#44; it is not proper to do so&#44; due to the lack of data regarding genetic predisposition&#46;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;23</span></a> These conditions are actually more suitably designated as acquired forms of Brugada ECG pattern or BrS&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">23</span></a></p><p id="par0355" class="elsevierStylePara elsevierViewall">Psychotropic and anesthetic drugs are the most common non-cardiovascular agents involved in BrS ECG phenotype&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a> Postema et al&#46; founded the website <a id="intr0040" class="elsevierStyleInterRef" href="http://www.brugadadrugs.org/">www&#46;brugadadrugs&#46;org</a> to guarantee the worldwide availability of cardiac safety information regarding drug prescription in BrS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Antiarrhythmic drugs</span><p id="par0360" class="elsevierStylePara elsevierViewall">Type 1 BrS ECG pattern is aggravated by drugs that block the cardiac Na<span class="elsevierStyleSup">&#43;</span> channel&#46; Corroborating this finding&#44; some of them &#40;i&#46;e&#46;&#44; ajmaline&#44; flecainide&#44; pilsicainide and procainamide&#41; are currently used for diagnostic purposes to unmask such a typical pattern in concealed BrS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">15</span></a> Nevertheless&#44; it is noteworthy that flecainide has demonstrated an increased risk of SCD when administered to treat AF&#46;<a class="elsevierStyleCrossRef" href="#bib0900"><span class="elsevierStyleSup">88</span></a></p><p id="par0365" class="elsevierStylePara elsevierViewall">BrS ECG type 1 and type 3 patterns were reported while amiodarone was prophylactically used for AF&#44; following coronary artery bypass grafting&#46;<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">89</span></a></p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Antidepressants and antipsychotic drugs</span><p id="par0370" class="elsevierStylePara elsevierViewall">Some tricyclic and SSRI antidepressants and antipsychotics &#40;e&#46;g&#46;&#44; lithium&#41; can induce a BrS ECG phenotype by blocking I<span class="elsevierStyleInf">Na</span> currents&#46;<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">38&#44;87</span></a></p><p id="par0375" class="elsevierStylePara elsevierViewall">In a population-based study&#44; nortriptyline&#44; an example of such a drug&#44; was associated with a significant 4&#46;5-fold increase in the risk for SCA&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">5</span></a></p><p id="par0380" class="elsevierStylePara elsevierViewall">Although fluvoxamine and paroxetine at therapeutic doses and fluoxetine in overdose can trigger a BrS ECG pattern&#44; no severe VAs have been reported thus far&#46; Similarly&#44; phenothiazine antipsychotics &#40;including cyamemazine&#44; perphenazine and thioridazine&#41; are well-known culprit agents in drug-induced BrS&#44; but without causing fatal VAs&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a></p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Epilepsy and antiepileptic drug therapy</span><p id="par0385" class="elsevierStylePara elsevierViewall">Epilepsy is considered to be an independent risk factor for life-threatening arrhythmias and SCD&#46; In fact&#44; epilepsy has been associated with a two- to three-fold higher risk for SCD than in the general population and with a six-fold higher risk in poorly controlled patients&#46;<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">90</span></a></p><p id="par0390" class="elsevierStylePara elsevierViewall">Recently&#44; Ishizue et al&#46; concluded that the concomitant use of sodium channel-blocking antiepileptic drugs&#44; including carbamazepine&#44; phenytoin and lamotrigine&#44; significantly caused a BrS type 1 pattern&#46; Conversely&#44; the authors admitted the inability to assess the 12-lead ECGs of a large proportion of epilepsy patients&#44; before and after antiepileptic therapy&#46; As a result&#44; epilepsy as a confounding factor cannot be ruled out&#46;<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">91</span></a></p><p id="par0395" class="elsevierStylePara elsevierViewall">Bardai et al&#46; revealed the increased risk of SCD with the use of sodium channel-blocking antiepileptics in epilepsy patients &#40;i&#46;e&#46;&#44; carbamazepine and gabapentin&#41; that was independent from the underlying epileptic condition&#46; In addition&#44; off-label drug use in non-epileptic patients has also been correlated with increased risk for SCD&#44; similarly to epilepsy per se&#46; If we transfer these conclusions to clinical practice&#44; measures involving seizure control with antiepileptic drugs are required&#44; but the risk of SCD must always be taken into account&#46;<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">90</span></a></p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Anesthetic drugs</span><p id="par0400" class="elsevierStylePara elsevierViewall">Despite having one of the safest profiles within modern anesthetics&#44; high doses of propofol can lead to SCD&#44; a condition termed &#8220;propofol infusion syndrome&#8221;&#46; A Brugada ECG pattern is commonly seen before &#8220;propofol infusion syndrome&#8221; occurs&#46; Thus BrS is&#44; until proven otherwise&#44; an underlying mechanism for potentially life-threatening arrhythmias and SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;87</span></a></p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Antiemetic drugs</span><p id="par0405" class="elsevierStylePara elsevierViewall">Metoclopramide has been reported to trigger typical BrS ECG features at therapeutic doses&#44; without being involved in serious arrhythmias&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a></p><p id="par0410" class="elsevierStylePara elsevierViewall">In a population-based nested case-control study&#44; oral exposure to metoclopramide demonstrated higher risk for developing SCD than oral exposure to domperidone&#46; However&#44; the authors alleged that this was an unexpected outcome and thus recommended further research in this regard&#46;<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">74</span></a></p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Antihistaminic drugs</span><p id="par0415" class="elsevierStylePara elsevierViewall">Both first- and second-generation antihistamines &#40;e&#46;g&#46;&#44; diphenhydramine almost exclusively in overdose and terfenadine&#41; have been involved in drug-induced BrS&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a></p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Non-therapeutic drugs</span><p id="par0420" class="elsevierStylePara elsevierViewall">Type 1 Brugada ECG pattern was documented in a woman with a family history of SCD&#44; who used topical nicotine patches for smoking cessation at high doses&#46;<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">92</span></a></p><p id="par0425" class="elsevierStylePara elsevierViewall">Cocaine and alcohol are two well-known triggers of BrS-like ECG pattern and VF&#44; both alone or with cocaethylene&#44; the ensuing metabolite of their combined use&#46;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">15&#44;87</span></a></p></span></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Discussion and conclusions</span><p id="par0430" class="elsevierStylePara elsevierViewall">An increasing number of cardiovascular and non-cardiovascular drugs have been broadly associated with proarrhythmia and SCD&#46; In fact&#44; drug-induced proarrhythmia should always be viewed as a prelude to SCD&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a> Hence&#44; it has been a growing challenge for physicians&#44; the regulatory agencies responsible for assessing drug safety and the pharmaceutical industry due to the pressure to create newer and safer agents&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a></p><p id="par0435" class="elsevierStylePara elsevierViewall">Physicians should weigh the risks of potentially fatal outcomes against therapeutic benefits when making decisions about drug prescriptions&#46; In the event of a suspicious drug-induced proarrhythmia&#44; withdrawal of the offending drugs is recommended&#44; but only after ruling out other concomitant risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">12</span></a></p><p id="par0440" class="elsevierStylePara elsevierViewall">Physicians who are aware of inherited arrhythmia syndrome should provide a letter or a similar useful tool to their patients and family members&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">15</span></a> Postema et al&#46; provide an example of such a letter&#44; available in various languages on their website&#44; which contains drugs that should be avoided or contraindicated in BrS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">26</span></a></p><p id="par0445" class="elsevierStylePara elsevierViewall">The uncertainty regarding the correlation between the magnitude of QT interval prolongation and the risk of TdP events should lead to a search for more knowledge on risk stratification of drug-induced TdP&#44; given the possible devastating consequences&#46;</p><p id="par0450" class="elsevierStylePara elsevierViewall">Post-approval safety studies provide reliable data for physicians about drug safety&#46; Given the tremendous significance in clinical practice&#44; this review highlights the need for synergy among physicians&#44; regulatory agencies and drug manufacturers&#44; and the need for routine spontaneous reporting and drug utilization analyses&#46;</p><p id="par0455" class="elsevierStylePara elsevierViewall">Future studies to obtain further knowledge and a better understanding of genetic variants related to pharmacokinetics and pharmacodynamics are crucial to more accurately predict drug-induced fatal outcomes for at-risk patients and to clarify which drugs can be administrated more safely&#46; This may avoid the inappropriate withdrawal of certain drugs from the market&#46; Undoubtedly&#44; the field of genetics is growing faster than expected&#44; and it will surely play a key role in this major health concern&#46;</p></span></span>"
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          "titulo" => "Introduction"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0010"
              "titulo" => "Sudden cardiac death"
            ]
            1 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Inherited channelopathies"
            ]
            2 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "QT prolongation&#44; torsades de pointes and congenital long QT syndrome"
            ]
            3 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Short QT syndrome"
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            4 => array:2 [
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              "titulo" => "Brugada syndrome"
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        6 => array:2 [
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          "identificador" => "sec0045"
          "titulo" => "Drug-induced proarrhythmia and SCD"
          "secciones" => array:22 [
            0 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Drug-induced LQTS"
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            1 => array:2 [
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              "titulo" => "Antiarrhythmic drugs"
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            2 => array:2 [
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            3 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Antidepressant and antipsychotic drugs"
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            4 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Antimicrobial drugs"
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            5 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Anesthetic drugs"
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              "titulo" => "Antiemetic drugs"
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              "identificador" => "sec0085"
              "titulo" => "Antihistaminic drugs"
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            8 => array:2 [
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              "titulo" => "Antineoplastic drugs"
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              "identificador" => "sec0095"
              "titulo" => "Opioid replacement drug therapy"
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            10 => array:2 [
              "identificador" => "sec0100"
              "titulo" => "Attention deficit hyperactivity disorder drug therapy"
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              "identificador" => "sec0105"
              "titulo" => "Non-therapeutic drugs"
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              "titulo" => "Drug-induced SQTS"
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              "titulo" => "Antiepileptic drugs"
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              "titulo" => "Drug-induced BrS"
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            15 => array:2 [
              "identificador" => "sec0125"
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            16 => array:2 [
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              "titulo" => "Antidepressants and antipsychotic drugs"
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            17 => array:2 [
              "identificador" => "sec0135"
              "titulo" => "Epilepsy and antiepileptic drug therapy"
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              "identificador" => "sec0140"
              "titulo" => "Anesthetic drugs"
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            19 => array:2 [
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              "titulo" => "Antiemetic drugs"
            ]
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              "titulo" => "Antihistaminic drugs"
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              "identificador" => "sec0155"
              "titulo" => "Non-therapeutic drugs"
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          "titulo" => "Discussion and conclusions"
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec987200"
          "palabras" => array:6 [
            0 => "Sudden cardiac death"
            1 => "Long QT syndrome"
            2 => "Torsades de pointes"
            3 => "Short QT syndrome"
            4 => "Brugada syndrome"
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          "palabras" => array:6 [
            0 => "Morte s&#250;bita card&#237;aca"
            1 => "S&#237;ndrome do QT longo"
            2 => "<span class="elsevierStyleItalic">Torsades de pointes</span>"
            3 => "S&#237;ndrome do QT curto"
            4 => "S&#237;ndrome de Brugada"
            5 => "Prepara&#231;&#245;es farmac&#234;uticas"
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Sudden cardiac death is a major public health challenge&#44; which can be caused by genetic or acquired structural or electrophysiological abnormalities&#46; These abnormalities include hereditary channelopathies&#58; long QT&#44; short QT and Brugada syndromes&#46; These syndromes are a notable concern&#44; particularly in young people&#44; due to their high propensity for severe ventricular arrhythmias and sudden cardiac death&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Current evidence suggests the involvement of an increasing number of drugs in acquired forms of long QT and Brugada syndromes&#46; However&#44; drug-induced short QT syndrome is still a rarely reported condition&#46; Therefore&#44; there has been speculation on its clinical significance&#44; since few fatal arrhythmias and sudden cardiac death cases have been described so far&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Drug-induced proarrhythmia is a growing challenge for physicians&#44; regulatory agencies and the pharmaceutical industry&#46; Physicians should weigh the risks of potentially fatal outcomes against the therapeutic benefits&#44; when making decisions about drug prescriptions&#46; Growing concerns about its safety and the need for more accurate predictive models for drug-induced fatal outcomes justify further research in these fields&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The aim of this article is to comprehensively and critically review the recently published evidence with regard to drug-induced life-threatening arrhythmias and sudden cardiac death&#46; This article will take into account the provision of data to physicians that are useful in the identification of the culprit drugs&#44; and thus&#44; contribute to the prompt recognition and management of these serious clinical conditions&#46;</p></span>"
      ]
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A morte s&#250;bita card&#237;aca &#233; um desafio significativo para a sa&#250;de p&#250;blica&#44; pode desencadear-se de anormalidades estruturais ou eletrofisiol&#243;gicas&#44; tanto gen&#233;ticas como adquiridas&#44; e abranger as assim chamadas canalopatias heredit&#225;rias&#58; s&#237;ndromes do QT longo&#44; QT curto e Brugada&#46; Essas s&#237;ndromes s&#227;o um problema consider&#225;vel&#44; particularmente para os jovens&#44; pela sua elevada propens&#227;o para arritmias ventriculares graves e morte s&#250;bita card&#237;aca&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A evid&#234;ncia atual sugere o envolvimento de um n&#250;mero crescente de f&#225;rmacos nas formas adquiridas das s&#237;ndromes do QT longo e Brugada&#46; No entanto&#44; a s&#237;ndrome do QT curto induzida por f&#225;rmacos &#233; ainda uma condi&#231;&#227;o raramente reportada&#46; Consequentemente&#44; especula&#231;&#227;o tem surgido sobre o seu significado cl&#237;nico&#44; uma vez que poucos casos de arritmias fatais e de morte s&#250;bita card&#237;aca foram descritos at&#233; ao momento&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A pr&#243;-arritmia induzida por f&#225;rmacos &#233; um desafio crescente tanto para m&#233;dicos como para entidades reguladoras e ind&#250;stria farmac&#234;utica&#46; Os m&#233;dicos devem pesar o risco de desfechos potencialmente fatais com os benef&#237;cios terap&#234;uticos&#44; aquando da tomada de decis&#245;es na prescri&#231;&#227;o de f&#225;rmacos&#46; As preocupa&#231;&#245;es crescentes sobre a sua seguran&#231;a e a necessidade de modelos preditivos mais precisos para desfechos fatais induzidos por f&#225;rmacos justificam pesquisas adicionais nesses dom&#237;nios&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">O objetivo deste artigo foi rever&#44; de forma abrangente e cr&#237;tica&#44; a evid&#234;ncia publicada recentemente&#44; no que diz respeito &#224;s arritmias potencialmente fatais e morte s&#250;bita card&#237;aca induzidas por f&#225;rmacos&#44; tendo em considera&#231;&#227;o o fornecimento de dados &#250;teis para m&#233;dicos na identifica&#231;&#227;o dos f&#225;rmacos respons&#225;veis e&#44; assim&#44; contribuir para o pronto reconhecimento e gest&#227;o desses quadros cl&#237;nicos graves&#46;</p></span>"
      ]
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Adapted from the website <a class="elsevierStyleInterRef" target="_blank" id="intr0005" href="http://www.crediblemeds.org/">www&#46;crediblemeds&#46;org</a><a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">25</span></a> &#40;accessed January 12&#44; 2017&#41;&#46; For an extensive and systematically updated list of all available evidence about the offending drugs and corresponding TdP risk categories&#44; please visit <a class="elsevierStyleInterRef" target="_blank" id="intr0010" href="http://www.crediblemeds.org/">www&#46;crediblemeds&#46;org</a>&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; GI&#58; gastrointestinal&#59; SNRI&#58; serotonin and norepinephrine reuptake inhibitors&#59; SSRI&#58; selective serotonin reuptake inhibitors&#59; TdP&#58; torsades de pointes&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug Class&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Risk category<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">&#42;&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Generic name&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antianginals</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bepridil<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ranolazine<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiarrhythmics&#44; class Ia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Disopyramide&#44;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">19&#44;38</span></a> Procainamide&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Quinidine<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">13&#44;14&#44;19&#44;27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiarrhythmics&#44; class III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amiodarone&#44;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">1&#44;10&#44;14&#44;19&#44;27&#44;38&#44;40&#44;42</span></a><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#8225;</span></a> Dofetilide&#44;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">14&#44;19&#44;27</span></a> Ibutilide<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">19&#44;27&#44;38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiarrhythmics&#47;Beta blockers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sotalol<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">1&#44;10&#44;13&#44;14&#44;19&#44;27&#44;38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antibiotics&#44; macrolides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Azithromycin&#44;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">36&#44;42&#44;71</span></a> Clarithromycin&#44;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">1&#44;27&#44;36</span></a> Erythromycin<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">1&#44;27&#44;36&#44;38&#44;40</span></a><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antibiotics&#44; quinolones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ciprofloxacin&#44;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">42</span></a> Grepafloxacin&#44;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a> Levofloxacin&#44;<a class="elsevierStyleCrossRefs" href="#bib0670"><span class="elsevierStyleSup">42&#44;71</span></a> Moxifloxacin&#44;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">14</span></a> Sparfloxacin<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antiemetics</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Domperidone&#44;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">37&#44;73</span></a> Ondansetron<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">19&#44;42&#44;75</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dolasetron&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Granisetron<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antifungals</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fluconazole&#44;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a> Pentamidine<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Voriconazole<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antihistamines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diphenhydramine<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antimania&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lithium<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;38&#44;55&#44;87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antimalarials</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Halofantrine<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Quinine sulfate<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antineoplastics</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Arsenic trioxide&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a> Vandetanib<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dasatinib&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a> Lapatinib&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a> Nilotinib&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a> Sunitinib&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a> Vemurafenib&#44;<a class="elsevierStyleCrossRefs" href="#bib0845"><span class="elsevierStyleSup">77&#44;78</span></a> Vorinostat<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antipsychotics</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Haloperidol&#44;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;9&#44;14&#44;27&#44;38&#44;40&#44;41&#44;48&#44;53&#8211;56&#44;63&#44;67</span></a> Levomepromazine&#44;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;45&#44;48&#44;53&#44;55&#44;63</span></a> Mesoridazine&#44;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a> Pimozide&#44;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">55</span></a> Thioridazine<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;9&#44;14&#44;38&#44;41&#44;67</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cyamemazine &#40;cyamepromazine&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#44;54&#44;63</span></a> Flupentixol&#44;<a class="elsevierStyleCrossRefs" href="#bib0735"><span class="elsevierStyleSup">55&#44;56</span></a> Perphenazine<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">Antipsychotics&#44; atypical</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sulpiride<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Aripiprazole&#44;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">56</span></a> Clozapine&#44;<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">38&#44;41&#44;53&#8211;55&#44;63</span></a> Iloperidone&#44;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">14</span></a> Paliperidone&#44;<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">38&#44;55&#44;66</span></a> Risperidone&#44;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">14&#44;38&#44;41&#44;53&#8211;56&#44;63&#44;65</span></a> Sertindole&#44;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;38&#44;63</span></a> Tiapride<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">56</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amisulpride&#44;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#8211;56&#44;63</span></a> Olanzapine&#44;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">14&#44;41&#44;53&#44;54&#44;56&#44;63</span></a> Quetiapine&#44;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">14&#44;27&#44;38&#44;39&#44;41&#44;53&#8211;55&#44;63&#44;64</span></a> Ziprasidone<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;9&#44;14&#44;38&#44;41&#44;53&#8211;55&#44;63</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antipsychotics&#47;antiemetics</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Chlorpromazine&#44;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;38&#44;45&#44;53&#44;54&#44;63</span></a> Droperidol<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">19&#44;53&#44;54</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Promethazine<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GI stimulants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cisapride&#44;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">General anesthetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sevoflurane<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">19&#44;72</span></a><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Opioid agonists&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Levomethadyl acetate&#44;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Methadone<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">9&#44;14&#44;19&#44;34&#44;35&#44;55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Opioid receptor modulator&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Buprenorphine<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Psychostimulants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Atomoxetine<a class="elsevierStyleCrossRef" href="#bib0855"><span class="elsevierStyleSup">79</span></a><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SNRI antidepressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Venlafaxine<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">38&#44;41&#44;50&#44;55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">SSRI antidepressants</td><td class="td" title="table-entry  " align="left" valign="top">Known&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Citalopram&#44;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;27&#44;41&#44;46&#8211;48&#44;55</span></a> Escitalopram<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">8&#44;27&#44;38&#44;41&#44;46&#44;48&#44;55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fluoxetine&#44;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">41</span></a> Sertraline<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Tricyclic antidepressants</td><td class="td" title="table-entry  " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clomipramine&#44;<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">45&#44;55</span></a> Desipramine&#44;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">45</span></a> Imipramine &#40;melipramine&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0665"><span class="elsevierStyleSup">41&#44;45&#44;55</span></a> Nortriptyline<a class="elsevierStyleCrossRefs" href="#bib0665"><span class="elsevierStyleSup">41&#44;45&#44;55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conditional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amitriptyline&#44;<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">45&#44;55</span></a> Doxepin<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other therapeutic drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not applicable<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amoxapine&#44;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">45</span></a> Atropine&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Bromperidol&#44;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">53</span></a> Bupropion&#44;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">50</span></a><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#8224;</span></a> Cetirizine&#44;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a> Chlorprothixene&#44;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#44;55&#44;63</span></a> Clotiapine&#44;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">48</span></a> Depsipeptide&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">77</span></a> Desflurane&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Desloratadine&#44;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a> Enflurane&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Fexofenadine&#44;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a> Fluphenazine&#44;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">53&#44;63</span></a> Ganciclovir&#44;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">56</span></a> Glycopyrrolate&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Halothane&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Hydroquinidine&#44;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a> Isoflurane&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Levocetirizine&#44;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">56</span></a> Loratadine&#44;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">76</span></a> Mizolastine&#44;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">38</span></a> Moclobemide&#44;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">55</span></a> Nitric oxide&#44;<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">72</span></a><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#8225;</span></a> Oxatomide&#44;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">56</span></a> Oxycodone&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Pentobarbital&#44;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">10</span></a> Pilsicainide&#44;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">43</span></a> Promazine&#44;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">48</span></a> Propericiazine&#44;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">45</span></a> Propoxyphene&#44;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#167;</span></a><a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Prothipendyl&#44;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">53</span></a> Succinylcholine&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a> Verapamil&#44;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">39</span></a> Zuclopenthixol<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">53</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Non-therapeutic drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not applicable<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Alcohol&#44;<a class="elsevierStyleCrossRef" href="#bib0870"><span class="elsevierStyleSup">82</span></a><a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">&#42;&#42;</span></a> Ginseng&#44;<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">83</span></a><br>Licorice root compounds &#40;glycyrrhizin&#44; flavones&#41;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">84</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Not included in the original drug list of CredibleMeds&#46;</p>"
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            1 => array:3 [
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              "etiqueta" => "&#8224;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Only in Overdose&#46;</p>"
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            2 => array:3 [
              "identificador" => "tblfn0015"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Concomitant use of QT-prolonging drugs&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Removed from market&#46;</p>"
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              "identificador" => "tblfn0025"
              "etiqueta" => "&#42;&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Only in binge drinking &#40;i&#46;e&#46;&#44; &#8805;5 alcoholic beverages in one day&#44; during the previous 12 months&#41;&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Agents implicated in drug-induced QT prolongation and&#47;or torsades de pointes&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug class&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Generic name&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiarrhythmics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Digitalis<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiepileptics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rufinamide&#44;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;86</span></a> Lamotrigine&#44;<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">86</span></a><a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">&#42;</span></a> Valproic acid<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">86</span></a><a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            0 => array:3 [
              "identificador" => "tblfn0035"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Combined with rufinamide&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Agents implicated in drug-induced QT shortening and&#47;or life-threatening arrhythmias&#46;</p>"
        ]
      ]
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        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Adapted from the website <a class="elsevierStyleInterRef" target="_blank" id="intr0015" href="http://www.brugadadrugs.org/">www&#46;brugadadrugs&#46;org</a><a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">26</span></a> &#40;accessed January 12&#44; 2017&#41;&#46; For an extensive and systematically updated list of all available evidence about the offending drugs&#44; corresponding risk categories and classes of recommendation&#44; please visit <a class="elsevierStyleInterRef" target="_blank" id="intr0020" href="http://www.brugadadrugs.org/">www&#46;brugadadrugs&#46;org</a>&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; SSRI&#58; selective serotonin reuptake inhibitors&#46;</p>"
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug class&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Risk category<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Generic name&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Class&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Anesthetics&#47;analgesics</td><td class="td" title="table-entry  " align="left" valign="top">To be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine&#44;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;21&#44;23&#44;87</span></a> Procaine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;23&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Propofol<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;21&#44;23&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ketamine<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Tramadol<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antianginals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not to be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diltiazem&#44;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a> Nicorandil&#44;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a> Nifedipine&#44;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a> Nitroglycerine<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antiarrhythmics&#44; class Ia</td><td class="td" title="table-entry  " align="left" valign="top">To be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ajmaline&#44;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">7&#44;10&#44;15&#44;21&#44;23&#44;63&#44;87</span></a> Procainamide<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">7&#44;10&#44;15&#44;21&#44;23&#44;87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cibenzoline&#44;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a> Disopyramide<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antiarrhythmics&#44; class Ic</td><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">To be avoided</td><td class="td" title="table-entry  " align="left" valign="top">Flecainide&#44;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">7&#44;10&#44;15&#44;21&#44;23&#44;63&#44;87</span></a> Pilsicainide<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">7&#44;10&#44;15&#44;21&#44;23&#44;87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Propafenone<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiarrhythmics&#44; class III &#40;also Ia&#44; II and IV effects&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amiodarone<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">89</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiarrhythmics&#44; class IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verapamil<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiemetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dimenhydrinate&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a> Metoclopramide<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antiepileptics</td><td class="td" title="table-entry  " align="left" valign="top">To be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oxcarbazepine<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Carbamazepine&#44;<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">91</span></a><a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">&#8225;</span></a> Lamotrigine&#44;<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">91</span></a><a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">&#8225;</span></a> Phenytoin<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">91</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antihistamines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diphenhydramine&#44;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Terfenadine&#47;Fexofenadine<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Antipsychotics</td><td class="td" title="table-entry  " align="left" valign="top">To be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Loxapine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a> Trifluoperazine<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cyamemazine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;38&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Perphenazine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Thioridazine<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SSRI antidepressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fluoxetine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;38&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Fluvoxamine&#44;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a> Paroxetine<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tetracyclic Antidepressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Maprotiline<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;38&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Tricyclic Antidepressants</td><td class="td" title="table-entry  " align="left" valign="top">To be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amytriptiline&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Clomipramine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;38&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Desipramine&#44;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">21&#44;87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Nortriptyline<a class="elsevierStyleCrossRefs" href="#bib0485"><span class="elsevierStyleSup">5&#44;21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preferentially avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dosulepin&#44;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Doxepin&#44;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a> Imipramine<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other antidepressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">To be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lithium<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;23&#44;38</span></a><a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">&#8225;</span></a><a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">Substances</td><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">To be avoided</td><td class="td" title="table-entry  " align="left" valign="top">Acetylcholine&#44;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">15&#44;21&#44;87</span></a> Cocaine<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">10&#44;15&#44;21</span></a><a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">&#8224;</span></a><a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">23&#44;87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
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              "etiqueta" => "1"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death&#58; The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology &#40;ESC&#41; Endorsed by&#58; Association for European Paediatric and Congenital Cardiology &#40;AEPC&#41;"
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                          "etal" => true
                          "autores" => array:3 [ …3]
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                    0 => array:2 [
                      "doi" => "10.1093/europace/euv319"
                      "Revista" => array:6 [
                        "tituloSerie" => "Europace"
                        "fecha" => "2015"
                        "volumen" => "17"
                        "paginaInicial" => "1601"
                        "paginaFinal" => "1687"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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              "identificador" => "bib0470"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sudden cardiac death in young adult"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12012-014-9255-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cardiovasc Toxicol"
                        "fecha" => "2014"
                        "volumen" => "14"
                        "paginaInicial" => "379"
                        "paginaFinal" => "386"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0475"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ventricular arrhythmias and sudden cardiac death"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(12)61413-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2012"
                        "volumen" => "380"
                        "paginaInicial" => "1520"
                        "paginaFinal" => "1529"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0480"
              "etiqueta" => "4"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pathophysiology and prevention of sudden cardiac death"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1139/cjpp-2015-0366"
                      "Revista" => array:6 [
                        "tituloSerie" => "Can J Physiol Pharmacol"
                        "fecha" => "2016"
                        "volumen" => "94"
                        "paginaInicial" => "237"
                        "paginaFinal" => "244"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0485"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sudden cardiac arrest associated with use of a non-cardiac drug that reduces cardiac excitability&#58; evidence from bench&#44; bedside&#44; and community"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/eht054"
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                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2013"
                        "volumen" => "34"
                        "paginaInicial" => "1506"
                        "paginaFinal" => "1516"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
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              "identificador" => "bib0490"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antipsychotic drugs are associated with pulseless electrical activity&#58; the Oregon Sudden Unexpected Death Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.hrthm.2012.12.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart Rhythm"
                        "fecha" => "2013"
                        "volumen" => "10"
                        "paginaInicial" => "526"
                        "paginaFinal" => "530"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
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              "identificador" => "bib0495"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ventricular arrhythmias in the absence of structural heart disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2012.01.036"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2012"
                        "volumen" => "59"
                        "paginaInicial" => "1733"
                        "paginaFinal" => "1744"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antipsychotic medication and QT prolongation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.12669/pjms.315.8998"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pak J Med Sci"
                        "fecha" => "2015"
                        "volumen" => "31"
                        "paginaInicial" => "1269"
                        "paginaFinal" => "1271"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Assessing QT interval prolongation and its associated risks with antipsychotics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2165/11587800-000000000-00000"
                      "Revista" => array:6 [
                        "tituloSerie" => "CNS Drugs"
                        "fecha" => "2011"
                        "volumen" => "25"
                        "paginaInicial" => "473"
                        "paginaFinal" => "490"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanisms of drug-induced proarrhythmia in clinical practice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4330/wjc.v5.i6.175"
                      "Revista" => array:6 [
                        "tituloSerie" => "World J Cardiol"
                        "fecha" => "2013"
                        "volumen" => "5"
                        "paginaInicial" => "175"
                        "paginaFinal" => "185"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
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                ]
              ]
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              "identificador" => "bib0515"
              "etiqueta" => "11"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevention of torsade de pointes in hospital settings&#58; a scientific statement from the American Heart Association and the American College of Cardiology Foundation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2010.01.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2010"
                        "volumen" => "55"
                        "paginaInicial" => "934"
                        "paginaFinal" => "947"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
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              "identificador" => "bib0520"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced prolongation of the QT interval"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra032426"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2004"
                        "volumen" => "350"
                        "paginaInicial" => "1013"
                        "paginaFinal" => "1022"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Unveiling specific triggers and precipitating factors for fatal cardiac events in inherited arrhythmia syndromes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1253/circj.CJ-15-0322"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circ J"
                        "fecha" => "2015"
                        "volumen" => "79"
                        "paginaInicial" => "1185"
                        "paginaFinal" => "1192"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacogenetics of drug-induced QT interval prolongation&#58; an update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40264-015-0316-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Drug Saf"
                        "fecha" => "2015"
                        "volumen" => "38"
                        "paginaInicial" => "855"
                        "paginaFinal" => "867"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
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              "identificador" => "bib0535"
              "etiqueta" => "15"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiac sodium channels and inherited electrophysiological disorders&#58; an update on the pharmacotherapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1517/14656566.2014.936380"
                      "Revista" => array:6 [
                        "tituloSerie" => "Expert Opin Pharmacother"
                        "fecha" => "2014"
                        "volumen" => "15"
                        "paginaInicial" => "1875"
                        "paginaFinal" => "1887"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0540"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HRS&#47;EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies&#58; this document was developed as a partnership between the Heart Rhythm Society &#40;HRS&#41; and the European Heart Rhythm Association &#40;EHRA&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/europace/eur245"
                      "Revista" => array:6 [
                        "tituloSerie" => "Europace"
                        "fecha" => "2011"
                        "volumen" => "13"
                        "paginaInicial" => "1077"
                        "paginaFinal" => "1109"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0545"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "QTc behavior during exercise and genetic testing for the long-QT syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.111.062182"
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                        "tituloSerie" => "Circulation"
                        "fecha" => "2011"
                        "volumen" => "124"
                        "paginaInicial" => "2181"
                        "paginaFinal" => "2184"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0550"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Idiopathic short QT interval&#58; a new clinical syndrome&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000047299"
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                        "tituloSerie" => "Cardiology"
                        "fecha" => "2000"
                        "volumen" => "94"
                        "paginaInicial" => "99"
                        "paginaFinal" => "102"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0555"
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              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Sudden cardiac death and disorders of the QT interval&#58; anesthetic implications and focus on perioperative management"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.jvca.2015.07.026"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cardiothorac Vasc Anesth"
                        "fecha" => "2015"
                        "volumen" => "29"
                        "paginaInicial" => "1723"
                        "paginaFinal" => "1733"
                        "link" => array:1 [
                          0 => array:2 [ …2]
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              ]
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              "identificador" => "bib0560"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Right bundle branch block&#44; persistent ST segment elevation and sudden cardiac death&#58; a distinct clinical and electrocardiographic syndrome&#46; A multicenter report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "1992"
                        "volumen" => "20"
                        "paginaInicial" => "1391"
                        "paginaFinal" => "1396"
                        "link" => array:1 [
                          0 => array:2 [ …2]
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              "identificador" => "bib0565"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brugada syndrome&#58; clinical&#44; genetic&#44; molecular&#44; cellular&#44; and ionic aspects"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cpcardiol.2015.06.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Probl Cardiol"
                        "fecha" => "2016"
                        "volumen" => "41"
                        "paginaInicial" => "7"
                        "paginaFinal" => "57"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
                  ]
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              "identificador" => "bib0570"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetics of Brugada syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.joa.2016.07.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Arrhythm"
                        "fecha" => "2016"
                        "volumen" => "32"
                        "paginaInicial" => "418"
                        "paginaFinal" => "425"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
                  ]
                ]
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              "identificador" => "bib0575"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "J-Wave syndromes expert consensus conference report&#58; emerging concepts and gaps in knowledge&#58; endorsed by the Asia Pacific Heart Rhythm Society &#40;APHRS&#41;&#44; the European Heart Rhythm Association &#40;EHRA&#41;&#44; the Heart Rhythm Society &#40;HRS&#41;&#44; and the Latin American Society of Cardiac Pacing and Electrophysiology &#40;Sociedad Latinoamericana de Estimulaci&#243;n Card&#237;aca y Electrofisiolog&#237;a &#91;SOLAECE&#93;&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Europace"
                        "fecha" => "2016"
                      ]
                    ]
                  ]
                ]
              ]
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            23 => array:3 [
              "identificador" => "bib0580"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HRS&#47;EHRA&#47;APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes&#58; document endorsed by HRS&#44; EHRA&#44; and APHRS in May 2013 and by ACCF&#44; AHA&#44; PACES&#44; and AEPC in June 2013"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.hrthm.2013.05.014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart Rhythm"
                        "fecha" => "2013"
                        "volumen" => "10"
                        "paginaInicial" => "1932"
                        "paginaFinal" => "1963"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0585"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Woosley R&#44; Heise CW&#44; Romero KA&#46; QTdrugs List&#46; AZCERT&#44; Inc&#46;&#44; 1822 Innovation Park Dr&#46;&#44; Oro Valley&#44; AZ 85755&#46; <a id="intr0045" class="elsevierStyleInterRef" href="http://www.crediblemeds.org/">www&#46;CredibleMeds&#46;org</a> &#91;accessed 12&#46;01&#46;17&#93;&#46;"
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            25 => array:3 [
              "identificador" => "bib0590"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safe drug use in long QT syndrome and Brugada syndrome&#58; comparison of website statistics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/europace/eut018"
                      "Revista" => array:6 [
                        "tituloSerie" => "Europace"
                        "fecha" => "2013"
                        "volumen" => "15"
                        "paginaInicial" => "1042"
                        "paginaFinal" => "1049"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
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              "identificador" => "bib0595"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced proarrhythmia&#58; risk factors and electrophysiological mechanisms"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrcardio.2015.110"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Cardiol"
                        "fecha" => "2016"
                        "volumen" => "13"
                        "paginaInicial" => "36"
                        "paginaFinal" => "47"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
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              "identificador" => "bib0600"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetics of congenital and drug-induced long QT syndromes&#58; current evidence and future research perspectives"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10840-013-9779-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Interv Card Electrophysiol"
                        "fecha" => "2013"
                        "volumen" => "37"
                        "paginaInicial" => "9"
                        "paginaFinal" => "19"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
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              "identificador" => "bib0605"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of smoking on Tp-e interval&#44; Tp-e&#47;QT and Tp-e&#47;QTc ratios as indices of ventricular arrhythmogenesis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.hlc.2014.03.016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart Lung Circ"
                        "fecha" => "2014"
                        "volumen" => "23"
                        "paginaInicial" => "827"
                        "paginaFinal" => "832"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
                  ]
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              "identificador" => "bib0610"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effects of cigarette smoking on the Tp-e interval&#44; Tp-e&#47;QT ratio and Tp-e&#47;QTc ratio"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Adv Clin Exp Med"
                        "fecha" => "2015"
                        "volumen" => "24"
                        "paginaInicial" => "973"
                        "paginaFinal" => "978"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
                  ]
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            30 => array:3 [
              "identificador" => "bib0615"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of psychotropic drugs on QT interval dispersion in adult patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arq Bras Cardiol"
                        "fecha" => "2014"
                        "volumen" => "102"
                        "paginaInicial" => "465"
                        "paginaFinal" => "472"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
                  ]
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            31 => array:3 [
              "identificador" => "bib0620"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Psychiatric medications and sudden cardiac death&#58; putting the risk in perspective"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3928/02793695-20150527-55"
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                        "tituloSerie" => "J Psychosoc Nurs Ment Health Serv"
                        "fecha" => "2015"
                        "volumen" => "53"
                        "paginaInicial" => "23"
                        "paginaFinal" => "25"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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            32 => array:3 [
              "identificador" => "bib0625"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Non-cardiovascular drugs that inhibit hERG-encoded potassium channels and risk of sudden cardiac death"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/hrt.2009.188367"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart"
                        "fecha" => "2011"
                        "volumen" => "97"
                        "paginaInicial" => "215"
                        "paginaFinal" => "220"
                        "link" => array:1 [
                          0 => array:2 [ …2]
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                    ]
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            33 => array:3 [
              "identificador" => "bib0630"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A possible mechanistic link between the CYP2C19 genotype&#44; the methadone metabolite ethylidene-1&#44;5-dimethyl-3&#44;3-diphenylpyrrolidene &#40;EDDP&#41;&#44; and methadone-induced corrected QT interval prolongation in a pilot study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40291-015-0137-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Diagn Ther"
                        "fecha" => "2015"
                        "volumen" => "19"
                        "paginaInicial" => "131"
                        "paginaFinal" => "138"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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            34 => array:3 [
              "identificador" => "bib0635"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "QT interval prolongation&#58; prevalence&#44; risk factors and pharmacovigilance data among methadone-treated patients in France"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1472-8206.2010.00871.x"
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                        "tituloSerie" => "Fundam Clin Pharmacol"
                        "fecha" => "2011"
                        "volumen" => "25"
                        "paginaInicial" => "503"
                        "paginaFinal" => "510"
                        "link" => array:1 [
                          0 => array:2 [ …2]
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              "identificador" => "bib0640"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of macrolide antibiotics in increasing cardiovascular risk"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2015.09.029"
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                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2015"
                        "volumen" => "66"
                        "paginaInicial" => "2173"
                        "paginaFinal" => "2184"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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              "identificador" => "bib0645"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Domperidone in Parkinson&#39;s disease&#58; a perilous arrhythmogenic or the gold standard&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Drug Saf"
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                        "paginaInicial" => "63"
                        "paginaFinal" => "68"
                        "link" => array:1 [
                          0 => array:2 [ …2]
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              "identificador" => "bib0650"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sudden death of cardiac origin and psychotropic drugs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
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                  "host" => array:1 [
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                        "tituloSerie" => "Front Pharmacol"
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                        "volumen" => "3"
                        "paginaInicial" => "76"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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              "identificador" => "bib0655"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Nitric oxide synthase 1 adaptor protein&#44; an emerging new genetic marker for QT prolongation and sudden cardiac death"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Cardiol Sin"
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                        "volumen" => "29"
                        "paginaInicial" => "217"
                        "paginaFinal" => "225"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
                  ]
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              "identificador" => "bib0660"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced long QT syndrome and fatal arrhythmias in the intensive care unit"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
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                        "tituloSerie" => "Acta Anaesthesiol Scand"
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                        "paginaInicial" => "266"
                        "paginaFinal" => "272"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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                    ]
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              "identificador" => "bib0665"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of age and sex on QT prolongation in patients receiving psychotropics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
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                      "doi" => "10.1177/070674371506000502"
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                        "tituloSerie" => "Can J Psychiatry"
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                        "paginaInicial" => "206"
                        "paginaFinal" => "214"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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              "identificador" => "bib0670"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Acquired long QT syndrome&#58; frequency&#44; onset&#44; and risk factors in intensive care patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
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                    0 => array:2 [
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                        "tituloSerie" => "Crit Care Nurse"
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                        "paginaInicial" => "32"
                        "paginaFinal" => "41"
                        "link" => array:1 [
                          0 => array:2 [ …2]
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            42 => array:3 [
              "identificador" => "bib0675"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A case of sudden cardiac death due to pilsicainide-induced torsades de pointes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4070/kcj.2014.44.2.122"
                      "Revista" => array:6 [
                        "tituloSerie" => "Korean Circ J"
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                        "volumen" => "44"
                        "paginaInicial" => "122"
                        "paginaFinal" => "124"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
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            43 => array:3 [
              "identificador" => "bib0680"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The risk of sudden cardiac death in patients with non-ST elevation acute coronary syndrome and prolonged QTc interval&#58; effect of ranolazine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/europace/eus400"
                      "Revista" => array:6 [
                        "tituloSerie" => "Europace"
                        "fecha" => "2013"
                        "volumen" => "15"
                        "paginaInicial" => "429"
                        "paginaFinal" => "436"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0685"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk factors for QT prolongation associated with acute psychotropic drug overdose"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ajem.2014.09.048"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Emerg Med"
                        "fecha" => "2015"
                        "volumen" => "33"
                        "paginaInicial" => "142"
                        "paginaFinal" => "149"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0690"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiac toxicity in selective serotonin reuptake inhibitor users"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/PAF.0000000000000205"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Forensic Med Pathol"
                        "fecha" => "2015"
                        "volumen" => "36"
                        "paginaInicial" => "293"
                        "paginaFinal" => "297"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0695"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Meta-analysis of selective serotonin reuptake inhibitor-associated QTc prolongation"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4088/JCP.13r08672"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Psychiatry"
                        "fecha" => "2014"
                        "volumen" => "75"
                        "paginaInicial" => "e441"
                        "paginaFinal" => "e449"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0700"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced long QT in adult psychiatric inpatients&#58; the 5-year cross-sectional ECG Screening Outcome in Psychiatry study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1176/appi.ajp.2013.12060860"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Psychiatry"
                        "fecha" => "2013"
                        "volumen" => "170"
                        "paginaInicial" => "1468"
                        "paginaFinal" => "1476"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0705"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Citalopram&#44; QTc interval prolongation&#44; and torsade de pointes&#46; How should we apply the recent FDA ruling&#63;"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.amjmed.2011.12.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med"
                        "fecha" => "2012"
                        "volumen" => "125"
                        "paginaInicial" => "859"
                        "paginaFinal" => "868"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0710"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of QT&#47;QTc prolongation among newer non-SSRI antidepressants"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/1060028014550645"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Pharmacother"
                        "fecha" => "2014"
                        "volumen" => "48"
                        "paginaInicial" => "1620"
                        "paginaFinal" => "1628"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0715"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antidepressants and the risk of sudden cardiac death and ventricular arrhythmia"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/pds.2181"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacoepidemiol Drug Saf"
                        "fecha" => "2011"
                        "volumen" => "20"
                        "paginaInicial" => "903"
                        "paginaFinal" => "913"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0720"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antipsychotic drugs and the risk of ventricular arrhythmia and&#47;or sudden cardiac death&#58; a nation-wide case-crossover study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "J Am Heart Assoc"
                        "fecha" => "2015"
                        "volumen" => "4"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0725"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Torsadogenic risk of antipsychotics&#58; combining adverse event reports with drug utilization data across Europe"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0081208"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS ONE"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "paginaInicial" => "e81208"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0730"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antipsychotics and torsadogenic risk&#58; signals emerging from the US FDA Adverse Event Reporting System database"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40264-013-0032-z"
                      "Revista" => array:6 [
                        "tituloSerie" => "Drug Saf"
                        "fecha" => "2013"
                        "volumen" => "36"
                        "paginaInicial" => "467"
                        "paginaFinal" => "479"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0735"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of arrhythmia induced by psychotropic medications&#58; a proposal for clinical management"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehu100"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2014"
                        "volumen" => "35"
                        "paginaInicial" => "1306"
                        "paginaFinal" => "1315"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0740"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The contribution of national spontaneous reporting systems to detect signals of torsadogenicity&#58; issues emerging from the ARITMO project"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40264-015-0353-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Drug Saf"
                        "fecha" => "2016"
                        "volumen" => "39"
                        "paginaInicial" => "59"
                        "paginaFinal" => "68"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0745"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antipsychotics and the risks of sudden cardiac death and all-cause death&#58; cohort studies in Medicaid and dually-eligible Medicaid-Medicare beneficiaries of five states"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4172/2155-9880.S10-006"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Exp Cardiolog"
                        "fecha" => "2013"
                        "volumen" => "10"
                        "numero" => "Suppl"
                        "paginaInicial" => "1"
                        "paginaFinal" => "9"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0750"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "QTc prolongation&#58; is clozapine safe&#63; Study of 82 cases before and after clozapine treatment"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hup.1221"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hum Psychopharmacol"
                        "fecha" => "2011"
                        "volumen" => "26"
                        "paginaInicial" => "397"
                        "paginaFinal" => "403"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0755"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparative mortality associated with ziprasidone and olanzapine in real-world use among 18&#44;154 patients with schizophrenia&#58; The Ziprasidone Observational Study of Cardiac Outcomes &#40;ZODIAC&#41;"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1176/appi.ajp.2010.08040484"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Psychiatry"
                        "fecha" => "2011"
                        "volumen" => "168"
                        "paginaInicial" => "193"
                        "paginaFinal" => "201"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0760"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Methodological challenges in the coding and adjudication of sudden deaths in a large simple trial with observational follow-up&#58; the ziprasidone observational study of cardiac outcomes &#40;ZODIAC&#41;"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/pds.2185"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacoepidemiol Drug Saf"
                        "fecha" => "2011"
                        "volumen" => "20"
                        "paginaInicial" => "1192"
                        "paginaFinal" => "1198"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0765"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug safety evaluation of ziprasidone"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1517/14740338.2011.560114"
                      "Revista" => array:6 [
                        "tituloSerie" => "Expert Opin Drug Saf"
                        "fecha" => "2011"
                        "volumen" => "10"
                        "paginaInicial" => "437"
                        "paginaFinal" => "448"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0770"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The cardiac safety of aripiprazole treatment in patients at high risk for torsade&#58; a systematic review with a meta-analytic approach"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Psychopharmacology &#40;Berl&#41;"
                        "fecha" => "2015"
                        "volumen" => "232"
                        "paginaInicial" => "3297"
                        "paginaFinal" => "3308"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0775"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiovascular safety of antipsychotics&#58; a clinical overview"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1517/14740338.2016.1161021"
                      "Revista" => array:6 [
                        "tituloSerie" => "Expert Opin Drug Saf"
                        "fecha" => "2016"
                        "volumen" => "15"
                        "paginaInicial" => "679"
                        "paginaFinal" => "688"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0780"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Quetiapine&#44; QTc interval prolongation&#44; and torsade de pointes&#58; a review of case reports"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/2045125313510194"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ther Adv Psychopharmacol"
                        "fecha" => "2014"
                        "volumen" => "4"
                        "paginaInicial" => "130"
                        "paginaFinal" => "138"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0785"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased risk of antipsychotic-related QT prolongation during nighttime&#58; a 24-hour holter electrocardiogram recording study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/JCP.0b013e31823f6f21"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Psychopharmacol"
                        "fecha" => "2012"
                        "volumen" => "32"
                        "paginaInicial" => "18"
                        "paginaFinal" => "22"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0790"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "QT prolongation of the antipsychotic risperidone is predominantly related to its 9-hydroxy metabolite paliperidone"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hup.1258"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hum Psychopharmacol"
                        "fecha" => "2012"
                        "volumen" => "27"
                        "paginaInicial" => "39"
                        "paginaFinal" => "42"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0795"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prescribing pattern of antipsychotic drugs during the years 1996&#8211;2010&#58; a population-based database study in Europe with a focus on torsadogenic drugs"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/bcp.12955"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Clin Pharmacol"
                        "fecha" => "2016"
                        "volumen" => "82"
                        "paginaInicial" => "487"
                        "paginaFinal" => "497"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0800"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "QTc prolongation in patients acutely admitted to hospital for psychosis and treated with second generation antipsychotics"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1155/2013/375020"
                      "Revista" => array:5 [
                        "tituloSerie" => "Schizophr Res Treatment"
                        "fecha" => "2013"
                        "volumen" => "2013"
                        "paginaInicial" => "375020"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0805"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antipsychotic drug administration does not correlate with prolonged rate-corrected QT interval in children and adolescents&#58; results from a nested case-control study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1089/cap.2011.0024"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Child Adolesc Psychopharmacol"
                        "fecha" => "2011"
                        "volumen" => "21"
                        "paginaInicial" => "365"
                        "paginaFinal" => "368"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0810"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Azithromycin and the risk of cardiovascular death"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1003833"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2012"
                        "volumen" => "366"
                        "paginaInicial" => "1881"
                        "paginaFinal" => "1890"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0815"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Azithromycin and levofloxacin use and increased risk of cardiac arrhythmia and death"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1370/afm.1601"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Fam Med"
                        "fecha" => "2014"
                        "volumen" => "12"
                        "paginaInicial" => "121"
                        "paginaFinal" => "127"
                        "link" => array:1 [ …1]
                      ]
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              "identificador" => "bib0820"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sudden cardiac arrest during anesthesia in a 30-month-old boy with syndactyly&#58; a case of genetically proven Timothy syndrome"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3346/jkms.2013.28.5.788"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Korean Med Sci"
                        "fecha" => "2013"
                        "volumen" => "28"
                        "paginaInicial" => "788"
                        "paginaFinal" => "791"
                        "link" => array:1 [ …1]
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                    ]
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              ]
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              "identificador" => "bib0825"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Domperidone and risk of ventricular arrhythmia and cardiac death&#58; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40261-015-0360-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Drug Investig"
                        "fecha" => "2016"
                        "volumen" => "36"
                        "paginaInicial" => "97"
                        "paginaFinal" => "107"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0830"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of out-of-hospital sudden cardiac death in users of domperidonem proton pump inhibitors&#44; or metoclopramide&#58; a population-based nested case-control study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40264-015-0338-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Drug Saf"
                        "fecha" => "2015"
                        "volumen" => "38"
                        "paginaInicial" => "1187"
                        "paginaFinal" => "1199"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0835"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intravenous ondansetron and the QT interval in adult emergency department patients&#58; an observational study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/acem.12836"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acad Emerg Med"
                        "fecha" => "2016"
                        "volumen" => "23"
                        "paginaInicial" => "102"
                        "paginaFinal" => "105"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0840"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pro-arrhythmic potential of oral antihistamines &#40;H1&#41;&#58; combining adverse event reports with drug utilization data across Europe"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0119551"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLOS ONE"
                        "fecha" => "2015"
                        "volumen" => "10"
                        "paginaInicial" => "e0119551"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib0845"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chemotherapy and QT prolongation&#58; overview with clinical perspective"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s11936-014-0303-8"
                      "Revista" => array:5 [
                        "tituloSerie" => "Curr Treat Options Cardiovasc Med"
                        "fecha" => "2014"
                        "volumen" => "16"
                        "paginaInicial" => "303"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib0850"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "What links BRAF to the heart function&#63; New insights from the cardiotoxicity of BRAF inhibitors in cancer treatment"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.18632/oncotarget.5853"
                      "Revista" => array:6 [
                        "tituloSerie" => "Oncotarget"
                        "fecha" => "2015"
                        "volumen" => "6"
                        "paginaInicial" => "35589"
                        "paginaFinal" => "35601"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            78 => array:3 [
              "identificador" => "bib0855"
              "etiqueta" => "79"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of serious cardiovascular problems with medications for attention-deficit hyperactivity disorder"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40263-012-0019-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "CNS Drugs"
                        "fecha" => "2013"
                        "volumen" => "27"
                        "paginaInicial" => "15"
                        "paginaFinal" => "30"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            79 => array:3 [
              "identificador" => "bib0860"
              "etiqueta" => "80"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Do prescription stimulants increase the risk of adverse cardiovascular events&#63;&#58; A systematic review"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2261-12-41"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Cardiovasc Disord"
                        "fecha" => "2012"
                        "volumen" => "12"
                        "paginaInicial" => "41"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            80 => array:3 [
              "identificador" => "bib0865"
              "etiqueta" => "81"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Methylphenidate and risk of serious cardiovascular events in adults"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1176/appi.ajp.2011.11010125"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Psychiatry"
                        "fecha" => "2012"
                        "volumen" => "169"
                        "paginaInicial" => "178"
                        "paginaFinal" => "185"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            81 => array:3 [
              "identificador" => "bib0870"
              "etiqueta" => "82"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Coffee&#44; alcohol&#44; smoking&#44; physical activity and QT interval duration&#58; results from the Third National Health and Nutrition Examination Survey"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0017584"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS ONE"
                        "fecha" => "2011"
                        "volumen" => "6"
                        "paginaInicial" => "e17584"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            82 => array:3 [
              "identificador" => "bib0875"
              "etiqueta" => "83"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ginseng&#58; a potential cause of long QT"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jelectrocard.2010.08.007"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Electrocardiol"
                        "fecha" => "2011"
                        "volumen" => "44"
                        "paginaInicial" => "357"
                        "paginaFinal" => "358"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            83 => array:3 [
              "identificador" => "bib0880"
              "etiqueta" => "84"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Polymorphic ventricular tachycardia &#40;Torsades de pointes&#41; due to licorice root tea"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Turk Kardiyol Dern Ars"
                        "fecha" => "2013"
                        "volumen" => "41"
                        "paginaInicial" => "241"
                        "paginaFinal" => "244"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            84 => array:3 [
              "identificador" => "bib0885"
              "etiqueta" => "85"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced QT interval shortening&#58; potential harbinger of proarrhythmia and regulatory perspectives"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1476-5381.2009.00191.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Pharmacol"
                        "fecha" => "2010"
                        "volumen" => "159"
                        "paginaInicial" => "58"
                        "paginaFinal" => "69"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            85 => array:3 [
              "identificador" => "bib0890"
              "etiqueta" => "86"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.hrthm.2012.01.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart Rhythm"
                        "fecha" => "2012"
                        "volumen" => "9"
                        "paginaInicial" => "776"
                        "paginaFinal" => "781"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            86 => array:3 [
              "identificador" => "bib0895"
              "etiqueta" => "87"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced Brugada syndrome by noncardiac agents"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/pace.12234"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pacing Clin Electrophysiol"
                        "fecha" => "2013"
                        "volumen" => "36"
                        "paginaInicial" => "1570"
                        "paginaFinal" => "1577"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            87 => array:3 [
              "identificador" => "bib0900"
              "etiqueta" => "88"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The safety of flecainide treatment of atrial fibrillation&#58; long-term incidence of sudden cardiac death and proarrhythmic events"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2796.2011.02395.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Intern Med"
                        "fecha" => "2011"
                        "volumen" => "270"
                        "paginaInicial" => "281"
                        "paginaFinal" => "290"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            88 => array:3 [
              "identificador" => "bib0905"
              "etiqueta" => "89"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brugada electrocardiogram pattern &#8220;unmasked&#8221; by amiodarone infusion"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.mjt.0000433948.16654.91"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Ther"
                        "fecha" => "2014"
                        "volumen" => "21"
                        "paginaInicial" => "540"
                        "paginaFinal" => "541"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            89 => array:3 [
              "identificador" => "bib0910"
              "etiqueta" => "90"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sudden cardiac death is associated both with epilepsy and with use of antiepileptic medications"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/heartjnl-2014-305664"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart"
                        "fecha" => "2015"
                        "volumen" => "101"
                        "paginaInicial" => "17"
                        "paginaFinal" => "22"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            90 => array:3 [
              "identificador" => "bib0915"
              "etiqueta" => "91"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Polytherapy with sodium channel-blocking antiepileptic drugs is associated with arrhythmogenic ST-T abnormality in patients with epilepsy"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.seizure.2016.06.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Seizure"
                        "fecha" => "2016"
                        "volumen" => "40"
                        "paginaInicial" => "81"
                        "paginaFinal" => "87"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            91 => array:3 [
              "identificador" => "bib0920"
              "etiqueta" => "92"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Type 1 Brugada pattern associated with nicotine toxicity"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jemermed.2015.08.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Emerg Med"
                        "fecha" => "2015"
                        "volumen" => "49"
                        "paginaInicial" => "e183"
                        "paginaFinal" => "e186"
                        "link" => array:1 [ …1]
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                  ]
                ]
              ]
            ]
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