Renal denervation in the treatment of resistant hypertension: Dead, alive or surviving? | Revista Portuguesa de Cardiologia (English edition)

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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "531" "paginaFinal" => "538" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Ahmad Al-Fakhouri, Nephertiti Efeovbokhan, Rami Nakhla, Rami N. Khouzam" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Ahmad" "apellidos" => "Al-Fakhouri" "email" => array:1 [ 0 => "fakhouri_md@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Nephertiti" "apellidos" => "Efeovbokhan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Rami" "apellidos" => "Nakhla" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Rami N." "apellidos" => "Khouzam" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Medicine, Methodist South Hospital, Memphis, TN, United States" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Medicine, Division of Cardiovascular Diseases, University of Tennessee Health Science Center, Memphis, TN, United States" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Ain Shams University School of Medicine, Cairo, Egypt" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Desnervação renal no tratamento da hipertensão arterial resistente: morta, viva ou sobrevivendo?" ] ] "textoCompleto" => "IntroductionHypertension is one of the most common chronic clinical problems encountered by physicians. Resistant hypertension is defined as systolic blood pressure (BP) ≥160 mmHg or (≥150 mmHg in patients with type 2 diabetes mellitus) refractory to medical treatment despite the use of optimal doses of three or more different drug types including a diuretic.<a class="elsevierStyleCrossRef" href="#bib0240">1</a> The prevalence of resistant hypertension is estimated at 9% in the US.<a class="elsevierStyleCrossRef" href="#bib0245">2</a> In a study of 205750 treated hypertensive patients, 1 in 50 developed resistant hypertension within a median of 1.5 years from the initial treatment.<a class="elsevierStyleCrossRef" href="#bib0250">3</a> In the same study, patients with resistant hypertension were shown to be at higher risk for adverse cardiovascular events.<a class="elsevierStyleCrossRef" href="#bib0250">3</a> The increased morbidity and mortality associated with this condition supports greater efforts to improve treatment options.Historical perspectiveAfter a link was established between the sympathetic nervous system and the development of resistant hypertension, surgical sympathectomy was introduced in the 1930s, but was abandoned shortly afterwards due to multiple side effects such as postural hypotension, tachycardia, bladder, bowel and erectile dysfunction, and high periprocedural mortality.<a class="elsevierStyleCrossRef" href="#bib0255">4</a> The proximity of the afferent and efferent renal sympathetic nerves to the adventitia of the renal arteries suggested the feasibility of an endovascular, selective, minimally invasive approach to renal denervation (RDN). In the endovascular approach, a treatment catheter is introduced through a guiding catheter into the renal arteries. The catheter is placed in close proximity to the vessel wall to ensure stable contact. Low-energy radiofrequency ablations are then applied moving the catheter from distal to proximal locations in the renal arteries.<a class="elsevierStyleCrossRef" href="#bib0260">5</a>Anatomical and physiological effects of renal denervationThe renal nerves arise from T10-L2 and follow the course of the renal artery lying in the adventitia. Renal sympathetic nerves play an important role in the development of hypertension, mediated via sodium and water retention, increased renin release, and alterations in renal blood flow.<a class="elsevierStyleCrossRef" href="#bib0260">5</a>Experimental studies established the important concept that sub-vasoconstrictor levels of renal sympathetic activity can increase renin secretion and renal sodium retention without changing renal hemodynamics.<a class="elsevierStyleCrossRef" href="#bib0265">6</a> Assessment of regional overflow of norepinephrine (NE) from the kidneys to plasma has demonstrated that renal NE spillover rates can be markedly elevated in patients with essential hypertension and are associated with hypertensive end-organ damage.<a class="elsevierStyleCrossRefs" href="#bib0260">5,31</a> Measurement of NE excretion in the urine, now largely obsolete, was performed in order to quantify sympathetic nervous system activity in humans.<a class="elsevierStyleCrossRef" href="#bib0265">6</a> In the light of these findings, RDN therapy was considered a logical therapeutic approach in the treatment of hypertension.The sympathetic nervous system and cardiovascular disease<a class="elsevierStyleCrossRef" href="#bib0270">7</a>Surgical sympathectomy was first introduced in the 1930s and was effective in lowering high BP in patients with severe hypertension.<a class="elsevierStyleCrossRefs" href="#bib0275">8,9</a> However, the side effects associated with the procedure and the introduction of ganglionic blockers made it obsolete.<a class="elsevierStyleCrossRef" href="#bib0285">10</a> For a long time, it was difficult to study and assess the role of the sympathetic nervous system (SNS) in the pathogenesis of hypertension, due not to uncertainty concerning the relation between the two, but rather to the difficulty of testing and assessing that relation. Previous techniques included the measurement of serum and urinary excretion of NE and its derivatives, yielding a rough estimate of SNS activity in the whole body.<a class="elsevierStyleCrossRef" href="#bib0290">11</a> Hagbarth and Vallbo reported microneurography as a newer tool to study SNS nerve firing in subcutaneous tissues and skeletal muscles.<a class="elsevierStyleCrossRef" href="#bib0295">12</a> The NE spillover technique was first used by Esler et al.,<a class="elsevierStyleCrossRef" href="#bib0300">13</a> measuring organ-specific NE release in its efferent veins as an indirect measurement of SNS nerve fiber firing in an individual organ,<a class="elsevierStyleCrossRef" href="#bib0305">14</a> and that technique was later used to demonstrate that heart failure caused SNS overactivity.<a class="elsevierStyleCrossRef" href="#bib0310">15</a> Accumulated evidence underlines the role of sustained chronic SNS activity in many diseases including ischemic heart disease,<a class="elsevierStyleCrossRef" href="#bib0315">16</a> heart failure,<a class="elsevierStyleCrossRefs" href="#bib0320">17,18</a> hypertension,<a class="elsevierStyleCrossRefs" href="#bib0330">19–21</a> kidney disease,<a class="elsevierStyleCrossRef" href="#bib0345">22</a> type 2 diabetes,<a class="elsevierStyleCrossRef" href="#bib0350">23</a> obesity,<a class="elsevierStyleCrossRef" href="#bib0350">23</a> metabolic syndrome,<a class="elsevierStyleCrossRef" href="#bib0350">23</a> obstructive sleep apnea,<a class="elsevierStyleCrossRef" href="#bib0355">24</a> depression,<a class="elsevierStyleCrossRef" href="#bib0360">25</a> and inflammatory bowel disease.<a class="elsevierStyleCrossRef" href="#bib0365">26</a>In the cardiovascular system, chronic SNS activation not only raises BP but also causes hypertrophy and proliferation of vascular smooth muscle cells and cardiac myocytes, thus increasing LV mass and wall thickness.<a class="elsevierStyleCrossRef" href="#bib0370">27</a> In addition, increased SNS activity, in the presence of endothelial dysfunction and endothelial cell damage, has been shown to contribute to the development of atherosclerosis.<a class="elsevierStyleCrossRefs" href="#bib0360">25,27,29</a> Contradicting previous assumptions, high levels of NE spillover from the heart in heart failure<a class="elsevierStyleCrossRef" href="#bib0375">28</a> demonstrated increased sympathetic activity in the failing heart, which was the rationale for the subsequent use of beta-blockers in heart failure.<a class="elsevierStyleCrossRef" href="#bib0380">29</a> In essential hypertension, SNS outflow to the kidneys is elevated and is directly proportional to the severity of hypertension.<a class="elsevierStyleCrossRefs" href="#bib0330">19,21,25</a> This finding is also supported by regional measurements of NE spillover to the kidneys.<a class="elsevierStyleCrossRef" href="#bib0385">30</a> Renal sympathetic activity is a major factor contributing to the pathogenesis of essential hypertension through its influence on activation of the renin-angiotensin system, sodium and water excretion, peripheral vasoconstriction, cardiac contraction, and venous capacitance.<a class="elsevierStyleCrossRef" href="#bib0360">25</a> The recent introduction of safe and efficient methods for RDN has led to a renewed interest in the role of SNS activation in essential hypertension.Evidence of the efficacy of renal denervation in the treatment of resistant hypertensionThe Rapid Renal Sympathetic Denervation for Resistant Hypertension Using the OneShot™ Ablation System (RAPID) study<a class="elsevierStyleCrossRef" href="#bib0395">32</a> was a prospective, multicenter, non-randomized, single-arm trial that included 50 patients with mean office BP of 181±20.8/95±15.5 mmHg, on a mean of five antihypertensive medications, who received RDN. The primary endpoint studied was the rate of office systolic BP (SBP) reduction: ≥10 mmHg at six months in comparison to baseline. Change in 24-hour ambulatory BP (ABP) was also evaluated. At the six-month mark, there was a decrease in mean office BP of -20/-8 mmHg (p<0.0001/p=0.0002) in comparison to baseline. This trend was sustained at 12 months, with a decrease in mean office BP of -22/-8 mmHg (p<0.0001/p=0.0014). Likewise, there was a significant reduction in 24-hour ABP, of -11/-6 mmHg at six months in comparison to baseline (p=0.0085/p=0.037). At 12 months, the reduction in 24-hour ABP was -9/-5 mmHg (p=0.054/p=0.073). Device- and/or procedure-related adverse effects occurred in three patients up to 12 months, namely one access site infection, one renal artery stenosis, and one groin paresthesia. The authors concluded that RDN led to significant and sustained reductions in office and 24-hour ambulatory BP at six and 12 months, respectively.The REDUCE-HTN study<a class="elsevierStyleCrossRef" href="#bib0400">33</a> was a prospective, non-randomized, single-arm trial that included 146 patients with mean baseline office and ambulatory BP of 182±18.4/100±14.0 and 153±15.1/87±13.2 mmHg, respectively, who received RDN using the Vessix renal denervation system. The primary efficacy endpoints were reductions in office and 24-hour ambulatory SBP and diastolic blood pressure (DBP) at six months, which were 24.7±22.1/10.3±12.7 mmHg (p<0.0001) and 8.4±14.4/5.9±9.1 mmHg (p<0.0001), respectively. Regarding the safety endpoints, no acute renal injury requiring acute renal intervention occurred and only one patient developed renal artery stenosis that required a stent. In addition, mean glomerular filtration rate remained stable. The authors concluded that renal artery denervation reduced both office and ambulatory BP at six months in patients with resistant hypertension.The EnligHTN I study<a class="elsevierStyleCrossRef" href="#bib0405">34</a> was a prospective, non-randomized trial that included 46 patients with mean baseline office, 24-hour ambulatory and home BP of 176/96, 150/83 and 158/90 mmHg, respectively, who underwent RDN using the EnligHTN multielectrode radiofrequency ablation system. The primary efficacy endpoint was change in office BP in comparison to baseline. The mean reductions in office BP at 1, 3, 6, and 12 months were -28/-10, -27/-10, -26/-10, and -27/-11 mmHg, respectively (p<0.001 for all). Likewise, mean reductions in 24-hour ABP were -10/-5, -10/-5, and -10/-6 mmHg at 1, 3, 6 months (p<0.001 for all), and -7/-4 mmHg at 12 months (p<0.0094). Mean reductions in home measurements were -9/-4, -8/-5, -10/-7, and -11/-6 mmHg (p<0.001 at 12 months). There were no signs of worsening renal function at 12 months. One patient required renal artery stenting (non-occlusive renal stenosis was present at baseline). The authors concluded that the EnligHTN ablation system was safe and effective in reducing office, 24-ambulatory and home BP in patients with resistant hypertension.Oslo RDN<a class="elsevierStyleCrossRef" href="#bib0410">35</a> was a prospective randomized trial in which 19 patients with true treatment-resistant hypertension were randomized to RDN (n=9) performed with the Symplicity Catheter System vs. clinically adjusted drug treatment (n=10). True treatment-resistant hypertension was confirmed after excluding patients with confounding poor drug adherence. The primary endpoint was change in office systolic blood pressure (SBP) from randomization to six months. The study was stopped early as RDN had uncertain BP-lowering effects. At six months, office SBP and DBP changed significantly from 160±14/88±13 mmHg to 132±10/77±8 mmHg compared to baseline in the drug-adjusted group (p<0.0005 and p=0.02), whereas in the RDN group there was no significant change in office SBP and DBP at six months compared to baseline (156±13/91±15 to 148±7/89±8 mmHg, p=0.42 and p=0.48). SBP and DBP were significantly lower in the drug-adjusted group at six months (p=0.002 and p=0.004, respectively), and absolute changes in SBP were larger in the drug-adjusted group (p=0.008). ABP changed in parallel to office BP. The authors concluded that the BP-lowering effect of adjusted drug treatment were superior to that of RDN in patients with true treatment-resistant hypertension.The Prague-15 study<a class="elsevierStyleCrossRef" href="#bib0415">36</a> was a prospective, open-label multicenter trial in which 106 patients with resistant hypertension were randomized to RDN (n=52) or intensified pharmacological treatment (n=54). RDN was performed using the Symplicity Renal Denervation System. At six months, a comparable significant reduction in mean 24-hour SBP was noted in both groups, of -8.6 mmHg (95% confidence interval [CI]: -11.8, -5.3); p<0.001 in RDN, vs. -8.1 (95% CI: -12.7, -3.4) mmHg in the pharmacological group. Likewise, a significant reduction in office SBP was observed in both groups mmHg (-12.4 [95% CI: -17.0, -7.8]; p<0.001 in RDN vs. -14.3 mmHg [95% CI: -19.7, -8.9]; p<0.001 in the pharmacological group). The authors concluded that RDN was safe; however in the setting of true resistant hypertension with confirmed compliance, it was not proved superior to intensified pharmacological treatment.The DENERHTN trial<a class="elsevierStyleCrossRef" href="#bib0420">37</a> was a prospective, open-label randomized controlled trial that assigned 106 patients to receive either RDN plus a standardized stepped-care antihypertensive treatment (SSAHT) regimen (RDN group, n=53) or SSAHT alone (control group, n=53). Prior to randomization, treatment resistance was confirmed by ABP monitoring after patients received oral antihypertensives for a period of four weeks. The primary endpoint studied was the mean change in daytime SBP from baseline to six months as assessed by ambulatory BP monitoring. The safety outcomes were the incidence of acute adverse events of the RDN procedure and the change in estimated glomerular filtration rate from baseline to six months. At six months, the mean change in daytime ambulatory SBP was -15.8 mmHg (95% CI -19.7 to -11.9) in the RDN group and -9.9 mmHg (-13.6 to -6.2) in the group receiving SSAHT alone, a baseline-adjusted difference of -5.9 mmHg (-11.3 to -0.5; p=0.0329). The numbers of antihypertensive drugs and drug adherence at six months were similar between the two groups. Three minor RDN-related adverse events were noted (lumbar pain in two patients and mild groin hematoma in one patient). The authors concluded that RDN plus SSAHT decreases ambulatory BP more than the same SSAHT alone at six months in patients with well-defined resistant hypertension.The Symplicity HTN studiesThe Symplicity HTN-1 study<a class="elsevierStyleCrossRef" href="#bib0425">38</a> was a proof-of-principle trial of therapeutic renal sympathetic denervation. The trial included 50 patients with resistant hypertension who received percutaneous radiofrequency catheter-based RDN using the Symplicity catheter, with a one-year follow-up post procedure. The primary endpoints were office BP and safety data before and at 1, 3, 6, 9, and 12 months after procedure. Out of the 50 patients enrolled, five were excluded for anatomical reasons. Treated patients were on a mean of 4.7 antihypertensive medications, with baseline mean office BP of 177/101 mmHg. Office BP readings after the procedure were reduced by -14/-10, -21/-10, -22/-11, -24/-11, and -27/-17 mmHg at 1, 3, 6, 9, and 12 months, respectively. In the five non-treated patients, mean rise in office BP was +3/-2, +2/+3, +14/+9, and +26/+17 mmHg at 1, 3, 6, and 9 months, respectively. The only reported complication was one intraprocedural renal artery dissection which occurred before radiofrequency energy delivery. The authors concluded that catheter-based RDN leads to substantial and sustained BP reduction, without serious adverse events, in patients with resistant hypertension.Following the success achieved in the Symplicity HTN-1 trial, the Symplicity HTN-2 trial<a class="elsevierStyleCrossRef" href="#bib0430">39</a> was designed to assess the effectiveness and safety of catheter-based RDN for BP reduction in patients with treatment-resistant hypertension. A total of 106 patients with resistant hypertension were randomly assigned to either RDN with medical treatment (treatment arm, n=52) or medical treatment alone (control arm, n=54). The primary endpoint of the study was change in office-based measurement of SBP at six months. At six months, there was a significant reduction in office-based BP measurements in the treatment arm (change of 32/12 mmHg, standard deviation [SD] 23/11, baseline of 178/96 mmHg), compared to the control arm (change of 1/0 mmHg, SD 21/10, baseline of 178/97 mmHg). Between-group differences in BP at six months were 33/11 mmHg (p<0.0001). Additionally, at six months, 41 (84%) out of 49 patients in the treatment arm had a reduction in SBP of 10 mmHg or more, compared with 18 (35%) of 51 controls (p<0.0001). No serious procedural complications were noted. The authors concluded that catheter-based RDN can safely be used to substantially reduce BP in treatment-resistant hypertensive patients. Follow-up at 36 months in 40 of the 52 patients in the initial RDN group and at 30 months in 30 of 37 patients who crossed over and received RDN at six months<a class="elsevierStyleCrossRef" href="#bib0435">40</a> showed that SBP decreased by 34 mmHg (95% CI: -40, -27, p<0.01) and DBP decreased by 13 mmHg (95% CI: -16, -10, p<0.01) from a baseline of 184±19/99±16 mmHg. SBP and DBP reductions at 36 months for the initial RDN group was -33 mmHg (95% CI: -40, -25, p<0.01) and -14 mmHg (95% CI: -17, -10, p<0.01), respectively.In an attempt to further explore the robustness of RDN in the treatment of resistant hypertension, the Symplicity HTN-3 trial<a class="elsevierStyleCrossRef" href="#bib0440">41</a> was conducted. Unlike the previous two studies, blinding and sham-control were added in the design of this trial. A total of 535 patients with severe resistant hypertension receiving a stable antihypertensive regimen involving maximally tolerated doses of at least three drugs including a diuretic were randomly assigned in a 2:1 ratio to undergo RDN (n=364) or a sham procedure (n=171).The primary efficacy endpoint, change in office SBP at six months, was not significantly different between the two groups (-14.13±23.93 mmHg in the denervation group compared to -11.74±25.94 mmHg in the sham-procedure group [p<0.001 for both comparisons of the change from baseline], a difference of -2.39 mmHg [95% CI: -6.89 to 2.12; p=0.26 for superiority with a margin of 5 mm Hg]). Likewise, for the secondary efficacy endpoint, the change in mean 24-hour ambulatory SBP, no between-group differences were noted -6.75±15.11 mmHg in the denervation group and -4.79±17.25 mmHg in the sham-procedure group, for a difference of -1.96 mmHg (95% CI: -4.97 to 1.06; p=0.98 for superiority with a margin of 2 mmHg). The primary safety endpoint (a composite of death, end-stage renal disease, an embolic event resulting in end-organ damage, renovascular complications, or hypertensive crisis within 30 days or new renal-artery stenosis of more than 70% within six months) was not significantly different between the two groups. The authors concluded that their blinded trial did not show a significant reduction of SBP in patients with resistant hypertension six months after renal-artery denervation compared with a sham control.<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows a summary of trials of RDN.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>DiscussionThe role of RDN in the treatment of resistant hypertension is still to be fully clarified. While the results of the RAPID, REDUCE-HTN, EnligHTN, Symplicity HTN-1 and -2, and DENERHTN trials were positive, this was not the case in the Oslo RDN, Prague-15 and Symplicity HTN-3 trials. The varying results may be explained by several factors. Symplicity HTN-3, the largest trial to date, was also the only one that included a sham-control group. As shown by Meissner et al.,<a class="elsevierStyleCrossRef" href="#bib0465">46</a> sham procedures may be associated with a significant positive response – the placebo effect – that could be misinterpreted as a real treatment effect. Kandzari et al.<a class="elsevierStyleCrossRef" href="#bib0445">42</a> investigated potential reasons for the discordant results noted in Symplicity HTN-3. Their findings showed that between randomization and the six-month endpoint, 39% of patients underwent medication changes involving alteration in both the dose and class of prescribed medications. In addition, African-Americans were more likely to be prescribed vasodilators than non-African-Americans in both study arms. A total of 56% of African-American sham patients and 46.7% of African-American RDN patients were receiving a vasodilator, compared to 40.5% of non-African-American sham control patients and 33.7% of non-African-American RDN patients who were receiving a vasodilator at baseline. African-Americans in the sham control study arm receiving a vasodilator showed an enormous decline in SBP (-21.9+29.1 mmHg), which was not noted in the other subgroups. This unexpectedly large SBP decline in African-American control patients may indicate a change in medical adherence or type of therapy in this specific group. Likewise, increasing number of ablations and energy delivery in a four-quadrant pattern was associated with greater reductions in office and ambulatory SBP and heart rate.The ablation catheters used in the above studies had some design features that are worthy of mention. The EnligHTN denervation system is a unique multielectrode catheter that allows a predictable pattern of four simultaneous ablations. The Vessix denervation system used in the REDUCE-HTN trial delivered bipolar radiofrequency energy as opposed to the monopolar radiofrequency energy delivered by the Symplicity denervation system (used in the Symplicity HTN studies). As suggested by Kandazari et al.,<a class="elsevierStyleCrossRef" href="#bib0445">42</a> differences in ablation energy may affect the efficacy of denervation therapy.The futureSeveral trials are underway to investigate the role of RDN in specific patient populations such as those with chronic renal disease and moderate hypertension.<a class="elsevierStyleCrossRefs" href="#bib0450">43–45</a>The SPYRAL HTN Global Clinical Trial Program<a class="elsevierStyleCrossRef" href="#bib0470">47</a> is a phased series of clinical trials designed to establish the efficacy of RDN therapy in patients with hypertension. The SPYRAL HTN-OFF MED trial aims to confirm the basic hypothesis that RDN therapy lowers BP in patients with hypertension without treatment, while the parallel SPYRAL HTN-ON MED trial is designed to assess the efficacy of RDN integrated with antihypertensive medications.ConclusionsThe results of the RAPID, REDUCE-HTN, EnligHTN, Symplicity HTN-1 and -2, and DENERHTN trials suggested an important role for RDN in the treatment of resistant hypertension. The results of the Oslo RDN, Prague-15 and Symplicity HTN-3 suggested differently. Of note, all these studies showing favorable benefits of RDN were either non-randomized single-arm trials or randomized unblinded trials without a sham control group. As shown by Meissner et al.,<a class="elsevierStyleCrossRef" href="#bib0465">46</a> sham procedures may be associated with a significant positive response – the placebo effect – that could be misinterpreted as a real treatment effect. Symplicity HTN-3, a well-designed randomized, blinded, sham control trial, casts doubt on the benefits of RDN in the treatment of resistant hypertension. The results of the Symplicity HTN-3 emphasize the need always to assess for a potential placebo effect by including sham control study groups when assessing the efficacy of new devices. In addition, future studies should ensure consistent medical therapy and delivery of radiofrequency ablation across treatment arms, as post-hoc analysis showed these differences to be important in the neutral results noted in Symplicity HTN-3.Currently, the role of RDN in addition to medical therapy in the treatment of resistant hypertension is still to be fully clarified. Nevertheless, RDN is certainly not dead, but further well-designed clinical trials are needed to ascertain the benefits or otherwise of RDN in treatment-resistant hypertension.Conflicts of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres740736" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec744948" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres740737" "titulo" => "Resumo" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec744947" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Historical perspective" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Anatomical and physiological effects of renal denervation" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "The sympathetic nervous system and cardiovascular disease" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Evidence of the efficacy of renal denervation in the treatment of resistant hypertension" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "The Symplicity HTN studies" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "The future" ] 12 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusions" ] 13 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of interest" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-12-26" "fechaAceptado" => "2016-06-06" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec744948" "palabras" => array:4 [ 0 => "Hypertension" 1 => "Resistant hypertension" 2 => "Renal denervation" 3 => "Sympathetic nervous system" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec744947" "palabras" => array:4 [ 0 => "Hipertensão" 1 => "Hipertensão arterial resistente" 2 => "Desnervação renal" 3 => "Sistema nervoso simpático" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Hypertension is one of the most common chronic clinical problems encountered by physicians. The prevalence of resistant hypertension is estimated at 9% in the US. Patients with resistant hypertension have been shown to be at higher risk for adverse cardiovascular events, hence the need for greater efforts in improving the treatment of hypertension. The renal sympathetic nerves play an important role in the development of hypertension, mediated via sodium and water retention, increased renin release and alterations in renal blood flow. The proximity of the afferent and efferent renal sympathetic nerves to the adventitia of the renal arteries suggested the feasibility of an endovascular, selective, minimally invasive approach to renal denervation; a potential treatment option for resistant hypertension. While the RAPID, Reduce-HTN, EnligHTN, DENERHTN and Symplicity HTN-1 and -2 studies showed significant benefit of renal denervation in the treatment of resistant hypertension, the results of Oslo RDN, Prague-15 and Symplicity HTN-3 were not so favorable. Future well-designed clinical trials are needed to ascertain the benefits or otherwise of renal denervation in treatment-resistant hypertension." ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "A hipertensão arterial é um dos problemas clínicos crónicos mais frequentes. Nos EUA a prevalência de hipertensão arterial resistente está estimada em 9%. Os doentes com hipertensão resistente têm um maior risco de eventos cardiovasculares adversos, o que justifica maiores esforços na melhoria do tratamento da hipertensão. A inervação simpática renal tem um papel importante no desenvolvimento da hipertensão, mediada através da retenção de sódio e água, com aumento da libertação de renina e de alterações do fluxo sanguíneo renal. A anatomia da inervação simpática renal, com os seus nervos aferentes e eferentes em relação de proximidade com a adventícia, permite uma abordagem endovascular, seletiva e minimamente invasiva para a desnervação renal, e constitui uma opção de tratamento potencial para a hipertensão arterial resistente. Enquanto os estudos RAPID, Reduce-HTN, EngliHTN, DENERHTN e Simplicity HTN 1,2 mostraram um benefício significativo da desnervação renal no tratamento da hipertensão arterial resistente, os resultados dos estudos Oslo-RDN, Prague-15 e Simplicity HTN 3 não foram tão favoráveis. Serão necessários ensaios clínicos bem estruturados para confirmar ou infirmar os potenciais benefícios da desnervação renal no tratamento da hipertensão arterial resistente." ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ABPM: ambulatory blood pressure monitoring; AH: antihypertensive; BP: blood pressure; eGFR: estimated glomerular filtration rate; N/A: not applicable; RDN: renal denervation; RF: radiofrequency; SSAHT: standardized stepped-care antihypertensive treatment; SD: standard deviation." "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 name/year of publication \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">Study design \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">Baseline office and ambulatory BP (mmHg) \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">Mean no. of AH drugs \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">% of patients under aldosterone antagonists \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">Ablation catheter \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">Study description \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">Study endpoints \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">Main findings \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RAPID/2014<a class="elsevierStyleCrossRef" href="#bib0395">32</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prospective, multicenter, single arm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Baseline office 181.6±20.8/95.5±15.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OneShot™ RF balloon catheter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50 patients enrolled to receive percutaneous RF renal nerve ablation. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary endpoint: rate of office SBP reduction ≥10 mmHg at 6 months in comparison to baseline. Change in 24-hour ambulatory BP was also evaluated. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Significant reduction in office and ambulatory BP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">REDUCE-HTN/2014<a class="elsevierStyleCrossRef" href="#bib0400">33</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prospective, non-randomized, single arm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Baseline office 182±18.4/100±14.0; baseline ambulatory 153±15.1/87±13.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vessix RF catheter (Boston Scientific) Bipolar RF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">146 patients enrolled to receive percutaneous RF renal nerve ablation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary efficacy endpoints: reductions in office and 24-hour ambulatory SBP and DBP at six months. Acute and long-term safety, with a focus on the renal artery and eGFR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Significant reduction in office and ambulatory BP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EnligHTN/2014<a class="elsevierStyleCrossRef" href="#bib0405">34</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prospective, non-randomized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Baseline office 176/96; baseline ambulatory 150/83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.7±1.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">EnligHTN multielectrode RF catheter (St. Jude Medical) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46 patients enrolled to receive percutaneous RF renal nerve ablation using a multielectrode system \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary efficacy endpoint: office BP change from baseline. Primary safety objective: the rate of adverse events. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Significant reductions in office, ambulatory and home BP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oslo RDN/2014<a class="elsevierStyleCrossRef" href="#bib0410">35</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prospective, randomized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Baseline office 156/91; baseline ambulatory 152/93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Symplicity single-electrode RF catheter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 patients randomly assigned to RDN (9) or clinically adjusted drug treatment (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary end-point: change in office SBP from randomization to 6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Significant reduction in office SBP in patients assigned to clinically adjusted drug treatment; no change in those assigned to RDN \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prague-15/2015<a class="elsevierStyleCrossRef" href="#bib0415">36</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prospective, randomized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Baseline office 159±19/92±14; baseline ambulatory 149±12/86±10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.1±1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Symplicity single-electrode RF catheter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">106 patients randomly assigned to RDN (52) or intensified pharmacotherapy (54) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Efficacy of RDN assessed by 24-hour ABPM and office BP at 6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Significant reduction in 24-hour ambulatory and office BP in both groups, with no differences between groups \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DENERHTN/ 2015<a class="elsevierStyleCrossRef" href="#bib0420">37</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prospective, randomized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Symplicity RF catheter (Medtronic) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">106 patients randomly assigned to RDN + SSAHT (53) or SSAHT alone (53) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary end-point: change in daytime SBP assessed by ambulatory BPM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Significant reduction in daytime SBP in patients assigned to RDN + SSSAHT as compared to SSAHT alone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Symplicity HTN-1/2009<a class="elsevierStyleCrossRef" href="#bib0425">38</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prospective, non-randomized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Baseline office 177/101 (SD 20/15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Symplicity single-electrode RF catheter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50 patients enrolled to receive percutaneous RF renal nerve ablation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary endpoint: change in office BP at 1, 3, 6, 9, and 12 months after procedure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Significant reduction in office BP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Symplicity HTN-2/2010<a class="elsevierStyleCrossRefs" href="#bib0430">39,40</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prospective, randomized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Baseline office 178±18/97±16 \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">19% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Symplicity single-electrode RF catheter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">106 patients randomly assigned to RDN (52) or medical treatment (54) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary endpoint: change in office-based measurement of SBP at 6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Significant reduction in office BP in patients treated with RDN compared with those treated with medical therapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Symplicity HTN-3/2014<a class="elsevierStyleCrossRef" href="#bib0440">41</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prospective, randomized, blinded, sham-controlled \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \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">22.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Symplicity single-electrode RF catheter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">535 patients randomly assigned to undergo RDN (364) or sham procedure (171) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary endpoint: change in office BP at 6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No significant difference in office BP between the two groups \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1224413.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Summary of trials of renal denervation." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:47 [ 0 => array:3 [ "identificador" => "bib0240" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2007 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 [ 0 => "G. Mancia" 1 => "G. De Backer" 2 => "A. Dominiczak" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/HJH.0b013e3281fc975a" "Revista" => array:7 [ "tituloSerie" => "J Hypertens" "fecha" => "2007" "volumen" => "25" "paginaInicial" => "1105" "paginaFinal" => "1187" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17563527" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109705025027" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0245" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of resistant hypertension in the United States, 2003-2008" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S.D. Persell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.111.170308" "Revista" => array:7 [ "tituloSerie" => "Hypertension" "fecha" => "2011" "volumen" => "57" "paginaInicial" => "1076" "paginaFinal" => "1080" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21502568" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109707011345" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0250" "etiqueta" => "3" "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 [ 0 => "S.L. Daugherty" 1 => "J.D. Powers" 2 => "D.J. Magid" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22379110" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0255" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sympathectomy in the treatment of hypertension: review of 122 cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.M. Morrissey" 1 => "V.S. Brookes" 2 => "W.T. Cooke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2215-0366(14)00003-0" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1953" "volumen" => "1" "paginaInicial" => "403" "paginaFinal" => "408" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26361179" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0260" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "International expert consensus statement: percutaneous transluminal renal denervation for the treatment of resistant hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.P. Schlaich" 1 => "R.E. Schmieder" 2 => "G. Bakris" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2013.08.1616" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2013" "volumen" => "62" "paginaInicial" => "2031" "paginaFinal" => "2045" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24021387" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0265" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The human sympathetic nervous system: its relevance in hypertension and heart failure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G1. Parati" 1 => "M. Esler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehs041" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2012" "volumen" => "33" "paginaInicial" => "1058" "paginaFinal" => "1066" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22507981" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0270" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal denervation for resistant hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. de Sousa Almeida" 1 => "P. de Araújo Gonçalves" 2 => "E. Infante de Oliveira" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.repc.2014.07.011" "Revista" => array:6 [ "tituloSerie" => "Rev Port Cardiol" "fecha" => "2015" "volumen" => "34" "paginaInicial" => "125" "paginaFinal" => "135" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25662472" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0275" "etiqueta" => "8" "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 [ 0 => "S.W. Hoobler" 1 => "J.T. Manning" 2 => "W.G. Paine" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Circulation" "fecha" => "1951" "volumen" => "4" "paginaInicial" => "173" "paginaFinal" => "183" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14859394" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S073510970000752X" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0280" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Kinsey D. Surgical approach to the treatment of essential hypertension. Results of therapy (medical and surgical)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.H. Smithwick" 1 => "G.P. Whitelaw" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14037735" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0285" "etiqueta" => "10" "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 [ 0 => "M. Harington" 1 => "P. Kincaid-Smith" 2 => "M.J. McMichael" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/788855" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0290" "etiqueta" => "11" "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 [ 0 => "U.S. Von Euler" 1 => "S. Hellner" 2 => "A. Purkhold" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13186788" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0295" "etiqueta" => "12" "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 [ 0 => "K.E. Hagbarth" 1 => "A.B. Vallbo" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4235387" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0300" "etiqueta" => "13" "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 [ 0 => "M. Esler" 1 => "G. Jackman" 2 => "A. Bobik" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/513964" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0305" "etiqueta" => "14" "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 [ 0 => "P.A. Blombery" 1 => "B.G. Heinzow" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Circ Res" "fecha" => "1983" "volumen" => "53" "paginaInicial" => "688" "paginaFinal" => "694" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6627617" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109706028853" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0310" "etiqueta" => "15" "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 [ 0 => "G.J. Hasking" 1 => "M.D. Esler" 2 => "G.L. Jennings" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3948363" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0315" "etiqueta" => "16" "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 [ 0 => "L.N. Graham" 1 => "P.A. Smith" 2 => "R.J. Huggett" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15117852" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0320" "etiqueta" => "17" "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 [ 0 => "T. Kishi" 1 => "Y. Hirooka" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Cardiol Res Pract" "fecha" => "2012" "volumen" => "2012" "paginaInicial" => "1" "paginaFinal" => "7" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0325" "etiqueta" => "18" "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 [ 0 => "F. Triposkiadis" 1 => "G. Karayannis" 2 => "G. Giamouzis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2009.05.015" "Revista" => array:7 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2009" "volumen" => "54" "paginaInicial" => "1747" "paginaFinal" => "1782" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19874988" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109707031142" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0330" "etiqueta" => "19" "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 [ 0 => "M. Esler" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10921528" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0335" "etiqueta" => "20" "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 [ 0 => "M. Esler" 1 => "M. Rumantir" 2 => "D. Kaye" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Clin Exp Pharmacol Physiol" "fecha" => "2001" "volumen" => "28" "paginaInicial" => "986" "paginaFinal" => "989" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11903299" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109707014878" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0340" "etiqueta" => "21" "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 [ 0 => "M. Esler" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10874851" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0345" "etiqueta" => "22" "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 [ 0 => "J. Neumann" 1 => "G. Ligtenberg" 2 => "I.H. Klein" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17224471" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0350" "etiqueta" => "23" "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 [ 0 => "M. Esler" 1 => "M. Rumantir" 2 => "G. Wiesner" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:8 [ "tituloSerie" => "Am J Hypertens" "fecha" => "2001" "volumen" => "14" "numero" => "11 Pt 2" "paginaInicial" => "304S" "paginaFinal" => "309S" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11721888" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673603121137" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0355" "etiqueta" => "24" "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 [ 0 => "K. Narkiewicz" 1 => "V.K. Somers" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9488212" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0360" "etiqueta" => "25" "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 [ 0 => "M. Esler" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19940096" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0365" "etiqueta" => "26" "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 [ 0 => "R. Furlan" 1 => "S. Ardizzone" 2 => "L. Palazzolo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajpregu.00442.2005" "Revista" => array:7 [ "tituloSerie" => "Am J Physiol Regul Integr Comp Physiol" "fecha" => "2006" "volumen" => "290" "paginaInicial" => "R224" "paginaFinal" => "R232" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16123227" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109705030329" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0370" "etiqueta" => "27" "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 [ 0 => "J.P. Fisher" 1 => "C.N. Young" 2 => "P.J. Fadel" ] ] ] ] ] "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 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19268634" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0375" "etiqueta" => "28" "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 [ "etal" => false "autores" => array:2 [ 0 => "J.A. Thomas" 1 => "B.H. Marks" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Am J Cardiol" "fecha" => "1978" "volumen" => "41" "paginaInicial" => "233" "paginaFinal" => "243" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/203177" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109704004954" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0380" "etiqueta" => "29" "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:7 [ "tituloSerie" => "Lancet" "fecha" => "1999" "volumen" => "353" "paginaInicial" => "9" "paginaFinal" => "13" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10023943" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109704001731" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0385" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "[discussion 2016]" "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 [ "etal" => false "autores" => array:3 [ 0 => "M. Esler" 1 => "E. Lambert" 2 => "M. Schlaich" ] ] ] ] ] "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 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20185633" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0390" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and angiotensin neuromodulation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.P. Schlaich" 1 => "E. Lambert" 2 => "D.M. Kaye" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/01.HYP.0000103160.35395.9E" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2004" "volumen" => "43" "paginaInicial" => "169" "paginaFinal" => "175" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14610101" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0395" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Epub ahead of print" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Twelve-month results of the Rapid Renal Sympathetic Denervation for Resistant Hypertension Using the OneShot™ Ablation System (RAPID) study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Verheye" 1 => "J. Ormiston" 2 => "M. Bergmann" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "EuroIntervention" "fecha" => "2014" ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0400" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Epub ahead of print" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal denervation with a percutaneous bipolar radiofrequency balloon catheter in patients with resistant hypertension: 6-month results from the REDUCE-HTN clinical study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "H. Sievert" 1 => "J. Schofer" 2 => "J. Ormiston" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "EuroIntervention" "fecha" => "2014" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0405" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Catheter-based renal denervation for resistant hypertension: 12-month results of the EnligHTN I first-in-human study using a multielectrode ablation system" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "V. Papademetriou" 1 => "C.P. Tsioufis" 2 => "A. Sinhal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.114.03605" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2014" "volumen" => "64" "paginaInicial" => "565" "paginaFinal" => "572" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24935940" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0410" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F. Elmula" 1 => "P. Hoffman" 2 => "A. Larstorp" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.114.03246" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2014" "volumen" => "63" "paginaInicial" => "991" "paginaFinal" => "999" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24591332" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0415" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomized comparison of renal denervation versus intensified pharmacotherapy including spironolactone in true-resistant hypertension: six-month results from the Prague-15 study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J. Rosa" 1 => "P. Widimsky" 2 => "P. Tousek" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.114.04019" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2015" "volumen" => "65" "paginaInicial" => "407" "paginaFinal" => "413" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25421981" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0420" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. Azizi" 1 => "M. Sapoval" 2 => "P. Goose" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Lancet" "fecha" => "2015" "volumen" => "385" "paginaInicial" => "1956" "paginaFinal" => "1965" ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0425" "etiqueta" => "38" "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 [ 0 => "H. Krum" 1 => "M. Schlaich" 2 => "R. Whitbourn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(09)60566-3" "Revista" => array:7 [ "tituloSerie" => "Lancet" "fecha" => "2009" "volumen" => "373" "paginaInicial" => "1275" "paginaFinal" => "1281" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19332353" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109704013749" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0430" "etiqueta" => "39" "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 [ "etal" => true "autores" => array:3 [ 0 => "M.D. Esler" 1 => "H. Krum" 2 => "P.A. Sobotka" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(10)62039-9" "Revista" => array:7 [ "tituloSerie" => "Lancet" "fecha" => "2010" "volumen" => "376" "paginaInicial" => "1903" "paginaFinal" => "1909" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21093036" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109708037996" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0435" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized clinical trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.D. Esler" 1 => "M. Bohm" 2 => "H. Sievert" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehu209" "Revista" => array:7 [ "tituloSerie" => "Eur Heart J" "fecha" => "2014" "volumen" => "35" "paginaInicial" => "1752" "paginaFinal" => "1759" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24898552" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109705023612" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0440" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "SYMPLICITY HTN-3 Investigators. A controlled trial of renal denervation for resistant hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "D.L. Bhatt" 1 => "D.E. Kandzari" 2 => "W.W. 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Review article

Renal denervation in the treatment of resistant hypertension: Dead, alive or surviving?

Desnervação renal no tratamento da hipertensão arterial resistente: morta, viva ou sobrevivendo?

Ahmad Al-Fakhouria,

Corresponding author

fakhouri_md@yahoo.com

Corresponding author.

, Nephertiti Efeovbokhanb, Rami Nakhlac, Rami N. Khouzamb

a Department of Medicine, Methodist South Hospital, Memphis, TN, United States

b Department of Medicine, Division of Cardiovascular Diseases, University of Tennessee Health Science Center, Memphis, TN, United States

c Ain Shams University School of Medicine, Cairo, Egypt

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            "entidad" => "Department of Medicine&#44; Methodist South Hospital&#44; Memphis&#44; TN&#44; United States"
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          1 => array:3 [
            "entidad" => "Department of Medicine&#44; Division of Cardiovascular Diseases&#44; University of Tennessee Health Science Center&#44; Memphis&#44; TN&#44; United States"
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    "titulosAlternativos" => array:1 [
      "pt" => array:1 [
        "titulo" => "Desnerva&#231;&#227;o renal no tratamento da hipertens&#227;o arterial resistente&#58; morta&#44; viva ou sobrevivendo&#63;"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hypertension is one of the most common chronic clinical problems encountered by physicians&#46; Resistant hypertension is defined as systolic blood pressure &#40;BP&#41; &#8805;160 mmHg or &#40;&#8805;150 mmHg in patients with type 2 diabetes mellitus&#41; refractory to medical treatment despite the use of optimal doses of three or more different drug types including a diuretic&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">1</span></a> The prevalence of resistant hypertension is estimated at 9&#37; in the US&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">2</span></a> In a study of 205<span class="elsevierStyleHsp" style=""></span>750 treated hypertensive patients&#44; 1 in 50 developed resistant hypertension within a median of 1&#46;5 years from the initial treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">3</span></a> In the same study&#44; patients with resistant hypertension were shown to be at higher risk for adverse cardiovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">3</span></a> The increased morbidity and mortality associated with this condition supports greater efforts to improve treatment options&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Historical perspective</span><p id="par0010" class="elsevierStylePara elsevierViewall">After a link was established between the sympathetic nervous system and the development of resistant hypertension&#44; surgical sympathectomy was introduced in the 1930s&#44; but was abandoned shortly afterwards due to multiple side effects such as postural hypotension&#44; tachycardia&#44; bladder&#44; bowel and erectile dysfunction&#44; and high periprocedural mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">4</span></a> The proximity of the afferent and efferent renal sympathetic nerves to the adventitia of the renal arteries suggested the feasibility of an endovascular&#44; selective&#44; minimally invasive approach to renal denervation &#40;RDN&#41;&#46; In the endovascular approach&#44; a treatment catheter is introduced through a guiding catheter into the renal arteries&#46; The catheter is placed in close proximity to the vessel wall to ensure stable contact&#46; Low-energy radiofrequency ablations are then applied moving the catheter from distal to proximal locations in the renal arteries&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Anatomical and physiological effects of renal denervation</span><p id="par0015" class="elsevierStylePara elsevierViewall">The renal nerves arise from T10-L2 and follow the course of the renal artery lying in the adventitia&#46; Renal sympathetic nerves play an important role in the development of hypertension&#44; mediated via sodium and water retention&#44; increased renin release&#44; and alterations in renal blood flow&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Experimental studies established the important concept that sub-vasoconstrictor levels of renal sympathetic activity can increase renin secretion and renal sodium retention without changing renal hemodynamics&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">6</span></a> Assessment of regional overflow of norepinephrine &#40;NE&#41; from the kidneys to plasma has demonstrated that renal NE spillover rates can be markedly elevated in patients with essential hypertension and are associated with hypertensive end-organ damage&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">5&#44;31</span></a> Measurement of NE excretion in the urine&#44; now largely obsolete&#44; was performed in order to quantify sympathetic nervous system activity in humans&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">6</span></a> In the light of these findings&#44; RDN therapy was considered a logical therapeutic approach in the treatment of hypertension&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">The sympathetic nervous system and cardiovascular disease<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">7</span></a></span><p id="par0025" class="elsevierStylePara elsevierViewall">Surgical sympathectomy was first introduced in the 1930s and was effective in lowering high BP in patients with severe hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">8&#44;9</span></a> However&#44; the side effects associated with the procedure and the introduction of ganglionic blockers made it obsolete&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">10</span></a> For a long time&#44; it was difficult to study and assess the role of the sympathetic nervous system &#40;SNS&#41; in the pathogenesis of hypertension&#44; due not to uncertainty concerning the relation between the two&#44; but rather to the difficulty of testing and assessing that relation&#46; Previous techniques included the measurement of serum and urinary excretion of NE and its derivatives&#44; yielding a rough estimate of SNS activity in the whole body&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">11</span></a> Hagbarth and Vallbo reported microneurography as a newer tool to study SNS nerve firing in subcutaneous tissues and skeletal muscles&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">12</span></a> The NE spillover technique was first used by Esler et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">13</span></a> measuring organ-specific NE release in its efferent veins as an indirect measurement of SNS nerve fiber firing in an individual organ&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">14</span></a> and that technique was later used to demonstrate that heart failure caused SNS overactivity&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">15</span></a> Accumulated evidence underlines the role of sustained chronic SNS activity in many diseases including ischemic heart disease&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">16</span></a> heart failure&#44;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">17&#44;18</span></a> hypertension&#44;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">19&#8211;21</span></a> kidney disease&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">22</span></a> type 2 diabetes&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">23</span></a> obesity&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">23</span></a> metabolic syndrome&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">23</span></a> obstructive sleep apnea&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">24</span></a> depression&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">25</span></a> and inflammatory bowel disease&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">26</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In the cardiovascular system&#44; chronic SNS activation not only raises BP but also causes hypertrophy and proliferation of vascular smooth muscle cells and cardiac myocytes&#44; thus increasing LV mass and wall thickness&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">27</span></a> In addition&#44; increased SNS activity&#44; in the presence of endothelial dysfunction and endothelial cell damage&#44; has been shown to contribute to the development of atherosclerosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">25&#44;27&#44;29</span></a> Contradicting previous assumptions&#44; high levels of NE spillover from the heart in heart failure<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">28</span></a> demonstrated increased sympathetic activity in the failing heart&#44; which was the rationale for the subsequent use of beta-blockers in heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">29</span></a> In essential hypertension&#44; SNS outflow to the kidneys is elevated and is directly proportional to the severity of hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">19&#44;21&#44;25</span></a> This finding is also supported by regional measurements of NE spillover to the kidneys&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">30</span></a> Renal sympathetic activity is a major factor contributing to the pathogenesis of essential hypertension through its influence on activation of the renin-angiotensin system&#44; sodium and water excretion&#44; peripheral vasoconstriction&#44; cardiac contraction&#44; and venous capacitance&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">25</span></a> The recent introduction of safe and efficient methods for RDN has led to a renewed interest in the role of SNS activation in essential hypertension&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Evidence of the efficacy of renal denervation in the treatment of resistant hypertension</span><p id="par0035" class="elsevierStylePara elsevierViewall">The Rapid Renal Sympathetic Denervation for Resistant Hypertension Using the OneShot&#8482; Ablation System &#40;RAPID&#41; study<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">32</span></a> was a prospective&#44; multicenter&#44; non-randomized&#44; single-arm trial that included 50 patients with mean office BP of 181&#177;20&#46;8&#47;95&#177;15&#46;5 mmHg&#44; on a mean of five antihypertensive medications&#44; who received RDN&#46; The primary endpoint studied was the rate of office systolic BP &#40;SBP&#41; reduction&#58; &#8805;10 mmHg at six months in comparison to baseline&#46; Change in 24-hour ambulatory BP &#40;ABP&#41; was also evaluated&#46; At the six-month mark&#44; there was a decrease in mean office BP of -20&#47;-8 mmHg &#40;p&#60;0&#46;0001&#47;p&#61;0&#46;0002&#41; in comparison to baseline&#46; This trend was sustained at 12 months&#44; with a decrease in mean office BP of -22&#47;-8 mmHg &#40;p&#60;0&#46;0001&#47;p&#61;0&#46;0014&#41;&#46; Likewise&#44; there was a significant reduction in 24-hour ABP&#44; of -11&#47;-6 mmHg at six months in comparison to baseline &#40;p&#61;0&#46;0085&#47;p&#61;0&#46;037&#41;&#46; At 12 months&#44; the reduction in 24-hour ABP was -9&#47;-5 mmHg &#40;p&#61;0&#46;054&#47;p&#61;0&#46;073&#41;&#46; Device- and&#47;or procedure-related adverse effects occurred in three patients up to 12 months&#44; namely one access site infection&#44; one renal artery stenosis&#44; and one groin paresthesia&#46; The authors concluded that RDN led to significant and sustained reductions in office and 24-hour ambulatory BP at six and 12 months&#44; respectively&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The REDUCE-HTN study<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">33</span></a> was a prospective&#44; non-randomized&#44; single-arm trial that included 146 patients with mean baseline office and ambulatory BP of 182&#177;18&#46;4&#47;100&#177;14&#46;0 and 153&#177;15&#46;1&#47;87&#177;13&#46;2 mmHg&#44; respectively&#44; who received RDN using the Vessix renal denervation system&#46; The primary efficacy endpoints were reductions in office and 24-hour ambulatory SBP and diastolic blood pressure &#40;DBP&#41; at six months&#44; which were 24&#46;7&#177;22&#46;1&#47;10&#46;3&#177;12&#46;7 mmHg &#40;p&#60;0&#46;0001&#41; and 8&#46;4&#177;14&#46;4&#47;5&#46;9&#177;9&#46;1 mmHg &#40;p&#60;0&#46;0001&#41;&#44; respectively&#46; Regarding the safety endpoints&#44; no acute renal injury requiring acute renal intervention occurred and only one patient developed renal artery stenosis that required a stent&#46; In addition&#44; mean glomerular filtration rate remained stable&#46; The authors concluded that renal artery denervation reduced both office and ambulatory BP at six months in patients with resistant hypertension&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The EnligHTN I study<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">34</span></a> was a prospective&#44; non-randomized trial that included 46 patients with mean baseline office&#44; 24-hour ambulatory and home BP of 176&#47;96&#44; 150&#47;83 and 158&#47;90 mmHg&#44; respectively&#44; who underwent RDN using the EnligHTN multielectrode radiofrequency ablation system&#46; The primary efficacy endpoint was change in office BP in comparison to baseline&#46; The mean reductions in office BP at 1&#44; 3&#44; 6&#44; and 12 months were -28&#47;-10&#44; -27&#47;-10&#44; -26&#47;-10&#44; and -27&#47;-11 mmHg&#44; respectively &#40;p&#60;0&#46;001 for all&#41;&#46; Likewise&#44; mean reductions in 24-hour ABP were -10&#47;-5&#44; -10&#47;-5&#44; and -10&#47;-6 mmHg at 1&#44; 3&#44; 6 months &#40;p&#60;0&#46;001 for all&#41;&#44; and -7&#47;-4 mmHg at 12 months &#40;p&#60;0&#46;0094&#41;&#46; Mean reductions in home measurements were -9&#47;-4&#44; -8&#47;-5&#44; -10&#47;-7&#44; and -11&#47;-6 mmHg &#40;p&#60;0&#46;001 at 12 months&#41;&#46; There were no signs of worsening renal function at 12 months&#46; One patient required renal artery stenting &#40;non-occlusive renal stenosis was present at baseline&#41;&#46; The authors concluded that the EnligHTN ablation system was safe and effective in reducing office&#44; 24-ambulatory and home BP in patients with resistant hypertension&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Oslo RDN<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">35</span></a> was a prospective randomized trial in which 19 patients with true treatment-resistant hypertension were randomized to RDN &#40;n&#61;9&#41; performed with the Symplicity Catheter System vs&#46; clinically adjusted drug treatment &#40;n&#61;10&#41;&#46; True treatment-resistant hypertension was confirmed after excluding patients with confounding poor drug adherence&#46; The primary endpoint was change in office systolic blood pressure &#40;SBP&#41; from randomization to six months&#46; The study was stopped early as RDN had uncertain BP-lowering effects&#46; At six months&#44; office SBP and DBP changed significantly from 160&#177;14&#47;88&#177;13 mmHg to 132&#177;10&#47;77&#177;8 mmHg compared to baseline in the drug-adjusted group &#40;p&#60;0&#46;0005 and p&#61;0&#46;02&#41;&#44; whereas in the RDN group there was no significant change in office SBP and DBP at six months compared to baseline &#40;156&#177;13&#47;91&#177;15 to 148&#177;7&#47;89&#177;8 mmHg&#44; p&#61;0&#46;42 and p&#61;0&#46;48&#41;&#46; SBP and DBP were significantly lower in the drug-adjusted group at six months &#40;p&#61;0&#46;002 and p&#61;0&#46;004&#44; respectively&#41;&#44; and absolute changes in SBP were larger in the drug-adjusted group &#40;p&#61;0&#46;008&#41;&#46; ABP changed in parallel to office BP&#46; The authors concluded that the BP-lowering effect of adjusted drug treatment were superior to that of RDN in patients with true treatment-resistant hypertension&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The Prague-15 study<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">36</span></a> was a prospective&#44; open-label multicenter trial in which 106 patients with resistant hypertension were randomized to RDN &#40;n&#61;52&#41; or intensified pharmacological treatment &#40;n&#61;54&#41;&#46; RDN was performed using the Symplicity Renal Denervation System&#46; At six months&#44; a comparable significant reduction in mean 24-hour SBP was noted in both groups&#44; of -8&#46;6 mmHg &#40;95&#37; confidence interval &#91;CI&#93;&#58; -11&#46;8&#44; -5&#46;3&#41;&#59; p&#60;0&#46;001 in RDN&#44; vs&#46; -8&#46;1 &#40;95&#37; CI&#58; -12&#46;7&#44; -3&#46;4&#41; mmHg in the pharmacological group&#46; Likewise&#44; a significant reduction in office SBP was observed in both groups mmHg &#40;-12&#46;4 &#91;95&#37; CI&#58; -17&#46;0&#44; -7&#46;8&#93;&#59; p&#60;0&#46;001 in RDN vs&#46; -14&#46;3 mmHg &#91;95&#37; CI&#58; -19&#46;7&#44; -8&#46;9&#93;&#59; p&#60;0&#46;001 in the pharmacological group&#41;&#46; The authors concluded that RDN was safe&#59; however in the setting of true resistant hypertension with confirmed compliance&#44; it was not proved superior to intensified pharmacological treatment&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The DENERHTN trial<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">37</span></a> was a prospective&#44; open-label randomized controlled trial that assigned 106 patients to receive either RDN plus a standardized stepped-care antihypertensive treatment &#40;SSAHT&#41; regimen &#40;RDN group&#44; n&#61;53&#41; or SSAHT alone &#40;control group&#44; n&#61;53&#41;&#46; Prior to randomization&#44; treatment resistance was confirmed by ABP monitoring after patients received oral antihypertensives for a period of four weeks&#46; The primary endpoint studied was the mean change in daytime SBP from baseline to six months as assessed by ambulatory BP monitoring&#46; The safety outcomes were the incidence of acute adverse events of the RDN procedure and the change in estimated glomerular filtration rate from baseline to six months&#46; At six months&#44; the mean change in daytime ambulatory SBP was -15&#46;8 mmHg &#40;95&#37; CI -19&#46;7 to -11&#46;9&#41; in the RDN group and -9&#46;9 mmHg &#40;-13&#46;6 to -6&#46;2&#41; in the group receiving SSAHT alone&#44; a baseline-adjusted difference of -5&#46;9 mmHg &#40;-11&#46;3 to -0&#46;5&#59; p&#61;0&#46;0329&#41;&#46; The numbers of antihypertensive drugs and drug adherence at six months were similar between the two groups&#46; Three minor RDN-related adverse events were noted &#40;lumbar pain in two patients and mild groin hematoma in one patient&#41;&#46; The authors concluded that RDN plus SSAHT decreases ambulatory BP more than the same SSAHT alone at six months in patients with well-defined resistant hypertension&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">The Symplicity HTN studies</span><p id="par0065" class="elsevierStylePara elsevierViewall">The Symplicity HTN-1 study<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">38</span></a> was a proof-of-principle trial of therapeutic renal sympathetic denervation&#46; The trial included 50 patients with resistant hypertension who received percutaneous radiofrequency catheter-based RDN using the Symplicity catheter&#44; with a one-year follow-up post procedure&#46; The primary endpoints were office BP and safety data before and at 1&#44; 3&#44; 6&#44; 9&#44; and 12 months after procedure&#46; Out of the 50 patients enrolled&#44; five were excluded for anatomical reasons&#46; Treated patients were on a mean of 4&#46;7 antihypertensive medications&#44; with baseline mean office BP of 177&#47;101 mmHg&#46; Office BP readings after the procedure were reduced by -14&#47;-10&#44; -21&#47;-10&#44; -22&#47;-11&#44; -24&#47;-11&#44; and -27&#47;-17 mmHg at 1&#44; 3&#44; 6&#44; 9&#44; and 12 months&#44; respectively&#46; In the five non-treated patients&#44; mean rise in office BP was &#43;3&#47;-2&#44; &#43;2&#47;&#43;3&#44; &#43;14&#47;&#43;9&#44; and &#43;26&#47;&#43;17 mmHg at 1&#44; 3&#44; 6&#44; and 9 months&#44; respectively&#46; The only reported complication was one intraprocedural renal artery dissection which occurred before radiofrequency energy delivery&#46; The authors concluded that catheter-based RDN leads to substantial and sustained BP reduction&#44; without serious adverse events&#44; in patients with resistant hypertension&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Following the success achieved in the Symplicity HTN-1 trial&#44; the Symplicity HTN-2 trial<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">39</span></a> was designed to assess the effectiveness and safety of catheter-based RDN for BP reduction in patients with treatment-resistant hypertension&#46; A total of 106 patients with resistant hypertension were randomly assigned to either RDN with medical treatment &#40;treatment arm&#44; n&#61;52&#41; or medical treatment alone &#40;control arm&#44; n&#61;54&#41;&#46; The primary endpoint of the study was change in office-based measurement of SBP at six months&#46; At six months&#44; there was a significant reduction in office-based BP measurements in the treatment arm &#40;change of 32&#47;12 mmHg&#44; standard deviation &#91;SD&#93; 23&#47;11&#44; baseline of 178&#47;96 mmHg&#41;&#44; compared to the control arm &#40;change of 1&#47;0 mmHg&#44; SD 21&#47;10&#44; baseline of 178&#47;97 mmHg&#41;&#46; Between-group differences in BP at six months were 33&#47;11 mmHg &#40;p&#60;0&#46;0001&#41;&#46; Additionally&#44; at six months&#44; 41 &#40;84&#37;&#41; out of 49 patients in the treatment arm had a reduction in SBP of 10 mmHg or more&#44; compared with 18 &#40;35&#37;&#41; of 51 controls &#40;p&#60;0&#46;0001&#41;&#46; No serious procedural complications were noted&#46; The authors concluded that catheter-based RDN can safely be used to substantially reduce BP in treatment-resistant hypertensive patients&#46; Follow-up at 36 months in 40 of the 52 patients in the initial RDN group and at 30 months in 30 of 37 patients who crossed over and received RDN at six months<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">40</span></a> showed that SBP decreased by 34 mmHg &#40;95&#37; CI&#58; -40&#44; -27&#44; p&#60;0&#46;01&#41; and DBP decreased by 13 mmHg &#40;95&#37; CI&#58; -16&#44; -10&#44; p&#60;0&#46;01&#41; from a baseline of 184&#177;19&#47;99&#177;16 mmHg&#46; SBP and DBP reductions at 36 months for the initial RDN group was -33 mmHg &#40;95&#37; CI&#58; -40&#44; -25&#44; p&#60;0&#46;01&#41; and -14 mmHg &#40;95&#37; CI&#58; -17&#44; -10&#44; p&#60;0&#46;01&#41;&#44; respectively&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In an attempt to further explore the robustness of RDN in the treatment of resistant hypertension&#44; the Symplicity HTN-3 trial<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">41</span></a> was conducted&#46; Unlike the previous two studies&#44; blinding and sham-control were added in the design of this trial&#46; A total of 535 patients with severe resistant hypertension receiving a stable antihypertensive regimen involving maximally tolerated doses of at least three drugs including a diuretic were randomly assigned in a 2&#58;1 ratio to undergo RDN &#40;n&#61;364&#41; or a sham procedure &#40;n&#61;171&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The primary efficacy endpoint&#44; change in office SBP at six months&#44; was not significantly different between the two groups &#40;-14&#46;13&#177;23&#46;93 mmHg in the denervation group compared to -11&#46;74&#177;25&#46;94 mmHg in the sham-procedure group &#91;p&#60;0&#46;001 for both comparisons of the change from baseline&#93;&#44; a difference of -2&#46;39 mmHg &#91;95&#37; CI&#58; -6&#46;89 to 2&#46;12&#59; p&#61;0&#46;26 for superiority with a margin of 5 mm Hg&#93;&#41;&#46; Likewise&#44; for the secondary efficacy endpoint&#44; the change in mean 24-hour ambulatory SBP&#44; no between-group differences were noted -6&#46;75&#177;15&#46;11 mmHg in the denervation group and -4&#46;79&#177;17&#46;25 mmHg in the sham-procedure group&#44; for a difference of -1&#46;96 mmHg &#40;95&#37; CI&#58; -4&#46;97 to 1&#46;06&#59; p&#61;0&#46;98 for superiority with a margin of 2 mmHg&#41;&#46; The primary safety endpoint &#40;a composite of death&#44; end-stage renal disease&#44; an embolic event resulting in end-organ damage&#44; renovascular complications&#44; or hypertensive crisis within 30 days or new renal-artery stenosis of more than 70&#37; within six months&#41; was not significantly different between the two groups&#46; The authors concluded that their blinded trial did not show a significant reduction of SBP in patients with resistant hypertension six months after renal-artery denervation compared with a sham control&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows a summary of trials of RDN&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The role of RDN in the treatment of resistant hypertension is still to be fully clarified&#46; While the results of the RAPID&#44; REDUCE-HTN&#44; EnligHTN&#44; Symplicity HTN-1 and -2&#44; and DENERHTN trials were positive&#44; this was not the case in the Oslo RDN&#44; Prague-15 and Symplicity HTN-3 trials&#46; The varying results may be explained by several factors&#46; Symplicity HTN-3&#44; the largest trial to date&#44; was also the only one that included a sham-control group&#46; As shown by Meissner et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">46</span></a> sham procedures may be associated with a significant positive response &#8211; the placebo effect &#8211; that could be misinterpreted as a real treatment effect&#46; Kandzari et al&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">42</span></a> investigated potential reasons for the discordant results noted in Symplicity HTN-3&#46; Their findings showed that between randomization and the six-month endpoint&#44; 39&#37; of patients underwent medication changes involving alteration in both the dose and class of prescribed medications&#46; In addition&#44; African-Americans were more likely to be prescribed vasodilators than non-African-Americans in both study arms&#46; A total of 56&#37; of African-American sham patients and 46&#46;7&#37; of African-American RDN patients were receiving a vasodilator&#44; compared to 40&#46;5&#37; of non-African-American sham control patients and 33&#46;7&#37; of non-African-American RDN patients who were receiving a vasodilator at baseline&#46; African-Americans in the sham control study arm receiving a vasodilator showed an enormous decline in SBP &#40;-21&#46;9&#43;29&#46;1 mmHg&#41;&#44; which was not noted in the other subgroups&#46; This unexpectedly large SBP decline in African-American control patients may indicate a change in medical adherence or type of therapy in this specific group&#46; Likewise&#44; increasing number of ablations and energy delivery in a four-quadrant pattern was associated with greater reductions in office and ambulatory SBP and heart rate&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The ablation catheters used in the above studies had some design features that are worthy of mention&#46; The EnligHTN denervation system is a unique multielectrode catheter that allows a predictable pattern of four simultaneous ablations&#46; The Vessix denervation system used in the REDUCE-HTN trial delivered bipolar radiofrequency energy as opposed to the monopolar radiofrequency energy delivered by the Symplicity denervation system &#40;used in the Symplicity HTN studies&#41;&#46; As suggested by Kandazari et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">42</span></a> differences in ablation energy may affect the efficacy of denervation therapy&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">The future</span><p id="par0100" class="elsevierStylePara elsevierViewall">Several trials are underway to investigate the role of RDN in specific patient populations such as those with chronic renal disease and moderate hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">43&#8211;45</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">The SPYRAL HTN Global Clinical Trial Program<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">47</span></a> is a phased series of clinical trials designed to establish the efficacy of RDN therapy in patients with hypertension&#46; The SPYRAL HTN-OFF MED trial aims to confirm the basic hypothesis that RDN therapy lowers BP in patients with hypertension without treatment&#44; while the parallel SPYRAL HTN-ON MED trial is designed to assess the efficacy of RDN integrated with antihypertensive medications&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusions</span><p id="par0110" class="elsevierStylePara elsevierViewall">The results of the RAPID&#44; REDUCE-HTN&#44; EnligHTN&#44; Symplicity HTN-1 and -2&#44; and DENERHTN trials suggested an important role for RDN in the treatment of resistant hypertension&#46; The results of the Oslo RDN&#44; Prague-15 and Symplicity HTN-3 suggested differently&#46; Of note&#44; all these studies showing favorable benefits of RDN were either non-randomized single-arm trials or randomized unblinded trials without a sham control group&#46; As shown by Meissner et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">46</span></a> sham procedures may be associated with a significant positive response &#8211; the placebo effect &#8211; that could be misinterpreted as a real treatment effect&#46; Symplicity HTN-3&#44; a well-designed randomized&#44; blinded&#44; sham control trial&#44; casts doubt on the benefits of RDN in the treatment of resistant hypertension&#46; The results of the Symplicity HTN-3 emphasize the need always to assess for a potential placebo effect by including sham control study groups when assessing the efficacy of new devices&#46; In addition&#44; future studies should ensure consistent medical therapy and delivery of radiofrequency ablation across treatment arms&#44; as post-hoc analysis showed these differences to be important in the neutral results noted in Symplicity HTN-3&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Currently&#44; the role of RDN in addition to medical therapy in the treatment of resistant hypertension is still to be fully clarified&#46; Nevertheless&#44; RDN is certainly not dead&#44; but further well-designed clinical trials are needed to ascertain the benefits or otherwise of RDN in treatment-resistant hypertension&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflicts of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "titulo" => "Anatomical and physiological effects of renal denervation"
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          "titulo" => "The sympathetic nervous system and cardiovascular disease"
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          "titulo" => "Evidence of the efficacy of renal denervation in the treatment of resistant hypertension"
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          "titulo" => "The Symplicity HTN studies"
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            2 => "Renal denervation"
            3 => "Sympathetic nervous system"
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            0 => "Hipertens&#227;o"
            1 => "Hipertens&#227;o arterial resistente"
            2 => "Desnerva&#231;&#227;o renal"
            3 => "Sistema nervoso simp&#225;tico"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hypertension is one of the most common chronic clinical problems encountered by physicians&#46; The prevalence of resistant hypertension is estimated at 9&#37; in the US&#46; Patients with resistant hypertension have been shown to be at higher risk for adverse cardiovascular events&#44; hence the need for greater efforts in improving the treatment of hypertension&#46; The renal sympathetic nerves play an important role in the development of hypertension&#44; mediated via sodium and water retention&#44; increased renin release and alterations in renal blood flow&#46; The proximity of the afferent and efferent renal sympathetic nerves to the adventitia of the renal arteries suggested the feasibility of an endovascular&#44; selective&#44; minimally invasive approach to renal denervation&#59; a potential treatment option for resistant hypertension&#46; While the RAPID&#44; Reduce-HTN&#44; EnligHTN&#44; DENERHTN and Symplicity HTN-1 and -2 studies showed significant benefit of renal denervation in the treatment of resistant hypertension&#44; the results of Oslo RDN&#44; Prague-15 and Symplicity HTN-3 were not so favorable&#46; Future well-designed clinical trials are needed to ascertain the benefits or otherwise of renal denervation in treatment-resistant hypertension&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A hipertens&#227;o arterial &#233; um dos problemas cl&#237;nicos cr&#243;nicos mais frequentes&#46; Nos EUA a preval&#234;ncia de hipertens&#227;o arterial resistente est&#225; estimada em 9&#37;&#46; Os doentes com hipertens&#227;o resistente t&#234;m um maior risco de eventos cardiovasculares adversos&#44; o que justifica maiores esfor&#231;os na melhoria do tratamento da hipertens&#227;o&#46; A inerva&#231;&#227;o simp&#225;tica renal tem um papel importante no desenvolvimento da hipertens&#227;o&#44; mediada atrav&#233;s da reten&#231;&#227;o de s&#243;dio e &#225;gua&#44; com aumento da liberta&#231;&#227;o de renina e de altera&#231;&#245;es do fluxo sangu&#237;neo renal&#46; A anatomia da inerva&#231;&#227;o simp&#225;tica renal&#44; com os seus nervos aferentes e eferentes em rela&#231;&#227;o de proximidade com a advent&#237;cia&#44; permite uma abordagem endovascular&#44; seletiva e minimamente invasiva para a desnerva&#231;&#227;o renal&#44; e constitui uma op&#231;&#227;o de tratamento potencial para a hipertens&#227;o arterial resistente&#46; Enquanto os estudos RAPID&#44; <span class="elsevierStyleItalic">Reduce</span>-HTN&#44; EngliHTN&#44; DENERHTN e <span class="elsevierStyleItalic">Simplicity</span> HTN 1&#44;2 mostraram um benef&#237;cio significativo da desnerva&#231;&#227;o renal no tratamento da hipertens&#227;o arterial resistente&#44; os resultados dos estudos Oslo-RDN&#44; <span class="elsevierStyleItalic">Prague</span>-15 e <span class="elsevierStyleItalic">Simplicity</span> HTN 3 n&#227;o foram t&#227;o favor&#225;veis&#46; Ser&#227;o necess&#225;rios ensaios cl&#237;nicos bem estruturados para confirmar ou infirmar os potenciais benef&#237;cios da desnerva&#231;&#227;o renal no tratamento da hipertens&#227;o arterial resistente&#46;</p></span>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">ABPM&#58; ambulatory blood pressure monitoring&#59; AH&#58; antihypertensive&#59; BP&#58; blood pressure&#59; eGFR&#58; estimated glomerular filtration rate&#59; N&#47;A&#58; not applicable&#59; RDN&#58; renal denervation&#59; RF&#58; radiofrequency&#59; SSAHT&#58; standardized stepped-care antihypertensive treatment&#59; SD&#58; standard deviation&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Trial name&#47;year of publication&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">Study design&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">Baseline office and ambulatory BP &#40;mmHg&#41;&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">Mean no&#46; of AH drugs&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">&#37; of patients under aldosterone antagonists&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">Ablation catheter&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">Study description&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">Study endpoints&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">Main findings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RAPID&#47;2014<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">32</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">Prospective&#44; multicenter&#44; single arm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Baseline office 181&#46;6&#177;20&#46;8&#47;95&#46;5&#177;15&#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;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&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; RF balloon catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50 patients enrolled to receive percutaneous RF renal nerve ablation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Primary endpoint&#58; rate of office SBP reduction &#8805;10 mmHg at 6 months in comparison to baseline&#46; Change in 24-hour ambulatory BP was also evaluated&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Significant reduction in office and ambulatory BP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">REDUCE-HTN&#47;2014<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">33</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">Prospective&#44; non-randomized&#44; single arm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Baseline office 182&#177;18&#46;4&#47;100&#177;14&#46;0&#59; baseline ambulatory 153&#177;15&#46;1&#47;87&#177;13&#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">&#62;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vessix RF catheter &#40;Boston Scientific&#41;<br>Bipolar RF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">146 patients enrolled to receive percutaneous RF renal nerve ablation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Primary efficacy endpoints&#58; reductions in office and 24-hour ambulatory SBP and DBP at six months&#46; Acute and long-term safety&#44; with a focus on the renal artery and eGFR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Significant reduction in office and ambulatory BP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EnligHTN&#47;2014<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">34</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">Prospective&#44; non-randomized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Baseline office 176&#47;96&#59; baseline ambulatory 150&#47;83&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;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">EnligHTN multielectrode RF catheter &#40;St&#46; Jude Medical&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46 patients enrolled to receive percutaneous RF renal nerve ablation using a multielectrode system&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Primary efficacy endpoint&#58; office BP change from baseline&#46; Primary safety objective&#58; the rate of adverse events&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Significant reductions in office&#44; ambulatory and home BP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oslo RDN&#47;2014<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">35</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">Prospective&#44; randomized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Baseline office 156&#47;91&#59; baseline ambulatory 152&#47;93&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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">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">Symplicity single-electrode RF catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19 patients randomly assigned to RDN &#40;9&#41; or clinically adjusted drug treatment &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Primary end-point&#58; change in office SBP from randomization to 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Significant reduction in office SBP in patients assigned to clinically adjusted drug treatment&#59; no change in those assigned to RDN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prague-15&#47;2015<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">36</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">Prospective&#44; randomized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Baseline office 159&#177;19&#47;92&#177;14&#59; baseline ambulatory 149&#177;12&#47;86&#177;10&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;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Symplicity single-electrode RF catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">106 patients randomly assigned to RDN &#40;52&#41; or intensified pharmacotherapy &#40;54&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Efficacy of RDN assessed by 24-hour ABPM and office BP at 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Significant reduction in 24-hour ambulatory and office BP in both groups&#44; with no differences between groups&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DENERHTN&#47; 2015<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">37</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">Prospective&#44; randomized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Symplicity RF catheter<br>&#40;Medtronic&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">106 patients randomly assigned to RDN &#43; SSAHT &#40;53&#41; or SSAHT alone &#40;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Primary end-point&#58; change in daytime SBP assessed by ambulatory BPM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Significant reduction in daytime SBP in patients assigned to RDN &#43; SSSAHT as compared to SSAHT alone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Symplicity HTN-1&#47;2009<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">38</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">Prospective&#44; non-randomized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Baseline office 177&#47;101 &#40;SD 20&#47;15&#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&#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">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Symplicity single-electrode RF catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50 patients enrolled to receive percutaneous RF renal nerve ablation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Primary endpoint&#58; change in office BP at 1&#44; 3&#44; 6&#44; 9&#44; and 12 months after procedure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Significant reduction in office BP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Symplicity HTN-2&#47;2010<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">39&#44;40</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">Prospective&#44; randomized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Baseline office 178&#177;18&#47;97&#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">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">19&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Symplicity single-electrode RF catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">106 patients randomly assigned to RDN &#40;52&#41; or medical treatment &#40;54&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Primary endpoint&#58; change in office-based measurement of SBP at 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Significant reduction in office BP in patients treated with RDN compared with those treated with medical therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Symplicity HTN-3&#47;2014<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">41</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">Prospective&#44; randomized&#44; blinded&#44; sham-controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&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">22&#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">Symplicity single-electrode RF catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">535 patients randomly assigned to undergo RDN &#40;364&#41; or sham procedure &#40;171&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Primary endpoint&#58; change in office BP at 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No significant difference in office BP between the two groups&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Summary of trials of renal denervation&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:47 [
            0 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2007 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 [
                            0 => "G&#46; Mancia"
                            1 => "G&#46; De Backer"
                            2 => "A&#46; Dominiczak"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/HJH.0b013e3281fc975a"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hypertens"
                        "fecha" => "2007"
                        "volumen" => "25"
                        "paginaInicial" => "1105"
                        "paginaFinal" => "1187"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17563527"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109705025027"
                          "estado" => "S300"
                          "issn" => "07351097"
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                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of resistant hypertension in the United States&#44; 2003-2008"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46;D&#46; Persell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/HYPERTENSIONAHA.111.170308"
                      "Revista" => array:7 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "2011"
                        "volumen" => "57"
                        "paginaInicial" => "1076"
                        "paginaFinal" => "1080"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21502568"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109707011345"
                          "estado" => "S300"
                          "issn" => "07351097"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "3"
              "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 [
                            0 => "S&#46;L&#46; Daugherty"
                            1 => "J&#46;D&#46; Powers"
                            2 => "D&#46;J&#46; Magid"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "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 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22379110"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sympathectomy in the treatment of hypertension&#58; review of 122 cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "D&#46;M&#46; Morrissey"
                            1 => "V&#46;S&#46; Brookes"
                            2 => "W&#46;T&#46; Cooke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2215-0366(14)00003-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1953"
                        "volumen" => "1"
                        "paginaInicial" => "403"
                        "paginaFinal" => "408"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26361179"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "International expert consensus statement&#58; percutaneous transluminal renal denervation for the treatment of resistant hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46;P&#46; Schlaich"
                            1 => "R&#46;E&#46; Schmieder"
                            2 => "G&#46; Bakris"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2013.08.1616"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2013"
                        "volumen" => "62"
                        "paginaInicial" => "2031"
                        "paginaFinal" => "2045"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24021387"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The human sympathetic nervous system&#58; its relevance in hypertension and heart failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G1&#46; Parati"
                            1 => "M&#46; Esler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehs041"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2012"
                        "volumen" => "33"
                        "paginaInicial" => "1058"
                        "paginaFinal" => "1066"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22507981"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal denervation for resistant hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46; de Sousa Almeida"
                            1 => "P&#46; de Ara&#250;jo Gon&#231;alves"
                            2 => "E&#46; Infante de Oliveira"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.repc.2014.07.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Port Cardiol"
                        "fecha" => "2015"
                        "volumen" => "34"
                        "paginaInicial" => "125"
                        "paginaFinal" => "135"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25662472"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "8"
              "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 [
                            0 => "S&#46;W&#46; Hoobler"
                            1 => "J&#46;T&#46; Manning"
                            2 => "W&#46;G&#46; Paine"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "1951"
                        "volumen" => "4"
                        "paginaInicial" => "173"
                        "paginaFinal" => "183"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14859394"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S073510970000752X"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Kinsey D&#46; 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:2 [
                            0 => "R&#46;H&#46; Smithwick"
                            1 => "G&#46;P&#46; Whitelaw"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "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 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14037735"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "10"
              "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 [
                            0 => "M&#46; Harington"
                            1 => "P&#46; Kincaid-Smith"
                            2 => "M&#46;J&#46; McMichael"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "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 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/788855"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "11"
              "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 [
                            0 => "U&#46;S&#46; Von Euler"
                            1 => "S&#46; Hellner"
                            2 => "A&#46; Purkhold"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "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 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13186788"
                            "web" => "Medline"
                          ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Pulse and respiratory grouping of sympathetic impulses in human muscle-nerves"
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                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46;E&#46; Hagbarth"
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                          ]
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                    ]
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                    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 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4235387"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            12 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Determination of norepinephrine apparent release rate and clearance in humans"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46; Esler"
                            1 => "G&#46; Jackman"
                            2 => "A&#46; Bobik"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "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 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/513964"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "etiqueta" => "14"
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                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 [
                            0 => "P&#46;A&#46; Blombery"
                            1 => "B&#46;G&#46; Heinzow"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Circ Res"
                        "fecha" => "1983"
                        "volumen" => "53"
                        "paginaInicial" => "688"
                        "paginaFinal" => "694"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6627617"
                            "web" => "Medline"
                          ]
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                          "pii" => "S0735109706028853"
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              ]
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            14 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "15"
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                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"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "G&#46;J&#46; Hasking"
                            1 => "M&#46;D&#46; Esler"
                            2 => "G&#46;L&#46; Jennings"
                          ]
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                      ]
                    ]
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                  "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 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3948363"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0315"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sympathetic drive in anterior and inferior uncomplicated acute myocardial infarction"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "L&#46;N&#46; Graham"
                            1 => "P&#46;A&#46; Smith"
                            2 => "R&#46;J&#46; Huggett"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "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 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15117852"
                            "web" => "Medline"
                          ]
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                    ]
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              "identificador" => "bib0320"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Central mechanisms of abnormal sympathoexcitation in chronic heart failure"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "T&#46; Kishi"
                            1 => "Y&#46; Hirooka"
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Cardiol Res Pract"
                        "fecha" => "2012"
                        "volumen" => "2012"
                        "paginaInicial" => "1"
                        "paginaFinal" => "7"
                      ]
                    ]
                  ]
                ]
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            17 => array:3 [
              "identificador" => "bib0325"
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                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"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "F&#46; Triposkiadis"
                            1 => "G&#46; Karayannis"
                            2 => "G&#46; Giamouzis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2009.05.015"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2009"
                        "volumen" => "54"
                        "paginaInicial" => "1747"
                        "paginaFinal" => "1782"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19874988"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0330"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The sympathetic system and hypertension"
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                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46; Esler"
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                    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 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10921528"
                            "web" => "Medline"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Sympathetic nerve biology in essential hypertension"
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                          "autores" => array:3 [
                            0 => "M&#46; Esler"
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                            2 => "D&#46; Kaye"
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                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Exp Pharmacol Physiol"
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                        "volumen" => "28"
                        "paginaInicial" => "986"
                        "paginaFinal" => "989"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11903299"
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              "identificador" => "bib0340"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The sympathetic system in essential hypertension"
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                            0 => "M&#46; Esler"
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                      "Revista" => array:7 [
                        "tituloSerie" => "Rev Port Cardiol"
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                        "volumen" => "19"
                        "numero" => "Suppl 2"
                        "paginaInicial" => "II9"
                        "paginaFinal" => "II14"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10874851"
                            "web" => "Medline"
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              "identificador" => "bib0345"
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                      "titulo" => "Sympathetic hyperactivity in hypertensive chronic kidney disease patients is reduced during standard treatment"
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                            0 => "J&#46; Neumann"
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                            2 => "I&#46;H&#46; Klein"
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                    0 => array:2 [
                      "doi" => "10.1161/01.HYP.0000256530.39695.a3"
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                        "tituloSerie" => "Hypertension"
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                        "paginaFinal" => "510"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17224471"
                            "web" => "Medline"
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              "identificador" => "bib0350"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Sympathetic nervous system and insulin resistance&#58; from obesity to diabetes"
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46; Esler"
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                            2 => "G&#46; Wiesner"
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                    0 => array:1 [
                      "Revista" => array:8 [
                        "tituloSerie" => "Am J Hypertens"
                        "fecha" => "2001"
                        "volumen" => "14"
                        "numero" => "11 Pt 2"
                        "paginaInicial" => "304S"
                        "paginaFinal" => "309S"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11721888"
                            "web" => "Medline"
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                          "pii" => "S0140673603121137"
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                          "issn" => "01406736"
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              "identificador" => "bib0355"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The sympathetic nervous system and obstructive sleep apnea&#58; implications for hypertension"
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                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46; Narkiewicz"
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                  "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 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9488212"
                            "web" => "Medline"
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              "identificador" => "bib0360"
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                0 => array:2 [
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                    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"
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                        0 => array:2 [
                          "etal" => false
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "J Appl Physiol"
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                        "paginaInicial" => "227"
                        "paginaFinal" => "237"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19940096"
                            "web" => "Medline"
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                            0 => "R&#46; Furlan"
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                    0 => array:2 [
                      "doi" => "10.1152/ajpregu.00442.2005"
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                        "tituloSerie" => "Am J Physiol Regul Integr Comp Physiol"
                        "fecha" => "2006"
                        "volumen" => "290"
                        "paginaInicial" => "R224"
                        "paginaFinal" => "R232"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16123227"
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              "identificador" => "bib0370"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Central sympathetic overactivity&#58; maladies and mechanisms"
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                      ]
                    ]
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                    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 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19268634"
                            "web" => "Medline"
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              "identificador" => "bib0375"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Plasma norepinephrine in congestive heart failure"
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                            0 => "J&#46;A&#46; Thomas"
                            1 => "B&#46;H&#46; Marks"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Cardiol"
                        "fecha" => "1978"
                        "volumen" => "41"
                        "paginaInicial" => "233"
                        "paginaFinal" => "243"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/203177"
                            "web" => "Medline"
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                0 => array:2 [
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                    0 => array:1 [
                      "titulo" => "The Cardiac Insufficiency Bisoprolol Study II &#40;CIBIS-II&#41;&#58; a randomised trial"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet"
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                        "volumen" => "353"
                        "paginaInicial" => "9"
                        "paginaFinal" => "13"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10023943"
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                0 => array:3 [
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                    0 => array:2 [
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                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Esler"
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                      ]
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                  "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 [
                          0 => array:2 [
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Article information

ISSN: 21742049
Original language: English

DOI:10.1016/j.repce.2016.06.007

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	5	4	9
2024 October	31	30	61
2024 September	46	21	67
2024 August	44	24	68
2024 July	30	29	59
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2024 May	39	25	64
2024 April	33	24	57
2024 March	37	29	66
2024 February	30	33	63
2024 January	30	43	73
2023 December	25	24	49
2023 November	30	21	51
2023 October	15	15	30
2023 September	32	18	50
2023 August	18	13	31
2023 July	20	9	29
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2023 May	43	18	61
2023 April	34	3	37
2023 March	55	27	82
2023 February	41	20	61
2023 January	21	15	36
2022 December	75	22	97
2022 November	69	31	100
2022 October	56	18	74
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2022 August	23	29	52
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2022 March	32	38	70
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2021 December	18	35	53
2021 November	37	36	73
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2021 August	27	29	56
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2021 April	61	44	105
2021 March	49	22	71
2021 February	45	17	62
2021 January	34	16	50
2020 December	57	8	65
2020 November	26	17	43
2020 October	21	16	37
2020 September	48	11	59
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2020 July	54	10	64
2020 June	37	8	45
2020 May	41	9	50
2020 April	31	11	42
2020 March	48	13	61
2020 February	89	11	100
2020 January	41	9	50
2019 December	35	5	40
2019 November	32	10	42
2019 October	36	10	46
2019 September	60	9	69
2019 August	54	8	62
2019 July	40	10	50
2019 June	40	8	48
2019 May	37	8	45
2019 April	33	22	55
2019 March	67	11	78
2019 February	76	12	88
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2018 November	152	14	166
2018 October	468	13	481
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2018 August	29	6	35
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2018 February	12	2	14
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2017 July	23	9	32
2017 June	37	11	48
2017 May	22	22	44
2017 April	36	14	50
2017 March	37	24	61
2017 February	31	7	38
2017 January	21	13	34
2016 December	45	19	64
2016 November	40	21	61
2016 October	46	21	67

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