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A perspective on sympathetic renal denervation in chronic congestive heart failure

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Abstract

Medical therapy has indisputably been the mainstay of management for chronic congestive heart failure. However, a significant percentage of patients continue to experience worsening heart failure (HF) symptoms despite treatment with multiple therapeutic agents. Recently, catheter-based interventional strategies that interrupt the renal sympathetic nervous system have shown promising results in providing better symptom control in patients with HF. In this article, we will review the pathophysiology of HF for better understanding of the interplay between the cardiovascular system and the kidney. Subsequently, we will briefly discuss pivotal renal denervation (RDN) therapy trials in patients with resistant hypertension and then present the available evidence on the role of RDN in HF therapy.

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References

  1. Francis GS, Goldsmith SR, Levine TB, Olivari MT, Cohn JN (1984) The neurohumoral axis in congestive heart failure. Ann Intern Med 101(3):370–377

    Article  PubMed  CAS  Google Scholar 

  2. Hasking GJ, Esler MD, Jennings GL, Burton D, Korner P (1986) Norepinephrine spillover to plasma in patients with congestive heart failure: evidence for increased overall and cardiorenal sympathetic nervous activity. Circulation 73(4):615–621

    Article  PubMed  CAS  Google Scholar 

  3. Meredith IT, Eisenhofer G, Lambert GW, Dewar EM, Jennings GL, Esler MD (1993) Cardiac sympathetic activity in congestive heart failure: evidence for increased neuronal norepinephrine release and preserved neuronal uptake. Circulation 88(1):136–145

    Article  PubMed  CAS  Google Scholar 

  4. Kaye DM, Lambert GW, Lefkovits J, Morris M, Jennings G, Esler MD (1994) Neurochemical evidence of cardiac sympathetic activation and increased central nervous system norepinephrine turnover in severe congestive heart failure. J Am Coll Cardiol 23(3):570–578

    Article  Google Scholar 

  5. Schlaich MP, Kaye DM, Lambert E, Sommerville M, Socratous F, Esler MD (2003) Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy. Circulation 108(5):560–565

    Article  PubMed  Google Scholar 

  6. Schwarlz PJ. Billman GE, Stone HL (1984) Autonomic mechanisms in ventricular fibrillation induced by myocardial ischemia in dogs with healed myocardial infarction. Circulation 69(4):790–800

    Article  Google Scholar 

  7. Meredith IT, Broughton A, Jennings GL, Esler MD (1991) Evidence of a selective increase in cardiac sympathetic activity in patients with sustained ventricular arrhythmias. N Engl J Med 325(9):618–624

    Article  PubMed  CAS  Google Scholar 

  8. Mann DL, Kent RL, Parsons B, Cooper G (1995) Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation 85(2):790–804

    Article  Google Scholar 

  9. Kaye DM, Lefkovits J, Jennings GL, Bergin P, Broughton A, Esler MD (1995) Adverse consequences of high sympathetic nervous activity in the failing human heart. J Am Coll Cardiol 26(5):1257–1263

    Article  PubMed  CAS  Google Scholar 

  10. Azevedo ER, Newton GE, Floras JS, Parker JD (2000) Reducing cardiac filling pressure lowers norepinephrine spillover in patients with chronic heart failure. Circulation 101(17):2053–2059

    Article  PubMed  CAS  Google Scholar 

  11. Anand IS, Fisher LD, Chiang YT, Latini R, Masson S, Maggioni AP, Glazer RD, Tognoni G, Cohn JN (2003) Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT). Circulation 107(9):1278–1283

    Article  Google Scholar 

  12. Cohn JN, Pfeffer MA, Rouleau J, Sharpe N, Swedberg K, Straub M, Wiltse C, Wright TJ, MOXCON Investigators (2003) Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail 5(5):659–667

    Article  PubMed  CAS  Google Scholar 

  13. Packer M, Bristow MR, Cohn JN (1996) The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 334(1349):1355

    Google Scholar 

  14. CIBIS-II Investigators and Committees (1999) The cardiac insufficiency bisoprolol study II (CIBIS-II): a randomized trial. Lancet 353(9):13

    Google Scholar 

  15. Sobotka PA, Krum H, Böhm M, Francis DP, Schlaich MP (2012) The role of renal denervation in the treatment of heart failure. Curr Cardiol Rep 14(3):285–292

    Article  PubMed  Google Scholar 

  16. Sadoshima J, Xu Y, Slayter HS (1993) Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vivo. Cell 75:977–984

    Article  PubMed  CAS  Google Scholar 

  17. Sadoshima J, Izumo S (1993) Molecular characterization of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype. Circ Res 73:413–423

    Article  PubMed  CAS  Google Scholar 

  18. Weber KT, Brilla CG (1991) Pathological hypertrophy and the cardiac interstitium. Fibrosis and the renin–angiotensin–aldosterone system. Circulation 83:1849–1865

    Article  PubMed  CAS  Google Scholar 

  19. Brilla CG, Zhou G, Matsubara L, Weber KT (1994) Collagen metabolism in cultured adult rat cardiac fibroblasts: response to angiotensin II and aldosterone. J Mol Cell Immunol 26:809–820

    CAS  Google Scholar 

  20. Dostal DE, Baker KM (1999) The cardiac renin–angiotensin system: conceptual, or a regulator of cardiac function? Circ Res 85:643

    Article  PubMed  CAS  Google Scholar 

  21. Marcus LS, Hart D, Packer M (1996) Hemodynamics and renal excretory effects of human brain natriuretic peptide infusion In patients with congestive heart failure. Circulation 94:3184–3189

    Article  PubMed  CAS  Google Scholar 

  22. Hobbs RE, Miller LW, Bott-Silverman C (1996) Hemodynamics effects of a single intravenous injection of synthetic human brain natriuretic peptide in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 78:896–901

    Article  PubMed  CAS  Google Scholar 

  23. Yamamoto K, Burnett JCJ, Redfield MM (1997) Effects of the endogenous natriuretic peptide system on ventricular and coronary function in the failing heart. Am J Physiol 273:H2406–H2414

    PubMed  CAS  Google Scholar 

  24. Clarkson PBM, Wheeldon NM, Macleod C (1995) Brain natriuretic peptide: effect on left ventricular filling patterns in healthy subjects. Clin Sci 88:159–164

    Article  PubMed  CAS  Google Scholar 

  25. Krum H, Schlaich M, Sobotka P, Scheffers I, Kroon AA, de Leeuw PW (2011) Novel procedure- and device-based strategies in the management of systemic hypertension. Eur Heart J 32(5):537–544

    Article  PubMed  Google Scholar 

  26. Grassi G, Seravalle G, Cattaneo BM, Lanfranchi A, Vailati S, Giannattasio C, Del Bo A, Sala C, Bolla GB, Pozzi M (1995) Sympathetic activation and loss of reflex sympathetic control in mild congestive heart failure. Circulation 92(11):3206–3211

    Article  PubMed  CAS  Google Scholar 

  27. Leier CV, Dei Cas L, Metra M (1994) Clinical relevance and management of the major electrolyte abnormalities in congestive heart failure: hyponatremia, hypokalemia, and hypomagnesemia. Am Heart J 128(3):564–574

    Article  PubMed  CAS  Google Scholar 

  28. Lee WH, Packer M (1986) Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure. Circulation 73(2):257–267

    Article  PubMed  CAS  Google Scholar 

  29. Thomas G, Shishehbor MH, Bravo EL, Nally JV (2012) Renal denervation to treat resistant hypertension: guarded optimism. Cleve Clin J Med 79(7):501–510

    Article  PubMed  Google Scholar 

  30. Smithwick RH (1955) Hypertensive vascular disease: results of and indications for splanchnicectomy. J Chronic Dis 1(5):477–496

    Article  PubMed  CAS  Google Scholar 

  31. Webster W Jr, Scherlag BJ, Scherlag MA, Schauerte P (1999) Method and apparatus for transvascular treatment of tachycardia and fibrillation. US Patent 6,292,695. June 17, 1999

  32. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham WT, Esler M (2009) Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 373(9671):1275–1281

    Article  PubMed  Google Scholar 

  33. Worthley SG, Tsioufis CP, Worthley MI, Sinhal A, Chew DP, Meredith IT et al (2013) Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnligHTN I trial. Eur Heart J 34(28):2132–2140

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  34. Ahmed H, Neuzil P, Skoda J, Petru J, Sediva L, Schejbalova M et al (2012) Renal sympathetic denervation using an irrigated radiofrequency ablation catheter for the management of drug-resistant hypertension. JACC Cardiovasc Interv 5:758–765

    Article  PubMed  Google Scholar 

  35. Ormiston JA, Watson T, van Pelt N, Stewart R, Haworth P, Stewart JT et al (2013) First-in-human use of the OneShot renal denervation system from Covidien. EuroIntervention 8:1090–1094

    Article  PubMed  Google Scholar 

  36. Mabin T, Sapoval M, Cabane V, Stemmett J, Iyer M (2012) First experience with endovascular ultrasound renal denervation for the treatment of resistant hypertension. EuroIntervention 8:57–61

    Article  PubMed  Google Scholar 

  37. Stefanadis C, Toutouzas K, Vlachopoulos C, Tsioufis C, Synetos A, Pietri P et al (2013) Chemical denervation of the renal artery with vincristine for the treatment of resistant arterial hypertension: first-in-man application. Hell J Cardiol 54:318–321

    Google Scholar 

  38. Okada T, Pellerin O, Savard S, Curis E, Monge M, Frank M, Bobrie G, Yamaguchi M, Sugimoto K, Plouin PF, Azizi M, Sapoval M (2015) Eligibility for renal denervation: anatomical classification and results in essential resistant hypertension. Cardiovasc Interv Radiol 38(1):79–87. doi:10.1007/s00270-014-0865-6

    Article  Google Scholar 

  39. Id D, Kaltenbach B, Bertog SC, Hornung M, Hofmann I, Vaskelyte L, Sievert H (2013) Does the presence of accessory renal arteries affect the efficacy of renal denervation? JACC Cardiovasc Interv 6(10):1085–1091

    Article  PubMed  Google Scholar 

  40. Persu A, Jin Y, Baelen M, Vink E, Verloop WL, Schmidt B, Blicher MK, Severino F, Wuerzner G, Taylor A, Pechère-Bertschi A, Jokhaji F, Fadl Elmula FE, Rosa J, Czarnecka D, Ehret G, Kahan T, Renkin J, Widimsky JI Jr, Jacobs L, Spiering W, Burnier M, Mark PB, Menne J, Olsen MH, Blankestijn PJ, Kjeldsen S, Bots ML, Staessen JA (2014) Eligibility for renal denervation: experience at 11 European expert centers. Hypertension 63(6):1319–1325

    Article  PubMed  CAS  Google Scholar 

  41. Krum H, Schlaich MP, Sobotka PA, Böhm M, Mahfoud F, Rocha-Singh K, Katholi R, Esler MD (2014) Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study. Lancet 383(9917):622–629

    Article  PubMed  Google Scholar 

  42. Esler MD, Böhm M, Sievert H, Rump CL, Schmieder RE, Krum H, Mahfoud F, Schlaich MP (2014) Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized clinical trial. Eur Heart J 35(26):1752–1759

    Article  PubMed  Google Scholar 

  43. 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 (2014) A controlled trial of renal denervation for resistant hypertension. N Engl J Med 370(15):1393–1401

    Article  PubMed  CAS  Google Scholar 

  44. Templin C, Jaguszewski M, Ghadri JR, Sudano I, Gaehwiler R, Hellermann JP, Schoenenberger-Berzins R, Landmesser U, Erne P, Noll G, Lüscher TF (2013) Vascular lesions induced by renal nerve ablation as assessed by optical coherence tomography: pre- and post-procedural comparison with the Simplicity catheter system and the EnligHTN multi-electrode renal denervation catheter. Eur Heart J 34(28):2141–2148. doi:10.1093/eurheartj/eht141

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  45. Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Böhm M, Hoppe UC (2012) Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol 59(10):901–909

    Article  PubMed  Google Scholar 

  46. Mahfoud F, Urban D, Teller D, Linz D, Stawowy P, Hassel JH, Fries P, Dreysse S, Wellnhofer E, Schneider G, Buecker A, Schneeweis C, Doltra A, Schlaich MP, Esler MD, Fleck E, Böhm M, Kelle S (2014) Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial. Eur Heart J 35(33):2224–2231

    Article  PubMed  Google Scholar 

  47. Bakris GL, Townsend RR, Flack JM, Brar S, Cohen SA, D’Agostino R, Kandzari DE, Katzen BT, Leon MB, Mauri L, Negoita M, O’Neill WW, Oparil S, Rocha-Singh K, Bhatt DL, SYMPLICITY HTN-3 Investigators (2015) 12-month blood pressure results of catheter-based renal artery denervation for resistant hypertension: The SYMPLICITY HTN-3 trial. J Am Coll Cardiol 65(13):1314–1321. doi:10.1016/j.jacc.2015.01.037

    Article  PubMed  Google Scholar 

  48. Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M, Flack JM, Katzen BT, Lea J, Lee DP, Leon MB, Ma A, Massaro J, Mauri L, Oparil S, O’Neill WW, Patel MR, Rocha-Singh K, Sobotka PA, Svetkey L, Townsend RR, Bakris GL (2015) Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. Eur Heart J 36(4):219–227

    Article  PubMed  Google Scholar 

  49. Azizi M, Sapoval M, Gosse P, Monge M, Bobrie G, Delsart P, Midulla M, Mounier-Véhier C, Courand PY, Lantelme P, Denolle T, Dourmap-Collas C, Trillaud H, Pereira H, Plouin PF, Chatellier G, Renal Denervation for Hypertension (DENERHTN) Investigators (2015) Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial. Lancet. doi:10.1016/S0140-6736(14)61942-5

    Google Scholar 

  50. Xie Y, LiuLiu Q, Xu Y, Gao J, Yan P, Zhang W, Sun J, Wang M, Jin H, Jiang J, Liu Z (2014) Effect of catheter-based renal sympathetic denervation in pigs with rapid pacing induced heart failure. Zhonghua Xin Xue Guan Bing Za Zhi 42(1):48–52

    PubMed  Google Scholar 

  51. Tan LH, Li XG, Guo YZ, Tang XH, Yang K, Jiang WH (2013) Effect of renal sympathetic denervation on left ventricular hypertrophy and inflammatory factors in spontaneously hypertensive rats. Zhejiang Da Xue Xue Bao Yi Xue Ban 42(5):550–555

    PubMed  CAS  Google Scholar 

  52. 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(3):189–192

    Article  PubMed  Google Scholar 

  53. Schirmer SH, Sayed MM, Reil JC, Ukena C, Linz D, Kindermann M, Laufs U, Mahfoud F, Böhm M (2014) Improvements of left-ventricular hypertrophy and diastolic function following renal denervation—effects beyond blood pressure and heart rate reduction. J Am Coll Cardiol 63(18):1916–1923

    Article  PubMed  Google Scholar 

  54. Verloop WL, Beeftink MM, Nap A, Bots ML, Velthuis BK, Appelman YE, Cramer MJ, Agema WR, Scholtens AM, Doevendans PA, Allaart CP, Voskuil M (2013) Renal denervation in heart failure with normal left ventricular ejection fraction. Rationale and design of the DIASTOLE (DenervatIon of the renAl Sympathetic nerves in hearT failure with nOrmal Lv Ejection fraction) trial. Eur J Heart Fail 15(12):1429–1437

    Article  PubMed  CAS  Google Scholar 

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    Authors and Affiliations

    1. Center for Advanced Cardiac Therapeutics, St. Francis Hospital – The Heart Center®, 100 Port Washington Blvd., Roslyn, NY, 11576-1348, USA

      Raef Madanieh, Abed Madanieh & Timothy J. Vittorio

    2. Presence Saint Joseph Hospital, Chicago, IL, USA

      Mohammed El-Hunjul

    3. Elmhurst Hospital Center, Icahn School of Medicine at Mount Sinai, Elmhurst, NY, USA

      Hassan Alkhawam

    4. Mount Sinai Hospital Center, Icahn School of Medicine, New York, NY, USA

      Constantine E. Kosmas

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    1. Raef Madanieh
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    Correspondence to Raef Madanieh.

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    Dr. Raef Madanieh and Dr. Mohammed El-Hunjul have contributed equally to this manuscript.

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    Madanieh, R., El-Hunjul, M., Alkhawam, H. et al. A perspective on sympathetic renal denervation in chronic congestive heart failure. Heart Fail Rev 21, 1–10 (2016). https://doi.org/10.1007/s10741-015-9516-5

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