Renal denervation for resistant hypertension | Revista Portuguesa de Cardiologia (English edition)

array:24 ["pii" => "S2174204915000343" "issn" => "21742049" "doi" => "10.1016/j.repce.2014.07.009" "estado" => "S300" "fechaPublicacion" => "2015-02-01" "aid" => "588" "copyright" => "Sociedade Portuguesa de Cardiologia" "copyrightAnyo" => "2014" "documento" => "article" "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2015;34:125-35" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3445 "formatos" => array:3 [ "EPUB" => 190 "HTML" => 2650 "PDF" => 605 ] ] "Traduccion" => array:1 [ "en" => array:19 [ "pii" => "S0870255115000086" "issn" => "08702551" "doi" => "10.1016/j.repc.2014.07.011" "estado" => "S300" "fechaPublicacion" => "2015-02-01" "aid" => "588" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "ssu" "cita" => "Rev Port Cardiol. 2015;34:125-35" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5408 "formatos" => array:3 [ "EPUB" => 182 "HTML" => 4442 "PDF" => 784 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "Renal denervation for resistant hypertension" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "125" "paginaFinal" => "135" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Desnervação renal para hipertensão arterial resistente" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Manuel de Sousa Almeida, Pedro de Araújo Gonçalves, Eduardo Infante de Oliveira, Henrique Cyrne de Carvalho" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Manuel" "apellidos" => "de Sousa Almeida" ] 1 => array:2 [ "nombre" => "Pedro" "apellidos" => "de Araújo Gonçalves" ] 2 => array:2 [ "nombre" => "Eduardo" "apellidos" => "Infante de Oliveira" ] 3 => array:2 [ "nombre" => "Henrique" "apellidos" => "Cyrne de Carvalho" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204915000343" "doi" => "10.1016/j.repce.2014.07.009" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204915000343?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255115000086?idApp=UINPBA00004E" "url" => "/08702551/0000003400000002/v3_201706020139/S0870255115000086/v3_201706020139/en/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2174204915000355" "issn" => "21742049" "doi" => "10.1016/j.repce.2014.08.022" "estado" => "S300" "fechaPublicacion" => "2015-02-01" "aid" => "589" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Rev Port Cardiol. 2015;34:137.e1-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3636 "formatos" => array:3 [ "EPUB" => 227 "HTML" => 2876 "PDF" => 533 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Case report" "titulo" => "Prosthetic aortic valve: A bone in the system" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "137.e1" "paginaFinal" => "137.e4" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Prótese valvular aórtica: «um osso na engrenagem»" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 862 "Ancho" => 2501 "Tamanyo" => 254845 ] ] "descripcion" => array:1 [ "en" => "Transesophageal echocardiogram in mid-esophageal short- (A) and long-axis (B) views of the aortic prosthesis, showing two abscesses (A, asterisk) surrounding the single-disc mechanical prosthetic valve (A, cross). There appears to be no rupture from these abscesses (B, white arrow) to the left ventricular outflow tract." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Vitor Hugo Pereira, Joana Guardado, Marina Fernandes, Mário Lourenço, Inocência Machado, Isabel Quelhas, Olga Azevedo, António Lourenço" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Vitor Hugo" "apellidos" => "Pereira" ] 1 => array:2 [ "nombre" => "Joana" "apellidos" => "Guardado" ] 2 => array:2 [ "nombre" => "Marina" "apellidos" => "Fernandes" ] 3 => array:2 [ "nombre" => "Mário" "apellidos" => "Lourenço" ] 4 => array:2 [ "nombre" => "Inocência" "apellidos" => "Machado" ] 5 => array:2 [ "nombre" => "Isabel" "apellidos" => "Quelhas" ] 6 => array:2 [ "nombre" => "Olga" "apellidos" => "Azevedo" ] 7 => array:2 [ "nombre" => "António" "apellidos" => "Lourenço" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0870255115000098" "doi" => "10.1016/j.repc.2014.08.023" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255115000098?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204915000355?idApp=UINPBA00004E" "url" => "/21742049/0000003400000002/v2_201502270337/S2174204915000355/v2_201502270337/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2174204915000331" "issn" => "21742049" "doi" => "10.1016/j.repce.2014.08.021" "estado" => "S300" "fechaPublicacion" => "2015-02-01" "aid" => "587" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2015;34:117-23" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2979 "formatos" => array:3 [ "EPUB" => 181 "HTML" => 2272 "PDF" => 526 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Musculoskeletal complaints in cardiac rehabilitation: Prevalence and impact on cardiovascular risk factor profile and functional and psychosocial status" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "117" "paginaFinal" => "123" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Dor músculo-esquelética em reabilitação cardíaca: prevalência e impacto no perfil de risco cardiovascular e estado funcional e psicossocial" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José Afonso Rocha, Thomas G. Allison, José Miguel Santoalha, Vítor Araújo, Fernando Parada Pereira, Maria Júlia Maciel" "autores" => array:6 [ 0 => array:2 [ "nombre" => "José Afonso" "apellidos" => "Rocha" ] 1 => array:2 [ "nombre" => "Thomas G." "apellidos" => "Allison" ] 2 => array:2 [ "nombre" => "José Miguel" "apellidos" => "Santoalha" ] 3 => array:2 [ "nombre" => "Vítor" "apellidos" => "Araújo" ] 4 => array:2 [ "nombre" => "Fernando" "apellidos" => "Parada Pereira" ] 5 => array:2 [ "nombre" => "Maria Júlia" "apellidos" => "Maciel" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0870255115000074" "doi" => "10.1016/j.repc.2014.08.022" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255115000074?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204915000331?idApp=UINPBA00004E" "url" => "/21742049/0000003400000002/v2_201502270337/S2174204915000331/v2_201502270337/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "Renal denervation for resistant hypertension" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "125" "paginaFinal" => "135" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Manuel de Sousa Almeida, Pedro de Araújo Gonçalves, Eduardo Infante de Oliveira, Henrique Cyrne de Carvalho" "autores" => array:4 [ 0 => array:3 [ "nombre" => "Manuel" "apellidos" => "de Sousa Almeida" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Pedro" "apellidos" => "de Araújo Gonçalves" "email" => array:1 [ 0 => "paraujogoncalves@yahoo.co.uk" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Eduardo" "apellidos" => "Infante de Oliveira" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 3 => array:3 [ "nombre" => "Henrique" "apellidos" => "Cyrne de Carvalho" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] 1 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Serviço de Cardiologia, Hospital de Santa Cruz – CHLO, Carnaxide, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Fisiopatologia, Faculdade de Ciências Médicas, UNL, Lisboa, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Serviço de Cardiologia, Hospital de Santa Maria, CHLN, Lisboa, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Instituto de Fisiologia, Faculdade de Medicina de Lisboa, UL, Lisboa, Portugal" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Serviço de Cardiologia, Hospital de Santo Antonio, CHP, Portugal" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Unidade Curricular de Medicina I, Instituto de Ciências Biomédicas Abel Salazar, UP, Porto, Portugal" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Desnervação renal para hipertensão arterial resistente" ] ] "textoCompleto" => "IntroductionHypertension is the leading global risk factor for cardiovascular mortality, accounting for more than nine million deaths worldwide in 2010.<a class="elsevierStyleCrossRef" href="#bib0475">1</a> Its close association with myocardial infarction, heart failure, stroke, end-stage renal disease and cardiovascular death is well established, with 54% of stroke and 47% of ischemic heart disease worldwide attributable to high blood pressure (BP).<a class="elsevierStyleCrossRef" href="#bib0480">2</a> Effective BP lowering has consistently been shown to reduce overall cardiovascular risk,<a class="elsevierStyleCrossRef" href="#bib0485">3</a> but rates of adequate BP control remain suboptimal, despite the wide range of antihypertensive drugs available and strong evidence supporting their use. A recently published study confirmed that rates of BP control in European countries are low, with only 37% of treated hypertensive patients achieving recommended BP values.<a class="elsevierStyleCrossRef" href="#bib0490">4</a>The blame for such low rates cannot be attributed only to poor treatment. Resistant hypertension has a prevalence ranging from 15% to 30% of treated hypertensive patients,<a class="elsevierStyleCrossRef" href="#bib0495">5</a> and is an important cause of failure of BP control. Most importantly, these patients exhibit a worse prognosis, with a higher risk for cardiovascular events, compared to hypertensive patients without resistant hypertension.<a class="elsevierStyleCrossRef" href="#bib0500">6</a>In recent decades, the renin-angiotensin-aldosterone system (RAAS) has been the central focus of hypertension treatment and management. The availability of safe, effective and evidence-based drugs that block this system has meant that the role of other systems, particularly the autonomic nervous system, has been neglected.The sympathetic nervous system (SNS) and its possible role in the pathogenesis of hypertension is receiving increasing attention. The aim of this review is to provide an update on the current understanding of the role of the SNS in blood pressure control and its implications for sympathetic renal denervation (RDN).The sympathetic nervous system and cardiovascular diseaseThe development of open surgical sympathectomy in the 1930s highlighted the role of the SNS in severe hypertension, since it appeared to be effective in lowering high BP in patients with severe hypertension.<a class="elsevierStyleCrossRefs" href="#bib0505">7,8</a> However, the procedure was abandoned due to its poorly tolerated side effects and high surgical risk, especially after the appearance of ganglionic blockers, the first effective antihypertensive drug class.<a class="elsevierStyleCrossRef" href="#bib0515">9</a>The recent development of a new device-based approach to treat severe resistant hypertension, through RDN, focused attention on the already well-known role of the SNS in initiating and maintaining high BP in patients with essential hypertension.<a class="elsevierStyleCrossRefs" href="#bib0520">10,11</a>Assessment of the sympathetic nervous system in humansThe major reason that the SNS has been so neglected is not because there are doubts concerning its critical role in the pathogenesis of hypertension and other cardiovascular diseases, but because it has been difficult to study and test this relation, due to the complex and clinically impractical methods used for assessing the SNS in humans. Until the early 1970s, the most common techniques were measurements of blood levels and urine excretion rates of norepinephrine and its derivatives, which provide a gross estimate of whole-body sympathetic activity at best.<a class="elsevierStyleCrossRef" href="#bib0530">12</a> Since then, new methods have emerged for measuring sympathetic nerve firing rates in subcutaneous nerves and for assaying plasma concentrations of sympathetic transmitters.Microneurography, a technique reported first by Hagbarth and Vallbo,<a class="elsevierStyleCrossRef" href="#bib0535">13</a> provided a tool to study nerve firing in subcutaneous sympathetic nerves in skin and skeletal muscle vessels. It is based on recording bursts of nerve activity, synchronous with the heartbeat, generated in skeletal muscle vascular efferent nerves, through tungsten electrodes inserted in the skin. It is highly reproducible and closely related to sympathetic traffic directed to other structures and can be repeated over time, allowing assessment of the effects of interventions, direct quantification of sympathetic nerve traffic regulating vasomotor tone, and study of instantaneous reactions to rapid stimuli.The spillover technique for measurement of norepinephrine release, first applied by Esler et al,<a class="elsevierStyleCrossRef" href="#bib0540">14</a> is an isotope dilution method that calculates the clearance and spillover of norepinephrine, using an intravenous infusion of tritium-labeled norepinephrine. The relationship between the sympathetic nerve fiber firing rate of an organ and the rate of norepinephrine spillover into the venous effluent of that organ provides the rationale for using measures of regional norepinephrine release as a surrogate for sympathetic tone in individual organs,<a class="elsevierStyleCrossRef" href="#bib0545">15</a> enabling assessment of regional sympathetic nervous function in humans.This technique was central to the demonstration that heart failure patients had sympathetic overactivity rather than sympathetic denervation, as thought at the time, and opened the way to the routine use of beta-blockers in heart failure.<a class="elsevierStyleCrossRef" href="#bib0550">16</a>Sympathetic nervous system overactivityBesides its central role in cardiovascular homeostasis, by controlling vascular tone through vasoconstriction of small resistance arteries, the sympathetic system also affects and regulates numerous other physiological processes (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). There is growing evidence that sustained chronic changes in sympathetic activity are involved in the pathogenesis of many disease states, from metabolic to psychological disorders, including ischemic heart disease,<a class="elsevierStyleCrossRef" href="#bib0555">17</a> chronic heart failure,<a class="elsevierStyleCrossRefs" href="#bib0560">18,19</a> hypertension,<a class="elsevierStyleCrossRefs" href="#bib0570">20–22</a> kidney disease,<a class="elsevierStyleCrossRef" href="#bib0585">23</a> type 2 diabetes,<a class="elsevierStyleCrossRef" href="#bib0590">24</a> obesity,<a class="elsevierStyleCrossRef" href="#bib0590">24</a> metabolic syndrome,<a class="elsevierStyleCrossRef" href="#bib0590">24</a> obstructive sleep apnea,<a class="elsevierStyleCrossRef" href="#bib0595">25</a> depression<a class="elsevierStyleCrossRef" href="#bib0600">26</a> and inflammatory bowel disease.<a class="elsevierStyleCrossRef" href="#bib0605">27</a> A chronically overactive sympathetic system is linked to a worse prognosis in patients with heart failure and end-stage renal disease.<a class="elsevierStyleCrossRefs" href="#bib0610">28,29</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Sympathetic nervous system overactivity and cardiovascular diseaseThere is growing evidence that the deleterious effects on blood vessels and myocardium of an overactive SNS are independent of increased BP.<a class="elsevierStyleCrossRef" href="#bib0620">30</a> Chronic SNS activation without an increase in BP can cause hypertrophy and proliferation of vascular smooth muscle cells as well as having a direct trophic effect on cardiac myocytes, increasing left ventricular (LV) mass and wall thickness,<a class="elsevierStyleCrossRef" href="#bib0620">30</a> while BP reduction after catheter-based RDN has been shown to lead to a significant reduction in LV mass and improvement in diastolic function.<a class="elsevierStyleCrossRef" href="#bib0625">31</a>These structural changes in the myocardium and the direct effects of an overactive SNS contribute to the high incidence of arrhythmias commonly seen in patients with hypertension.<a class="elsevierStyleCrossRef" href="#bib0630">32</a>The link between mental stress, psychiatric illness and cardiovascular disease, although best established for heart disease consequential to acute mental stress and depressive illness, has been much more difficult to establish.<a class="elsevierStyleCrossRef" href="#bib0600">26</a> Acute mental stress can trigger sympathetic outflow to the heart and adrenal secretion of epinephrine. In patients with pre-existing atherosclerosis, not only can increased epinephrine cause ventricular arrhythmias (especially in the presence of coronary artery stenosis), but the attendant BP surge can fissure coronary plaques and promote platelet aggregation, predisposing to thrombosis.<a class="elsevierStyleCrossRef" href="#bib0600">26</a> Takotsubo (stress) cardiomyopathy is a good example of extreme acute activation of cardiac sympathetic outflow to the heart,<a class="elsevierStyleCrossRef" href="#bib0600">26</a> as are panic attacks accompanied by coronary spasm and cardiac arrhythmias.<a class="elsevierStyleCrossRef" href="#bib0635">33</a> In patients with depressive illness, chronic cardiac sympathetic outflow is at almost the same level as seen in patients with heart failure, and is accepted as a primary cause for heart disease, associated with a worse prognosis.The sympathetic nervous system and atherosclerosisThe pivotal role of endothelial impairment in the development of atherosclerosis and in future cardiovascular risk is well established. Less known is the interaction between the SNS and endothelial function. Virtually all cardiovascular risk factors and diseases in which increased adrenergic drive is involved are also characterized by endothelial dysfunction.<a class="elsevierStyleCrossRef" href="#bib0640">34</a> Nitric oxide (NO), one of the main mediators of endothelial function, is also an important neurotransmitter, involved in the autonomic regulation of cardiovascular function, and acts as a sympathoinhibitory substance within the central nervous system.<a class="elsevierStyleCrossRef" href="#bib0645">35</a> Acute and chronic increases in SNS activity, through endothelial dysfunction and endothelial cell damage, have been shown to contribute to the subsequent development of atherosclerosis.<a class="elsevierStyleCrossRefs" href="#bib0600">26,30,34</a>SNS overactivity has also been linked to the development of metabolic disturbances such as insulin resistance and dyslipidemia.<a class="elsevierStyleCrossRef" href="#bib0650">36</a> Not only can increased SNS activity in itself lead to insulin resistance, particularly in hypertensive patients,<a class="elsevierStyleCrossRef" href="#bib0650">36</a> but also elevated circulating insulin levels due to insulin resistance in obese patients can precipitate an increase in SNS activity, leading to hypertension.<a class="elsevierStyleCrossRefs" href="#bib0620">30,36,37</a> There is abundant evidence that statins, through their numerous pleiotropic effects, reduce and even normalize excessive SNS activity, improving LV function and arterial baroreflex sensitivity.<a class="elsevierStyleCrossRefs" href="#bib0600">26,30,34</a>Sympathetic nervous system function and heart failureThe observation that norepinephrine concentrations were reduced in the failing heart suggested the existence of sympathetic denervation,<a class="elsevierStyleCrossRef" href="#bib0660">38</a> despite the increased concentrations in peripheral venous plasma commonly found in patients with heart failure,<a class="elsevierStyleCrossRef" href="#bib0665">39</a> indicating overall increased SNS activity except in the heart. Later studies confirmed very high levels of norepinephrine spillover from the heart in heart failure, up to 50 times the normal range in untreated patients,<a class="elsevierStyleCrossRef" href="#bib0600">26</a> demonstrating high sympathetic tone in the failing heart. This was later explained by a reduction in the concentration of beta-1 adrenoreceptors in the failing myocardium, due to downregulation of these receptors by increased sympathetic activity in the failing heart.<a class="elsevierStyleCrossRef" href="#bib0600">26</a>This increased sympathetic activity in the peripheral circulation and kidneys leads to adverse effects, causing vasoconstriction, increasing cardiac work, and promoting sodium retention and ventricular overfilling. The strong link between the level of sympathetic activity in heart failure, progressive ventricular deterioration, the development of ventricular arrhythmias, sudden death and reduced survival<a class="elsevierStyleCrossRef" href="#bib0600">26</a> provided the rationale for the subsequent use of beta-blockers in heart failure.<a class="elsevierStyleCrossRef" href="#bib0670">40</a>Sympathetic nervous system function and essential hypertensionA well-known consequence of an overactive SNS is an increase in BP. Previous studies showed not only that sympathetic outflow to the kidneys was increased, but that the extent of the outflow was also related to the degree of essential hypertension.<a class="elsevierStyleCrossRefs" href="#bib0570">20,22,26,41</a> Regional measurements of norepinephrine spillover to the kidneys support this concept, and indicate that more than 50% of cases of essential hypertension present significant sympathetic hyperactivation.<a class="elsevierStyleCrossRef" href="#bib0680">42</a> Renal sympathetic nerve activity is pivotal in the pathogenesis of essential hypertension, through its influence on renin release, sodium and water excretion, peripheral vasoconstriction, cardiac contraction and venous capacitance.<a class="elsevierStyleCrossRef" href="#bib0600">26</a>The safety and efficacy of BP lowering achieved recently with RDN has led to renewed interest in the role of sympathetic activity in the pathogenesis of essential hypertension. Correct identification of sympathetic hyperactivation in patients with essential hypertension can lead to better selection of patients for RDN treatment.Resistant hypertensionData from the PAP study involving 5023 adult patients showed that the prevalence of hypertension in Portugal was 42%, of whom only 46.1% were aware of the fact, 39% were taking medication and only 11.2% had BP values below the recommended thresholds.<a class="elsevierStyleCrossRef" href="#bib0685">43</a>Not all patients with uncontrolled hypertension are considered to be resistant, as there are several factors that can contribute to lack of control, including inadequate treatment regimens (type and/or dosage of drugs), poor adherence to medical therapy, and undetected secondary causes of hypertension. A diagnosis of resistant hypertension should therefore only be made after ruling out other factors.Resistant hypertension has been defined as BP values above 140/90 mmHg (or >130/80 mmHg in patients with diabetes or chronic kidney disease) in patients treated with three or more antihypertensive drugs at appropriate doses, including if possible a diuretic.<a class="elsevierStyleCrossRef" href="#bib0690">44</a> In an alternative definition, patients with target BP values can be considered to have resistant hypertension if they need to take at least four different antihypertensive drugs; this is known as controlled resistant hypertension.<a class="elsevierStyleCrossRef" href="#bib0695">45</a> The prevalence of resistant hypertension has been reported as 5–30%,<a class="elsevierStyleCrossRefs" href="#bib0700">46–48</a> the figure varying according to the hypertensive population being studied, with higher percentages in cohorts from centers specializing in the treatment of hypertension compared to community-based cohorts.At the present time, and in the light of the available clinical studies, patients considered to be good candidates for RDN should have more severe treatment-resistant hypertension, defined as office systolic BP of at least 160 mmHg (150 mmHg in type 2 diabetes).<a class="elsevierStyleCrossRefs" href="#bib0715">49–51</a>Renal denervationAssessment of a potential candidate for RDN should follow several steps (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>) designed to select candidates expected to benefit from this intervention. According to a recent European Society of Hypertension (ESH) position paper on RDN,<a class="elsevierStyleCrossRef" href="#bib0730">52</a> it is recommended that patients should undergo careful assessment in centers that have considerable experience in dealing with hypertension (ideally ESH excellence centers).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The first step should be to exclude pseudoresistance, secondary causes of hypertension and conditions that maintain high BP values. Pseudoresistance can be excluded by 24-hour ambulatory BP monitoring, which is recommended not only for pre-RDN assessment but as good practice in the assessment of all patients with hypertension.<a class="elsevierStyleCrossRefs" href="#bib0495">5,53</a> In patients with severe resistant hypertension considered for RDN, the initial assessment should also include investigation of possible secondary causes of hypertension, including primary aldosteronism, renal artery stenosis, pheochromocytoma, Cushing's disease, hyperparathyroidism and aortic coarctation, although some of these are very uncommon.<a class="elsevierStyleCrossRef" href="#bib0690">44</a> Some conditions that can maintain high BP values should also be treated when possible, such as severe obesity, high salt and alcohol intake, concomitant use of drugs that raise BP and the presence of obstructive sleep apnea.The second step should be the optimization of antihypertensive treatment, including the use of diuretics and aldosterone blockers, optimization of dosages and combinations, and reassessment of BP control with 24-hour ambulatory BP monitoring (ABPM).The third step should be assessment of renal artery anatomy, as there are relative contraindications for RDN related to the number of renal arteries (multiple main arteries) and their diameter (ideally >4 mm) and length (ideally >20 mm) as well as eGFR, which should be above 45 ml/min/1.73 m2. Some of these are considered contraindications to RDN, because they were excluded from RDN trials, but are regarded in clinical practice as relative contraindications; some of these patients have been treated with RDN and included in small studies and registries.<a class="elsevierStyleCrossRefs" href="#bib0740">54–56</a>Experimental studies on renal denervationThe finding that renal sympathetic activity is increased in spontaneously hypertensive rats, the animal model most often used in investigation of essential hypertension, has shone light on the role of the renal SNS in the pathogenesis of hypertension.<a class="elsevierStyleCrossRef" href="#bib0755">57</a> In an experimental model of hypertension and obesity in dogs subjected to a high-fat diet, RDN not only prevented the appearance of hypertension but also increased urinary sodium excretion by 50%.<a class="elsevierStyleCrossRef" href="#bib0760">58</a> In another animal model of chronic renal failure, sympathectomy prevented hypertension and was associated with decreased adrenergic activity in the hypothalamic nuclei.<a class="elsevierStyleCrossRef" href="#bib0765">59</a>Renal lesions induced by injection of phenol cause a sustained rise in BP and norepinephrine release by the hypothalamus without changing eGFR. RDN of these animals prevented the rise in BP.<a class="elsevierStyleCrossRef" href="#bib0770">60</a> In different animal models, the effects of RDN have consistently shown the important role of the renal SNS in the pathophysiology of hypertension.In humans, surgical sympathectomy lowers high BP and improves the cardiovascular prognosis of patients with severe hypertension.<a class="elsevierStyleCrossRefs" href="#bib0505">7–9,61–63</a> Its poorly tolerated side effects, which include severe orthostatic hypotension, anhidrosis, intestinal disturbances and sexual dysfunction, and its high surgical risk, have led to the technique being abandoned. Nevertheless, it has proved the importance of the SNS in BP control beyond doubt.Clinical studies on percutaneous sympathetic renal denervationSymplicity HTN-1,<a class="elsevierStyleCrossRef" href="#bib0525">11</a> a proof-of-principle study, was the first to evaluate RDN in patients with severe resistant hypertension. One year after the procedure, mean office BP fall was 27 mmHg systolic and 17 mmHg diastolic, and was maintained until 24 months of follow-up, with 13% non-responders. A subgroup analysis assessing renal and systemic sympathetic activity showed a 47% reduction in renal norepinephrine spillover in these patients.<a class="elsevierStyleCrossRef" href="#bib0790">64</a>In the Symplicity HTN-2 multicenter clinical trial,<a class="elsevierStyleCrossRefs" href="#bib0790">64,65</a> 106 patients with severe resistant hypertension under medication were randomized to optimal antihypertensive medical therapy alone or to RDN plus optimal antihypertensive medical therapy. The primary endpoint was change in office BP at six-month follow-up. A significant fall in BP was observed in patients who underwent RDN: −32 mmHg in systolic BP and −12 mmHg in diastolic BP (p<0.01) compared to an increase of 1 mmHg in systolic BP and no change in diastolic BP (p=NS) in patients under optimal medical therapy alone at six months following RDN. A subgroup analysis of 24-hour ABPM data revealed a similar pattern, a fall of 11 mmHg in systolic BP and 7 mmHg in diastolic BP in the RDN group (p<0.001) compared to a fall of 3 mmHg and 1 mmHg on medical therapy alone (p=NS). The magnitude of the difference in BP fall between RDN and optimal medical therapy alone was maintained at 12-month follow-up.<a class="elsevierStyleCrossRef" href="#bib0790">64</a>Alongside its efficacy, RDN was a safe procedure. In both studies, only minor vascular complications occurred, mainly at the puncture site: hematomas and pseudoaneurysms (four patients), one renal artery dissection during the diagnostic procedure, successfully treated with a stent, and no major complications. Regarding renal function, there were no significant changes in eGFR during follow-up.<a class="elsevierStyleCrossRefs" href="#bib0715">49,66</a>The recently published EnlightHTN I trial<a class="elsevierStyleCrossRef" href="#bib0725">51</a> also revealed a significant fall in both office BP and mean 24-hour ABPM values at six months, with a good safety profile.The published data indicate that RDN has an excellent short-term safety profile, although data on the long-term risk of renal artery stenosis are lacking. The results of the Symplicity trials and EnlightHTN I are certainly promising, but their open design meant that bias in BP measurements, or even the extent of the placebo effect in treated patients, could not be properly addressed. Some of these limitations were addressed in the recently published randomized SYMPLICITY HTN-3 trial.<a class="elsevierStyleCrossRefs" href="#bib0805">67,68</a> This was the first blinded sham-controlled study of RDN for treatment of resistant hypertension. The primary efficacy endpoint was the mean change in office systolic BP from baseline to six months in the RDN arm (n=364) compared to the control arm (n=171). At six-month follow-up, there was a difference of 2.39 mmHg in the change in systolic BP (−14.13±23.93 mmHg in the RDN arm vs. −11.74±25.94 mmHg in the sham procedure arm), which did not reach statistical significance (95% confidence interval [CI]: −6.89 to 2.12, p=0.26).The secondary efficacy endpoint was the change in mean 24-hour ambulatory BP at six months. A statistically non-significant difference of 1.96 mmHg (95% CI: −4.97 to 1.06, p=0.98) was seen at six months (−6.75±15.11 mm Hg in the RDN arm vs. −4.79±17.25 mm Hg in the control arm).The rate of major adverse events at six months was 4% in the RDN arm vs. 5.8% in the control arm (p=0.37). The primary safety endpoint (a composite of major adverse events) rate was 1.4% in the RDN arm, less than the pre-specified objective of 9.8%, reaching statistical significance (p<0.001).These conflicting results between Symplicity HTN-3<a class="elsevierStyleCrossRef" href="#bib0810">68</a> and the previous Symplicity trials, HTN-1<a class="elsevierStyleCrossRef" href="#bib0525">11</a> and HTN-2<a class="elsevierStyleCrossRef" href="#bib0795">65</a> (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>), may be related to a different and more rigorous design adopted in HTN-3, a different study population, more aggressive antihypertensive medication, and the requirement that no changes in antihypertensive medication could be made in the six months after the procedure. There was also potential for procedural variability due to the large number of centers involved in the HTN-3 study and a low case load per operator, each performing only three procedures on average (most performed their first and only RDN procedure for the trial). The inclusion for the first time of a large proportion of African-American patients (24.8% of the RDN arm and 29.2% of the control arm), a population known to be resistant to RAAS blockers, could have had a negative impact on the efficacy of RDN; a subgroup analysis revealed a statistically significant difference favoring the RDN arm in non-African-American patients. Overall antihypertensive medication was more intensive than in previous studies, probably reflecting the more severe hypertensive patients included. Regression to the mean may also at least partially explain the differences.<a class="elsevierStyleCrossRef" href="#bib0815">69</a> The presence for the first time of a sham procedure in the control arm (renal angiography was performed in all patients before randomization) may have diluted the expected placebo effect favoring the treated group.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Puzzling findings in Symplicity HTN-3 include the smaller decrease in office systolic BP from baseline to six months in the RDN arm, about half that observed in the Symplicity HTN-2 RDN group, despite similar baseline BP in the two studies, raising doubts as to whether RF energy was properly delivered. A larger decrease in BP was also observed in the HTN-3 control group compared to the much smaller decrease in the HTN-2 control group. These findings raise the question of whether a less effective denervation procedure allied to more aggressive medical therapy could have played a major role in the HTN-3 results.The fact that there was no measurement to confirm that the renal nerves were in fact denervated by the procedure, because there is no test that can be easily performed in a large trial, is a major limitation to this and to almost all of these trials.While the Symplicity HTN-3 follow-up will continue as planned for up to five years, the fact that many patients crossed over from the control arm to the RDN arm at six months will make it more difficult to draw significant conclusions concerning the long-term clinical results of RDN therapy and to assess the placebo effect over time.Nevertheless, the Symplicity HTN-3 trial is a landmark in the development of RDN treatment, signaling the start of its reflection phase, in which new hypotheses generated by this trial can be addressed.Renal denervation: new devicesThe high expectations and enthusiasm created in the medical device industry has led many companies to develop new or improved technical solutions for RDN, some of which are commercially available (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>From predictable improvements of the original procedure to out-of-the-box ideas, many innovations are being integrated in the new designs. These include alternative mechanisms of action, like ultrasound catheters and balloons with microinjection systems to deliver neurotoxins. Simultaneously activated multi-electrodes not only significantly shorten procedural time but also increase reproducibility, ensuring that all quadrants are adequately denervated, while radial access reduces access site vascular complications, and manipulating renal catheters by a craniocaudal approach is generally less challenging and safer. Pain control is also a challenge, as electric current, tissue burning, and nerve damage, although essential components of the procedure, all cause discomfort. The more recent radiofrequency catheters with bipolar electrodes reportedly reduce discomfort due to a significantly smaller electric field during activation, but this is not yet clinically proven; the absence of an acute procedural efficacy endpoint is still a major limitation. Procedural success is difficult to determine and to correlate with BP response. Efforts are being made to find a biomarker or physiological test that indicates acute RDN success.Sympathetic renal denervation: potential future indicationsThe overall decrease in SNS drive through RDN may be a valid alternative in clinical scenarios characterized by sympathetic hyperactivity other than resistant hypertension. A few of these alternative applications have already been explored and show promising results.The association between heart failure and increased sympathetic drive is well known. Interestingly, cardiac and renal norepinephrine spillover is more closely associated with mortality than circulating catecholamine concentrations, although both are associated with worse outcomes.<a class="elsevierStyleCrossRefs" href="#bib0550">16,70</a> This suggests that reducing norepinephrine spillover from the kidney could have beneficial symptomatic and prognostic effects.<a class="elsevierStyleCrossRefs" href="#bib0825">71,72</a>In animal models, RDN after myocardial infarction led to improvement in sodium excretion,<a class="elsevierStyleCrossRef" href="#bib0835">73</a> increased cardiac output, improved renal blood flow,<a class="elsevierStyleCrossRef" href="#bib0840">74</a> and down-regulation of angiotensin AT1 receptors mediating maladaptive responses.<a class="elsevierStyleCrossRef" href="#bib0845">75</a> In a multicenter study of patients with resistant hypertension treated by RDN with anatomical and functional myocardial parameters assessed by MRI, a subgroup of patients with LV dysfunction had significantly increased ejection fraction and circumferential strain.<a class="elsevierStyleCrossRef" href="#bib0850">76</a>The REACH pilot study in heart failure provided evidence that RDN improved six-minute walk distances without affecting BP (mean 120 mmHg at baseline).<a class="elsevierStyleCrossRef" href="#bib0855">77</a> Other ongoing clinical trials will provide further evidence on the potential of RDN to influence the course and outcome of heart failure. Type 2 diabetes and insulin resistance are other conditions that have a strong association with resistant hypertension. Half of resistant hypertension patients are considered to be insulin resistant, increasing the risk for type 2 diabetes, and since insulin resistance is dependent on sympathetic activity it appears likely that it could also be a target for RDN.<a class="elsevierStyleCrossRefs" href="#bib0860">78,79</a> In a pilot study, along with reducing BP, RDN improved fasting glucose, insulin, and C-peptide concentrations, as well as homeostasis model assessment-insulin resistance indices in patients with resistant hypertension and metabolic disease, suggesting that RDN might improve diabetic status in these patients.<a class="elsevierStyleCrossRef" href="#bib0870">80</a> Witkowski et al. showed a decline in glycated hemoglobin concentrations after RDN.<a class="elsevierStyleCrossRef" href="#bib0875">81</a>The association between obstructive sleep apnea and resistant hypertension is well known.<a class="elsevierStyleCrossRef" href="#bib0875">81</a> In 2011 Witkowski et al. published a pilot study on the effect of RDN in 10 patients with resistant hypertension and obstructive sleep apnea. At six months there was an improvement in apnea-hypopnea indices.<a class="elsevierStyleCrossRef" href="#bib0875">81</a> In an experimental model, it has been shown that RDN reduces post-apneic BP rise, renal hypoperfusion during apnea and RAAS activation in the kidney.<a class="elsevierStyleCrossRefs" href="#bib0880">82,83</a> The value of these findings is still controversial and confirmatory studies are needed.In an animal model<a class="elsevierStyleCrossRef" href="#bib0890">84</a> of obstructive sleep apnea and induced atrial fibrillation (AF), RDN decreased the atrial refractory period and AF recurrence,<a class="elsevierStyleCrossRef" href="#bib0880">82</a> providing better rate control.<a class="elsevierStyleCrossRef" href="#bib0895">85</a> In a pilot trial, patients with resistant hypertension and symptomatic paroxysmal or persistent atrial fibrillation refractory to ≥2 antiarrhythmic drugs were randomized to pulmonary vein isolation alone or associated with RDN. At 12-month follow-up 69% of patients treated with RDN were AF-free, compared to 29% of those treated with pulmonary vein isolation only.<a class="elsevierStyleCrossRef" href="#bib0900">86</a> These experimental findings indicate the potential usefulness of RDN in AF treatment.The evidence for the fundamental role of sympathetic activity in ventricular arrhythmias is overwhelming. In an animal model of ischemia/reperfusion arrhythmias, RDN decreased the occurrence of ventricular arrhythmias/fibrillation and attenuated the rise in LV end-diastolic pressure during LV ischemia without influencing infarct size, changes in ventricular contractility, BP or reperfusion arrhythmias.<a class="elsevierStyleCrossRef" href="#bib0905">87</a> In a small case series involving patients with chronic heart failure and ventricular electrical storm, RDN reduced discharges from implantable cardioverter-defibrillators and ventricular ectopies.<a class="elsevierStyleCrossRef" href="#bib0910">88</a> Hoffmann et al.<a class="elsevierStyleCrossRef" href="#bib0915">89</a> reported that RDN can be safely and effectively performed as an adjunct to cardiac catheter ablation, in a hemodynamically unstable patient with ventricular storm after ST-elevation myocardial infarction. Although these are early and preliminary findings, the underlying biological plausibility will certainly heighten interest in these potential future applications of RDN.ConclusionsIt is now accepted that an overactive sympathetic system has a pivotal role in the pathophysiology of several diseases besides essential hypertension. Related conditions like depression, mental stress, hypertension, diabetes, obesity, sleep apnea, metabolic syndrome, ischemic heart disease, heart failure and chronic renal failure, all have a common link, the often neglected hyperactive SNS. In a new era with new tools to control and treat sympathetic hyperactivity, perhaps this system will finally receive the attention it deserves.The inability to treat hypertension effectively is due in part to a lack of understanding of the fundamental mechanisms involved in BP control. There is a complex mixture of hormonal, neural and intrinsic factors, all acting together, over different time scales and with different feedback control pathways, and it seems unlikely that any of the current treatment approaches is actually targeting the factors that originally led to the rise in BP. Catheter-based RDN is a truly innovative approach to treat hypertension by changing sympathetic activity. In patients with resistant hypertension, the technique has significantly reduced BP as well as sympathetic nerve activity and norepinephrine spillover, with high safety levels. These achievements are well documented in several international multicenter trials and registries. Along with its proven efficacy in BP reduction, it has the potential to positively affect insulin resistance and diabetes, LV mass, proteinuria and arrhythmias, as indicated by various small proof-of-concept studies.Nevertheless, there are still important issues that need to be addressed in the near future, like the impossibility of determining whether denervation was effective, what level of denervation is needed to achieve clinical success, which patients have an appropriate phenotype for RDN, and what endpoints should be used to define RDN success (merely BP reduction or reduction in target organ damage). Much needs to be done and will be in the coming years, but a new window has certainly been opened not only to address hypertension, but most importantly to address SNS dysfunction.Conflicts of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres439418" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec462607" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres439417" "titulo" => "Resumo" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec462606" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "The sympathetic nervous system and cardiovascular disease" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Assessment of the sympathetic nervous system in humans" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Sympathetic nervous system overactivity" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Sympathetic nervous system overactivity and cardiovascular disease" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "The sympathetic nervous system and atherosclerosis" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Sympathetic nervous system function and heart failure" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Sympathetic nervous system function and essential hypertension" ] ] ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Resistant hypertension" ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Renal denervation" ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Experimental studies on renal denervation" ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "Clinical studies on percutaneous sympathetic renal denervation" ] 10 => array:2 [ "identificador" => "sec0065" "titulo" => "Renal denervation: new devices" ] 11 => array:2 [ "identificador" => "sec0070" "titulo" => "Sympathetic renal denervation: potential future indications" ] 12 => array:2 [ "identificador" => "sec0075" "titulo" => "Conclusions" ] 13 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflicts of interest" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-07-22" "fechaAceptado" => "2014-07-31" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec462607" "palabras" => array:3 [ 0 => "Hypertension" 1 => "Sympathetic nervous system" 2 => "Renal denervation" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec462606" "palabras" => array:3 [ 0 => "Hipertensão arterial" 1 => "Sistema nervoso simpático" 2 => "Desnervação renal" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "There is a marked contrast between the high prevalence of hypertension and the low rates of adequate control. A subset of patients with suboptimal blood pressure control have drug-resistant hypertension, in the pathophysiology of which chronic sympathetic hyperactivation is significantly involved. Sympathetic renal denervation has recently emerged as a device-based treatment for resistant hypertension. In this review, the pathophysiological mechanisms linking the sympathetic nervous system and cardiovascular disease are reviewed, focusing on resistant hypertension and the role of sympathetic renal denervation. An update on experimental and clinical results is provided, along with potential future indications for this device-based technique in other cardiovascular diseases." ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "A elevada prevalência da hipertensão está em claro contraste com a sua ainda insuficiente taxa de controlo. Um importante subgrupo destes doentes apresenta uma hipertensão resistente aos fármacos, na qual a hiperativação crónica do sistema nervoso simpático tem importantes implicações fisiopatológicas. Recentemente, a desnervação simpática renal emergiu como um tratamento de intervenção para a hipertensão arterial resistente. No presente artigo, são revistos os mecanismos fisiopatológicos subjacentes à interação entre o sistema nervoso simpático e as doenças cardiovasculares, com particular enfâse na hipertensão arterial resistente e no papel da desnervação simpática renal. É igualmente feita uma atualização dos resultados de estudos experimentais e clínicos, bem como de potenciais futuras indicações desta técnica de intervenção noutras doenças do foro cardiovascular." ] ] "nomenclatura" => array:1 [ 0 => array:3 [ "identificador" => "nom0005" "titulo" => "List of abbreviations" "listaDefinicion" => array:1 [ 0 => array:1 [ "definicion" => array:7 [ 0 => array:2 [ "termino" => "BP" "descripcion" => "blood pressure" ] 1 => array:2 [ "termino" => "CI" "descripcion" => "confidence interval" ] 2 => array:2 [ "termino" => "eGFR" "descripcion" => "estimated glomerular filtration rate" ] 3 => array:2 [ "termino" => "SNS" "descripcion" => "sympathetic nervous system" ] 4 => array:2 [ "termino" => "RAAS" "descripcion" => "renin-angiotensin-aldosterone system" ] 5 => array:2 [ "termino" => "RDN" "descripcion" => "renal denervation" ] 6 => array:2 [ "termino" => "RF" "descripcion" => "radiofrequency" ] ] ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "RAAS: renin-angiotensin-aldosterone system." "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Vascular \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Smooth muscle cell hypertrophy and proliferation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Endothelial dysfunction and damage \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Arterial stiffness \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Impairment of postural blood pressure control and syncope \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hypertension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Atherosclerosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Cardiac \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Myocyte hypertrophy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Left ventricular hypertrophy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Arrhythmia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Psychogenic heart disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Renal \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Renal artery vasoconstriction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Sodium and fluid retention \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Microalbuminuria \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">RAAS activation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Metabolic \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Insulin resistance \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Dyslipidemia \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab685936.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Effects of increased sympathetic nerve activity." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "ABPM: ambulatory blood pressure monitoring; BP: blood pressure; CT: computed tomography; eGFR: estimated glomerular filtration rate; MRI: magnetic resonance imaging." "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1st step \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Exclusion of pseudoresistance (by 24-hour ABPM) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Exclusion of secondary causes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Search for conditions that maintain high BP values \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2nd step \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Modification of antihypertensive treatment (optimization of dosages and combinations; use of aldosterone blockers if possible) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Reassessment of BP control with 24-hour ABPM \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3rd step \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Assessment of renal artery anatomy (CT, MRI or invasive angiography; Doppler ultrasound) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Assessment of renal function (eGFR ideally >45 ml/min/1.73 m2) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab685934.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Evaluation of patients with resistant hypertension considered to be potential candidates for renal denervation." ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "ABPM: ambulatory blood pressure monitoring; NA: not available; RDN: renal denervation; RF: radiofrequency; SBP: systolic blood pressure." "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">Trial \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">Symplicity HTN-1<a class="elsevierStyleCrossRef" href="#bib0525">11</a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Symplicity HTN-2<a class="elsevierStyleCrossRef" href="#bib0795">65</a></th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Symplicity HTN-3<a class="elsevierStyleCrossRef" href="#bib0810">68</a></th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">EnlightHTN-1<a class="elsevierStyleCrossRef" href="#bib0725">51</a> \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">RAPID<a class="elsevierStyleCrossRef" href="#bib0920">90</a> \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">REDUCE-HTN FIM<a class="elsevierStyleCrossRef" href="#bib0925">91</a> \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 " align="left" valign="top">Device \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF, single-electrode(Symplicity®) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF, single-electrode(Symplicity®) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No RDN \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF, single-electrode(Symplicity®) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No RDN (sham) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF, multi-electrode (EnlightHTN®) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF, balloon (OneShot®) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF, balloon (Vessix®) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">No. of patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">564 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">171 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Randomized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="center" valign="top">Yes</td><td class="td" title="table-entry " colspan="2" align="center" valign="top">Yes</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Sham control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Black (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.2<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean baseline office SBP (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">177±20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">178±18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">178±16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">179±16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">180±17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">176 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">181.6±20.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">183±18.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean no. of antihypertensive drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.7±1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.2±1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.3±1.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.1±1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.2±1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.1±0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.1±1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Aldosterone blockers (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Office SBP change at 6 months (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−32±23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1±21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−14.1±23.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−11.7±25.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−27.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">24-hour ABMP SBP change at 6 months (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−11<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−11±15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−3±19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−6.8±15.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−4.8±17.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−8.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Response rate (≥10 mmHg change in office SBP from baseline) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">87% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">84% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58.3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">85% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab685933.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Described as non-white." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Only nine RDN responder patients had adequate ABPM at baseline and longer than 30 days." ] ] ] "descripcion" => array:1 [ "en" => "Studies of renal denervation." ] ] 3 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "RF: radiofrequency." "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">Company \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">Medtronic \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">Medtronic \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">St. Jude \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">Maya/Covidien \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">ReCor Medical \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">Boston Scientific \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">Terumo \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">Cordis \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 " align="left" valign="top">Product \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Symplicity Flex™ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Symplicity Spyral™ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">EnlightHTN™ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OneShot™ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Paradise™ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vessix V2™ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Iberis™ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Renlane™ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Catheter size \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6F \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Energy type \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ultrasound \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RF \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Catheter design \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Single-electrode, monopolar \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Multi-electrode (4), monopolar \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Multi-electrode, monopolar \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Multi-electrode, monopolar, irrigated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ultrasound; balloon with cooling \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Multi-electrode, bipolar, non-compliant balloon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Single-electrode, monopolar \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Multi-electrode, monopolar \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Over-the-wire \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Energy delivery time \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 sec \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 sec \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Total treatment time \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16–24 min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16–24 min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unknown \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Vessel obstruction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Trials \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Symplicity HTN-1<a class="elsevierStyleCrossRef" href="#bib0525">11</a>, Symplicity HTN-2<a class="elsevierStyleCrossRef" href="#bib0790">64</a>, Symplicity HTN-3<a class="elsevierStyleCrossRef" href="#bib0810">68</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FIM<a class="elsevierStyleCrossRef" href="#bib0930">92</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">EnlightHTN-1<a class="elsevierStyleCrossRef" href="#bib0725">51</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RHAS<a class="elsevierStyleCrossRef" href="#bib0920">90</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PARADISE<a class="elsevierStyleCrossRef" href="#bib0935">93</a>, REALISE<a class="elsevierStyleCrossRef" href="#bib0940">94</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reduce HTN<a class="elsevierStyleCrossRef" href="#bib0925">91</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RENABLATE I<a class="elsevierStyleCrossRef" href="#bib0945">95</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab685935.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Sympathetic renal denervation devices." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:95 [ 0 => array:3 [ "identificador" => "bib0475" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(12)61766-8" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2012" "volumen" => "380" "paginaInicial" => "2224" "paginaFinal" => "2260" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0480" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global burden of blood-pressure-related disease, 2001" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(08)60655-8" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2008" "volumen" => "371" "paginaInicial" => "1513" "paginaFinal" => "1518" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0485" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2003" "volumen" => "362" "paginaInicial" => "1527" "paginaFinal" => "1535" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0490" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood pressure control in Italy: analysis of clinical data from 2005–2011 surveys on hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/HJH.0b013e3283535993" "Revista" => array:6 [ "tituloSerie" => "J Hypertens" "fecha" => "2012" "volumen" => "30" "paginaInicial" => "1065" "paginaFinal" => "1074" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0495" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.hjh.0000431740.32696.cc" "Revista" => array:6 [ "tituloSerie" => "J Hypertens" "fecha" => "2013" "volumen" => "31" "paginaInicial" => "1281" "paginaFinal" => "1357" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0500" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence and prognosis of resistant hypertension in hypertensive patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.111.068064" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2012" "volumen" => "125" "paginaInicial" => "1635" "paginaFinal" => "1642" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0505" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effects of splanchnicectomy on the blood pressure in hypertension; a controlled study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "1951" "volumen" => "4" "paginaInicial" => "173" "paginaFinal" => "183" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0510" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Surgical approach to the treatment of essential hypertension. Results of therapy (medical and surgical)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Cardiol" "fecha" => "1962" "volumen" => "9" "paginaInicial" => "893" "paginaFinal" => "899" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0515" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Results of treatment in malignant hypertension: a seven-year experience in 94 cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br Med J" "fecha" => "1959" "volumen" => "2" "paginaInicial" => "969" "paginaFinal" => "980" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0520" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Translational medicine: the antihypertensive effect of renal denervation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajpregu.00647.2009" "Revista" => array:6 [ "tituloSerie" => "Am J Physiol Regul Integr Comp Physiol" "fecha" => "2010" "volumen" => "298" "paginaInicial" => "R245" "paginaFinal" => "R253" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0525" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(09)60566-3" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2009" "volumen" => "373" "paginaInicial" => "1275" "paginaFinal" => "1281" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0530" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Excretion of noradrenaline in urine in hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Scand J Clin Lab Invest" "fecha" => "1954" "volumen" => "6" "paginaInicial" => "54" "paginaFinal" => "59" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0535" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pulse and respiratory grouping of sympathetic impulses in human muscle-nerves" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1748-1716.1968.tb04218.x" "Revista" => array:6 [ "tituloSerie" => "Acta Physiol Scand" "fecha" => "1968" "volumen" => "74" "paginaInicial" => "96" "paginaFinal" => "108" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0540" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Determination of norepinephrine apparent release rate and clearance in humans" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Life Sci" "fecha" => "1979" "volumen" => "25" "paginaInicial" => "1461" "paginaFinal" => "1470" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0545" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac and pulmonary norepinephrine release and removal in the dog" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Circ Res" "fecha" => "1983" "volumen" => "53" "paginaInicial" => "688" "paginaFinal" => "694" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0550" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "1986" "volumen" => "73" "paginaInicial" => "615" "paginaFinal" => "621" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0555" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sympathetic drive in anterior and inferior uncomplicated acute myocardial infarction" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/01.CIR.0000129252.96341.8B" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2004" "volumen" => "109" "paginaInicial" => "2285" "paginaFinal" => "2289" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0560" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Central mechanisms of abnormal sympathoexcitation in chronic heart failure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Cardiol Res Pract" "fecha" => "2012" "volumen" => "2012" "paginaInicial" => "1" "paginaFinal" => "7" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0565" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Sympathetic nervous system in heart failure. Physiology, pathophysiology, and clinical implications" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2009.05.015" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2009" "volumen" => "54" "paginaInicial" => "1747" "paginaFinal" => "1782" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0570" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The sympathetic system and hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Am J Hypertens" "fecha" => "2000" "volumen" => "13" "numero" => "6 Pt 2" "paginaInicial" => "99S" "paginaFinal" => "105S" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0575" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sympathetic nerve biology in essential hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Exp Pharmacol Physiol" "fecha" => "2001" "volumen" => "28" "paginaInicial" => "986" "paginaFinal" => "989" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0580" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The sympathetic system in essential hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Rev Port Cardiol" "fecha" => "2000" "volumen" => "19" "numero" => "Suppl 2" "paginaInicial" => "II9" "paginaFinal" => "II14" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0585" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sympathetic hyperactivity in hypertensive chronic kidney disease patients is reduced during standard treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/01.HYP.0000256530.39695.a3" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2007" "volumen" => "49" "paginaInicial" => "506" "paginaFinal" => "510" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0590" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sympathetic nervous system and insulin resistance: from obesity to diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Am J Hypertens" "fecha" => "2001" "volumen" => "14" "numero" => "11 Pt 2" "paginaInicial" => "304S" "paginaFinal" => "309S" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0595" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The sympathetic nervous system and obstructive sleep apnea: implications for hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Hypertens" "fecha" => "1997" "volumen" => "15" "numero" => "12 Pt 2" "paginaInicial" => "1613" "paginaFinal" => "1619" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0600" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The 2009 Carl Ludwig Lecture: pathophysiology of the human sympathetic nervous system in cardiovascular diseases: the transition from mechanisms to medical management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/japplphysiol.00832.2009" "Revista" => array:6 [ "tituloSerie" => "J Appl Physiol" "fecha" => "2010" "volumen" => "108" "paginaInicial" => "227" "paginaFinal" => "237" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0605" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sympathetic overactivity in active ulcerative colitis: effects of clonidine" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajpregu.00442.2005" "Revista" => array:6 [ "tituloSerie" => "Am J Physiol Regul Integr Comp Physiol" "fecha" => "2006" "volumen" => "290" "paginaInicial" => "R224" "paginaFinal" => "R232" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0610" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adverse consequences of high sympathetic nervous activity in the failing human heart" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/0735-1097(95)00332-0" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "1995" "volumen" => "26" "paginaInicial" => "1257" "paginaFinal" => "1263" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0615" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2002" "volumen" => "105" "paginaInicial" => "1354" "paginaFinal" => "1359" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0620" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Central sympathetic overactivity: maladies and mechanisms" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.autneu.2009.02.003" "Revista" => array:6 [ "tituloSerie" => "Auton Neurosci" "fecha" => "2009" "volumen" => "148" "paginaInicial" => "5" "paginaFinal" => "15" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0625" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Improvements in left ventricular hypertrophy and diastolic function following renal denervation: effects beyond blood pressure and heart rate reduction" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2013" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0630" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neural activity and ventricular fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM197605202942107" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1976" "volumen" => "294" "paginaInicial" => "1165" "paginaFinal" => "1170" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0635" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac sympathetic nerve biology and brain monoamine turnover in panic disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1196/annals.1296.062" "Revista" => array:6 [ "tituloSerie" => "Ann NY Acad Sci" "fecha" => "2004" "volumen" => "1018" "paginaInicial" => "505" "paginaFinal" => "514" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0640" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sympathetic regulation of vascular function in health and disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true …1 ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fphys.2012.00001" "Revista" => array:6 [ "tituloSerie" => "Front Physiol" "fecha" => "2012" "volumen" => "3" "paginaInicial" => "1" "paginaFinal" => "15" "link" => array:1 [ …1] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0645" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajpregu.00426.2010" "Revista" => array:6 [ "tituloSerie" => "Am J Physiol Regul Integr Comp Physiol" "fecha" => "2011" "volumen" => "300" "paginaInicial" => "R818" "paginaFinal" => "R826" "link" => array:1 [ …1] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0650" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Insulin-mediated sympathetic stimulation: role in the pathogenesis of obesity-related hypertension (or, how insulin affects blood pressure, and why)" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Hypertens" "fecha" => "2001" "volumen" => "19" "numero" => "3 Pt 2" "paginaInicial" => "523" "paginaFinal" => "528" "link" => array:1 [ …1] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0655" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Excessive sympathetic activation in heart failure with obesity and metabolic syndrome: characteristics and mechanisms" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/01.HYP.0000255983.32896.b9" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2007" "volumen" => "49" "paginaInicial" => "535" "paginaFinal" => "541" "link" => array:1 [ …1] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0660" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Myocardial norepinephrine concentration in man. Effects of reserpine and of congestive heart failure" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM196309262691302" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1963" "volumen" => "269" "paginaInicial" => "653" "paginaFinal" => "658" "link" => array:1 [ …1] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0665" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasma norepinephrine in congestive heart failure" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Cardiol" "fecha" => "1978" "volumen" => "41" "paginaInicial" => "233" "paginaFinal" => "243" "link" => array:1 [ …1] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0670" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised, trial" ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1999" "volumen" => "353" "paginaInicial" => "9" "paginaFinal" => "13" "link" => array:1 [ …1] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0675" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The sympathetic nervous system through the ages: from Thomas Willis to resistant hypertension" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1113/expphysiol.2010.052332" "Revista" => array:6 [ "tituloSerie" => "Exp Physiol" "fecha" => "2011" "volumen" => "96" "paginaInicial" => "611" "paginaFinal" => "622" "link" => array:1 [ …1] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0680" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Point: chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/japplphysiol.00182.2010" "Revista" => array:6 [ "tituloSerie" => "J Appl Physiol" "fecha" => "2010" "volumen" => "109" "paginaInicial" => "1996" "paginaFinal" => "1998" "link" => array:1 [ …1] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0685" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence, awareness, treatment and control of hypertension in Portugal: the PAP study" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Port Cardiol" "fecha" => "2007" "volumen" => "26" "paginaInicial" => "21" "paginaFinal" => "39" "link" => array:1 [ …1] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0690" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.108.189141" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2008" "volumen" => "117" "paginaInicial" => "e510" "paginaFinal" => "e526" "link" => array:1 [ …1] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0695" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Resistant hypertension – its identification and epidemiology" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrneph.2012.260" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Nephrol" "fecha" => "2013" "volumen" => "9" "paginaInicial" => "51" "paginaFinal" => "58" "link" => array:1 [ …1] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0700" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.110.168948" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2011" "volumen" => "57" "paginaInicial" => "898" "paginaFinal" => "902" "link" => array:1 [ …1] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0705" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Uncontrolled and apparent treatment resistant hypertension in the United States, 1988 to 2008" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.111.030189" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2011" "volumen" => "124" "paginaInicial" => "1046" "paginaFinal" => "1058" "link" => array:1 [ …1] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0710" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood pressure control and knowledge of target blood pressure in coronary patients across Europe: results from the EUROASPIRE III survey" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/HJH.0b013e328348efa7" "Revista" => array:6 [ "tituloSerie" => "J Hypertens" "fecha" => "2011" "volumen" => "29" "paginaInicial" => "1641" "paginaFinal" => "1648" "link" => array:1 [ …1] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0715" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.110.163014" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2011" "volumen" => "57" "paginaInicial" => "911" "paginaFinal" => "917" "link" => array:1 [ …1] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0720" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal sympathetic denervation for treatment of drug-resistant hypertension: one-year results from the Symplicity HTN-2 randomized, controlled trial" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.112.130880" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2012" "volumen" => "126" "paginaInicial" => "2976" "paginaFinal" => "2982" "link" => array:1 [ …1] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0725" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnlightHTN I trial" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/eht197" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2013" "volumen" => "34" "paginaInicial" => "2132" "paginaFinal" => "2140" "link" => array:1 [ …1] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0730" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Updated ESH position paper on interventional therapy of resistant hypertension" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4244/EIJV9SRA11" "Revista" => array:7 [ "tituloSerie" => "EuroIntervention" "fecha" => "2013" "volumen" => "9" "numero" => "R" "paginaInicial" => "R58" "paginaFinal" => "R66" "link" => array:1 [ …1] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0735" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Hypertension: Clinical management of primary hypertension in adults. This guideline partially updates and replaces NICE clinical guideline 34" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2011" ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0740" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Feasibility of catheter-based renal nerve ablation and effects on sympathetic nerve activity and blood pressure in patients with end-stage renal disease" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijcard.2013.01.218" "Revista" => array:6 [ "tituloSerie" => "Int J Cardiol" "fecha" => "2013" "volumen" => "168" "paginaInicial" => "2214" "paginaFinal" => "2220" "link" => array:1 [ …1] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0745" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rationale and design of a large registry on renal denervation: the Global SYMPLICITY registry" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4244/EIJV9I4A78" "Revista" => array:6 [ "tituloSerie" => "EuroIntervention" "fecha" => "2013" "volumen" => "9" "paginaInicial" => "484" "paginaFinal" => "492" "link" => array:1 [ …1] ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0750" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Desnervação Renal para HTA Resistente: Resultados Iniciais de um Registo Nacional" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Port Cardiol" "fecha" => "2013" "volumen" => "32" "numero" => "Espec Congr" "paginaInicial" => "12" "paginaFinal" => "13" ] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0755" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efferent renal nerve traffic in the spontaneously hypertensive rat" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Exp Hypertension A: Theory Pract" "fecha" => "1987" "volumen" => "9" "numero" => "Suppl 1" "paginaInicial" => "259" "paginaFinal" => "279" ] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0760" "etiqueta" => "58" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal denervation attenuates the sodium retention and hypertension associated with obesity" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Hypertension" "fecha" => "1995" "volumen" => "25" "numero" => "4 Pt 2" "paginaInicial" => "893" "paginaFinal" => "897" "link" => array:1 [ …1] ] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0765" "etiqueta" => "59" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal afferent denervation prevents hypertension in rats with chronic renal failure" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Hypertension" "fecha" => "1995" "volumen" => "25" "numero" => "4 Pt 2" "paginaInicial" => "878" "paginaFinal" => "882" "link" => array:1 [ …1] ] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0770" "etiqueta" => "60" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal injury caused by intrarenal injection of phenol increases afferent and efferent renal sympathetic nerve activity" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Hypertens" "fecha" => "2002" "volumen" => "15" "paginaInicial" => "717" "paginaFinal" => "724" "link" => array:1 [ …1] ] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0775" "etiqueta" => "61" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The surgical treatment of hypertension" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Adv Intern Med" "fecha" => "1947" "volumen" => "2" "paginaInicial" => "173" "paginaFinal" => "194" "link" => array:1 [ …1] ] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0780" "etiqueta" => "62" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The surgical treatment of hypertension with particular reference to adrenalectomy and sympathectomy" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Trans Am Coll Cardiol" "fecha" => "1955" "volumen" => "5" "paginaInicial" => "107" "paginaFinal" => "112" "link" => array:1 [ …1] ] ] ] ] ] ] 62 => array:3 [ "identificador" => "bib0785" "etiqueta" => "63" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Should sympathectomy for arterial hypertension be abandoned? Review of surgical therapy at the Lahey Clinic: 1950–1954" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Surg Clin N Am" "fecha" => "1957" "volumen" => "37" "paginaInicial" => "871" "paginaFinal" => "889" "link" => array:1 [ …1] ] ] ] ] ] ] 63 => array:3 [ "identificador" => "bib0790" "etiqueta" => "64" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal sympathetic denervation for treatment of drug-resistant hypertension: one-year results from the Symplicity HTN-2 randomized, controlled trial" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.112.130880" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2012" "volumen" => "126" "paginaInicial" => "2976" "paginaFinal" => "2982" "link" => array:1 [ …1] ] ] ] ] ] ] 64 => array:3 [ "identificador" => "bib0795" "etiqueta" => "65" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(10)62039-9" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2010" "volumen" => "376" "paginaInicial" => "1903" "paginaFinal" => "1909" "link" => array:1 [ …1] ] ] ] ] ] ] 65 => array:3 [ "identificador" => "bib0800" "etiqueta" => "66" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.112.193870" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2012" "volumen" => "60" "paginaInicial" => "419" "paginaFinal" => "424" "link" => array:1 [ …1] ] ] ] ] ] ] 66 => array:3 [ "identificador" => "bib0805" "etiqueta" => "67" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 Trial" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/clc.22008" "Revista" => array:6 [ "tituloSerie" => "Clin Cardiol" "fecha" => "2012" "volumen" => "35" "paginaInicial" => "528" "paginaFinal" => "535" "link" => array:1 [ …1] ] ] ] ] ] ] 67 => array:3 [ "identificador" => "bib0810" "etiqueta" => "68" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A controlled trial of renal denervation for resistant hypertension" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1402670" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2014" "volumen" => "370" "paginaInicial" => "1393" "paginaFinal" => "1401" "link" => array:1 [ …1] ] ] ] ] ] ] 68 => array:3 [ "identificador" => "bib0815" "etiqueta" => "69" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regression to the mean: what it is and how to deal with it" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ije/dyh299" "Revista" => array:6 [ "tituloSerie" => "Int J Epidemiol" "fecha" => "2005" "volumen" => "34" "paginaInicial" => "215" "paginaFinal" => "220" "link" => array:1 [ …1] ] ] ] ] ] ] 69 => array:3 [ "identificador" => "bib0820" "etiqueta" => "70" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehi184" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2005" "volumen" => "26" "paginaInicial" => "906" "paginaFinal" => "913" "link" => array:1 [ …1] ] ] ] ] ] ] 70 => array:3 [ "identificador" => "bib0825" "etiqueta" => "71" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal sympathetic denervation: applications in hypertension and beyond" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrcardio.2013.89" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Cardiol" "fecha" => "2013" "volumen" => "10" "paginaInicial" => "465" "paginaFinal" => "476" "link" => array:1 [ …1] ] ] ] ] ] ] 71 => array:3 [ "identificador" => "bib0830" "etiqueta" => "72" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal denervation and heart failure" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Eur J Heart Fail" "fecha" => "2014" ] ] ] ] ] ] 72 => array:3 [ "identificador" => "bib0835" "etiqueta" => "73" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of renal denervation on postprandial sodium excretion in experimental heart failure" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Am J Physiol" "fecha" => "1994" "volumen" => "266" "numero" => "5 Pt 2" "paginaInicial" => "R1599" "paginaFinal" => "R1604" "link" => array:1 [ …1] ] ] ] ] ] ] 73 => array:3 [ "identificador" => "bib0840" "etiqueta" => "74" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dynamic arterial baroreflex in rabbits with heart failure induced by rapid pacing" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Am J Physiol" "fecha" => "1994" "volumen" => "267" "numero" => "1 Pt 2" "paginaInicial" => "H92" "paginaFinal" => "H99" "link" => array:1 [ …1] ] ] ] ] ] ] 74 => array:3 [ "identificador" => "bib0845" "etiqueta" => "75" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal denervation modulates angiotensin receptor expression in the renal cortex of rabbits with chronic heart failure" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajprenal.00088.2010" "Revista" => array:6 [ "tituloSerie" => "Am J Physiol Renal Physiol" "fecha" => "2011" "volumen" => "300" "paginaInicial" => "F31" "paginaFinal" => "F39" "link" => array:1 [ …1] ] ] ] ] ] ] 75 => array:3 [ "identificador" => "bib0850" "etiqueta" => "76" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehu152" "Revista" => array:3 [ "tituloSerie" => "Eur Heart J" "fecha" => "2014" "link" => array:1 [ …1] ] ] ] ] ] ] 76 => array:3 [ "identificador" => "bib0855" "etiqueta" => "77" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "First-in-man safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACH-Pilot study" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijcard.2012.09.019" "Revista" => array:6 [ "tituloSerie" => "Int J Cardiol" "fecha" => "2013" "volumen" => "162" "paginaInicial" => "189" "paginaFinal" => "192" "link" => array:1 [ …1] ] ] ] ] ] ] 77 => array:3 [ "identificador" => "bib0860" "etiqueta" => "78" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The sympathetic nervous system and the metabolic syndrome" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/HJH.0b013e328048d004" "Revista" => array:6 [ "tituloSerie" => "J Hypertens" "fecha" => "2007" "volumen" => "25" "paginaInicial" => "909" "paginaFinal" => "920" "link" => array:1 [ …1] ] ] ] ] ] ] 78 => array:3 [ "identificador" => "bib0865" "etiqueta" => "79" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of type 2 diabetes mellitus on sympathetic neural mechanisms in hypertension" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/01.CIR.0000103123.66264.FE" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2003" "volumen" => "108" "paginaInicial" => "3097" "paginaFinal" => "3101" "link" => array:1 [ …1] ] ] ] ] ] ] 79 => array:3 [ "identificador" => "bib0870" "etiqueta" => "80" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.110.991869" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2011" "volumen" => "123" "paginaInicial" => "1940" "paginaFinal" => "1946" "link" => array:1 [ …1] ] ] ] ] ] ] 80 => array:3 [ "identificador" => "bib0875" "etiqueta" => "81" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.111.173799" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2011" "volumen" => "58" "paginaInicial" => "559" "paginaFinal" => "565" "link" => array:1 [ …1] ] ] ] ] ] ] 81 => array:3 [ "identificador" => "bib0880" "etiqueta" => "82" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal sympathetic denervation suppresses postapneic blood pressure rises and atrial fibrillation in a model for sleep apnea" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.112.191965" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2012" "volumen" => "60" "paginaInicial" => "172" "paginaFinal" => "178" "link" => array:1 [ …1] ] ] ] ] ] ] 82 => array:3 [ "identificador" => "bib0885" "etiqueta" => "83" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of renal denervation on neurohumoral activation triggering atrial fibrillation in obstructive sleep apnea" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.113.01728" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2013" "volumen" => "62" "paginaInicial" => "767" "paginaFinal" => "774" "link" => array:1 [ …1] ] ] ] ] ] ] 83 => array:3 [ "identificador" => "bib0890" "etiqueta" => "84" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Negative tracheal pressure during obstructive respiratory events promotes atrial fibrillation by vagal activation" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.hrthm.2011.03.053" "Revista" => array:6 [ "tituloSerie" => "Heart Rhythm" "fecha" => "2011" "volumen" => "8" "paginaInicial" => "1436" "paginaFinal" => "1443" "link" => array:1 [ …1] ] ] ] ] ] ] 84 => array:3 [ "identificador" => "bib0895" "etiqueta" => "85" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal sympathetic denervation provides ventricular rate control but does not prevent atrial electrical remodeling during atrial fibrillation" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.111.00182" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2013" "volumen" => "61" "paginaInicial" => "225" "paginaFinal" => "231" "link" => array:1 [ …1] ] ] ] ] ] ] 85 => array:3 [ "identificador" => "bib0900" "etiqueta" => "86" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2012.05.036" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2012" "volumen" => "60" "paginaInicial" => "1163" "paginaFinal" => "1170" "link" => array:1 [ …1] ] ] ] ] ] ] 86 => array:3 [ "identificador" => "bib0905" "etiqueta" => "87" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal denervation suppresses ventricular arrhythmias during acute ventricular ischemia in pigs" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.hrthm.2013.07.015" "Revista" => array:6 [ "tituloSerie" => "Heart Rhythm" "fecha" => "2013" "volumen" => "10" "paginaInicial" => "1525" "paginaFinal" => "1530" "link" => array:1 [ …1] ] ] ] ] ] ] 87 => array:3 [ "identificador" => "bib0910" "etiqueta" => "88" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal sympathetic denervation for treatment of electrical storm: first-in-man experience" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00392-011-0365-5" "Revista" => array:6 [ "tituloSerie" => "Clin Res Cardiol" "fecha" => "2012" "volumen" => "101" "paginaInicial" => "63" "paginaFinal" => "67" "link" => array:1 [ …1] ] ] ] ] ] ] 88 => array:3 [ "identificador" => "bib0915" "etiqueta" => "89" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal sympathetic denervation as an adjunct to catheter ablation for the treatment of ventricular electrical storm in the setting of acute myocardial infarction" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "J Cardiovasc Electrophysiol" "fecha" => "2013" ] ] ] ] ] ] 89 => array:3 [ "identificador" => "bib0920" "etiqueta" => "90" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rapid renal sympathetic denervation for resistant hypertension using the OneShot™ Ablation System (RAPID) Study: Primary Endpoint 6-Month Results" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:2 [ "fecha" => "2013" "editorial" => "TCT" ] ] ] ] ] ] 90 => array:3 [ "identificador" => "bib0925" "etiqueta" => "91" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical evidence in catheter-based renal sympathetic denervation – building the data" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:2 [ "titulo" => "EuroPCR" "serieFecha" => "2013" ] ] ] ] ] ] 91 => array:3 [ "identificador" => "bib0930" "etiqueta" => "92" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early results of first-in-man simultaneous multisite renal denervation treatment for resistant hypertension" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2013" ] ] ] ] ] ] 92 => array:3 [ "identificador" => "bib0935" "etiqueta" => "93" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ReCor Medical Paradise: first-in-man results of a novel circumferential catheter-based ultrasound technology for renal denervation" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2012" ] ] ] ] ] ] 93 => array:3 [ "identificador" => "bib0940" "etiqueta" => "94" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical Trial: Preliminary results demonstrate catheter based ultrasound renal denervation is associated with a decrease in sympathetic activity" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2014" ] ] ] ] ] ] 94 => array:3 [ "identificador" => "bib0945" "etiqueta" => "95" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "RENABLATE I Feasibility Study: 3 months results" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2014" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21742049/0000003400000002/v2_201502270337/S2174204915000343/v2_201502270337/en/main.assets" "Apartado" => array:4 [ "identificador" => "9924" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review Article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21742049/0000003400000002/v2_201502270337/S2174204915000343/v2_201502270337/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204915000343?idApp=UINPBA00004E"]

Statistics

Review article

Renal denervation for resistant hypertension

Desnervação renal para hipertensão arterial resistente

Manuel de Sousa Almeidaa, Pedro de Araújo Gonçalvesa,b,

Corresponding author

paraujogoncalves@yahoo.co.uk

Corresponding author.

, Eduardo Infante de Oliveirac,d, Henrique Cyrne de Carvalhoe,f

a Serviço de Cardiologia, Hospital de Santa Cruz – CHLO, Carnaxide, Portugal

b Departamento de Fisiopatologia, Faculdade de Ciências Médicas, UNL, Lisboa, Portugal

c Serviço de Cardiologia, Hospital de Santa Maria, CHLN, Lisboa, Portugal

d Instituto de Fisiologia, Faculdade de Medicina de Lisboa, UL, Lisboa, Portugal

e Serviço de Cardiologia, Hospital de Santo Antonio, CHP, Portugal

f Unidade Curricular de Medicina I, Instituto de Ciências Biomédicas Abel Salazar, UP, Porto, Portugal

Read

5815

Times
was read the article

1728

Total PDF

4087

Total HTML

Share statistics

 array:24 [
  "pii" => "S2174204915000343"
  "issn" => "21742049"
  "doi" => "10.1016/j.repce.2014.07.009"
  "estado" => "S300"
  "fechaPublicacion" => "2015-02-01"
  "aid" => "588"
  "copyright" => "Sociedade Portuguesa de Cardiologia"
  "copyrightAnyo" => "2014"
  "documento" => "article"
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "fla"
  "cita" => "Rev Port Cardiol. 2015;34:125-35"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 3445
    "formatos" => array:3 [
      "EPUB" => 190
      "HTML" => 2650
      "PDF" => 605
    ]
  ]
  "Traduccion" => array:1 [
    "en" => array:19 [
      "pii" => "S0870255115000086"
      "issn" => "08702551"
      "doi" => "10.1016/j.repc.2014.07.011"
      "estado" => "S300"
      "fechaPublicacion" => "2015-02-01"
      "aid" => "588"
      "copyright" => "Sociedade Portuguesa de Cardiologia"
      "documento" => "article"
      "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
      "subdocumento" => "ssu"
      "cita" => "Rev Port Cardiol. 2015;34:125-35"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:2 [
        "total" => 5408
        "formatos" => array:3 [
          "EPUB" => 182
          "HTML" => 4442
          "PDF" => 784
        ]
      ]
      "en" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>"
        "titulo" => "Renal denervation for resistant hypertension"
        "tienePdf" => "en"
        "tieneTextoCompleto" => "en"
        "tieneResumen" => array:2 [
          0 => "en"
          1 => "pt"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "125"
            "paginaFinal" => "135"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "pt" => array:1 [
            "titulo" => "Desnerva&#231;&#227;o renal para hipertens&#227;o arterial resistente"
          ]
        ]
        "contieneResumen" => array:2 [
          "en" => true
          "pt" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "en" => true
        ]
        "contienePdf" => array:1 [
          "en" => true
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Manuel de Sousa Almeida, Pedro de Ara&#250;jo Gon&#231;alves, Eduardo Infante de Oliveira, Henrique Cyrne de Carvalho"
            "autores" => array:4 [
              0 => array:2 [
                "nombre" => "Manuel"
                "apellidos" => "de Sousa Almeida"
              ]
              1 => array:2 [
                "nombre" => "Pedro"
                "apellidos" => "de Ara&#250;jo Gon&#231;alves"
              ]
              2 => array:2 [
                "nombre" => "Eduardo"
                "apellidos" => "Infante de Oliveira"
              ]
              3 => array:2 [
                "nombre" => "Henrique"
                "apellidos" => "Cyrne de Carvalho"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "en"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2174204915000343"
          "doi" => "10.1016/j.repce.2014.07.009"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => true
            "ES2" => true
            "LATM" => true
          ]
          "gratuito" => true
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204915000343?idApp=UINPBA00004E"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255115000086?idApp=UINPBA00004E"
      "url" => "/08702551/0000003400000002/v3_201706020139/S0870255115000086/v3_201706020139/en/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2174204915000355"
    "issn" => "21742049"
    "doi" => "10.1016/j.repce.2014.08.022"
    "estado" => "S300"
    "fechaPublicacion" => "2015-02-01"
    "aid" => "589"
    "copyright" => "Sociedade Portuguesa de Cardiologia"
    "documento" => "simple-article"
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "crp"
    "cita" => "Rev Port Cardiol. 2015;34:137&#46;e1-4"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 3636
      "formatos" => array:3 [
        "EPUB" => 227
        "HTML" => 2876
        "PDF" => 533
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Case report</span>"
      "titulo" => "Prosthetic aortic valve&#58; A bone in the system"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "pt"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "137&#46;e1"
          "paginaFinal" => "137&#46;e4"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "pt" => array:1 [
          "titulo" => "Pr&#243;tese valvular a&#243;rtica&#58; &#171;um osso na engrenagem&#187;"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0010"
          "etiqueta" => "Figure 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 862
              "Ancho" => 2501
              "Tamanyo" => 254845
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Transesophageal echocardiogram in mid-esophageal short- &#40;A&#41; and long-axis &#40;B&#41; views of the aortic prosthesis&#44; showing two abscesses &#40;A&#44; asterisk&#41; surrounding the single-disc mechanical prosthetic valve &#40;A&#44; cross&#41;&#46; There appears to be no rupture from these abscesses &#40;B&#44; white arrow&#41; to the left ventricular outflow tract&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Vitor Hugo Pereira, Joana Guardado, Marina Fernandes, M&#225;rio Louren&#231;o, Inoc&#234;ncia Machado, Isabel Quelhas, Olga Azevedo, Ant&#243;nio Louren&#231;o"
          "autores" => array:8 [
            0 => array:2 [
              "nombre" => "Vitor Hugo"
              "apellidos" => "Pereira"
            ]
            1 => array:2 [
              "nombre" => "Joana"
              "apellidos" => "Guardado"
            ]
            2 => array:2 [
              "nombre" => "Marina"
              "apellidos" => "Fernandes"
            ]
            3 => array:2 [
              "nombre" => "M&#225;rio"
              "apellidos" => "Louren&#231;o"
            ]
            4 => array:2 [
              "nombre" => "Inoc&#234;ncia"
              "apellidos" => "Machado"
            ]
            5 => array:2 [
              "nombre" => "Isabel"
              "apellidos" => "Quelhas"
            ]
            6 => array:2 [
              "nombre" => "Olga"
              "apellidos" => "Azevedo"
            ]
            7 => array:2 [
              "nombre" => "Ant&#243;nio"
              "apellidos" => "Louren&#231;o"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S0870255115000098"
        "doi" => "10.1016/j.repc.2014.08.023"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255115000098?idApp=UINPBA00004E"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204915000355?idApp=UINPBA00004E"
    "url" => "/21742049/0000003400000002/v2_201502270337/S2174204915000355/v2_201502270337/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2174204915000331"
    "issn" => "21742049"
    "doi" => "10.1016/j.repce.2014.08.021"
    "estado" => "S300"
    "fechaPublicacion" => "2015-02-01"
    "aid" => "587"
    "copyright" => "Sociedade Portuguesa de Cardiologia"
    "documento" => "article"
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Rev Port Cardiol. 2015;34:117-23"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 2979
      "formatos" => array:3 [
        "EPUB" => 181
        "HTML" => 2272
        "PDF" => 526
      ]
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
      "titulo" => "Musculoskeletal complaints in cardiac rehabilitation&#58; Prevalence and impact on cardiovascular risk factor profile and functional and psychosocial status"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "pt"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "117"
          "paginaFinal" => "123"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "pt" => array:1 [
          "titulo" => "Dor m&#250;sculo-esquel&#233;tica em reabilita&#231;&#227;o card&#237;aca&#58; preval&#234;ncia e impacto no perfil de risco cardiovascular e estado funcional e psicossocial"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Jos&#233; Afonso Rocha, Thomas G&#46; Allison, Jos&#233; Miguel Santoalha, V&#237;tor Ara&#250;jo, Fernando Parada Pereira, Maria J&#250;lia Maciel"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Jos&#233; Afonso"
              "apellidos" => "Rocha"
            ]
            1 => array:2 [
              "nombre" => "Thomas G&#46;"
              "apellidos" => "Allison"
            ]
            2 => array:2 [
              "nombre" => "Jos&#233; Miguel"
              "apellidos" => "Santoalha"
            ]
            3 => array:2 [
              "nombre" => "V&#237;tor"
              "apellidos" => "Ara&#250;jo"
            ]
            4 => array:2 [
              "nombre" => "Fernando"
              "apellidos" => "Parada Pereira"
            ]
            5 => array:2 [
              "nombre" => "Maria J&#250;lia"
              "apellidos" => "Maciel"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S0870255115000074"
        "doi" => "10.1016/j.repc.2014.08.022"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255115000074?idApp=UINPBA00004E"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204915000331?idApp=UINPBA00004E"
    "url" => "/21742049/0000003400000002/v2_201502270337/S2174204915000331/v2_201502270337/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>"
    "titulo" => "Renal denervation for resistant hypertension"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "125"
        "paginaFinal" => "135"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Manuel de Sousa Almeida, Pedro de Ara&#250;jo Gon&#231;alves, Eduardo Infante de Oliveira, Henrique Cyrne de Carvalho"
        "autores" => array:4 [
          0 => array:3 [
            "nombre" => "Manuel"
            "apellidos" => "de Sousa Almeida"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:4 [
            "nombre" => "Pedro"
            "apellidos" => "de Ara&#250;jo Gon&#231;alves"
            "email" => array:1 [
              0 => "paraujogoncalves&#64;yahoo&#46;co&#46;uk"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Eduardo"
            "apellidos" => "Infante de Oliveira"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Henrique"
            "apellidos" => "Cyrne de Carvalho"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">f</span>"
                "identificador" => "aff0030"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:6 [
          0 => array:3 [
            "entidad" => "Servi&#231;o de Cardiologia&#44; Hospital de Santa Cruz &#8211; CHLO&#44; Carnaxide&#44; Portugal"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Departamento de Fisiopatologia&#44; Faculdade de Ci&#234;ncias M&#233;dicas&#44; UNL&#44; Lisboa&#44; Portugal"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Servi&#231;o de Cardiologia&#44; Hospital de Santa Maria&#44; CHLN&#44; Lisboa&#44; Portugal"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Instituto de Fisiologia&#44; Faculdade de Medicina de Lisboa&#44; UL&#44; Lisboa&#44; Portugal"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Servi&#231;o de Cardiologia&#44; Hospital de Santo Antonio&#44; CHP&#44; Portugal"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
          5 => array:3 [
            "entidad" => "Unidade Curricular de Medicina I&#44; Instituto de Ci&#234;ncias Biom&#233;dicas Abel Salazar&#44; UP&#44; Porto&#44; Portugal"
            "etiqueta" => "f"
            "identificador" => "aff0030"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "pt" => array:1 [
        "titulo" => "Desnerva&#231;&#227;o renal para hipertens&#227;o arterial resistente"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introduction</span><p id="par0040" class="elsevierStylePara elsevierViewall">Hypertension is the leading global risk factor for cardiovascular mortality&#44; accounting for more than nine million deaths worldwide in 2010&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">1</span></a> Its close association with myocardial infarction&#44; heart failure&#44; stroke&#44; end-stage renal disease and cardiovascular death is well established&#44; with 54&#37; of stroke and 47&#37; of ischemic heart disease worldwide attributable to high blood pressure &#40;BP&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">2</span></a> Effective BP lowering has consistently been shown to reduce overall cardiovascular risk&#44;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">3</span></a> but rates of adequate BP control remain suboptimal&#44; despite the wide range of antihypertensive drugs available and strong evidence supporting their use&#46; A recently published study confirmed that rates of BP control in European countries are low&#44; with only 37&#37; of treated hypertensive patients achieving recommended BP values&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The blame for such low rates cannot be attributed only to poor treatment&#46; Resistant hypertension has a prevalence ranging from 15&#37; to 30&#37; of treated hypertensive patients&#44;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">5</span></a> and is an important cause of failure of BP control&#46; Most importantly&#44; these patients exhibit a worse prognosis&#44; with a higher risk for cardiovascular events&#44; compared to hypertensive patients without resistant hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In recent decades&#44; the renin-angiotensin-aldosterone system &#40;RAAS&#41; has been the central focus of hypertension treatment and management&#46; The availability of safe&#44; effective and evidence-based drugs that block this system has meant that the role of other systems&#44; particularly the autonomic nervous system&#44; has been neglected&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The sympathetic nervous system &#40;SNS&#41; and its possible role in the pathogenesis of hypertension is receiving increasing attention&#46; The aim of this review is to provide an update on the current understanding of the role of the SNS in blood pressure control and its implications for sympathetic renal denervation &#40;RDN&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">The sympathetic nervous system and cardiovascular disease</span><p id="par0060" class="elsevierStylePara elsevierViewall">The development of open surgical sympathectomy in the 1930s highlighted the role of the SNS in severe hypertension&#44; since it appeared to be effective in lowering high BP in patients with severe hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">7&#44;8</span></a> However&#44; the procedure was abandoned due to its poorly tolerated side effects and high surgical risk&#44; especially after the appearance of ganglionic blockers&#44; the first effective antihypertensive drug class&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">9</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The recent development of a new device-based approach to treat severe resistant hypertension&#44; through RDN&#44; focused attention on the already well-known role of the SNS in initiating and maintaining high BP in patients with essential hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">10&#44;11</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Assessment of the sympathetic nervous system in humans</span><p id="par0070" class="elsevierStylePara elsevierViewall">The major reason that the SNS has been so neglected is not because there are doubts concerning its critical role in the pathogenesis of hypertension and other cardiovascular diseases&#44; but because it has been difficult to study and test this relation&#44; due to the complex and clinically impractical methods used for assessing the SNS in humans&#46; Until the early 1970s&#44; the most common techniques were measurements of blood levels and urine excretion rates of norepinephrine and its derivatives&#44; which provide a gross estimate of whole-body sympathetic activity at best&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">12</span></a> Since then&#44; new methods have emerged for measuring sympathetic nerve firing rates in subcutaneous nerves and for assaying plasma concentrations of sympathetic transmitters&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Microneurography&#44; a technique reported first by Hagbarth and Vallbo&#44;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">13</span></a> provided a tool to study nerve firing in subcutaneous sympathetic nerves in skin and skeletal muscle vessels&#46; It is based on recording bursts of nerve activity&#44; synchronous with the heartbeat&#44; generated in skeletal muscle vascular efferent nerves&#44; through tungsten electrodes inserted in the skin&#46; It is highly reproducible and closely related to sympathetic traffic directed to other structures and can be repeated over time&#44; allowing assessment of the effects of interventions&#44; direct quantification of sympathetic nerve traffic regulating vasomotor tone&#44; and study of instantaneous reactions to rapid stimuli&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The spillover technique for measurement of norepinephrine release&#44; first applied by Esler et al&#44;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">14</span></a> is an isotope dilution method that calculates the clearance and spillover of norepinephrine&#44; using an intravenous infusion of tritium-labeled norepinephrine&#46; The relationship between the sympathetic nerve fiber firing rate of an organ and the rate of norepinephrine spillover into the venous effluent of that organ provides the rationale for using measures of regional norepinephrine release as a surrogate for sympathetic tone in individual organs&#44;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">15</span></a> enabling assessment of regional sympathetic nervous function in humans&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">This technique was central to the demonstration that heart failure patients had sympathetic overactivity rather than sympathetic denervation&#44; as thought at the time&#44; and opened the way to the routine use of beta-blockers in heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Sympathetic nervous system overactivity</span><p id="par0090" class="elsevierStylePara elsevierViewall">Besides its central role in cardiovascular homeostasis&#44; by controlling vascular tone through vasoconstriction of small resistance arteries&#44; the sympathetic system also affects and regulates numerous other physiological processes &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; There is growing evidence that sustained chronic changes in sympathetic activity are involved in the pathogenesis of many disease states&#44; from metabolic to psychological disorders&#44; including ischemic heart disease&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">17</span></a> chronic heart failure&#44;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">18&#44;19</span></a> hypertension&#44;<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">20&#8211;22</span></a> kidney disease&#44;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">23</span></a> type 2 diabetes&#44;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">24</span></a> obesity&#44;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">24</span></a> metabolic syndrome&#44;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">24</span></a> obstructive sleep apnea&#44;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">25</span></a> depression<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">26</span></a> and inflammatory bowel disease&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">27</span></a> A chronically overactive sympathetic system is linked to a worse prognosis in patients with heart failure and end-stage renal disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0610"><span class="elsevierStyleSup">28&#44;29</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Sympathetic nervous system overactivity and cardiovascular disease</span><p id="par0095" class="elsevierStylePara elsevierViewall">There is growing evidence that the deleterious effects on blood vessels and myocardium of an overactive SNS are independent of increased BP&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">30</span></a> Chronic SNS activation without an increase in BP can cause hypertrophy and proliferation of vascular smooth muscle cells as well as having a direct trophic effect on cardiac myocytes&#44; increasing left ventricular &#40;LV&#41; mass and wall thickness&#44;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">30</span></a> while BP reduction after catheter-based RDN has been shown to lead to a significant reduction in LV mass and improvement in diastolic function&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">31</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">These structural changes in the myocardium and the direct effects of an overactive SNS contribute to the high incidence of arrhythmias commonly seen in patients with hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">32</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">The link between mental stress&#44; psychiatric illness and cardiovascular disease&#44; although best established for heart disease consequential to acute mental stress and depressive illness&#44; has been much more difficult to establish&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">26</span></a> Acute mental stress can trigger sympathetic outflow to the heart and adrenal secretion of epinephrine&#46; In patients with pre-existing atherosclerosis&#44; not only can increased epinephrine cause ventricular arrhythmias &#40;especially in the presence of coronary artery stenosis&#41;&#44; but the attendant BP surge can fissure coronary plaques and promote platelet aggregation&#44; predisposing to thrombosis&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">26</span></a> Takotsubo &#40;stress&#41; cardiomyopathy is a good example of extreme acute activation of cardiac sympathetic outflow to the heart&#44;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">26</span></a> as are panic attacks accompanied by coronary spasm and cardiac arrhythmias&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">33</span></a> In patients with depressive illness&#44; chronic cardiac sympathetic outflow is at almost the same level as seen in patients with heart failure&#44; and is accepted as a primary cause for heart disease&#44; associated with a worse prognosis&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">The sympathetic nervous system and atherosclerosis</span><p id="par0110" class="elsevierStylePara elsevierViewall">The pivotal role of endothelial impairment in the development of atherosclerosis and in future cardiovascular risk is well established&#46; Less known is the interaction between the SNS and endothelial function&#46; Virtually all cardiovascular risk factors and diseases in which increased adrenergic drive is involved are also characterized by endothelial dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">34</span></a> Nitric oxide &#40;NO&#41;&#44; one of the main mediators of endothelial function&#44; is also an important neurotransmitter&#44; involved in the autonomic regulation of cardiovascular function&#44; and acts as a sympathoinhibitory substance within the central nervous system&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">35</span></a> Acute and chronic increases in SNS activity&#44; through endothelial dysfunction and endothelial cell damage&#44; have been shown to contribute to the subsequent development of atherosclerosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0600"><span class="elsevierStyleSup">26&#44;30&#44;34</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">SNS overactivity has also been linked to the development of metabolic disturbances such as insulin resistance and dyslipidemia&#46;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">36</span></a> Not only can increased SNS activity in itself lead to insulin resistance&#44; particularly in hypertensive patients&#44;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">36</span></a> but also elevated circulating insulin levels due to insulin resistance in obese patients can precipitate an increase in SNS activity&#44; leading to hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0620"><span class="elsevierStyleSup">30&#44;36&#44;37</span></a> There is abundant evidence that statins&#44; through their numerous pleiotropic effects&#44; reduce and even normalize excessive SNS activity&#44; improving LV function and arterial baroreflex sensitivity&#46;<a class="elsevierStyleCrossRefs" href="#bib0600"><span class="elsevierStyleSup">26&#44;30&#44;34</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Sympathetic nervous system function and heart failure</span><p id="par0120" class="elsevierStylePara elsevierViewall">The observation that norepinephrine concentrations were reduced in the failing heart suggested the existence of sympathetic denervation&#44;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">38</span></a> despite the increased concentrations in peripheral venous plasma commonly found in patients with heart failure&#44;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">39</span></a> indicating overall increased SNS activity except in the heart&#46; Later studies confirmed very high levels of norepinephrine spillover from the heart in heart failure&#44; up to 50 times the normal range in untreated patients&#44;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">26</span></a> demonstrating high sympathetic tone in the failing heart&#46; This was later explained by a reduction in the concentration of beta-1 adrenoreceptors in the failing myocardium&#44; due to downregulation of these receptors by increased sympathetic activity in the failing heart&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">26</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">This increased sympathetic activity in the peripheral circulation and kidneys leads to adverse effects&#44; causing vasoconstriction&#44; increasing cardiac work&#44; and promoting sodium retention and ventricular overfilling&#46; The strong link between the level of sympathetic activity in heart failure&#44; progressive ventricular deterioration&#44; the development of ventricular arrhythmias&#44; sudden death and reduced survival<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">26</span></a> provided the rationale for the subsequent use of beta-blockers in heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">40</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Sympathetic nervous system function and essential hypertension</span><p id="par0130" class="elsevierStylePara elsevierViewall">A well-known consequence of an overactive SNS is an increase in BP&#46; Previous studies showed not only that sympathetic outflow to the kidneys was increased&#44; but that the extent of the outflow was also related to the degree of essential hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">20&#44;22&#44;26&#44;41</span></a> Regional measurements of norepinephrine spillover to the kidneys support this concept&#44; and indicate that more than 50&#37; of cases of essential hypertension present significant sympathetic hyperactivation&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">42</span></a> Renal sympathetic nerve activity is pivotal in the pathogenesis of essential hypertension&#44; through its influence on renin release&#44; sodium and water excretion&#44; peripheral vasoconstriction&#44; cardiac contraction and venous capacitance&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">26</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The safety and efficacy of BP lowering achieved recently with RDN has led to renewed interest in the role of sympathetic activity in the pathogenesis of essential hypertension&#46; Correct identification of sympathetic hyperactivation in patients with essential hypertension can lead to better selection of patients for RDN treatment&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Resistant hypertension</span><p id="par0140" class="elsevierStylePara elsevierViewall">Data from the PAP study involving 5023 adult patients showed that the prevalence of hypertension in Portugal was 42&#37;&#44; of whom only 46&#46;1&#37; were aware of the fact&#44; 39&#37; were taking medication and only 11&#46;2&#37; had BP values below the recommended thresholds&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">43</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Not all patients with uncontrolled hypertension are considered to be resistant&#44; as there are several factors that can contribute to lack of control&#44; including inadequate treatment regimens &#40;type and&#47;or dosage of drugs&#41;&#44; poor adherence to medical therapy&#44; and undetected secondary causes of hypertension&#46; A diagnosis of resistant hypertension should therefore only be made after ruling out other factors&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Resistant hypertension has been defined as BP values above 140&#47;90 mmHg &#40;or &#62;130&#47;80 mmHg in patients with diabetes or chronic kidney disease&#41; in patients treated with three or more antihypertensive drugs at appropriate doses&#44; including if possible a diuretic&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">44</span></a> In an alternative definition&#44; patients with target BP values can be considered to have resistant hypertension if they need to take at least four different antihypertensive drugs&#59; this is known as controlled resistant hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">45</span></a> The prevalence of resistant hypertension has been reported as 5&#8211;30&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0700"><span class="elsevierStyleSup">46&#8211;48</span></a> the figure varying according to the hypertensive population being studied&#44; with higher percentages in cohorts from centers specializing in the treatment of hypertension compared to community-based cohorts&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">At the present time&#44; and in the light of the available clinical studies&#44; patients considered to be good candidates for RDN should have more severe treatment-resistant hypertension&#44; defined as office systolic BP of at least 160 mmHg &#40;150 mmHg in type 2 diabetes&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0715"><span class="elsevierStyleSup">49&#8211;51</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Renal denervation</span><p id="par0160" class="elsevierStylePara elsevierViewall">Assessment of a potential candidate for RDN should follow several steps &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41; designed to select candidates expected to benefit from this intervention&#46; According to a recent European Society of Hypertension &#40;ESH&#41; position paper on RDN&#44;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">52</span></a> it is recommended that patients should undergo careful assessment in centers that have considerable experience in dealing with hypertension &#40;ideally ESH excellence centers&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">The first step should be to exclude pseudoresistance&#44; secondary causes of hypertension and conditions that maintain high BP values&#46; Pseudoresistance can be excluded by 24-hour ambulatory BP monitoring&#44; which is recommended not only for pre-RDN assessment but as good practice in the assessment of all patients with hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">5&#44;53</span></a> In patients with severe resistant hypertension considered for RDN&#44; the initial assessment should also include investigation of possible secondary causes of hypertension&#44; including primary aldosteronism&#44; renal artery stenosis&#44; pheochromocytoma&#44; Cushing&#39;s disease&#44; hyperparathyroidism and aortic coarctation&#44; although some of these are very uncommon&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">44</span></a> Some conditions that can maintain high BP values should also be treated when possible&#44; such as severe obesity&#44; high salt and alcohol intake&#44; concomitant use of drugs that raise BP and the presence of obstructive sleep apnea&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The second step should be the optimization of antihypertensive treatment&#44; including the use of diuretics and aldosterone blockers&#44; optimization of dosages and combinations&#44; and reassessment of BP control with 24-hour ambulatory BP monitoring &#40;ABPM&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The third step should be assessment of renal artery anatomy&#44; as there are relative contraindications for RDN related to the number of renal arteries &#40;multiple main arteries&#41; and their diameter &#40;ideally &#62;4 mm&#41; and length &#40;ideally &#62;20 mm&#41; as well as eGFR&#44; which should be above 45 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#46; Some of these are considered contraindications to RDN&#44; because they were excluded from RDN trials&#44; but are regarded in clinical practice as relative contraindications&#59; some of these patients have been treated with RDN and included in small studies and registries&#46;<a class="elsevierStyleCrossRefs" href="#bib0740"><span class="elsevierStyleSup">54&#8211;56</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Experimental studies on renal denervation</span><p id="par0180" class="elsevierStylePara elsevierViewall">The finding that renal sympathetic activity is increased in spontaneously hypertensive rats&#44; the animal model most often used in investigation of essential hypertension&#44; has shone light on the role of the renal SNS in the pathogenesis of hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">57</span></a> In an experimental model of hypertension and obesity in dogs subjected to a high-fat diet&#44; RDN not only prevented the appearance of hypertension but also increased urinary sodium excretion by 50&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">58</span></a> In another animal model of chronic renal failure&#44; sympathectomy prevented hypertension and was associated with decreased adrenergic activity in the hypothalamic nuclei&#46;<a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">59</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Renal lesions induced by injection of phenol cause a sustained rise in BP and norepinephrine release by the hypothalamus without changing eGFR&#46; RDN of these animals prevented the rise in BP&#46;<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">60</span></a> In different animal models&#44; the effects of RDN have consistently shown the important role of the renal SNS in the pathophysiology of hypertension&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In humans&#44; surgical sympathectomy lowers high BP and improves the cardiovascular prognosis of patients with severe hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">7&#8211;9&#44;61&#8211;63</span></a> Its poorly tolerated side effects&#44; which include severe orthostatic hypotension&#44; anhidrosis&#44; intestinal disturbances and sexual dysfunction&#44; and its high surgical risk&#44; have led to the technique being abandoned&#46; Nevertheless&#44; it has proved the importance of the SNS in BP control beyond doubt&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Clinical studies on percutaneous sympathetic renal denervation</span><p id="par0195" class="elsevierStylePara elsevierViewall">Symplicity HTN-1&#44;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">11</span></a> a proof-of-principle study&#44; was the first to evaluate RDN in patients with severe resistant hypertension&#46; One year after the procedure&#44; mean office BP fall was 27 mmHg systolic and 17 mmHg diastolic&#44; and was maintained until 24 months of follow-up&#44; with 13&#37; non-responders&#46; A subgroup analysis assessing renal and systemic sympathetic activity showed a 47&#37; reduction in renal norepinephrine spillover in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">64</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">In the Symplicity HTN-2 multicenter clinical trial&#44;<a class="elsevierStyleCrossRefs" href="#bib0790"><span class="elsevierStyleSup">64&#44;65</span></a> 106 patients with severe resistant hypertension under medication were randomized to optimal antihypertensive medical therapy alone or to RDN plus optimal antihypertensive medical therapy&#46; The primary endpoint was change in office BP at six-month follow-up&#46; A significant fall in BP was observed in patients who underwent RDN&#58; &#8722;32 mmHg in systolic BP and &#8722;12 mmHg in diastolic BP &#40;p&#60;0&#46;01&#41; compared to an increase of 1 mmHg in systolic BP and no change in diastolic BP &#40;p&#61;NS&#41; in patients under optimal medical therapy alone at six months following RDN&#46; A subgroup analysis of 24-hour ABPM data revealed a similar pattern&#44; a fall of 11 mmHg in systolic BP and 7 mmHg in diastolic BP in the RDN group &#40;p&#60;0&#46;001&#41; compared to a fall of 3 mmHg and 1 mmHg on medical therapy alone &#40;p&#61;NS&#41;&#46; The magnitude of the difference in BP fall between RDN and optimal medical therapy alone was maintained at 12-month follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">64</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Alongside its efficacy&#44; RDN was a safe procedure&#46; In both studies&#44; only minor vascular complications occurred&#44; mainly at the puncture site&#58; hematomas and pseudoaneurysms &#40;four patients&#41;&#44; one renal artery dissection during the diagnostic procedure&#44; successfully treated with a stent&#44; and no major complications&#46; Regarding renal function&#44; there were no significant changes in eGFR during follow-up&#46;<a class="elsevierStyleCrossRefs" href="#bib0715"><span class="elsevierStyleSup">49&#44;66</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">The recently published EnlightHTN I trial<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">51</span></a> also revealed a significant fall in both office BP and mean 24-hour ABPM values at six months&#44; with a good safety profile&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The published data indicate that RDN has an excellent short-term safety profile&#44; although data on the long-term risk of renal artery stenosis are lacking&#46; The results of the Symplicity trials and EnlightHTN I are certainly promising&#44; but their open design meant that bias in BP measurements&#44; or even the extent of the placebo effect in treated patients&#44; could not be properly addressed&#46; Some of these limitations were addressed in the recently published randomized SYMPLICITY HTN-3 trial&#46;<a class="elsevierStyleCrossRefs" href="#bib0805"><span class="elsevierStyleSup">67&#44;68</span></a> This was the first blinded sham-controlled study of RDN for treatment of resistant hypertension&#46; The primary efficacy endpoint was the mean change in office systolic BP from baseline to six months in the RDN arm &#40;n&#61;364&#41; compared to the control arm &#40;n&#61;171&#41;&#46; At six-month follow-up&#44; there was a difference of 2&#46;39 mmHg in the change in systolic BP &#40;&#8722;14&#46;13&#177;23&#46;93 mmHg in the RDN arm vs&#46; &#8722;11&#46;74&#177;25&#46;94 mmHg in the sham procedure arm&#41;&#44; which did not reach statistical significance &#40;95&#37; confidence interval &#91;CI&#93;&#58; &#8722;6&#46;89 to 2&#46;12&#44; p&#61;0&#46;26&#41;&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">The secondary efficacy endpoint was the change in mean 24-hour ambulatory BP at six months&#46; A statistically non-significant difference of 1&#46;96 mmHg &#40;95&#37; CI&#58; &#8722;4&#46;97 to 1&#46;06&#44; p&#61;0&#46;98&#41; was seen at six months &#40;&#8722;6&#46;75&#177;15&#46;11 mm Hg in the RDN arm vs&#46; &#8722;4&#46;79&#177;17&#46;25 mm Hg in the control arm&#41;&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">The rate of major adverse events at six months was 4&#37; in the RDN arm vs&#46; 5&#46;8&#37; in the control arm &#40;p&#61;0&#46;37&#41;&#46; The primary safety endpoint &#40;a composite of major adverse events&#41; rate was 1&#46;4&#37; in the RDN arm&#44; less than the pre-specified objective of 9&#46;8&#37;&#44; reaching statistical significance &#40;p&#60;0&#46;001&#41;&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">These conflicting results between Symplicity HTN-3<a class="elsevierStyleCrossRef" href="#bib0810"><span class="elsevierStyleSup">68</span></a> and the previous Symplicity trials&#44; HTN-1<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">11</span></a> and HTN-2<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">65</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#44; may be related to a different and more rigorous design adopted in HTN-3&#44; a different study population&#44; more aggressive antihypertensive medication&#44; and the requirement that no changes in antihypertensive medication could be made in the six months after the procedure&#46; There was also potential for procedural variability due to the large number of centers involved in the HTN-3 study and a low case load per operator&#44; each performing only three procedures on average &#40;most performed their first and only RDN procedure for the trial&#41;&#46; The inclusion for the first time of a large proportion of African-American patients &#40;24&#46;8&#37; of the RDN arm and 29&#46;2&#37; of the control arm&#41;&#44; a population known to be resistant to RAAS blockers&#44; could have had a negative impact on the efficacy of RDN&#59; a subgroup analysis revealed a statistically significant difference favoring the RDN arm in non-African-American patients&#46; Overall antihypertensive medication was more intensive than in previous studies&#44; probably reflecting the more severe hypertensive patients included&#46; Regression to the mean may also at least partially explain the differences&#46;<a class="elsevierStyleCrossRef" href="#bib0815"><span class="elsevierStyleSup">69</span></a> The presence for the first time of a sham procedure in the control arm &#40;renal angiography was performed in all patients before randomization&#41; may have diluted the expected placebo effect favoring the treated group&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0235" class="elsevierStylePara elsevierViewall">Puzzling findings in Symplicity HTN-3 include the smaller decrease in office systolic BP from baseline to six months in the RDN arm&#44; about half that observed in the Symplicity HTN-2 RDN group&#44; despite similar baseline BP in the two studies&#44; raising doubts as to whether RF energy was properly delivered&#46; A larger decrease in BP was also observed in the HTN-3 control group compared to the much smaller decrease in the HTN-2 control group&#46; These findings raise the question of whether a less effective denervation procedure allied to more aggressive medical therapy could have played a major role in the HTN-3 results&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">The fact that there was no measurement to confirm that the renal nerves were in fact denervated by the procedure&#44; because there is no test that can be easily performed in a large trial&#44; is a major limitation to this and to almost all of these trials&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">While the Symplicity HTN-3 follow-up will continue as planned for up to five years&#44; the fact that many patients crossed over from the control arm to the RDN arm at six months will make it more difficult to draw significant conclusions concerning the long-term clinical results of RDN therapy and to assess the placebo effect over time&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Nevertheless&#44; the Symplicity HTN-3 trial is a landmark in the development of RDN treatment&#44; signaling the start of its reflection phase&#44; in which new hypotheses generated by this trial can be addressed&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Renal denervation&#58; new devices</span><p id="par0255" class="elsevierStylePara elsevierViewall">The high expectations and enthusiasm created in the medical device industry has led many companies to develop new or improved technical solutions for RDN&#44; some of which are commercially available &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0260" class="elsevierStylePara elsevierViewall">From predictable improvements of the original procedure to out-of-the-box ideas&#44; many innovations are being integrated in the new designs&#46; These include alternative mechanisms of action&#44; like ultrasound catheters and balloons with microinjection systems to deliver neurotoxins&#46; Simultaneously activated multi-electrodes not only significantly shorten procedural time but also increase reproducibility&#44; ensuring that all quadrants are adequately denervated&#44; while radial access reduces access site vascular complications&#44; and manipulating renal catheters by a craniocaudal approach is generally less challenging and safer&#46; Pain control is also a challenge&#44; as electric current&#44; tissue burning&#44; and nerve damage&#44; although essential components of the procedure&#44; all cause discomfort&#46; The more recent radiofrequency catheters with bipolar electrodes reportedly reduce discomfort due to a significantly smaller electric field during activation&#44; but this is not yet clinically proven&#59; the absence of an acute procedural efficacy endpoint is still a major limitation&#46; Procedural success is difficult to determine and to correlate with BP response&#46; Efforts are being made to find a biomarker or physiological test that indicates acute RDN success&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Sympathetic renal denervation&#58; potential future indications</span><p id="par0265" class="elsevierStylePara elsevierViewall">The overall decrease in SNS drive through RDN may be a valid alternative in clinical scenarios characterized by sympathetic hyperactivity other than resistant hypertension&#46; A few of these alternative applications have already been explored and show promising results&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">The association between heart failure and increased sympathetic drive is well known&#46; Interestingly&#44; cardiac and renal norepinephrine spillover is more closely associated with mortality than circulating catecholamine concentrations&#44; although both are associated with worse outcomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">16&#44;70</span></a> This suggests that reducing norepinephrine spillover from the kidney could have beneficial symptomatic and prognostic effects&#46;<a class="elsevierStyleCrossRefs" href="#bib0825"><span class="elsevierStyleSup">71&#44;72</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">In animal models&#44; RDN after myocardial infarction led to improvement in sodium excretion&#44;<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">73</span></a> increased cardiac output&#44; improved renal blood flow&#44;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">74</span></a> and down-regulation of angiotensin AT1 receptors mediating maladaptive responses&#46;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">75</span></a> In a multicenter study of patients with resistant hypertension treated by RDN with anatomical and functional myocardial parameters assessed by MRI&#44; a subgroup of patients with LV dysfunction had significantly increased ejection fraction and circumferential strain&#46;<a class="elsevierStyleCrossRef" href="#bib0850"><span class="elsevierStyleSup">76</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">The REACH pilot study in heart failure provided evidence that RDN improved six-minute walk distances without affecting BP &#40;mean 120 mmHg at baseline&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0855"><span class="elsevierStyleSup">77</span></a> Other ongoing clinical trials will provide further evidence on the potential of RDN to influence the course and outcome of heart failure&#46; Type 2 diabetes and insulin resistance are other conditions that have a strong association with resistant hypertension&#46; Half of resistant hypertension patients are considered to be insulin resistant&#44; increasing the risk for type 2 diabetes&#44; and since insulin resistance is dependent on sympathetic activity it appears likely that it could also be a target for RDN&#46;<a class="elsevierStyleCrossRefs" href="#bib0860"><span class="elsevierStyleSup">78&#44;79</span></a> In a pilot study&#44; along with reducing BP&#44; RDN improved fasting glucose&#44; insulin&#44; and C-peptide concentrations&#44; as well as homeostasis model assessment-insulin resistance indices in patients with resistant hypertension and metabolic disease&#44; suggesting that RDN might improve diabetic status in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0870"><span class="elsevierStyleSup">80</span></a> Witkowski et al&#46; showed a decline in glycated hemoglobin concentrations after RDN&#46;<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">81</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">The association between obstructive sleep apnea and resistant hypertension is well known&#46;<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">81</span></a> In 2011 Witkowski et al&#46; published a pilot study on the effect of RDN in 10 patients with resistant hypertension and obstructive sleep apnea&#46; At six months there was an improvement in apnea-hypopnea indices&#46;<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">81</span></a> In an experimental model&#44; it has been shown that RDN reduces post-apneic BP rise&#44; renal hypoperfusion during apnea and RAAS activation in the kidney&#46;<a class="elsevierStyleCrossRefs" href="#bib0880"><span class="elsevierStyleSup">82&#44;83</span></a> The value of these findings is still controversial and confirmatory studies are needed&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">In an animal model<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">84</span></a> of obstructive sleep apnea and induced atrial fibrillation &#40;AF&#41;&#44; RDN decreased the atrial refractory period and AF recurrence&#44;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">82</span></a> providing better rate control&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">85</span></a> In a pilot trial&#44; patients with resistant hypertension and symptomatic paroxysmal or persistent atrial fibrillation refractory to &#8805;2 antiarrhythmic drugs were randomized to pulmonary vein isolation alone or associated with RDN&#46; At 12-month follow-up 69&#37; of patients treated with RDN were AF-free&#44; compared to 29&#37; of those treated with pulmonary vein isolation only&#46;<a class="elsevierStyleCrossRef" href="#bib0900"><span class="elsevierStyleSup">86</span></a> These experimental findings indicate the potential usefulness of RDN in AF treatment&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">The evidence for the fundamental role of sympathetic activity in ventricular arrhythmias is overwhelming&#46; In an animal model of ischemia&#47;reperfusion arrhythmias&#44; RDN decreased the occurrence of ventricular arrhythmias&#47;fibrillation and attenuated the rise in LV end-diastolic pressure during LV ischemia without influencing infarct size&#44; changes in ventricular contractility&#44; BP or reperfusion arrhythmias&#46;<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">87</span></a> In a small case series involving patients with chronic heart failure and ventricular electrical storm&#44; RDN reduced discharges from implantable cardioverter-defibrillators and ventricular ectopies&#46;<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">88</span></a> Hoffmann et al&#46;<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">89</span></a> reported that RDN can be safely and effectively performed as an adjunct to cardiac catheter ablation&#44; in a hemodynamically unstable patient with ventricular storm after ST-elevation myocardial infarction&#46; Although these are early and preliminary findings&#44; the underlying biological plausibility will certainly heighten interest in these potential future applications of RDN&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusions</span><p id="par0300" class="elsevierStylePara elsevierViewall">It is now accepted that an overactive sympathetic system has a pivotal role in the pathophysiology of several diseases besides essential hypertension&#46; Related conditions like depression&#44; mental stress&#44; hypertension&#44; diabetes&#44; obesity&#44; sleep apnea&#44; metabolic syndrome&#44; ischemic heart disease&#44; heart failure and chronic renal failure&#44; all have a common link&#44; the often neglected hyperactive SNS&#46; In a new era with new tools to control and treat sympathetic hyperactivity&#44; perhaps this system will finally receive the attention it deserves&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">The inability to treat hypertension effectively is due in part to a lack of understanding of the fundamental mechanisms involved in BP control&#46; There is a complex mixture of hormonal&#44; neural and intrinsic factors&#44; all acting together&#44; over different time scales and with different feedback control pathways&#44; and it seems unlikely that any of the current treatment approaches is actually targeting the factors that originally led to the rise in BP&#46; Catheter-based RDN is a truly innovative approach to treat hypertension by changing sympathetic activity&#46; In patients with resistant hypertension&#44; the technique has significantly reduced BP as well as sympathetic nerve activity and norepinephrine spillover&#44; with high safety levels&#46; These achievements are well documented in several international multicenter trials and registries&#46; Along with its proven efficacy in BP reduction&#44; it has the potential to positively affect insulin resistance and diabetes&#44; LV mass&#44; proteinuria and arrhythmias&#44; as indicated by various small proof-of-concept studies&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">Nevertheless&#44; there are still important issues that need to be addressed in the near future&#44; like the impossibility of determining whether denervation was effective&#44; what level of denervation is needed to achieve clinical success&#44; which patients have an appropriate phenotype for RDN&#44; and what endpoints should be used to define RDN success &#40;merely BP reduction or reduction in target organ damage&#41;&#46; Much needs to be done and will be in the coming years&#44; but a new window has certainly been opened not only to address hypertension&#44; but most importantly to address SNS dysfunction&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0315" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:15 [
        0 => array:3 [
          "identificador" => "xres439418"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec462607"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres439417"
          "titulo" => "Resumo"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec462606"
          "titulo" => "Palavras-chave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "The sympathetic nervous system and cardiovascular disease"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Assessment of the sympathetic nervous system in humans"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Sympathetic nervous system overactivity"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Sympathetic nervous system overactivity and cardiovascular disease"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "The sympathetic nervous system and atherosclerosis"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Sympathetic nervous system function and heart failure"
            ]
            5 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Sympathetic nervous system function and essential hypertension"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Resistant hypertension"
        ]
        7 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Renal denervation"
        ]
        8 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Experimental studies on renal denervation"
        ]
        9 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Clinical studies on percutaneous sympathetic renal denervation"
        ]
        10 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Renal denervation&#58; new devices"
        ]
        11 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Sympathetic renal denervation&#58; potential future indications"
        ]
        12 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Conclusions"
        ]
        13 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Conflicts of interest"
        ]
        14 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2014-07-22"
    "fechaAceptado" => "2014-07-31"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec462607"
          "palabras" => array:3 [
            0 => "Hypertension"
            1 => "Sympathetic nervous system"
            2 => "Renal denervation"
          ]
        ]
      ]
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec462606"
          "palabras" => array:3 [
            0 => "Hipertens&#227;o arterial"
            1 => "Sistema nervoso simp&#225;tico"
            2 => "Desnerva&#231;&#227;o renal"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">There is a marked contrast between the high prevalence of hypertension and the low rates of adequate control&#46; A subset of patients with suboptimal blood pressure control have drug-resistant hypertension&#44; in the pathophysiology of which chronic sympathetic hyperactivation is significantly involved&#46; Sympathetic renal denervation has recently emerged as a device-based treatment for resistant hypertension&#46; In this review&#44; the pathophysiological mechanisms linking the sympathetic nervous system and cardiovascular disease are reviewed&#44; focusing on resistant hypertension and the role of sympathetic renal denervation&#46; An update on experimental and clinical results is provided&#44; along with potential future indications for this device-based technique in other cardiovascular diseases&#46;</p></span>"
      ]
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A elevada preval&#234;ncia da hipertens&#227;o est&#225; em claro contraste com a sua ainda insuficiente taxa de controlo&#46; Um importante subgrupo destes doentes apresenta uma hipertens&#227;o resistente aos f&#225;rmacos&#44; na qual a hiperativa&#231;&#227;o cr&#243;nica do sistema nervoso simp&#225;tico tem importantes implica&#231;&#245;es fisiopatol&#243;gicas&#46; Recentemente&#44; a desnerva&#231;&#227;o simp&#225;tica renal emergiu como um tratamento de interven&#231;&#227;o para a hipertens&#227;o arterial resistente&#46; No presente artigo&#44; s&#227;o revistos os mecanismos fisiopatol&#243;gicos subjacentes &#224; intera&#231;&#227;o entre o sistema nervoso simp&#225;tico e as doen&#231;as cardiovasculares&#44; com particular enf&#226;se na hipertens&#227;o arterial resistente e no papel da desnerva&#231;&#227;o simp&#225;tica renal&#46; &#201; igualmente feita uma atualiza&#231;&#227;o dos resultados de estudos experimentais e cl&#237;nicos&#44; bem como de potenciais futuras indica&#231;&#245;es desta t&#233;cnica de interven&#231;&#227;o noutras doen&#231;as do foro cardiovascular&#46;</p></span>"
      ]
    ]
    "nomenclatura" => array:1 [
      0 => array:3 [
        "identificador" => "nom0005"
        "titulo" => "<span class="elsevierStyleSectionTitle" id="sect0025">List of abbreviations</span>"
        "listaDefinicion" => array:1 [
          0 => array:1 [
            "definicion" => array:7 [
              0 => array:2 [
                "termino" => "BP"
                "descripcion" => "<p id="par0005" class="elsevierStylePara elsevierViewall">blood pressure</p>"
              ]
              1 => array:2 [
                "termino" => "CI"
                "descripcion" => "<p id="par0010" class="elsevierStylePara elsevierViewall">confidence interval</p>"
              ]
              2 => array:2 [
                "termino" => "eGFR"
                "descripcion" => "<p id="par0015" class="elsevierStylePara elsevierViewall">estimated glomerular filtration rate</p>"
              ]
              3 => array:2 [
                "termino" => "SNS"
                "descripcion" => "<p id="par0020" class="elsevierStylePara elsevierViewall">sympathetic nervous system</p>"
              ]
              4 => array:2 [
                "termino" => "RAAS"
                "descripcion" => "<p id="par0025" class="elsevierStylePara elsevierViewall">renin-angiotensin-aldosterone system</p>"
              ]
              5 => array:2 [
                "termino" => "RDN"
                "descripcion" => "<p id="par0030" class="elsevierStylePara elsevierViewall">renal denervation</p>"
              ]
              6 => array:2 [
                "termino" => "RF"
                "descripcion" => "<p id="par0035" class="elsevierStylePara elsevierViewall">radiofrequency</p>"
              ]
            ]
          ]
        ]
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">RAAS&#58; renin-angiotensin-aldosterone system&#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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Vascular</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Smooth muscle cell hypertrophy and proliferation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Endothelial dysfunction and damage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Arterial stiffness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Impairment of postural blood pressure control and syncope&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Atherosclerosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Cardiac</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Myocyte hypertrophy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Left ventricular hypertrophy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Arrhythmia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Psychogenic heart disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Renal</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Renal artery vasoconstriction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sodium and fluid retention&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Microalbuminuria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>RAAS activation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Metabolic</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Insulin resistance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dyslipidemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab685936.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Effects of increased sympathetic nerve activity&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">ABPM&#58; ambulatory blood pressure monitoring&#59; BP&#58; blood pressure&#59; CT&#58; computed tomography&#59; eGFR&#58; estimated glomerular filtration rate&#59; MRI&#58; magnetic resonance imaging&#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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">1st step</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Exclusion of pseudoresistance &#40;by 24-hour ABPM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Exclusion of secondary causes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Search for conditions that maintain high BP values&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">2nd step</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Modification of antihypertensive treatment &#40;optimization of dosages and combinations&#59; use of aldosterone blockers if possible&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Reassessment of BP control with 24-hour ABPM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">3rd step</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Assessment of renal artery anatomy &#40;CT&#44; MRI or invasive angiography&#59; Doppler ultrasound&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Assessment of renal function &#40;eGFR ideally &#62;45 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab685934.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluation of patients with resistant hypertension considered to be potential candidates for renal denervation&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">ABPM&#58; ambulatory blood pressure monitoring&#59; NA&#58; not available&#59; RDN&#58; renal denervation&#59; RF&#58; radiofrequency&#59; SBP&#58; systolic blood pressure&#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">Trial&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">Symplicity HTN-1<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">11</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Symplicity HTN-2<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">65</span></a></th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Symplicity HTN-3<a class="elsevierStyleCrossRef" href="#bib0810"><span class="elsevierStyleSup">68</span></a></th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">EnlightHTN-1<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">51</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">RAPID<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">90</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">REDUCE-HTN FIM<a class="elsevierStyleCrossRef" href="#bib0925"><span class="elsevierStyleSup">91</span></a>&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  " align="left" valign="top">Device&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&#44; single-electrode&#40;Symplicity<span class="elsevierStyleSup">&#174;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&#44; single-electrode&#40;Symplicity<span class="elsevierStyleSup">&#174;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No RDN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&#44; single-electrode&#40;Symplicity<span class="elsevierStyleSup">&#174;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No RDN &#40;sham&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&#44; multi-electrode &#40;EnlightHTN<span class="elsevierStyleSup">&#174;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&#44; balloon &#40;OneShot<span class="elsevierStyleSup">&#174;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&#44; balloon &#40;Vessix<span class="elsevierStyleSup">&#174;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">No&#46; of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">564&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">171&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Randomized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="center" valign="top">Yes</td><td class="td" title="table-entry  " colspan="2" align="center" valign="top">Yes</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Sham control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Black &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</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">2<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</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">4<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;2<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</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">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Mean baseline office SBP &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">177&#177;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">178&#177;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">178&#177;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">179&#177;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">180&#177;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">176&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">181&#46;6&#177;20&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">183&#177;18&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Mean no&#46; of antihypertensive drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;7&#177;1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;2&#177;1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;3&#177;1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;1&#177;1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;2&#177;1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;1&#177;0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;1&#177;1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Aldosterone blockers &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Office SBP change at 6 months &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;32&#177;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#177;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;14&#46;1&#177;23&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;11&#46;7&#177;25&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;27&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">24-hour ABMP SBP change at 6 months &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;11<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</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">&#8722;11&#177;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;3&#177;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;6&#46;8&#177;15&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;4&#46;8&#177;17&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Response rate &#40;&#8805;10 mmHg change in office SBP from baseline&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">87&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">84&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">48&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">85&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab685933.png"
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Described as non-white&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Only nine RDN responder patients had adequate ABPM at baseline and longer than 30 days&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Studies of renal denervation&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">RF&#58; radiofrequency&#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">Company&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">Medtronic&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">Medtronic&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">St&#46; Jude&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">Maya&#47;Covidien&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">ReCor Medical&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">Boston Scientific&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">Terumo&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">Cordis&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  " align="left" valign="top">Product&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Symplicity Flex&#8482;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Symplicity Spyral&#8482;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">EnlightHTN&#8482;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OneShot&#8482;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Paradise&#8482;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vessix V2&#8482;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Iberis&#8482;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Renlane&#8482;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Catheter size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Energy type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ultrasound&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Catheter design&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Single-electrode&#44; monopolar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Multi-electrode &#40;4&#41;&#44; monopolar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Multi-electrode&#44; monopolar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Multi-electrode&#44; monopolar&#44; irrigated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ultrasound&#59; balloon with cooling&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Multi-electrode&#44; bipolar&#44; non-compliant balloon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Single-electrode&#44; monopolar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Multi-electrode&#44; monopolar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Over-the-wire&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Energy delivery time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30 sec&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30 sec&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Total treatment time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#8211;24 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Unknown&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#8211;24 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Unknown&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Vessel obstruction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Trials&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Symplicity HTN-1<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">11</span></a>&#44; Symplicity HTN-2<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">64</span></a>&#44; Symplicity HTN-3<a class="elsevierStyleCrossRef" href="#bib0810"><span class="elsevierStyleSup">68</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">FIM<a class="elsevierStyleCrossRef" href="#bib0930"><span class="elsevierStyleSup">92</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">EnlightHTN-1<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">51</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">RHAS<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">90</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">PARADISE<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">93</span></a>&#44; REALISE<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">94</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">Reduce HTN<a class="elsevierStyleCrossRef" href="#bib0925"><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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RENABLATE I<a class="elsevierStyleCrossRef" href="#bib0945"><span class="elsevierStyleSup">95</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab685935.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Sympathetic renal denervation devices&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:95 [
            0 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions&#44; 1990&#8211;2010&#58; a systematic analysis for the Global Burden of Disease Study 2010"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(12)61766-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2012"
                        "volumen" => "380"
                        "paginaInicial" => "2224"
                        "paginaFinal" => "2260"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global burden of blood-pressure-related disease&#44; 2001"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(08)60655-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2008"
                        "volumen" => "371"
                        "paginaInicial" => "1513"
                        "paginaFinal" => "1518"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of different blood-pressure-lowering regimens on major cardiovascular events&#58; results of prospectively-designed overviews of randomised trials"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2003"
                        "volumen" => "362"
                        "paginaInicial" => "1527"
                        "paginaFinal" => "1535"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0490"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Blood pressure control in Italy&#58; analysis of clinical data from 2005&#8211;2011 surveys on hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/HJH.0b013e3283535993"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hypertens"
                        "fecha" => "2012"
                        "volumen" => "30"
                        "paginaInicial" => "1065"
                        "paginaFinal" => "1074"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2013 ESH&#47;ESC Guidelines for the management of arterial hypertension&#58; the Task Force for the management of arterial hypertension of the European Society of Hypertension &#40;ESH&#41; and of the European Society of Cardiology &#40;ESC&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.hjh.0000431740.32696.cc"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hypertens"
                        "fecha" => "2013"
                        "volumen" => "31"
                        "paginaInicial" => "1281"
                        "paginaFinal" => "1357"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incidence and prognosis of resistant hypertension in hypertensive patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.111.068064"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2012"
                        "volumen" => "125"
                        "paginaInicial" => "1635"
                        "paginaFinal" => "1642"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effects of splanchnicectomy on the blood pressure in hypertension&#59; a controlled study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "1951"
                        "volumen" => "4"
                        "paginaInicial" => "173"
                        "paginaFinal" => "183"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Surgical approach to the treatment of essential hypertension&#46; Results of therapy &#40;medical and surgical&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Cardiol"
                        "fecha" => "1962"
                        "volumen" => "9"
                        "paginaInicial" => "893"
                        "paginaFinal" => "899"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Results of treatment in malignant hypertension&#58; a seven-year experience in 94 cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Br Med J"
                        "fecha" => "1959"
                        "volumen" => "2"
                        "paginaInicial" => "969"
                        "paginaFinal" => "980"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Translational medicine&#58; the antihypertensive effect of renal denervation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajpregu.00647.2009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Regul Integr Comp Physiol"
                        "fecha" => "2010"
                        "volumen" => "298"
                        "paginaInicial" => "R245"
                        "paginaFinal" => "R253"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Catheter-based renal sympathetic denervation for resistant hypertension&#58; a multicentre safety and proof-of-principle cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(09)60566-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2009"
                        "volumen" => "373"
                        "paginaInicial" => "1275"
                        "paginaFinal" => "1281"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Excretion of noradrenaline in urine in hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Scand J Clin Lab Invest"
                        "fecha" => "1954"
                        "volumen" => "6"
                        "paginaInicial" => "54"
                        "paginaFinal" => "59"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0535"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pulse and respiratory grouping of sympathetic impulses in human muscle-nerves"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1748-1716.1968.tb04218.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Physiol Scand"
                        "fecha" => "1968"
                        "volumen" => "74"
                        "paginaInicial" => "96"
                        "paginaFinal" => "108"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0540"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Determination of norepinephrine apparent release rate and clearance in humans"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Life Sci"
                        "fecha" => "1979"
                        "volumen" => "25"
                        "paginaInicial" => "1461"
                        "paginaFinal" => "1470"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0545"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiac and pulmonary norepinephrine release and removal in the dog"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Circ Res"
                        "fecha" => "1983"
                        "volumen" => "53"
                        "paginaInicial" => "688"
                        "paginaFinal" => "694"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0550"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Norepinephrine spillover to plasma in patients with congestive heart failure&#58; evidence of increased overall and cardiorenal sympathetic nervous activity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "1986"
                        "volumen" => "73"
                        "paginaInicial" => "615"
                        "paginaFinal" => "621"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0555"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sympathetic drive in anterior and inferior uncomplicated acute myocardial infarction"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/01.CIR.0000129252.96341.8B"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2004"
                        "volumen" => "109"
                        "paginaInicial" => "2285"
                        "paginaFinal" => "2289"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0560"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Central mechanisms of abnormal sympathoexcitation in chronic heart failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Cardiol Res Pract"
                        "fecha" => "2012"
                        "volumen" => "2012"
                        "paginaInicial" => "1"
                        "paginaFinal" => "7"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0565"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Sympathetic nervous system in heart failure&#46; Physiology&#44; pathophysiology&#44; and clinical implications"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2009.05.015"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2009"
                        "volumen" => "54"
                        "paginaInicial" => "1747"
                        "paginaFinal" => "1782"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0570"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The sympathetic system and hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Hypertens"
                        "fecha" => "2000"
                        "volumen" => "13"
                        "numero" => "6 Pt 2"
                        "paginaInicial" => "99S"
                        "paginaFinal" => "105S"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0575"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sympathetic nerve biology in essential hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Pharmacol Physiol"
                        "fecha" => "2001"
                        "volumen" => "28"
                        "paginaInicial" => "986"
                        "paginaFinal" => "989"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0580"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The sympathetic system in essential hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Rev Port Cardiol"
                        "fecha" => "2000"
                        "volumen" => "19"
                        "numero" => "Suppl 2"
                        "paginaInicial" => "II9"
                        "paginaFinal" => "II14"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0585"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sympathetic hyperactivity in hypertensive chronic kidney disease patients is reduced during standard treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/01.HYP.0000256530.39695.a3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "2007"
                        "volumen" => "49"
                        "paginaInicial" => "506"
                        "paginaFinal" => "510"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0590"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sympathetic nervous system and insulin resistance&#58; from obesity to diabetes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Hypertens"
                        "fecha" => "2001"
                        "volumen" => "14"
                        "numero" => "11 Pt 2"
                        "paginaInicial" => "304S"
                        "paginaFinal" => "309S"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0595"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The sympathetic nervous system and obstructive sleep apnea&#58; implications for hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hypertens"
                        "fecha" => "1997"
                        "volumen" => "15"
                        "numero" => "12 Pt 2"
                        "paginaInicial" => "1613"
                        "paginaFinal" => "1619"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0600"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The 2009 Carl Ludwig Lecture&#58; pathophysiology of the human sympathetic nervous system in cardiovascular diseases&#58; the transition from mechanisms to medical management"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/japplphysiol.00832.2009"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Appl Physiol"
                        "fecha" => "2010"
                        "volumen" => "108"
                        "paginaInicial" => "227"
                        "paginaFinal" => "237"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0605"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sympathetic overactivity in active ulcerative colitis&#58; effects of clonidine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajpregu.00442.2005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Regul Integr Comp Physiol"
                        "fecha" => "2006"
                        "volumen" => "290"
                        "paginaInicial" => "R224"
                        "paginaFinal" => "R232"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0610"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adverse consequences of high sympathetic nervous activity in the failing human heart"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/0735-1097(95)00332-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "1995"
                        "volumen" => "26"
                        "paginaInicial" => "1257"
                        "paginaFinal" => "1263"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0615"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2002"
                        "volumen" => "105"
                        "paginaInicial" => "1354"
                        "paginaFinal" => "1359"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0620"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Central sympathetic overactivity&#58; maladies and mechanisms"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.autneu.2009.02.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Auton Neurosci"
                        "fecha" => "2009"
                        "volumen" => "148"
                        "paginaInicial" => "5"
                        "paginaFinal" => "15"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0625"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Improvements in left ventricular hypertrophy and diastolic function following renal denervation&#58; effects beyond blood pressure and heart rate reduction"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0630"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neural activity and ventricular fibrillation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM197605202942107"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1976"
                        "volumen" => "294"
                        "paginaInicial" => "1165"
                        "paginaFinal" => "1170"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0635"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiac sympathetic nerve biology and brain monoamine turnover in panic disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1196/annals.1296.062"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann NY Acad Sci"
                        "fecha" => "2004"
                        "volumen" => "1018"
                        "paginaInicial" => "505"
                        "paginaFinal" => "514"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0640"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sympathetic regulation of vascular function in health and disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                           …1
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fphys.2012.00001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Front Physiol"
                        "fecha" => "2012"
                        "volumen" => "3"
                        "paginaInicial" => "1"
                        "paginaFinal" => "15"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0645"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajpregu.00426.2010"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Regul Integr Comp Physiol"
                        "fecha" => "2011"
                        "volumen" => "300"
                        "paginaInicial" => "R818"
                        "paginaFinal" => "R826"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0650"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Insulin-mediated sympathetic stimulation&#58; role in the pathogenesis of obesity-related hypertension &#40;or&#44; how insulin affects blood pressure&#44; and why&#41;"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hypertens"
                        "fecha" => "2001"
                        "volumen" => "19"
                        "numero" => "3 Pt 2"
                        "paginaInicial" => "523"
                        "paginaFinal" => "528"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0655"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Excessive sympathetic activation in heart failure with obesity and metabolic syndrome&#58; characteristics and mechanisms"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/01.HYP.0000255983.32896.b9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "2007"
                        "volumen" => "49"
                        "paginaInicial" => "535"
                        "paginaFinal" => "541"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0660"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Myocardial norepinephrine concentration in man&#46; Effects of reserpine and of congestive heart failure"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM196309262691302"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1963"
                        "volumen" => "269"
                        "paginaInicial" => "653"
                        "paginaFinal" => "658"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0665"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Plasma norepinephrine in congestive heart failure"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Cardiol"
                        "fecha" => "1978"
                        "volumen" => "41"
                        "paginaInicial" => "233"
                        "paginaFinal" => "243"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0670"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "The Cardiac Insufficiency Bisoprolol Study II &#40;CIBIS-II&#41;&#58; a randomised&#44; trial"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1999"
                        "volumen" => "353"
                        "paginaInicial" => "9"
                        "paginaFinal" => "13"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0675"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The sympathetic nervous system through the ages&#58; from Thomas Willis to resistant hypertension"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1113/expphysiol.2010.052332"
                      "Revista" => array:6 [
                        "tituloSerie" => "Exp Physiol"
                        "fecha" => "2011"
                        "volumen" => "96"
                        "paginaInicial" => "611"
                        "paginaFinal" => "622"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0680"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Point&#58; chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/japplphysiol.00182.2010"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Appl Physiol"
                        "fecha" => "2010"
                        "volumen" => "109"
                        "paginaInicial" => "1996"
                        "paginaFinal" => "1998"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0685"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence&#44; awareness&#44; treatment and control of hypertension in Portugal&#58; the PAP study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Port Cardiol"
                        "fecha" => "2007"
                        "volumen" => "26"
                        "paginaInicial" => "21"
                        "paginaFinal" => "39"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0690"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Resistant hypertension&#58; diagnosis&#44; evaluation&#44; and treatment&#58; a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.108.189141"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2008"
                        "volumen" => "117"
                        "paginaInicial" => "e510"
                        "paginaFinal" => "e526"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0695"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Resistant hypertension &#8211; its identification and epidemiology"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrneph.2012.260"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Nephrol"
                        "fecha" => "2013"
                        "volumen" => "9"
                        "paginaInicial" => "51"
                        "paginaFinal" => "58"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0700"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/HYPERTENSIONAHA.110.168948"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "2011"
                        "volumen" => "57"
                        "paginaInicial" => "898"
                        "paginaFinal" => "902"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0705"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Uncontrolled and apparent treatment resistant hypertension in the United States&#44; 1988 to 2008"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.111.030189"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2011"
                        "volumen" => "124"
                        "paginaInicial" => "1046"
                        "paginaFinal" => "1058"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0710"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Blood pressure control and knowledge of target blood pressure in coronary patients across Europe&#58; results from the EUROASPIRE III survey"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/HJH.0b013e328348efa7"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hypertens"
                        "fecha" => "2011"
                        "volumen" => "29"
                        "paginaInicial" => "1641"
                        "paginaFinal" => "1648"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0715"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Catheter-based renal sympathetic denervation for resistant hypertension&#58; durability of blood pressure reduction out to 24 months"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/HYPERTENSIONAHA.110.163014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "2011"
                        "volumen" => "57"
                        "paginaInicial" => "911"
                        "paginaFinal" => "917"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0720"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal sympathetic denervation for treatment of drug-resistant hypertension&#58; one-year results from the Symplicity HTN-2 randomized&#44; controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.112.130880"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2012"
                        "volumen" => "126"
                        "paginaInicial" => "2976"
                        "paginaFinal" => "2982"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0725"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension&#58; the EnlightHTN I trial"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/eht197"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2013"
                        "volumen" => "34"
                        "paginaInicial" => "2132"
                        "paginaFinal" => "2140"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0730"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Updated ESH position paper on interventional therapy of resistant hypertension"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4244/EIJV9SRA11"
                      "Revista" => array:7 [
                        "tituloSerie" => "EuroIntervention"
                        "fecha" => "2013"
                        "volumen" => "9"
                        "numero" => "R"
                        "paginaInicial" => "R58"
                        "paginaFinal" => "R66"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0735"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Hypertension&#58; Clinical management of primary hypertension in adults&#46; This guideline partially updates and replaces NICE clinical guideline 34"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2011"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0740"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Feasibility of catheter-based renal nerve ablation and effects on sympathetic nerve activity and blood pressure in patients with end-stage renal disease"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ijcard.2013.01.218"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Cardiol"
                        "fecha" => "2013"
                        "volumen" => "168"
                        "paginaInicial" => "2214"
                        "paginaFinal" => "2220"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0745"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rationale and design of a large registry on renal denervation&#58; the Global SYMPLICITY registry"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4244/EIJV9I4A78"
                      "Revista" => array:6 [
                        "tituloSerie" => "EuroIntervention"
                        "fecha" => "2013"
                        "volumen" => "9"
                        "paginaInicial" => "484"
                        "paginaFinal" => "492"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0750"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Desnerva&#231;&#227;o Renal para HTA Resistente&#58; Resultados Iniciais de um Registo Nacional"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Port Cardiol"
                        "fecha" => "2013"
                        "volumen" => "32"
                        "numero" => "Espec Congr"
                        "paginaInicial" => "12"
                        "paginaFinal" => "13"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0755"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efferent renal nerve traffic in the spontaneously hypertensive rat"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Hypertension A&#58; Theory Pract"
                        "fecha" => "1987"
                        "volumen" => "9"
                        "numero" => "Suppl 1"
                        "paginaInicial" => "259"
                        "paginaFinal" => "279"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0760"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal denervation attenuates the sodium retention and hypertension associated with obesity"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "1995"
                        "volumen" => "25"
                        "numero" => "4 Pt 2"
                        "paginaInicial" => "893"
                        "paginaFinal" => "897"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0765"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal afferent denervation prevents hypertension in rats with chronic renal failure"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "1995"
                        "volumen" => "25"
                        "numero" => "4 Pt 2"
                        "paginaInicial" => "878"
                        "paginaFinal" => "882"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0770"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal injury caused by intrarenal injection of phenol increases afferent and efferent renal sympathetic nerve activity"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hypertens"
                        "fecha" => "2002"
                        "volumen" => "15"
                        "paginaInicial" => "717"
                        "paginaFinal" => "724"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0775"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The surgical treatment of hypertension"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Adv Intern Med"
                        "fecha" => "1947"
                        "volumen" => "2"
                        "paginaInicial" => "173"
                        "paginaFinal" => "194"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0780"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The surgical treatment of hypertension with particular reference to adrenalectomy and sympathectomy"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Trans Am Coll Cardiol"
                        "fecha" => "1955"
                        "volumen" => "5"
                        "paginaInicial" => "107"
                        "paginaFinal" => "112"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0785"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Should sympathectomy for arterial hypertension be abandoned&#63; Review of surgical therapy at the Lahey Clinic&#58; 1950&#8211;1954"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Surg Clin N Am"
                        "fecha" => "1957"
                        "volumen" => "37"
                        "paginaInicial" => "871"
                        "paginaFinal" => "889"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0790"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal sympathetic denervation for treatment of drug-resistant hypertension&#58; one-year results from the Symplicity HTN-2 randomized&#44; controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.112.130880"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2012"
                        "volumen" => "126"
                        "paginaInicial" => "2976"
                        "paginaFinal" => "2982"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0795"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal sympathetic denervation in patients with treatment-resistant hypertension &#40;The Symplicity HTN-2 Trial&#41;&#58; a randomised controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(10)62039-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2010"
                        "volumen" => "376"
                        "paginaInicial" => "1903"
                        "paginaFinal" => "1909"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0800"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/HYPERTENSIONAHA.112.193870"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "2012"
                        "volumen" => "60"
                        "paginaInicial" => "419"
                        "paginaFinal" => "424"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0805"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Catheter-based renal denervation for resistant hypertension&#58; rationale and design of the SYMPLICITY HTN-3 Trial"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/clc.22008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Cardiol"
                        "fecha" => "2012"
                        "volumen" => "35"
                        "paginaInicial" => "528"
                        "paginaFinal" => "535"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0810"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A controlled trial of renal denervation for resistant hypertension"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1402670"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2014"
                        "volumen" => "370"
                        "paginaInicial" => "1393"
                        "paginaFinal" => "1401"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0815"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regression to the mean&#58; what it is and how to deal with it"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ije/dyh299"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Epidemiol"
                        "fecha" => "2005"
                        "volumen" => "34"
                        "paginaInicial" => "215"
                        "paginaFinal" => "220"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0820"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehi184"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2005"
                        "volumen" => "26"
                        "paginaInicial" => "906"
                        "paginaFinal" => "913"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0825"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal sympathetic denervation&#58; applications in hypertension and beyond"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrcardio.2013.89"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Cardiol"
                        "fecha" => "2013"
                        "volumen" => "10"
                        "paginaInicial" => "465"
                        "paginaFinal" => "476"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0830"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal denervation and heart failure"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Eur J Heart Fail"
                        "fecha" => "2014"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0835"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of renal denervation on postprandial sodium excretion in experimental heart failure"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Physiol"
                        "fecha" => "1994"
                        "volumen" => "266"
                        "numero" => "5 Pt 2"
                        "paginaInicial" => "R1599"
                        "paginaFinal" => "R1604"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0840"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dynamic arterial baroreflex in rabbits with heart failure induced by rapid pacing"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Physiol"
                        "fecha" => "1994"
                        "volumen" => "267"
                        "numero" => "1 Pt 2"
                        "paginaInicial" => "H92"
                        "paginaFinal" => "H99"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0845"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal denervation modulates angiotensin receptor expression in the renal cortex of rabbits with chronic heart failure"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajprenal.00088.2010"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Renal Physiol"
                        "fecha" => "2011"
                        "volumen" => "300"
                        "paginaInicial" => "F31"
                        "paginaFinal" => "F39"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0850"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension&#58; data from a multi-centre cardiovascular magnetic resonance imaging trial"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehu152"
                      "Revista" => array:3 [
                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2014"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib0855"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "First-in-man safety evaluation of renal denervation for chronic systolic heart failure&#58; primary outcome from REACH-Pilot study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ijcard.2012.09.019"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Cardiol"
                        "fecha" => "2013"
                        "volumen" => "162"
                        "paginaInicial" => "189"
                        "paginaFinal" => "192"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib0860"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The sympathetic nervous system and the metabolic syndrome"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/HJH.0b013e328048d004"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hypertens"
                        "fecha" => "2007"
                        "volumen" => "25"
                        "paginaInicial" => "909"
                        "paginaFinal" => "920"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            78 => array:3 [
              "identificador" => "bib0865"
              "etiqueta" => "79"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of type 2 diabetes mellitus on sympathetic neural mechanisms in hypertension"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/01.CIR.0000103123.66264.FE"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2003"
                        "volumen" => "108"
                        "paginaInicial" => "3097"
                        "paginaFinal" => "3101"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            79 => array:3 [
              "identificador" => "bib0870"
              "etiqueta" => "80"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension&#58; a pilot study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.110.991869"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2011"
                        "volumen" => "123"
                        "paginaInicial" => "1940"
                        "paginaFinal" => "1946"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            80 => array:3 [
              "identificador" => "bib0875"
              "etiqueta" => "81"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of renal sympathetic denervation on blood pressure&#44; sleep apnea course&#44; and glycemic control in patients with resistant hypertension and sleep apnea"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/HYPERTENSIONAHA.111.173799"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "2011"
                        "volumen" => "58"
                        "paginaInicial" => "559"
                        "paginaFinal" => "565"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            81 => array:3 [
              "identificador" => "bib0880"
              "etiqueta" => "82"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal sympathetic denervation suppresses postapneic blood pressure rises and atrial fibrillation in a model for sleep apnea"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/HYPERTENSIONAHA.112.191965"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "2012"
                        "volumen" => "60"
                        "paginaInicial" => "172"
                        "paginaFinal" => "178"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            82 => array:3 [
              "identificador" => "bib0885"
              "etiqueta" => "83"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of renal denervation on neurohumoral activation triggering atrial fibrillation in obstructive sleep apnea"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/HYPERTENSIONAHA.113.01728"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "2013"
                        "volumen" => "62"
                        "paginaInicial" => "767"
                        "paginaFinal" => "774"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            83 => array:3 [
              "identificador" => "bib0890"
              "etiqueta" => "84"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Negative tracheal pressure during obstructive respiratory events promotes atrial fibrillation by vagal activation"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.hrthm.2011.03.053"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart Rhythm"
                        "fecha" => "2011"
                        "volumen" => "8"
                        "paginaInicial" => "1436"
                        "paginaFinal" => "1443"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            84 => array:3 [
              "identificador" => "bib0895"
              "etiqueta" => "85"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal sympathetic denervation provides ventricular rate control but does not prevent atrial electrical remodeling during atrial fibrillation"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/HYPERTENSIONAHA.111.00182"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "2013"
                        "volumen" => "61"
                        "paginaInicial" => "225"
                        "paginaFinal" => "231"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            85 => array:3 [
              "identificador" => "bib0900"
              "etiqueta" => "86"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2012.05.036"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2012"
                        "volumen" => "60"
                        "paginaInicial" => "1163"
                        "paginaFinal" => "1170"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            86 => array:3 [
              "identificador" => "bib0905"
              "etiqueta" => "87"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal denervation suppresses ventricular arrhythmias during acute ventricular ischemia in pigs"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.hrthm.2013.07.015"
                      "Revista" => array:6 [
                        "tituloSerie" => "Heart Rhythm"
                        "fecha" => "2013"
                        "volumen" => "10"
                        "paginaInicial" => "1525"
                        "paginaFinal" => "1530"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            87 => array:3 [
              "identificador" => "bib0910"
              "etiqueta" => "88"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal sympathetic denervation for treatment of electrical storm&#58; first-in-man experience"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00392-011-0365-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Res Cardiol"
                        "fecha" => "2012"
                        "volumen" => "101"
                        "paginaInicial" => "63"
                        "paginaFinal" => "67"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            88 => array:3 [
              "identificador" => "bib0915"
              "etiqueta" => "89"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal sympathetic denervation as an adjunct to catheter ablation for the treatment of ventricular electrical storm in the setting of acute myocardial infarction"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "J Cardiovasc Electrophysiol"
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            89 => array:3 [
              "identificador" => "bib0920"
              "etiqueta" => "90"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rapid renal sympathetic denervation for resistant hypertension using the OneShot&#8482; Ablation System &#40;RAPID&#41; Study&#58; Primary Endpoint 6-Month Results"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:2 [
                        "fecha" => "2013"
                        "editorial" => "TCT"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            90 => array:3 [
              "identificador" => "bib0925"
              "etiqueta" => "91"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical evidence in catheter-based renal sympathetic denervation &#8211; building the data"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:2 [
                        "titulo" => "EuroPCR"
                        "serieFecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            91 => array:3 [
              "identificador" => "bib0930"
              "etiqueta" => "92"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early results of first-in-man simultaneous multisite renal denervation treatment for resistant hypertension"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            92 => array:3 [
              "identificador" => "bib0935"
              "etiqueta" => "93"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "ReCor Medical Paradise&#58; first-in-man results of a novel circumferential catheter-based ultrasound technology for renal denervation"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2012"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            93 => array:3 [
              "identificador" => "bib0940"
              "etiqueta" => "94"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical Trial&#58; Preliminary results demonstrate catheter based ultrasound renal denervation is associated with a decrease in sympathetic activity"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2014"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            94 => array:3 [
              "identificador" => "bib0945"
              "etiqueta" => "95"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "RENABLATE I Feasibility Study&#58; 3 months results"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2014"
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/21742049/0000003400000002/v2_201502270337/S2174204915000343/v2_201502270337/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "9924"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Review Article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/21742049/0000003400000002/v2_201502270337/S2174204915000343/v2_201502270337/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204915000343?idApp=UINPBA00004E"
]

Article information

ISSN: 21742049
Original language: English

DOI:10.1016/j.repce.2014.07.009

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	4	4	8
2024 October	38	31	69
2024 September	29	29	58
2024 August	32	27	59
2024 July	30	32	62
2024 June	22	21	43
2024 May	30	21	51
2024 April	29	26	55
2024 March	20	16	36
2024 February	19	18	37
2024 January	19	29	48
2023 December	18	26	44
2023 November	28	22	50
2023 October	19	20	39
2023 September	23	23	46
2023 August	14	14	28
2023 July	19	6	25
2023 June	21	15	36
2023 May	31	24	55
2023 April	12	4	16
2023 March	18	20	38
2023 February	27	21	48
2023 January	16	11	27
2022 December	28	20	48
2022 November	33	25	58
2022 October	26	22	48
2022 September	25	37	62
2022 August	31	34	65
2022 July	28	25	53
2022 June	24	18	42
2022 May	20	36	56
2022 April	21	15	36
2022 March	27	37	64
2022 February	17	19	36
2022 January	20	24	44
2021 December	20	25	45
2021 November	23	29	52
2021 October	30	37	67
2021 September	20	25	45
2021 August	25	27	52
2021 July	30	31	61
2021 June	21	22	43
2021 May	26	26	52
2021 April	18	14	32
2021 March	39	17	56
2021 February	39	12	51
2021 January	21	13	34
2020 December	40	6	46
2020 November	22	11	33
2020 October	12	11	23
2020 September	46	1	47
2020 August	26	8	34
2020 July	44	11	55
2020 June	18	4	22
2020 May	32	6	38
2020 April	31	2	33
2020 March	31	9	40
2020 February	39	11	50
2020 January	19	10	29
2019 December	30	4	34
2019 November	22	16	38
2019 October	24	4	28
2019 September	27	6	33
2019 August	22	4	26
2019 July	34	11	45
2019 June	20	7	27
2019 May	28	6	34
2019 April	27	10	37
2019 March	19	9	28
2019 February	25	13	38
2019 January	10	2	12
2018 December	36	12	48
2018 November	150	7	157
2018 October	545	14	559
2018 September	172	15	187
2018 August	151	11	162
2018 July	21	5	26
2018 June	34	9	43
2018 May	39	7	46
2018 April	36	5	41
2018 March	28	7	35
2018 February	28	7	35
2018 January	31	7	38
2017 December	56	11	67
2017 November	42	11	53
2017 October	43	20	63
2017 September	38	14	52
2017 August	40	22	62
2017 July	30	27	57
2017 June	39	27	66
2017 May	35	16	51
2017 April	60	5	65
2017 March	41	15	56
2017 February	26	5	31
2017 January	18	6	24
2016 December	33	13	46
2016 November	19	4	23
2016 October	29	8	37
2016 September	15	6	21
2016 August	4	3	7
2016 July	22	8	30
2016 June	15	3	18
2016 May	16	3	19
2016 April	16	2	18
2016 March	31	17	48
2016 February	39	22	61
2016 January	25	21	46
2015 December	35	14	49
2015 November	25	12	37
2015 October	29	15	44
2015 September	30	8	38
2015 August	30	7	37
2015 July	21	4	25
2015 June	23	6	29
2015 May	42	10	52
2015 April	27	10	37
2015 March	43	14	57
2015 February	1	1	2

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter