Skip to main content
Log in

Effects of catheter-based renal denervation on heart failure with reduced ejection fraction: a meta-analysis of randomized controlled trials

Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Despite the major progress in the treatment of heart failure, the burden of heart failure is steadily increasing in the Western world. Heart failure is characterized by increased sympathetic activity, and chronic sympathetic activation is involved in the maintenance of the pathological state. Recent studies have shown that catheter-based renal denervation (RDN) presents a safe and minimally invasive treatment option for uncontrolled hypertension, a condition that is driven by increased sympathetic activity. Although randomized controlled trials (RCTs) have examined the effect of RDN in heart failure patients, results are inconsistent due partly to limited power with small sample sizes. We aimed to conduct a meta-analysis of RCTs on the effect of RDN in heart failure patients with reduced left ventricular (LV) ejection fraction (EF). Electronic search identified 5 RCTs including 177 patients. In the pooled analysis, RDN increased LVEF (weighted mean difference (WMD) [95% CI] = 6.289 [1.883, 10.695]%) and 6-min walk distance (61.063 [24.313, 97.813] m) and decreased B-type natriuretic peptide levels (standardized mean difference [95% CI] = − 1.139 [− 1.824, − 0.454]) compared with control. In contrast, RDN did not significantly change estimated glomerular filtration rate (WMD [95% CI] = 5.969 [− 2.595, 14.533] ml/min/1.73 m2) and systolic (− 1.991 [− 15.639, 11.655] mmHg) or diastolic (− 0.003 [− 10.325, 10.320] mmHg) blood pressure compared with control. Our meta-analysis suggests that RDN may improve LV function and exercise capacity in heart failure patients with reduced EF, providing the rationale to conduct large-scale multicenter trials to confirm the observed potential benefits of RDN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Conrad N, Judge A, Tran J, Mohseni H, Hedgecott D, Crespillo AP, Allison M, Hemingway H, Cleland JG, McMurray JJV, Rahimi K (2018) Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals. Lancet 391:572–580

    Article  Google Scholar 

  2. Francis GS, Goldsmith SR, Levine TB, Olivari MT, Cohn JN (1984) The neurohumoral axis in congestive heart failure. Ann Intern Med 101:370–377

    Article  Google Scholar 

  3. Triposkiadis F, Karayannis G, Giamouzis G, Skoularigis J, Louridas G, Butler J (2009) The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications. J Am Coll Cardiol 54:1747–1762

    Article  Google Scholar 

  4. Kandzari DE, Bohm M, Mahfoud F et al (2018) Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet 391:2346–2355

    Article  Google Scholar 

  5. Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Davies J, Basile J, Kirtane AJ, Wang Y, Lobo MD, Saxena M, Feyz L, Rader F, Lurz P, Sayer J, Sapoval M, Levy T, Sanghvi K, Abraham J, Sharp ASP, Fisher NDL, Bloch MJ, Reeve-Stoffer H, Coleman L, Mullin C, Mauri L, Wang Y, Jay D, Skeik N, Schwartz R, Rader F, Dohad S, Victor R, Sanghvi K, Costello J, Walsh C, Abraham J, Owan T, Abraham A, Fisher NDL, Mauri L, Sobieszczky P, Williams J, Bloch MJ, Roongsritong C, Todoran T, Basile J, Powers E, Hodskins E, Fong P, Laffer C, Gainer J, Robbins M, Reilly JP, Cash M, Goldman J, Aggarwal S, Ledley G, Hsi D, Martin S, Portnay E, Calhoun D, McElderry T, Maddox W, Oparil S, Huang PH, Jose P, Khuddus M, Zentko S, O'Meara J, Barb I, Garasic J, Drachman D, Zusman R, Rosenfield K, Devireddy C, Lea J, Wells B, Stouffer R, Hinderliter A, Pauley E, Potluri S, Biedermann S, Bangalore S, Williams S, Zidar D, Shishehbor M, Effron B, Costa M, Kirtane AJ, Radhakrishnan J, Lobo MD, Saxena M, Mathur A, Jain A, Sayer J, Iyer SG, Robinson N, Edroos SA, Levy T, Patel A, Beckett D, Bent C, Davies J, Chapman N, Shun-Shin M, Howard J, Sharp ASP, Joseph A, D'Souza R, Gerber R, Faris M, Marshall AJ, Elorz C, Lurz P, Höllriegel R, Fengler K, Rommel KP, Mahfoud F, Böhm M, Ewen S, Lucic J, Schmieder RE, Ott C, Schmid A, Uder M, Rump LC, Stegbauer J, Kröpil P, Azizi M, Sapoval M, Cornu E, Fouassier D, Gosse P, Cremer A, Trillaud H, Papadopoulos P, Pathak A, Honton B, Lantelme P, Berge C, Courand PY, Daemen J, Feyz L, Blankestijn PJ, Voskuil M, Rittersma Z, Kroon AA, van Zwam WH, Persu A, Renkin J (2018) Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet 391:2335–2345

    Article  Google Scholar 

  6. Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, Ewen S, Tsioufis K, Tousoulis D, Sharp ASP, Watkinson AF, Schmieder RE, Schmid A, Choi JW, East C, Walton A, Hopper I, Cohen DL, Wilensky R, Lee DP, Ma A, Devireddy CM, Lea JP, Lurz PC, Fengler K, Davies J, Chapman N, Cohen SA, DeBruin V, Fahy M, Jones DE, Rothman M, Böhm M, Aoki J, Batson B, Böhm M, Choi JW, Cohen DL, Dangas G, David S, Davies J, Devireddy CM, Kandzari D, Kario K, Lee DP, Lurz PC, Patel M, Patel K, Schmieder RE, Sharp ASP, Singh J, Tsioufis K, Walton A, Weber T, Weil J, Zeller T, Ziada K, Tanabe K, Wilkins R, Mahfoud F, East C, Wilensky R, Contreras J, Steigerwalt S, Chapman N, Lea JP, Reedus D, Hoshide S, Ma A, Fengler K, Svetkey L, Rao A, Schmid A, Watkinson AF, Brown A, Tousoulis D, Hopper I, Suppan M, Agdirlioglu T, Noory E, Chasen C (2017) Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet 390:2160–2170

    Article  Google Scholar 

  7. Dai Q, Lu J, Wang B, Ma G (2015) Effect of percutaneous renal sympathetic nerve radiofrequency ablation in patients with severe heart failure. Int J Clin Exp Med 8:9779–9785

    PubMed  PubMed Central  Google Scholar 

  8. Chen W, Ling Z, Xu Y, Liu Z, Su L, du H, Xiao P, Lan X, Shan Q, Yin Y (2017) Preliminary effects of renal denervation with saline irrigated catheter on cardiac systolic function in patients with heart failure: a prospective, randomized, controlled, pilot study. Catheter Cardiovasc Interv 89:E153–E161

    Article  Google Scholar 

  9. Davies JE, Manisty CH, Petraco R, Barron AJ, Unsworth B, Mayet J, Hamady M, Hughes AD, Sever PS, Sobotka PA, Francis DP (2013) First-in-man safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACH-Pilot study. Int J Cardiol 162:189–192

    Article  Google Scholar 

  10. Gao JQ, Xie Y, Yang W, Zheng JP, Liu ZJ (2017) Effects of percutaneous renal sympathetic denervation on cardiac function and exercise tolerance in patients with chronic heart failure. Rev Port Cardiol 36:45–51

    Article  Google Scholar 

  11. Fukuta H, Goto T, Wakami K, Ohte N (2017) Effects of catheter-based renal denervation on heart failure with reduced ejection fraction: a systematic review and meta-analysis. Heart Fail Rev 22:657–664

    Article  Google Scholar 

  12. Spadaro AG, Bocchi EA, Souza GE, Filho AE, Mariani J Jr, Campos CM, Lemos PA (2019) Renal denervation in patients with heart failure secondary to Chagas’ disease: a pilot randomized controlled trial. Catheter Cardiovasc Interv 94:644–650

    Article  Google Scholar 

  13. Drozdz T, Jastrzebski M, Moskal P et al (2019) Renal denervation in patients with symptomatic chronic heart failure despite resynchronization therapy - a pilot study. Postepy Kardiol Interwencyjnej 15:240–246

    PubMed  PubMed Central  Google Scholar 

  14. Gao JQ, Yang W, Liu ZJ (2019) Percutaneous renal artery denervation in patients with chronic systolic heart failure: a randomized controlled trial. Cardiol J 26:503–510

    Article  Google Scholar 

  15. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269 W64

    Article  Google Scholar 

  16. Follmann D, Elliott P, Suh I, Cutler J (1992) Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol 45:769–773

    Article  Google Scholar 

  17. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  Google Scholar 

  18. Spertus J, Peterson E, Conard MW, Heidenreich PA, Krumholz HM, Jones P, McCullough P, Pina I, Tooley J, Weintraub WS, Rumsfeld JS, Cardiovascular Outcomes Research Consortium (2005) Monitoring clinical changes in patients with heart failure: a comparison of methods. Am Heart J 150:707–715

    Article  Google Scholar 

  19. Tager T, Hanholz W, Cebola R et al (2014) Minimal important difference for 6-minute walk test distances among patients with chronic heart failure. Int J Cardiol 176:94–98

    Article  Google Scholar 

  20. Zhang Y, Guallar E, Blasco-Colmenares E, Butcher B, Norgard S, Nauffal V, Marine JE, Eldadah Z, Dickfeld T, Ellenbogen KA, Tomaselli GF, Cheng A (2015) Changes in follow-up left ventricular ejection fraction associated with outcomes in primary prevention implantable cardioverter-defibrillator and cardiac resynchronization therapy device recipients. J Am Coll Cardiol 66:524–531

    Article  Google Scholar 

  21. Sharp TE III, Polhemus DJ, Li Z, Spaletra P, Jenkins JS, Reilly JP, White CJ, Kapusta DR, Lefer DJ, Goodchild TT (2018) Renal denervation prevents heart failure progression via inhibition of the renin-angiotensin system. J Am Coll Cardiol 72:2609–2621

    Article  Google Scholar 

  22. Bohm M, Ewen S, Wolf M (2018) Renal denervation halts left ventricular remodeling and dysfunction in heart failure: new shores ahead. J Am Coll Cardiol 72:2622–2624

    Article  Google Scholar 

  23. Sakakura K, Ladich E, Cheng Q, Otsuka F, Yahagi K, Fowler DR, Kolodgie FD, Virmani R, Joner M (2014) Anatomic assessment of sympathetic peri-arterial renal nerves in man. J Am Coll Cardiol 64:635–643

    Article  Google Scholar 

  24. Sanders MF, Reitsma JB, Morpey M, Gremmels H, Bots ML, Pisano A, Bolignano D, Zoccali C, Blankestijn PJ (2017) Renal safety of catheter-based renal denervation: systematic review and meta-analysis. Nephrol Dial Transplant 32:1440–1447

    Article  Google Scholar 

  25. Lee SE, Lee HY, Cho HJ, Choe WS, Kim H, Choi JO, Jeon ES, Kim MS, Hwang KK, Chae SC, Baek SH, Kang SM, Choi DJ, Yoo BS, Kim KH, Cho MC, Kim JJ, Oh BH (2017) Reverse J-curve relationship between on-treatment blood pressure and mortality in patients with heart failure. JACC Heart Fail 5:810–819

    Article  Google Scholar 

  26. Tsao CW, Lyass A, Enserro D, Larson MG, Ho JE, Kizer JR, Gottdiener JS, Psaty BM, Vasan RS (2018) Temporal trends in the incidence of and mortality associated with heart failure with preserved and reduced ejection fraction. JACC Heart Fail 6:678–685

    Article  Google Scholar 

  27. van der Meer S, Zwerink M, van Brussel M, van der Valk P, Wajon E, van der Palen J (2012) Effect of outpatient exercise training programmes in patients with chronic heart failure: a systematic review. Eur J Prev Cardiol 19:795–803

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hidekatsu Fukuta.

Ethics declarations

Conflict of interest

Dr. Ohte has received lecture fees from Daiichi Sankyo Co. and grant support from Takeda Pharmaceutical Co., Ltd.; Daiichi Sankyo Co., Ltd.; and Otsuka Pharmaceutical Co., Ltd. Dr. Kamiya has received lecture fees from Astellas Pharma Inc. and Mochida Pharmaceutical Co., Ltd.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 65 kb)

ESM 2

(DOCX 14 kb)

ESM 3

(DOC 64 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fukuta, H., Goto, T., Wakami, K. et al. Effects of catheter-based renal denervation on heart failure with reduced ejection fraction: a meta-analysis of randomized controlled trials. Heart Fail Rev 27, 29–36 (2022). https://doi.org/10.1007/s10741-020-09974-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-020-09974-4

Keywords

Navigation