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contributing to a worldwide increasing population of adults with congenital heart disease &#40;CHD&#41;&#46; Despite good long-term survival&#44; survivors of TOF repair see their quality of life &#40;QoL&#41; and survival decrease&#44; most commonly once they reach the third decade of life&#46; There is a cumulative incidence of all cardiac events &#40;death&#44; cardiac reintervention&#44; symptomatic arrhythmia&#44; stroke&#44; heart failure&#44; endocarditis&#41;&#44; continuing to worsen in the third decade&#44; with event-free survival of only 25&#37; at 40 years&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">4</span></a> Survivors of TOF repair face not only complex medical issues but also social and psychological challenges which might impact on their QoL&#46; Studies found that the correlation between patients self-perceived QoL of the severity of their CHD stratified by their cardiologists is weak&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">5&#44;6</span></a> In this literature review&#44; we aim to summarize the current state of knowledge on the QoL of adults with repaired TOF&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Material and methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">A search was conducted on PubMed and results were reviewed for articles published between January of 2010 and June of 2020&#46; Search terms included &#8220;Tetralogy of Fallot&#8221;&#44; &#8220;repaired&#8221;&#44; &#8220;adults&#8221; and &#8220;quality of life&#8221;&#46; Only full-length studies published in English were reviewed&#46; Studies reporting the impact of a specific treatment variant &#40;pharmacological or surgical&#41; on QoL were excluded&#44; as the aim of this review is to understand the QoL of patients who received the current standard of care&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Results</span><p id="par0015" class="elsevierStylePara elsevierViewall">Nineteen studies were included in this literature review&#46; For the subjective health status evaluation&#44; most published studies used the Short-Form-36 &#40;SF-36&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">7&#8211;12</span></a> The SF-36 questionnaire consists of multiple-item scale to assess eight domains&#58; physical functioning&#44; role functioning-physical&#44; bodily pain&#44; general health&#44; vitality&#44; social functioning&#44; role limitations caused by emotional problems&#44; and mental health<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a>&#46; The definition of each component is described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The WHOQoL-BREFF questionnaire was also administered in a significant number of studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">2&#44;13</span></a> The WHOQoL-BREF is a 26-item questionnaire&#44; which assesses functioning in four domains&#58; physical health &#40;seven items&#41;&#44; psychological &#40;six items&#41;&#44; social relationships &#40;three items&#41;&#44; and environment &#40;eight items&#41;&#44; with the possible scores on each subscale ranging from 0 to 100&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a>One study used the EQ-5D questionnaire&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">14</span></a> The EQ-5D questionnaire was developed by the EuroQoL Group and enables the respondent to classify their health in five dimensions&#58; mobility&#44; self-care&#44; usual activities&#44; pain&#47;discomfort and anxiety&#47;depression<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">14</span></a>&#46; Another study used the Satisfaction with Life Scale &#40;SWLS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">15</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Most published studies aimed to assess both physical and mental domains&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">7&#8211;10&#44;12&#8211;14</span></a> Other studies specifically assessed psychosocial function&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">11&#44;15&#8211;18</span></a> Three studies addressed marital status&#44; fertility&#44; and reproducibility&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">19&#8211;21</span></a> We were only able to find one study designed to quantify the social burden of health-related costs associated with this population&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Physical functioning and exercise capacity</span><p id="par0030" class="elsevierStylePara elsevierViewall">The majority of studies agree that physical complex status is poorer for adult patients with repaired TOF than for controls&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">7&#44;9&#44;10&#44;12</span></a> Physical functioning and role physical&#44; as defined in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; are negatively correlated with time since repair and reoperation&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">7&#44;10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">D&#322;u&#380;niewska et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a> aimed to assess the QoL of adults with repaired TOF&#44; using the SF-36&#46; This study assessed the relationship between the QoL and exercise capacity&#46; Peak oxygen uptake &#40;Vo2 peak&#41; is considered the best objective measure of exercise capacity&#46; VO2 peak&#44; physical functioning&#44; general health&#44; and physical complex status were positively correlated&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a> However&#44; there is no consensus over the correlation between peak VO2 and physical functioning&#44; as other studies reported no correlation between objectively measured exercise capacity &#40;peak VO2&#41; and the subjective WHOQOL-BREF total score or the physical domain score&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Novakovi&#263; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a> performed a study to compare high-interval exercise training with moderate continuous training to improve exercise capacity&#44; cardiac autonomic function &#40;heart rate variability and post-exercise heart rate recovery&#41; and HRQoL&#44; in adult patients with repaired TOF&#46; Interval training seemed more successful at improving exercise capacity&#44; while continuous training was more successful in improving cardiac autonomic function and QoL&#46; However&#44; interval training had no effect on the physical or mental domain on the SF-36 questionnaire&#44; while continuous training was associated with improvements in the mental domain of only the HRQoL&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Knowles et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a> in a study comparing TOF survivors with their healthy siblings&#44; concluded that there were no significant differences in the level of activity undertaken by patients and siblings in their daily life or employment&#46; However&#44; the level of work represented by regular sporting and leisure activities was significantly less for patients than for their siblings&#46; It is uncertain whether these physical limitations are true restrictions imposed by the condition or self-imposed as a result of medical advice or perceived ill-health&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Mental health and psychosocial adjustment</span><p id="par0050" class="elsevierStylePara elsevierViewall">Mental complex status was lower for patients than for controls&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">7&#44;9</span></a> However&#44; patients reported similar satisfaction with their lives&#44; similar levels of social participation and family support&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a> Knowles et al&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a> reported no significant differences in the proportion of patients and siblings who attempted suicide&#46; Significantly&#44; fewer patients were current cigarette smokers and there were no significant differences in the proportions of patients and siblings who were in each alcohol consumption category&#46; Interestingly&#44; they also found that patients with repaired TOF were significantly more likely to be taking pharmacological therapies for hypertension as well as antibiotics in the preceding month&#44; but not other types of noncardiac medications &#40;pain relievers&#44; tranquillizers or antidepressants&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Other studies&#44; however&#44; reported no difference between patients and controls in the four psychosocial health domains of SF-36&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Opic et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">11</span></a> investigated the psychosocial impact of having an implantable cardioverter defibrillator &#40;ICD&#41; in adults with TOF&#46; To achieve this&#44; they used two control groups&#58; TOF-patients without an ICD and a group of ICD-patients of an older age without TOF &#40;patients with acquired heart diseases&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">11</span></a> TOF-patients with ICD showed diminished psychosocial functioning in comparison to TOF-patients without ICD&#46; This was reflected by diminished subjective general health perception and a lower life satisfaction&#46; More inappropriate shocks were found in TOF-patients with ICD compared to the older ICD-patients&#46; It is relevant to remember that the leading cause of mortality in adult patients with CHD is sudden cardiac death &#40;25&#8211;100-fold increased risk compared to the general population&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">11</span></a> Despite optimal programing&#44; 39&#37; of TOF-patients with ICD suffered from one or more inappropriate ICD interventions&#41;&#44; that may cause stress and anxiety &#40;related to the shock and fear of premature death&#41; and worsening psychological problems&#46; Moreover&#44; they reported avoidance behaviors&#44; which may be a limiting factor in social and sexual activities&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">It is very important to understand which variables have a detrimental effect on psychosocial adjustment and which ones increase resilience and ability to adapt&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Education and employment</span><p id="par0070" class="elsevierStylePara elsevierViewall">In a study conducted in a Portuguese hospital&#44; patients were assessed on their different neurocognitive functions&#44; including clinical measures of memory&#44; executive function&#44; processing speed&#44; attention and visual constructive ability&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">22</span></a> This study included patients with TOF but also included patients with other CHDs&#46; Self-report and observational questionnaires to assess psychosocial adjustment &#40;Adult Self-Report Form and Adult Behavior Checklist&#41; were administered&#46; Statistically significant differences were found between patients with CHD and the control group of healthy participants in all areas of neurocognitive performance&#44; with better results for the latter&#46; Areias et al&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">22</span></a> identified three neurocognitive phenotypes &#40;non-impaired&#44; moderately impaired and globally impaired&#41; and features associated with each&#46; The non-impaired cluster had larger head circumference and higher birth weight than the other two clusters&#46; They also presented higher 1 min and 5 min Apgar scores&#46; Participants in non and moderately impaired clusters had more years of schooling than those in the globally impaired cluster&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">22</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Despite these findings&#44; the majority of patients in published studies had a college or university degree&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">17&#44;23</span></a> However&#44; there are contradictory findings&#44; with studies reporting a poorer performance in the school domain&#44; while others report achieving an educational level superior to the reference average&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">13&#44;24</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Employment and work ability contribute to well-being and are nowadays crucial in daily life for most adults with CHD&#46; Higher rates of unemployment&#44; disease-related work absences&#44; and limitations at work have been reported in these patients compared to the general population in Netherland<span class="elsevierStyleCrossOut">s</span>&#44; Germany&#44; Denmark&#44; United Kingdom and United States of America&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">18&#44;19&#44;23</span></a> In contrast&#44; studies from Finland&#44; Sweden&#44; and Malta&#44; have reported employment rates similar to or even above those of the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a> These conflicting findings on employment and limitations at work in adults with CHD&#44; suggest that they might be influenced by other factors than solely CHD itself&#46; This conflict of evidence led Sluman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">17</span></a> to design a study aiming to explore employment&#44; work ability&#44; and the presence of limitations at work in a large international adult CHD population to investigate differences between countries and to identify predictors for employment and work limitations&#46; In their cohort&#44; 69&#37; of all patients were employed&#44; varying from 43&#37; in India to 80&#37; in Belgium&#46; Overall&#44; unemployment &#40;including job seeking&#41; was observed in 10&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">17</span></a> Factors associated with lower employment levels in multivariate logistic regression analyses were female gender&#44; worse New York Heart Association functional class&#44; and a history of congestive heart failure&#46; Higher education and having a partner were positively associated with being employed&#46; Part-time workers reported more limitations than patients who worked full-time&#46; They concluded that the most significant factors positively associated with employment were education and male gender and that&#44; despite employment rates being lower than in the general population in most countries&#44; there was substantial variation between countries&#46; More work limitations and a poor self-declared work ability were observed in economically disadvantaged countries&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">17</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In a Danish study&#44; 68 men who underwent repair of TOF between 1971 and 1991 were analyzed&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> Despite having an educational level similar to the general Danish population&#44; fewer were employed and more were retired&#44; in rehabilitation&#44; or receiving social benefits&#46; The authors explain that this phenomenon is probably multifactorial&#59; some of the patients are physically impaired and studies have shown a persistent effect of cyanosis in cognitive and academic performance&#46; Another aspect is that TOF is frequently associated with <span class="elsevierStyleItalic">22q11</span> deletion syndromes &#40;DiGeorge Syndrome&#44; for example&#41; and other chromosomal abnormalities&#46; These patients may have learning disabilities&#44; immunologic deficiencies&#44; and other physical impairments&#44; which may cause difficulties in employment&#46; Low cardiac output&#44; hypoxia&#44; and acidosis in the context of heart surgery may also have an impact on intellectual capacity&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">An interesting study published by Hunter et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a> sought to estimate the first 55 years health-related costs and outcomes for patients with TOF&#46; The outcome measure used in the model was quality adjusted life years &#40;QALYs&#41;&#46; QALYs represent both the quality and quantity of health related QoL &#40;HRQoL&#41;&#44; quality being measured by utility scores&#46; QALYs are the recommended outcome for use in economic evaluations&#44; as they are a common unit that allow for comparable decisions about resource allocation across different diseases&#46; The average cost per patient of the admission including repair of TOF was GBP 26<span class="elsevierStyleHsp" style=""></span>938&#46; The mean full life-time cost per patient was GBP 65<span class="elsevierStyleHsp" style=""></span>310 &#40;95&#37; CI GBP 64<span class="elsevierStyleHsp" style=""></span>981- GBP 65<span class="elsevierStyleHsp" style=""></span>729&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a> Patients with a repair had an average total of 35 QALYs with an average total of 3 QALYs for patients with no repair&#46; The mean cost per QALY gained over 10<span class="elsevierStyleHsp" style=""></span>000 simulations was GBP 2027&#46; Based on a willingness to pay of GBP 20<span class="elsevierStyleHsp" style=""></span>000 per QALY gained&#44; open repair of TOF is cost effective compared to doing nothing&#46; They concluded that repair of TOF is a worthwhile investment for the health care system given the QALYs gained&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Marital status&#44; fertility and reproduction rate</span><p id="par0095" class="elsevierStylePara elsevierViewall">Studies found no difference in the proportion of TOF patients that are married or living with a partner&#44; compared with control groups&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">9&#44;24</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Women who underwent surgery for TOF have normal fertility&#44; but they have a lower reproduction rate compared with the control female population and a higher frequency of CHD among their offspring&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> Offspring of mothers with TOF are more likely to have CHD&#44; with a reported incidence of approximately 3&#46;1&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a> A study from the Mayo Clinic reviewed the records of 147 female patients with TOF to determine pregnancy outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a> Patients had a rate of spontaneous fetal loss of 24&#37;&#44; which is substantially higher than the expected national average documented in the United States of America of 10&#37;&#44;&#46; In this cohort&#44; 23&#37; of the women had cesarean deliveries&#44; a rate very similar to the USA rate of up to 21&#46;8&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a> However&#44; this study included a residual number of the patients who did not undergo corrective surgery&#46; Another study from the Netherlands&#44; including 83 patients&#44; all with repaired TOF&#44; reported 63 pregnancies in 29 patients&#44; of which 13 ended in an abortion&#46; Fifty successful pregnancies were observed in 26 patients&#46; No clear relation between offspring mortality&#44; premature birth or small gestational age&#44; and cardiac characteristics of the mother was identified&#46; Fifty-seven patients were childless &#40;41 &#40;72&#37;&#41; voluntarily&#41;&#59; infertility was uncommon&#46; Recurrence risk for CHD was 2&#46;2&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">A previously mentioned Danish study&#44; reported an 8&#46;3&#37; incidence of CHD of 8 in newborns from men with TOF&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> On average&#44; men had 0&#46;65 children compared with an average of 1&#46;02 in the Danish male population&#44; at 33 years of age&#46; The fertility rate among women who underwent surgery for TOF was 0&#46;88 children per woman&#44; compared with 1&#46;84 in the Danish female population&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">Living with CHD affects patients not only physically&#44; but also emotionally and socially&#46; As survival rates improve&#44; psychosocial issues have emerged as a critical research area in this particular disease&#46; Assessment of HRQoL is well established as a subjective indicator of health&#46; QoL is defined as a multi-dimensional construct integrating physical&#44; emotional&#44; and social well-being and functioning as perceived by the individual and as the degree of overall life satisfaction that is positively or negatively influenced by individuals&#8217; perceptions of certain important aspects of life&#44; both related and unrelated to health status&#46; Examining the QoL of adults with repaired TOF contributes to the development of appropriate therapeutic strategies for these patients&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">A consistent finding of these studies are abnormal physical parameters compared to psychosocial issues&#46; Despite this&#44; patients&#8217; overall quality of life&#44; social functioning&#44; emotional and mental health well-being are not significantly different&#46; Patients appear to adjust well to their physical limitations or develop coping strategies&#46; In addition&#44; patients may have a greater appreciation of their health and social needs&#44; as evidenced by significantly lower rates of harmful behavior &#40;smoking&#44; for example&#41;&#46; The marital rate is comparable&#44; implying normal relationship development&#46; However&#44; the significantly lower prevalence of children among married TOF patients is interesting&#46; Taking into consideration that there is no evidence of reduced fertility in TOF patients&#44; issues that might influence reproduction rates are concerns about heritability of heart disease&#44; impaired body image&#44; fear of not being able to see their children growing up&#44; and fear of death during sex&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">A relevant area of future research includes mechanisms involved in poorer neurocognitive development and analysis of their relative contributions&#46; Current knowledge indicates causes arising in fetal life&#44; others occurring after birth and especially during or after surgery &#40;anoxia and perioperative ischemia&#41;&#46; Since studies demonstrate a positive effect on employment and limitations at work from higher education&#44; efforts should be made to maximize academic achievement in this population&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">From our perspective&#44; there are other pertinent aspects that might affect the quality of life of this population&#44; but have not been assessed by previous studies&#44; to the best of our knowledge&#46; These include difficulties in obtaining driving licenses&#44; as well as life insurance and&#44; consequently&#44; bank loans&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The needs of adults with repaired TOF are diverse and include multidisciplinary care&#44; involving cardiologists&#44; cardiac surgeons&#44; obstetrics&#44; genetics&#44; neurologists&#44; psychologists&#44; social workers and vocational counselors&#46; Our approach treating these patients should be coordinated&#44; taking into consideration all aspects affecting their quality of life&#46; Ideally&#44; this integrated approach should start in infancy and adolescence and include the patient&#39;s parents&#47;guardians and&#44; later&#44; their partners&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">A revision of the quality of life &#40;focusing on all the above-mentioned aspects of daily life&#41; of adult patients with repaired TOF followed-up at our institution or&#44; ideally&#44; in Portugal in a multicenter study&#44; would be of the outmost importance&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusion</span><p id="par0140" class="elsevierStylePara elsevierViewall">Due to improved care&#44; the number of adult patients with TOF is increasing worldwide&#46; However&#44; as survival rates increase&#44; concerns about long-term morbidity and quality of life also grow&#46; Despite abnormal physical functional status&#44; it is reassuring that the majority of adult patients with repaired TOF lead independent and productive lives&#44; meaning that the repair of TOF is a worthwhile investment for the health care systems&#46; A better understanding of factors impairing quality of life can lead to improvements in periodic follow-up programs&#44; aiming at a more integrated approach&#44; focusing on aspects such as genetic counseling&#44; academic&#47;educational support and physical activity recommendations&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflicts of interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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    "fechaRecibido" => "2020-11-14"
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            0 => "Tetralogy of Fallot"
            1 => "Quality of life"
            2 => "Adults"
            3 => "Physical"
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            0 => "Tetralogia de Fallot"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Tetralogy of Fallot &#40;TOF&#41; is the most common cyanotic congenital heart defect&#46; Survival into adulthood is currently expected following surgical repair&#44; leading to a growing population of adults with repaired TOF&#46; In this literature review&#44; we aim to summarize the current state of knowledge on the quality of life of adults with repaired TOF&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A search was conducted on PubMed and results were reviewed for articles published between January of 2010 and June of 2020&#46; Search terms included &#8220;Tetralogy of Fallot&#8221;&#44; &#8220;repaired&#8221;&#44; &#8220;adults&#8221; and &#8220;quality of life&#8221;&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">For the subjective health status evaluation&#44; most published studies used Short-Form-36&#46; Most studies agree that physical complex status is poorer for adult patients with repaired TOF than for controls&#46; Mental complex status was also lower&#46; Patients reported similar satisfaction with their lives and levels of social participation&#46; Most patients had a college or university degree&#46; Higher education&#44; male gender and having a partner were positively associated with being employed&#46; Studies found no difference in the proportion of patients that are married or living with a partner&#44; compared to control groups&#46; Patients operated for TOF have a lower reproduction rate compared with the background population&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A consistent finding of these studies is abnormal physical parameters compared to psychosocial issues&#46; The diverse needs of adults with repaired TOF require a multidisciplinary care&#44; that takes into consideration all aspects that affect their quality of life&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Despite abnormal physical functional status&#44; it is reassuring that most adult patients with TOF lead independent and productive lives&#46;</p></span>"
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      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Tetralogia de Fallot &#40;TOF&#41; &#233; a cardiopatia cong&#233;nita cian&#243;tica mais comum&#46; A sobreviv&#234;ncia at&#233; &#224; idade adulta ap&#243;s corre&#231;&#227;o cir&#250;rgica &#233; expect&#225;vel&#44; levando ao aumento da popula&#231;&#227;o de adultos com TOF corrigida&#46; Nesta revis&#227;o da literatura&#44; pretendemos sumarizar a evid&#234;ncia relativamente &#224; qualidade de vida &#40;QoL&#41; destes doentes&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Procedemos a uma pesquisa na Pub-Med de artigos publicados entre janeiro de 2010 e junho de 2020&#44; utilizando os termos &#8220;Tetralogy of Fallot&#8221;&#44; &#8220;repaired&#8221;&#44; &#8220;adults&#8221; e &#8220;quality of life&#8221;&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Para avalia&#231;&#227;o subjetiva do estado de sa&#250;de a maioria dos estudos usou o question&#225;rio Short-Form-36&#46; A maioria concluiu que os complexos f&#237;sico e mental s&#227;o inferiores nos adultos com TOF corrigida&#44; quando comparados aos grupos de controlo&#46; No entanto&#44; a maioria dos doentes refere n&#237;veis de satisfa&#231;&#227;o com as suas vidas e de participa&#231;&#227;o social semelhantes&#46; A maioria concluiu o ensino secund&#225;rio ou universit&#225;rio&#46; Um n&#237;vel de educa&#231;&#227;o superior&#44; g&#233;nero masculino e ter um companheiro foram positivamente associados a estar empregado&#46; Os estudos n&#227;o encontram diferen&#231;a na propor&#231;&#227;o de doentes casados ou a viver maritalmente&#46; Esta popula&#231;&#227;o apresenta taxa de reprodu&#231;&#227;o inferior &#224; popula&#231;&#227;o de controlo&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Um achado consistente entre os estudos &#233; a inferioridade dos par&#226;metros f&#237;sicos&#44; comparativamente ao desempenho psicossocial&#46; As necessidades diversas dos adultos com TOF corrigida requerem uma abordagem multidisciplinar&#44; que tenha em considera&#231;&#227;o todos os aspetos que podem influenciar a qualidade de vida destes doentes&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Apesar das limita&#231;&#245;es f&#237;sicas&#44; &#233; encorajador perceber que a maioria dos adultos com TOF corrigida conquista vidas independentes e produtivas&#46;</p></span>"
      ]
    ]
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                  <table border="0" frame="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Domain&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Description&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " rowspan="4" align="left" valign="\n
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                  \t\t\t\t">Physical complex</td><td class="td" title="\n
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                  \t\t\t\t">Physical functioning&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The extent to which health limits general physical activities such as walking&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The extent to which health limits performing specific physical tasks&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bodily pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The intensity and effect of pain on normal activities&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">General health&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Self-perception of current overall health&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mental complex</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Vitality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Feeling of energy&#44; rather than fatigue&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Social functioning&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">The extent to which health interferes with social activities&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">Mental health&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">General mental health well-being&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Role &#8211; emotional&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">The extent to which emotional problems interfere with daily activities&nbsp;\t\t\t\t\t\t\n
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Description of each domain of the SF-36 questionnaire &#40;adapted from Knowles et al&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a>&#41;&#46;</p>"
        ]
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    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:24 [
            0 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current outcomes and treatment of tetralogy of Fallot"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46;P&#46;G&#46; van der Ven"
                            1 => "E&#46; van den Bosch"
                            2 => "A&#46;J&#46;C&#46;C&#46; Bogers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "F1000Research"
                        "fecha" => "2019"
                        "volumen" => "8"
                        "paginaInicial" => "1530"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lifetime costs and outcomes of repair of tetralogy of fallot compared to natural progression of the disease&#58; great ormond street hospital cohort"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "R&#46;M&#46; Hunter"
                            1 => "M&#46; Isaac"
                            2 => "A&#46; Frigiola"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "PLOS ONE"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "paginaInicial" => "1"
                        "paginaFinal" => "7"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "Multimodality imaging guidelines for patients with repaired Tetralogy of fallot&#58; a report from the American society of echocardiography&#58; developed in collaboration with the society for cardiovascular magnetic resonance and the society for pediatric radiol"
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46;M&#46; Valente"
                            1 => "S&#46; Cook"
                            2 => "P&#46; Festa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.echo.2013.11.009"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Echocardiogr"
                        "fecha" => "2014"
                        "volumen" => "27"
                        "paginaInicial" => "111"
                        "paginaFinal" => "141"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24468055"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term survival of individuals born with congenital heart disease&#58; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46;E&#46; Best"
                            1 => "J&#46; Rankin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Am Heart Assoc"
                        "fecha" => "2016"
                        "volumen" => "5"
                        "paginaInicial" => "1"
                        "paginaFinal" => "16"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Is the severity of congenital heart disease associated with the quality of life and perceived health of adult patients&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "P&#46; Moons"
                            1 => "K&#46; Van Deyk"
                            2 => "S&#46; De Geest"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/hrt.2004.042234"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart"
                        "fecha" => "2005"
                        "volumen" => "91"
                        "paginaInicial" => "1193"
                        "paginaFinal" => "1198"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16103557"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "E&#46;N&#46; Kwon"
                            1 => "K&#46; Mussatto"
                            2 => "P&#46;M&#46; Simpson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Children and adolescents with repaired tetralogy of fallot report quality of life similar to healthy peers"
                        "fecha" => "2011"
                        "paginaInicial" => "18"
                        "paginaFinal" => "27"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Quality of life in adults with repaired tetralogy of Fallot"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "N&#46; Dluzniewska"
                            1 => "P&#46; Podolec"
                            2 => "M&#46; Olszowska"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Kardiochir Torakochir Pol"
                        "fecha" => "2018"
                        "volumen" => "15"
                        "paginaInicial" => "107"
                        "paginaFinal" => "113"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Exercise training in adults with repaired tetralogy of Fallot&#58; a randomized controlled pilot study of continuous versus interval training"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46; Novakovi&#263;"
                            1 => "K&#46; Prok&#353;elj"
                            2 => "U&#46; Rajkovi&#269;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ijcard.2017.12.105"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Cardiol"
                        "fecha" => "2018"
                        "volumen" => "255"
                        "paginaInicial" => "37"
                        "paginaFinal" => "44"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29338917"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Functional health status of adults with tetralogy of Fallot&#58; matched comparison with healthy siblings"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "R&#46; Knowles"
                            1 => "G&#46; Veldtman"
                            2 => "E&#46;J&#46; Hickey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.athoracsur.2011.09.056"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Thorac Surg"
                        "fecha" => "2012"
                        "volumen" => "94"
                        "paginaInicial" => "124"
                        "paginaFinal" => "132"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22429671"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Functional health status in adult survivors of operative repair of tetralogy of fallot"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "E&#46;J&#46; Hickey"
                            1 => "G&#46; Veldtman"
                            2 => "T&#46;J&#46; Bradley"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.amjcard.2011.10.051"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Cardiol"
                        "fecha" => "2012"
                        "volumen" => "109"
                        "paginaInicial" => "873"
                        "paginaFinal" => "880"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22244382"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Psychosocial impact of implantable cardioverter defibrillators &#40;ICD&#41; in young adults with Tetralogy of Fallot"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "P&#46; Opi&#263;"
                            1 => "E&#46;M&#46;W&#46;J&#46; Utens"
                            2 => "P&#46; Moons"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00392-012-0420-x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Res Cardiol"
                        "fecha" => "2012"
                        "volumen" => "101"
                        "paginaInicial" => "509"
                        "paginaFinal" => "519"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22314278"
                            "web" => "Medline"
                          ]
                        ]
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