Renal denervation for treatment of cardiac arrhythmias: state of the art and future directions

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Renal denervation for treatment of cardiac arrhythmias: State of the art

and future directions

Short title: Renal denervation and arrhythmias

Jedrzej Kosiuk*1, MD, Sebastian Hilbert*

1, MD, Evgeny Pokushalov

2, MD, Gerhard

Hindricks1, MD, PhD, Jonathan S. Steinberg

3, MD and Andreas Bollmann

1, MD, PhD

1 Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany

2State Research Institute of Circulation Pathology, Novosibirsk, Russian Federation

3 Arrhythmia Institute, The Valley Health System and the Mt. Sinai School of Medicine, New

York, NY, USA

Address for correspondence:

Jedrzej Kosiuk, MD

Department of Electrophysiology

Heart Center Leipzig

Strümpellstr. 39

04289 Leipzig, Germany

Phone: ++49 341 865 252083

Fax: ++49 341 865 1460

Email: [email protected]

mailto:[email protected]


Drs. Kosiuk and Hilbert contributed equally to this manuscript.

G. Hindricks reports research support and honoraria relevant to this topic from St. Jude Medical,

Biosense Webster, Boston Scientific, Medtronic, Biotronik, & Stereotaxis. J. Steinberg reports

participation on research grants supported by Biosense Webster, Boston Scientific & Medtronic, for

whom he also serves as a consultant. A. Bollmann reports moderate lecture fees from St. Jude

Medical. Other authors: No disclosures.

Abstract

It has now been more than a quarter of a century since modulation of the sympathetic nervous

system was proposed for the treatment of cardiac arrhythmias of different origins. But it has

also been some time since some of the early surgical attempts have been abandoned. With the

development of ablation techniques, however, new approaches and targets have been recently

introduced that have revolutionized our way of thinking about sympathetic modulation. Renal

nerve ablation technology is now being successfully used for the treatment of resistant

hypertension, but the indication spectrum might broaden and new therapeutic options might

arise in the near future.

This review focuses on the possible impact of renal sympathetic system modulation on

cardiac arrhythmias, the current evidence supporting this approach, and the ongoing trials of

this method in electrophysiological laboratories. We will discuss the potential roles that

sympathetic modulation may play in the future.


Keywords: renal denervation; ventricular tachycardia; catheter ablation; atrial fibrillation;

autonomic nervous system

Pathophysiology and past experience

Sympathetic activity plays an important role in the pathogenesis of ventricular

tachyarrhythmias (1) and the evidence for a major role of the sympathetic nervous system in

triggering cardiac events provided the rationale for antiadrenergic interventions such as left

cardiac sympathetic denervation (LCSD) (2,3). In the 1970s antiadrenergic interventions

were successfully used in patients with long-QT syndrome and later in patients suffering

from catecholaminergic polymorphic VTs. Those early strategies aiming at reducing

sympathetic activity had a potential to protect against ventricular arrhythmias by: I)

prevention/suppression of early afterdepolarizations and of reentrant mechanisms (4), II)

raising the ventricular fibrillation threshold (5), and III) shortening of the QT interval (2). As

of today, this surgical approach has been largely abandoned due to its high incidence of often

debilitating side effects such as orthostatic hypotension, palpitations, anhydrosis, intestinal

disturbances, loss of ejaculation, thoracic duct injuries, and atelectasis (6). However, the

concept of decreased sympathetic activity remained an important factor in the prevention and

treatment of ventricular arrhythmias as a target of multiple drugs including beta-blockers.

Despite recent data on RDN failing to perform better than in the placebo arm in resistant

hypertension (7), from a pathophysiological standpoint the antiarrhythmic effects of this

procedure may still be implied. Similarly to LCSD or percutaneus suppression of ganglion

stellatum, RDN results in a reduction of whole body norepinephrine spillover by 42% and

efferent muscle sympathetic nerve activity by 66% (8).


Asides from possible direct antiarrhythmic properties, RDN may ameliorate the symptoms of

chronic heart failure and therefore eliminate arrhythmias that are secondary to electrolyte

disturbances or cardiac decompensation.

Even though this hypothesis is based on contemporary pathophysiological considerations (9),

the effect of RDN on CHF has not yet been extensively studied. Nevertheless, the preliminary

results of a very recently published small series of studies are promising. Davies et al. (10)

performed RDN in 7 patients on maximal tolerated heart failure therapy with aggravated

symptoms of CHF. In this cohort, a subjective improvement of HF symptoms and increase of

6-minute walk distance at 6 months was observed. During the 2012 ESC session, similar

results were also reported by Taborsky et al. (11), who randomized 51 patients with

medically managed severe heart failure to either medical treatment (n = 25) or additional

RDN (N = 26) therapy. A significant improvement of ejection fraction, left ventricular end-

systolic volume index, left ventricular end-diastolic volume index, and NT-proBNP were

observed in the RDN treated group after 12 months follow-up. Furthermore, they reported a

relevant change in frequency of hospitalization and NYHA class in the RDN group.

Review of case series in patients with VT

In a short series published recently by Ukena et al. (12), RDN was tested in 2 patients with

primary non-obstructive hypertrophic and idiopathic dilated cardiomyopathy, who suffered

from therapy resistant electrical storm. Both patients were admitted with repetitive ventricular

arrhythmias including multiple monomorphic and also polymorphic VTs with rapid

degeneration into ventricular fibrillation. Previous attempts of interventional treatment via

endocardial or epicardial ablation were of limited efficacy or were declined by the patients.


In both cases, a combination of maximal beta-blockers dosage and other antiarrhythmic

drugs, including combinations of up to 3 agents, were ineffective. After exclusion of all

reversible causes, such as electrolyte disturbances, myocardial ischemia due to coronary

artery disease, QT-prolongation or cardiac decompensation and obtaining informed patient

consent, a bilateral RDN with six ablations at 8W for 2 minutes each was performed without

any apparent procedural complications. Even though both patients were relatively hypotonic

(mean blood pressure of 90/60 mmHg), the arterial pressure remained stable during the

procedure and most importantly during the following months. In the first few days after the

RDN procedure, both patients experienced recurrence of VT; but after this initial stabilization

phase, the antiarrhythmic effect of RDN was established as the VT burden dramatically

decreased and, as a consequence, the antiarrhythmic medication was reduced. Both patients

were discharged shortly after the procedure in good clinical condition and remain event-free

during the follow-up of up to 6 months.

Similar results have been recently published by Remo et al. (13). In 4 patients with different

etiologies (ischemic, hypertrophic and dilated cardiomyopathy) with mono- and polymorphic

VT, a bilateral RDN was performed. All patients had a history of previous cardiac ablations

and were treated with ≥ 2 antiarrhythmic drugs. Most interestingly, one of the patients had

undergone a bilateral cervical sympathectomy previously. In this difficult setting, RDN

proved to be a safe and effective tool for reduction and partial elimination of ventricular

arrhythmias. During the mid-term follow-up of 6 months, precluded by the short period of

recurrences, a significant decrease of VT burden was achieved.

Hoffmann at al. (14) reported similar adjuvant effect of RDN following VT ablation in a

acute setting of post-infarction fast VT/VF.

Those results are also reflected in our recent experience with a 23-year-old patient with


ischemic cardiomyopathy due to post-traumatic coronary artery dissection who was admitted

with recurrent VT. Despite two endo- and epicardial catheter ablations and maximum

tolerable dose of ß-blockers, the patient developed an electrical storm and received 33 ICD-

shocks within a month after the second ablation. Bundle branch reentrant VT episodes with a

pre-existing right bundle branch block and left posterior hemiblock morphology recurred

reproducibly on treadmill exercise testing even on a maximum dose of sotalol (360 mg per

day). Weighing the options (repeat catheter ablation with high risk of complete AV block vs

change in antiarrhythmic drug regimen vs RDN), bilateral RDN was preferred by the patient

and performed successfully (EnligHTN, St. Jude Medical). A 30-hour Holter ECG as well as

a treadmill exercise test 3 days after RDN showed no evidence of VT which allowed

reduction of antiarrhythmic drug dosage. Over the course of a 10-month follow-up period, no

VT events were recorded via remote monitoring of the ICD and the patient remained

asymptomatic.

Patient characteristics extracted from those series are presented in table 1.

Ongoing trials, future directions and open questions

All these cases provide encouraging preliminary data on the use of RDN for the treatment of

recurrent, refractory, and life-threatening arrhythmias. However, the role of RDN as an

adjunct or stand-alone therapeutic concept in patients with life-threatening arrhythmias and

heart failure is far from obvious and further evidence is needed. Recently a limited efficacy of

RDN in comparison to the shame procedure (7) in terms of blood pressure reduction was

reported. Although, those results might be partially caused by statistical trial design,

improved adhesion of control group during relatively a short follow-up period, increased


placebo effect, operator learning curve, and lacking intraprocedural endpoint must also be

taken under consideration when it comes to extending the indication for RDN.

The ongoing pioneer trials currently being conducted (Table 2) may be able to shed some

light on those questions.

Renal denervation for treatment of atrial fibrillation

Among all supraventricular arrhythmias, one has a special place due to extremely high

prevalence and strong association with morbidity and mortality (15): atrial fibrillation (AF).

Aside from several mechanisms such as atrial stretch and atrial remodeling (16-20), the

impairment of autonomic nervous system has been thought to contribute to the development

of AF substrates (21). In experimental animal models, the ß-adrenergic agonists (i.e.,

isoproterenol) in conjunction with rapid atrial pacing have been successfully used to induce

AF (22,23). Moreover, increased sympathetic activity is correlated with prolonged episodes

of AF and possibly a precondition for sustained AF (24). At the cellular level, it has been

observed that increased calcium levels along with subsequent shortening of the action

potential and refractoriness of` atrial myocardium may be related to sympathetic

overstimulation (25). Finally, recent series of animal studies have also shown that

sympathetic inhibition through RDN may suppress the development of AF induced by rapid

atrial pacing (26) and additionally, may inhibit atrial remodeling after prolonged AF (27).

Increased sympathetic activity and hypertension interacts also affect AF hemodynamically as

both acute and chronic blood pressure elevation can increase atrial stretching and dilation,

resulting in the promotion of arrhythmogenic substrate and/or induction of AF. Recently, it


has been shown in an animal model that the hypertensive group developed a progressive

increase in mean arterial pressure, longer mean effective atrial refractory periods, progressive

bi-atrial hypertrophy, atrial inflammation and left atrial dysfunction (28). All these

components are acknowledged risk factors for AF inducibility, which was also reported as

being significantly higher. Furthermore, the role of hypertension as a risk factor for the

development of AF in long- term follow-up has also been documented in large

epidemiological studies (29). This pathophysiological consideration, as well as experimental

and clinical observations, has been the background for the concept of RDN in the treatment

of AF.

The first attempts at evaluating RDN for AF treatment were designed to examine the adjunct

role of RDN in combination with catheter-based pulmonary vein isolation (PVI). The

breakthrough trial was recently reported as a randomized, prospective study by Pokushalov et

al. (30) describing the effect of RDN in patients with a history of refractory paroxysmal or

persistent atrial fibrillation (AF) who were on at least two antiarrhythmic drugs and had

resistant hypertension (systolic blood pressure 160 mm Hg despite triple drug therapy). In

the study, 27 patients were enrolled and randomized to either PVI only (n=14) or PVI and

RDN (n=13). During the scheduled 1-year follow-up visit, a significant reductions in systolic

(from 181 to 156 mm Hg, p < 0.001) and diastolic blood pressure (from 97 to 87mm Hg, p <

0.001) were observed in patients treated with PVI and RDN without significant change in the

PVI only group. The freedom from AF was also significantly improved in the experimental

group when compared with conventional PVI ablation only: 69% vs. 29% (p = 0.033).

Considering the relatively moderate success of radiofrequency ablation in the treatment of AF

in a long-term follow-up and the highly promising results of the additional RDN, this new

approach has a potential to become a clinically important therapeutic option for patients with


AF and hypertension.

Initial data in human studies testing the application of RDN as a stand-alone therapy are also

encouraging. Recently, a case report of persistent drug-resistant AF successfully being

treated with RDN instead of PVI was presented (31). Shortly after the procedure, a

spontaneous termination of persistent AF was observed and the AF recurrence did not appear

during the follow-up of 8 months. Furthermore, a left atrial size was also significantly

reduced from 45mm to 36mm at 6 months of follow-up.

Even though these data are definitively positive, they are still very weak to support the

potential antiarrhythmic role of RDN and its possible role in treatment of supra-ventricular

arrhythmias. However, more evidence is expected to come in the near future as a multitude of

clinical trials (Table 3) are ongoing.

References

1. Lown B, Verrier RL: Neural activity and ventricular fibrillation. N Engl J Med 1976;

294:1165–1170.

2. Schwartz PJ, Priori SG, Cerrone M, Spazzolini C, Odero A, Napolitano C, Bloise R, De

Ferrari GM, Klersy C, Moss AJ, Zareba W, Robinson JL, Hall WJ, Brink PA, Toivonen L,

Epstein AE, Li C, Hu D: Left cardiac sympathetic denervation in the management of high-

risk patients affected by the long-qt syndrome. Circulation 2004; 109:1826–1833.

3. Wilde AA, Bhuiyan ZA, Crotti L, Facchini M, De Ferrari GM, Paul T, Ferrandi C,

Koolbergen DR, Odero A, Schwartz PJ: Left cardiac sympathetic denervation for


catecholaminergic polymorphic ventricular tachycardia. N Engl J Med 2008; 358:2024–2029

4. Schwartz PJ, Priori SG: Sympathetic nervous system and cardiac arrhythmias. In: Zipes

DP, Jalife J, eds. Cardiac Electrophysiology: From Cell to Bedside. Philadelphia, Pa: WB

Saunders Co; 1990:330–343.

5. Schwartz PJ, Snebold NG, Brown AM: Effects of unilateral cardiac sympathetic

denervation on the ventricular fibrillation threshold. Am J Cardiol. 1976; 37:1034–1040.

6. Kadowaki MH, Levett JM: Sympathectomy in the treatment of angina and arrhythmias.

Ann Thorac Surg 1986: 41: 572-578.

7. Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen BT, Leon MB, Liu

M, Mauri L, Negoita M, Cohen SA, Oparil S, Rocha-Singh K, Townsend RR, Bakris GL;

SYMPLICITY HTN-3 Investigators: A controlled trial of renal denervation for resistant

hypertension. N Engl J Med 2014; 370:1393-1401

8. Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD: Renal sympathetic-nerve

ablation for uncontrolled hypertension. N Engl J Med 2009; 361:932–934.

9. Sobotka PA, Mahfoud F, Schlaich MP, Hoppe UC, Bohm M, Krum H: Sympatho-renal

axis in chronic disease. Clin Res Cardiol 2011;100:1049-57.

10. Davies JE, Manisty CH, Petraco R, Barron AJ, Unsworth B, Mayet J, Hamady M,

Hughes AD, Sever PS, Sobotka PA, Francis DP: First-in-man safety evaluation of renal

denervation for chronic systolic heart failure: primary outcome from REACH-Pilot study. Int

J Cardiol. 2013 20;162:189-92.

11. Taborsky M, Lazarova ML, Vaclavik J: The effect of renal denervation in patients with

advanced heart failure. ESC – Munich 2012. 2012: 190 (3148).

12. Ukena C, Bauer A, Mahfoud F, Schreieck J, Neuberger HR, Eick C, Sobotka PA, Gawaz

M, Böhm M. Renal sympathetic denervation for treatment of electrical storm: first-in-man


experience. Clin Res Cardiol. 2012;101:63-7.

13. Remo BF, Preminger M, Bradfield J, Mittal S, Boyle N, Gupta A, Shivkumar K,

Steinberg JS, Dickfeld T: Safety and efficacy of renal denervation as a novel treatment of

ventricular tachycardia storm in patients with cardiomyopathy. Heart Rhythm. 2014;11:541-

6.

14. Hoffmann BA, Steven D, Willems S, Sydow K: Renal sympathetic denervation as an

adjunct to catheter ablation for the treatment of ventricular electrical storm in the setting of

acute myocardial infarction. J Cardiovasc Electrophysiol. 2013;24:1175-1178.

15. Kirchhof P, Bax J, Blomstrom-Lundquist C, Calkins H, Camm AJ, Cappato R, Cosio F,

Crijns H, Diener HC, Goette A, Israel CW, Kuck KH, Lip GY, Nattel S, Page RL, Ravens U,

Schotten U, Steinbeck G, Vardas P, Waldo A, Wegscheider K, Willems S, Breithardt G:

Early and comprehensive management of atrial fibrillation: executive summary of the

proceedings from the 2nd AFNET-EHRA consensus conference “research perspectives in

AF.” Eur Heart J 2009;30:2969–77.

16. Nattel S: New ideas about atrial fibrillation 50 years on. Nature 2002;415:219 –26.

17. Wakili R, Voigt N, Kääb S, Dobrev D, Nattel S: Recent advances in the molecular

pathophysiology of atrial fibrillation. J Clin Invest 2011;121:2955–68.

18. Allessie MA, Boyden PA, Camm AJ, Kléber AG, Lab MJ, Legato MJ, Rosen MR,

Schwartz PJ, Spooner PM, Van Wagoner DR, Waldo AL: Pathophysiology and prevention of

atrial fibrillation. Circulation 2001;103:769 –77.

19. Schotten U, Verheule S, Kirchhof P, Goette A: Pathophysiological mechanisms of atrial

fibrillation: a translational appraisal. Physiol Rev 2011;91:265–325.

20. Iwasaki YK, Nishida K, Kato T, Nattel S: Atrial fibrillation pathophysiology:

implications for management. Circulation 2011;124:2264-74.


21. Arora R: Recent insights into the role of the autonomic nervous system in the creation of

substrate for atrial fibrillation: implications for therapies targeting the atrial autonomic

nervous system. Circ Arrhythm Electrophysiol 2012;5:850-9.

22. Sharifov OF, Fedorov VV, Beloshapko GG, Glukhov AV, Yushmanova AV,

Rosenshtraukh LV: Roles of adrenergic and cholinergic stimulation in spontaneous atrial

fibrillation in dogs. J Am Coll Cardiol 2004;43:483-490.

23. Oral H, Crawford T, Frederick M, Gadeela N, Wimmer A, Dey S, Sarrazin JF, Kuhne M,

Chalfoun N, Wells D, Good E, Jongnarangsin K, Chugh A, Bogun F, Pelosi F Jr, Morady F:

Inducibility of paroxysmal atrial fibrillation by isoproterenol and its relation to the mode of

onset of atrial fibrillation. J Cardiovasc Electrophysiol 2008;19:466-470.

24. Jayachandran JV, Sih HJ, Winkle W, Zipes DP, Hutchins GD, Olgin JE: Atrial

fibrillation produced by prolonged rapid atrial pacing is associated with heterogeneous

changes in atrial sympathetic innervation. Circulation 2000; 101:1185-1191.

25. Shen MJ, Choi EK, Tan AY, Lin SF, Fishbein MC, Chen LS, Chen PS: Neural

mechanisms of atrial arrhythmias. Nat Rev Cardiol 2011;9:30-39.

26. Zhao Q, Yu S, Zou M, Dai Z, Wang X, Xiao J, Huang C: Effect of renal sympathetic

denervation on the inducibility of atrial fibrillation during rapid atrial pacing. J Interv Card

Electrophysiol 2012:35:119-125.

27. Wang X, Zhao Q, Huang H, Tang Y, Xiao J, Dai Z, Yu S, Huang C: Effect of renal

sympathetic denervation on atrial substrate remodeling in ambulatory canines with prolonged

atrial pacing. PLoS One 2013; 8: e64611.

28. Lau DH, Mackenzie L, Kelly DJ, Psaltis PJ, Brooks AG, Worthington M, Rajendram A,

Kelly DR, Zhang Y, Kuklik P, Nelson AJ, Wong CX, Worthley SG, Rao M, Faull RJ,

Edwards J, Saint DA, Sanders P: Hypertension and atrial fibrillation: evidence of progressive


atrial remodeling with electrostructural correlate in a conscious chronically instrumented

ovine model. Heart Rhythm 2010;7:1282–90.

29. Huxley RR, Lopez FL, Folsom AR, Agarwal SK, Loehr LR, Soliman EZ, Maclehose R,

Konety S, Alonso A: Absolute and attributable risks of atrial fibrillation in relation to optimal

and borderline risk factors: the Atherosclerosis Risk in Communities (ARIC) study.

Circulation 2011; 123: 1501-1508

30. Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A,

Shirokova N, Karaskov A, Mittal S, Steinberg JS: A randomized comparison of pulmonary

vein isolation with versus without concomitant renal artery denervation in patients with

refractory symptomatic atrial fibrillation and resistant hypertension. J Am Coll Cardiol.

2013;62:1129-30.

31. Vollmann D, Sossalla S, Schroeter MR, Zabel M: Renal artery ablation instead of

pulmonary vein ablation in a hypertensive patient with symptomatic, drug-resistant, persistent

atrial fibrillation. Clin Res Cardiol 2013;102:315-318.


Table 1. Patients characteristics of VT case series

Case series Age/Sex Cardiomyopathy LVEF

(%)

Clinical

arrhythmias Prior Therapy Follow-up

Ukena et al. 67 M

non-obstructive

hypertrophic 40

multiple,

monomorphic VT

endo- and epicardial ablation;

amiodarone, mexiletine,

(lidocaine infusion)

2 episodes within first month, no episodes for 5 months, 1

episode at 6 months due to hypokalemia

57 M non-ischemic 28 polymorphic VT

or VF amiodarone

12 VF

episodes within first 24 h, no episodes for 6 months

Remo et al.

63 F ischemic 30 monomorphic VT

endo- and epicardial ablation,

bilateral cervical

sympathectomie; amiodarone

No episodes for 5 months.

4 ICD shocks @ month 5

83 M non-ischemic 30 monomorphic VT endocardial ablation;

amiodarone

Only 1 pace-terminated VT @ 1 month; 80% decrease in

VT; 64% decrease in NSVT episodes

60 M ischemic 20 multiple,

monomorphic VT

epicardial ablation;

amiodarone 2 episodes within first month, no episodes for 14 months

68 M non-obstructive

hypertrophic 45

multiple slow

uniform VTs

2x ablation; lidocaine,

procainamide Single slow VT requiring therapy and then no further VT

Hoffmann et al. 63 M ischemic 30 polymorphic VT

or VF

endocardial ablation;

amiodarone No episodes during 160 days follow-up

Kosiuk et al. 23 M ischemic 45 multiple,

monomorphic VT

endo- and epicardial ablation;

sotalol No episodes during 10 months follow-up


Table 2. Overview of ongoing trials in field of RDN and VT/CHF.

Focus Trial Identifier Official Title Sites Interventions Status Expected

Completion

Date

VT NCT01747837 REnal SympathetiC Denervation to sUpprEss

Ventricular Tachyarrhythmias

Mount Sinai School of Medicine,

New York, New York,US;

Heart Center St. Anne's University

Hospital, Brno, Czech Republic

ICD implantation vs

ICD implantation +

RDN

recruiting 10/2015

NCT01858194 REnal Sympathetic dEnervaTion as an a

Adjunct to Catheter-based VT Ablation

Mount Sinai School of Medicine,

New York, New York,US;

VT ablation vs VT

ablation + RDN

recruiting 11/2016

CHF NCT01870310 Long Term Study on the Possible Beneficial

Effects of Catheterised Renal Denervation in

Patients With Heart Failure and Left

Ventricular Systolic Dysfunction Who Are

Already on Standard Medical Therapy.

University Hospital, Olomouc,

Czech Republic,

RDN + best medical

therapy vs. best

medical therapy

recruiting 06/2016

NCT01392196 Renal Denervation in Patients With Chronic

Heart Failure & Renal Impairment

Alfred Hospital,Melbourne,

Victoria, Australia

RDN + best medical

therapy vs. best

medical therapy

recruiting 05/2017

NCT01954160 Promotion of Renal Sodium Excretion by

Renal Sympathetic Denervation in Congestive

Heart Failure

Emory Universito,Atlanta,

Georgia; Duke University Medical

Center, Durham, North Carolina;

University of Pennsylvania Health

System, Philadelphia,

Pennsylvania, US

early RDN vs. late RDN not yet

open

05/2016

NCT01639378 Impact of Renal Artery Denervation in

Patients With Chronic Heart Failure

Compared With Sham Procedure

Imperial College London, London,

United Kingdom

RDN + best medical

therapy vs. sham

procedure + best

medical therapy

recruiting 08/2014


NCT01790906 Safety and Effectiveness Study of

Percutaneous Catheter-base Renal

Sympathetic Denervation for Patients With

Chronic Heart Failure

First Affiliated Hospital of Nanjing

Medical University, Nanjing,

Jiangsu, China

RDN + best medical

therapy vs. best

medical therapy

recruiting 04/2017

NCT01402726 Renal Sympathetic Modification in Patients

With Heart Failure

The Second Affiliated Hospital of

Chongqing Medical University,

Chongqing, China

RDN + best medical

therapy vs. best

medical therapy

recruiting 04/2017


Table 3. Overview of ongoing trials in field of RDN and AF.

Trial

Identifier

Official Title Sites Interventions Status Expected

Completion

Date

NCT01952743 Concomitant Renal Denervation Therapy in

Hypertensive Patients Undergoing Atrial

Fibrillation Ablation - A Feasibility Study

Mayo Clinic, Rochester,

Minnesota, US

PVI + RDN vs. PVI only recruiting 09/2016

NCT01898910 Ganglionated Plexi Ablation vs Renal Denervation

in Patients Undergoing Pulmonary Vein Isolation.

A Randomized Comparison

Meshalkin Research Institute of

Pathology of Circulation,

Novosibirsk, Russian Federation

PVI + RDN vs. PVI +

Ganglionated Plexi ablation

completed 06/2013

NCT01907828 A Feasibility Study to Evaluate the Effect of

Concomitant Renal Denervation and Cardiac

Ablation on AF Recurrence

recruiting PVI + RDN vs. PVI only not yet

open

05/2016

NCT01897545 The Role of Renal Denervation in Improving

Outcomes of Catheter Ablation in Patients With

Atrial Fibrillation and Arterial Hypertension

The Valley Health System, New

York, US; Athens Euroclinic,

Athens, Greece; State Research

Institute of Circulation

Pathology, Novosibirsk, Russian

Federation

PVI + RDN vs. PVI only completed 6/2013

NCT01959997 Randomized Comparison of Redo Pulmonary Vein

Isolation With vs. Without Renal Denervation for

Recurrent Atrial Fibrillation After Initial

Pulmonary Vein Isolation


York, US; State Research



Federation

Redo PVI vs. Redo PVI + RDN recruiting 09/2016

NCT01686542 Circumferential Pulmonary Vein Isolation (CPVI) The Second Affiliated Hospital PVI + RDN vs. PVI only recruiting 12/2016


Plus Renal Sympathetic Modification Versus CPVI

Alone for AF Ablation: a Pilot Study

of Chongqing Medical

University Chongqing, China

NCT01635998 Adjunctive Renal Sympathetic Denervation to

Modify Hypertension as Upstream Therapy in the

Treatment of Atrial Fibrillation (H-FIB)

11 centers from US and Europe PVI + RDN vs. PVI only recruiting 07/2017

NCT01713270 Safety and Effectiveness Study of Percutaneous

Catheter-based Renal Sympathetic Denervation in

Patients With Drug-resistant Hypertension and

Symptomatic Atrial Fibrillation

First Affiliated Hospital of

Nanjing Medical University,

Nanjing, Jiangsu, China

RDN vs. best medical treatment

(hypertension) vs. Direct-Current

Cardioversion

recruiting 06/2015

NCT01873352 Evaluate Renal Artery Denervation In Addition to

Catheter Ablation To Eliminate Atrial Fibrillation

(ERADICATE--AF) Trial


York, US; State Research



Federation

PVI + RDN vs. PVI only recruiting 06/2014

NCT01814111 Safety and Effectiveness Study of Percutaneous

Catheter-based Sympathetic Denervation of the

Renal Arteries in Patients With Hypertension and

Paroxysmal Atrial Fibrillation

The First Hospital of Nanjing

Medical University, Nanjing,

Jiangsu, China

RDN vs. best medical treatment

(AF)

recruiting 06/2015

NCT01952925 Combined Atrial Fibrillation Ablation and Renal

Artery Denervation for the Maintenance of Sinus

Rhythm and Management of Resistant

Hypertension

Oregon Health & Science

University, Portland, Oregon,

United States

PVI + RDN vs. PVI only not yet

open

01/2019

Renal denervation for treatment of cardiac arrhythmias: state of the art and future directions

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