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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ERenal denervation is a new therapeutic intervention being studied for the treatment of resistant hypertension (HTN). The procedure has other potential applications in which it could be studied since other disease processes are characterized by increased sympathetic activity. Other renal interventions such as stenting may also relieve HTN and improve renal function, although the benefits have yet to be demonstrated. This article discusses sympathetic modulation in cardiovascular disease, including renal denervation for HTN and other potential applications, as well as multiple clinical trials.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInterventional Techniques \u0026amp; Devices\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInterventional Radiology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertensive Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERenal Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertension \u0026amp; Kidney Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInterventional Techniques \u0026amp; Devices\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology \u0026amp; Cardiovascular Medicine\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInterventional Radiology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertensive Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERenal Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertension \u0026amp; Kidney Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ERenal denervation is a new therapeutic intervention being studied for the treatment of resistant hypertension (HTN). The procedure has other potential applications in which it could be studied since other disease processes are characterized by increased sympathetic activity. Other renal interventions such as stenting may also relieve HTN and improve renal function, although the benefits have yet to be demonstrated.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EFelix Mahfoud, MD, University of Saarlandes, Homburg\/Saar, Germany, discussed sympathetic modulation in cardiovascular disease, including renal denervation for HTN and other potential applications. Renal denervation has been shown to reduce systolic and diastolic blood pressure in patients with very severe treatment-resistant HTN [Krum H et al. \u003Cem\u003ELancet\u003C\/em\u003E 2013]. Reductions in blood pressure (BP) have been sustained for \u22653 years in four trials for which results have been published [Krum H et al. \u003Cem\u003ELancet\u003C\/em\u003E 2013; Hering D et al. \u003Cem\u003EHypertension\u003C\/em\u003E 2012]. Initial concerns that renal sympathetic nerves might regrow have not been realized, and functional renervation has not been detected.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EAfferent renal sympathetic fibers contribute to central sympathetic activity and thereby to central sympathetic outflow when activated. The efferent fibers that connect to the heart may then increase heart rate and contractility, decrease ejection fraction, and trigger arrhythmias [Ewen S et al. \u003Cem\u003EHeart\u003C\/em\u003E 2013]. In addition, afferent sympathetic fibers in the kidney can contribute to HTN by activating the renin-angiotensin system and reducing renal blood flow and glomerular filtration rate. Renal denervation reduces central sympathetic activity. Since many cardiac diseases are characterized by increased sympathetic activity, there is a growing body of evidence that renal denervation might have beneficial effects on diabetes, renal function, myocardial dysfunction, heart failure, and arrhythmias [B\u00f6hm M et al. \u003Cem\u003ENat Rev Cardiol\u003C\/em\u003E 2013].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EIn patients treated with renal sympathetic denervation for resistant HTN, there was a significant decrease in resting heart rate in those who had an elevated heart rate at baseline, and the reduction was greatest in patients with the highest heart rate [Ukena C et al. \u003Cem\u003EInt J Cardiol\u003C\/em\u003E 2013]. Prof. Mahfoud and colleagues investigated renal denervation in a porcine model of obstructive sleep apnea (OSA) since this condition is characterized by an increase in sympathetic activity [Linz D et al. \u003Cem\u003EHypertension\u003C\/em\u003E 2012]. They found that renal denervation suppressed the BP rise which occurs following apnea. These results suggest that renal denervation could be studied in humans as a method of reducing the adverse effects of OSA. One patient with permanent atrial fibrillation (AF) showed a reduction in ventricular heart rate after renal sympathetic denervation, even during exercise. This observation led them to study the effect of renal denervation on AF. They found that they could no longer induce AF in the porcine model of OSA. A study from Russia [Pokushalov E et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2012] randomized 27 patients with symptomatic AF and drug-resistant HTN undergoing pulmonary vein isolation (PVI) to treatment with either concomitant renal artery denervation or no additional treatment. Patients who received renal denervation in addition to PVI were significantly more likely to have no AF within the first 12 months of treatment than patients who received only PVI (69% vs 29%; p=0.033).\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EProf. Mahfoud\u0027s cardiac core laboratory recently performed cardiac magnetic resonance imaging in 45 patients prior to baseline renal artery denervation and then again 6 months after treatment. They found that renal denervation used in patients with resistant HTN decreased BP and left ventricular mass [Mahfoud F, Kelle S. Unpublished data]. In the subset of patients with an left atrial enlargement, a known risk factor for developing AF, renal denervation decreased left atrial size. Renal denervation also improved circumferential strain, an early indicator of left ventricular dysfunction, by 35% (p=0.006) in patients with impaired strain at baseline. There were no significant changes in control patients who received only medical treatment.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThese results and the recent publication of results for the 7 initial patients in the REACH-Pilot of renal denervation for chronic heart failure trial [Davies JE et al. \u003Cem\u003EInt J Cardiol\u003C\/em\u003E 2013] have provided the rationale for assessing renal denervation in chronic heart failure. The RE-ADAPT-HF trial will examine the effect of renal denervation on 100 patients with heart failure and HTN. The inclusion criteria and schema of this trial are shown in \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/19\/26\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022RE-ADAPT-HF Trial Inclusion Criteria and Schema\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1155623300\u0022 data-figure-caption=\u0022RE-ADAPT-HF Trial Inclusion Criteria and Schema\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/19\/26\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/19\/26\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/19\/26\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13789\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003ERE-ADAPT-HF Trial Inclusion Criteria and Schema\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ECHF=congestive heart failure; eGFR=estimated glomerular filtration rate; LVEF=left ventricular ejection fraction; M=months; NYHA=New York Heart Association; SBP=systolic blood pressure.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from F Mahfoud, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003EIt is yet to be determined if renal denervation improves clinical outcomes in patients with resistant HTN. In addition, further studies are needed in order to determine if this therapy can improve outcomes of patients with chronic heart failure, obstructive sleep apnea, and chronic kidney disease.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EChristopher J. Cooper, MD, University of Toledo, Toledo, Ohio, USA, presented the rationale for another trial, Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions [CORAL; Cooper CJ et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2013], which was designed to compare medical therapy plus stenting of hemodynamically significant renal artery stenoses (RAS) versus medical therapy alone in patients with systolic HTN and RAS. Atherosclerotic RAS has been linked to secondary HTN and ischemic nephropathy. Balloon angioplasty of RAS has been performed since 1978, and data from registries suggest that stenting of atherosclerotic RAS lowers BP [Blum U et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 1997; Burket MW et al. \u003Cem\u003EAm Heart J\u003C\/em\u003E 2000] and stabilizes kidney function [Harden PN et al. \u003Cem\u003ELancet\u003C\/em\u003E 1997; Watson PS et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2000]; however, randomized clinical outcomes trials of renal angioplasty or stenting outcomes have not yet demonstrated benefit.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EThe CORAL trial was an open-label, randomized, international, multicenter controlled trial sponsored by the National Heart, Lung, and Blood Institute. In order to qualify for the trial, patients were required to have HTN on \u22652 drugs, chronic kidney disease, and evidence of atherosclerosis. Patients enrolled in the trial were then randomized to either medical therapy (which included antihypertensive medications, statins, diabetes management, and smoking cessation) or renal artery stenting. The primary endpoint of the trial was a composite of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for heart failure, progression of renal failure, or the need for renal-replacement therapy. Medical therapy significantly reduced systolic BP in patients with chronic kidney disease with or without diabetes. The demographics of the 947 patients randomly assigned to treatment are shown in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/13790\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/13790\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13790\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-12\u0022 class=\u0022first-child\u0022\u003EBaseline Demographic of the CORAL Population (n=947)\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-14\u0022\u003EThe CORAL trial has recently been completed, and data have shown that over a median follow-up period of 43 months, renal artery stenting was not better than medical management alone in preventing the primary composite endpoint (35.1% vs 35.8%; HR, 0.94; 95% CI, 0.76 to 1.17; p=0.58) [Cooper CJ et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2013].\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/13\/19\/26.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nznkj1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nznkj1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nznkj1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}