***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVES The aim of this prospect i ve r and omized study was to assess the impact of renal artery denervation in patients with a history of refractory atrial fibrillation ( AF ) and drug-resistant hypertension who were referred for pulmonary vein isolation ( PVI ) . BACKGROUND Hypertension is the most common cardiovascular condition responsible for the development and maintenance of AF . Treating drug-resistant hypertension with renal denervation has been reported to control blood pressure , but any effect on AF is unknown . METHODS Patients with a history of symptomatic paroxysmal or persistent AF refractory to ≥2 antiarrhythmic drugs and drug-resistant hypertension ( systolic blood pressure > 160 mm Hg despite triple drug therapy ) were eligible for enrolment . Consenting patients were r and omized to PVI only or PVI with renal artery denervation .  All patients were followed ≥1 year to assess maintenance of sinus rhythm and to monitor changes in blood pressure . RESULTS Twenty-seven patients were enrolled , and 14 were r and omized to PVI only , and 13 were r and omized to PVI with renal artery denervation . At the end of the follow-up , significant reductions in systolic ( from 181 ± 7 to 156 ± 5 , p < 0.001 ) and diastolic blood pressure ( from 97 ± 6 to 87 ± 4 , p < 0.001 ) were observed in patients treated with PVI with renal denervation without significant change in the PVI only group . Nine of the 13 patients ( 69 % ) treated with PVI with renal denervation were AF-free at the 12-month post-ablation follow-up examination versus 4 ( 29 % ) of the 14 patients in the PVI-only group ( p = 0.033 ) . CONCLUSIONS Renal artery denervation reduces systolic and diastolic blood pressure in patients with drug-resistant hypertension and reduces AF recurrences when combined with PVI Renal sympathetic hyperactivity is seminal in the maintenance and progression of hypertension . Catheter-based renal sympathetic denervation has been shown to significantly reduce blood pressure ( BP ) in patients with hypertension . Durability of effect beyond 1 year using this novel technique has never been reported . A cohort of 45 patients with resistant hypertension ( systolic BP ≥160 mm Hg on ≥3 antihypertension drugs , including a diuretic ) has been originally published . Herein , we report longer-term follow-up data on these and a larger group of similar patients subsequently treated with catheter-based renal denervation in a nonr and omized manner . We treated 153 patients with catheter-based renal sympathetic denervation at 19 centers in Australia , Europe , and the United States . Mean age was 57±11 years , 39 % were women , 31 % were diabetic , and 22 % had coronary artery disease . Baseline values included mean office BP of 176/98±17/15 mm Hg , mean of 5 antihypertension medications , and an estimated glomerular filtration rate of 83±20 mL/min per 1.73 m2 . The median time from first to last radiofrequency energy ablation was 38 minutes . The procedure was without complication in 97 % of patients ( 149 of 153 ) . The 4 acute procedural complications included 3 groin pseudoaneurysms and 1 renal artery dissection , all managed without further sequelae . Postprocedure office BPs were reduced by 20/10 , 24/11 , 25/11 , 23/11 , 26/14 , and 32/14 mm Hg at 1 , 3 , 6 , 12 , 18 , and 24 months , respectively . In conclusion , in patients with resistant hypertension  , catheter-based renal sympathetic denervation results in a substantial reduction in BP sustained out to ≥2 years of follow-up , without significant adverse events BACKGROUND Renal sympathetic hyperactivity is associated with hypertension and its progression , chronic kidney disease , and heart failure . We did a proof-of-principle trial of therapeutic renal sympathetic denervation in patients with resistant hypertension ( ie , systolic blood pressure > /=160 mm Hg on three or more antihypertensive medications , including a diuretic )  to assess safety and blood-pressure reduction effectiveness . METHODS We enrolled 50 patients at five Australian and European centres ; 5 patients were excluded for anatomical reasons ( mainly on the basis of dual renal artery systems ) . Patients received percutaneous radiofrequency catheter-based treatment between June , 2007 , and November , 2008 , with subsequent follow-up to 1 year . We assessed the effectiveness of renal sympathetic denervation with renal noradrenaline spillover in a subgroup of patients . Primary endpoints were office blood pressure and safety data before and at 1 , 3 , 6 , 9 , and 12 months after procedure . Renal angiography was done before , immediately after , and 14 - 30 days after procedure , and magnetic resonance angiogram 6 months after procedure . We assessed blood-pressure lowering effectiveness by repeated measures ANOVA . This study is registered in Australia and Europe with Clinical Trials.gov , numbers NCT 00483808 and NCT 00664638 . FINDINGS In treated patients , baseline mean office blood pressure was 177/101 mm Hg ( SD 20/15 ) , ( mean 4.7 antihypertensive medications ) ; estimated glomerular filtration rate was 81 mL/min/1.73m(2 ) ( SD 23 ) ; and mean reduction in renal noradrenaline spillover was 47 % ( 95 % CI 28 - 65 % ) . Office blood pressures after procedure were reduced by -14/-10 , -21/-10 , -22/-11 , -24/-11 , and -27/-17 mm Hg at 1 , 3 , 6 , 9 , and 12 months , respectively . In the five non-treated patients , mean rise in office blood pressure was + 3/-2 , + 2/+3 , + 14/+9 , and + 26/+17 mm Hg at 1 , 3 , 6 , and 9 months , respectively . One intraprocedural renal artery dissection occurred before radiofrequency energy delivery , without further sequelae . There were no other renovascular complications . INTERPRETATION Catheter-based renal denervation causes substantial and sustained blood-pressure reduction , without serious adverse events , in patients with resistant hypertension . Prospect i ve r and omised clinical trials are needed to investigate the usefulness of this procedure in the management of this condition BACKGROUND Activation of renal sympathetic nerves is key to pathogenesis of essential hypertension . We aim ed to assess effectiveness and safety of catheter-based renal denervation for reduction of blood pressure in patients with treatment-resistant hypertension . METHODS In this multicentre , prospect i ve , r and omised trial , patients who had a baseline systolic blood pressure of 160 mm Hg or more ( ≥150 mm Hg for patients with type 2 diabetes ) , despite taking three or more antihypertensive drugs , were r and omly allocated in a one-to-one ratio to undergo renal denervation with previous treatment or to maintain previous treatment alone ( control group )  at 24 participating centres . R and omisation was done with sealed envelopes . Data analysers were not masked to treatment assignment . The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months . Primary analysis included all patients remaining in follow-up at 6 months . This trial is registered with Clinical Trials.gov , number NCT00888433 . FINDINGS 106 ( 56 % ) of 190 patients screened for eligibility were r and omly allocated to renal denervation ( n=52 ) or control ( n=54 ) groups between June 9 , 2009 , and Jan 15 , 2010 . 49 ( 94 % ) of 52 patients who underwent renal denervation and 51 ( 94 % ) of 54 controls were assessed for the primary endpoint at 6 months . Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg ( SD 23/11 , baseline of 178/96 mm Hg , p<0·0001 ) , whereas they did not differ from baseline in the control group ( change of 1/0 mm Hg [ 21/10 ] , baseline of 178/97 mm Hg , p=0·77 systolic and p=0·83 diastolic ) . Between-group differences in blood pressure at 6 months were 33/11 mm Hg ( p<0·0001 ) . At 6 months , 41 ( 84 % ) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more , compared with 18 ( 35 % ) of 51 controls ( p<0·0001 ) . We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups ; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion , but required no treatment . INTERPRETATION Catheter-based renal denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertensive patients . FUNDING Ardian Hypertension represents a significant global public health concern , contributing to vascular and renal morbidity , cardiovascular mortality , and economic burden . The opportunity to influence clinical outcomes through hypertension management is therefore paramount . Despite adherence to multiple available medical therapies , a significant proportion of patients have persistent blood pressure elevation , a condition termed resistant hypertension . Recent recognition of the importance of the renal sympathetic and somatic nerves in modulating blood pressure and the development of a novel procedure that selectively removes these contributors to resistant hypertension represents an opportunity to provide clinical ly meaningful benefit across wide and varied patient population s. Early clinical evaluation with catheter‐based , selective renal sympathetic denervation in patients with resistant hypertension has mechanistically correlated sympathetic efferent denervation with decreased renal norepinephrine spillover and renin activity , increased renal plasma flow , and has demonstrated clinical ly significant , sustained reductions in blood pressure . The SYMPLICITY HTN‐3 Trial is a pivotal study design ed as a prospect i ve , r and omized , masked procedure , single‐blind trial evaluating the safety and effectiveness of catheter‐based bilateral renal denervation for the treatment of uncontrolled hypertension despite compliance with at least 3 antihypertensive medications of different classes ( at least one of which is a diuretic ) at maximal tolerable doses . The primary effectiveness endpoint is measured as the change in office‐based systolic blood pressure from baseline to 6 months . This manuscript describes the design and methodology of a regulatory trial of selective renal denervation for the treatment of hypertension among patients who have failed pharmacologic therapy . Clin . Cardiol . 2012 . doi : 
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CONCLUSIONS In conclusion , while poor quality unblinded studies provide evidence that renal denervation using catheter-based systems is effective in reducing systolic and diastolic blood pressure in resistant hypertension , the largest r and omised controlled trial to date ( SYMPLICITY HTN-3 ) failed to demonstrate any benefit