Cardiac Contractility Modulation and Baroreflex Activation Therapy in Heart Failure Patients
Purpose of Review
Despite advances in medical therapy, heart failure with reduced ejection fraction (HFrEF) is still a leading cause of mortality, hospitalizations, and healthcare costs. In this review, we describe two novel, implantable devices for the treatment of patients with HFrEF, cardiac contractility modulation (CCM), and baroreflex activation therapy (BAT), and summarize literature regarding these devices from the last 5 years.
CCM improves quality of life and functional capacity as assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, 6-min hall walk test (6MHWT) distance, New York Heart Association (NYHA) functional class, peak oxygen consumption (pVO2), heart failure (HF) hospitalizations, and mortality. BAT improves MLHFQ, 6-min walk test distance, NYHA functional class, and HF hospitalizations. Both devices have been shown to be safe.
CCM and BAT have been shown to be safe and effective treatment modalities for HFrEF. CCM has been approved for use in Europe and has been implanted in thousands of patients. BAT has also been approved in Europe and continues to show promise in treating patients with HFrEF who fail optimal medical therapy (OMT). At present, both therapies are considered investigational in the USA.
KeywordsCardiac contractility modulation Baroreflex activation therapy Device therapy for heart failure with reduced ejection fraction
Compliance with Ethical Standards
Conflict of Interest
James Mann declares he has no conflict of interest.
William Abraham has received consulting fees and speaking honoraria from CVRx and are members of the CVRx Heart Failure Executive Steering Committee and he has received consulting fees from Impulse Dynamics.
Human and Animal Rights and Informed Consent
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147–239.CrossRefGoogle Scholar
- 2.Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Card Fail. 2017;23(8):628–51.CrossRefGoogle Scholar
- 3.• Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al. Heart Disease and Stroke Statistics-2018 Update: a report from the American Heart Association. Circulation. 2018;137(12):e67–e492 This report from the American Heart Association has the most up-to-date statistics related to heart disease, stroke, and other cardiovascular and metabolic diseases. CrossRefGoogle Scholar
- 4.Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS, et al. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2013;127(3):e283–352.CrossRefGoogle Scholar
- 10.Pappone C, Rosanio S, Burkhoff D, Mika Y, Vicedomini G, Augello G, et al. Cardiac contractility modulation by electric currents applied during the refractory period in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2002;90(12):1307–13.CrossRefGoogle Scholar
- 13.Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18(8):891–975.CrossRefGoogle Scholar
- 14.Abraham WT, Lindenfeld J, Reddy VY, Hasenfuss G, Kuck KH, Boscardin J, et al. FIX-HF-5C Investigators and Coordinators. A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation in patients with moderately reduced left ventricular ejection fraction and a narrow QRS duration: study rationale and design. J Card Fail. 2015;21(1):16–23.CrossRefGoogle Scholar
- 15.•• Abraham WT, Kuck K, Goldsmith RL, Lindenfeld J, Reddy VY, Carson PE, et al. A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation. JACC: Heart Failure. 2018;6(10):874–83 This randomized controlled trial is central to confirming the place for CCM in patients with HFrEF and is the most recent.Google Scholar
- 17.Abraham WT, Nademanee K, Volosin K, Krueger S, Neelagaru S, Raval N, et al. FIX-HF-5 Investigators and Coordinators. Subgroup analysis of a randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. J Card Fail. 2011;17(9):710–7.CrossRefGoogle Scholar
- 18.Zhang Q, Chan YS, Liang YJ, Fang F, Lam YY, Chan CP, et al. Comparison of left ventricular reverse remodeling induced by cardiac contractility modulation and cardiac resynchronization therapy in heart failure patients with different QRS durations. Int J Cardiol. 2013 Aug 10;167(3):889–93.CrossRefGoogle Scholar
- 20.Giallauria F, Vigorito C, Piepoli MF, Stewart Coats AJ. Effects of cardiac contractility modulation by non-excitatory electrical stimulation on exercise capacity and quality of life: an individual patient's data meta-analysis of randomized controlled trials. Int J Cardiol. 2014;175(2):352–7.CrossRefGoogle Scholar
- 27.Bisognano JD, Bakris G, Nadim MK, Sanchez L, Kroon AA, Schafer J, et al. Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: results from the double-blind, randomized, placebo-controlled rheos pivotal trial. J Am Coll Cardiol. 2011;58(7):765–73.CrossRefGoogle Scholar
- 28.• Weaver FA, Abraham WT, Little WC, Butter C, Ducharme A, Halbach M, et al. Surgical experience and long-term results of baroreflex activation therapy for heart failure with reduced ejection fraction. Semin Thorac Cardiovasc Surg. 2016;28:320–8 Elsevier. This review is a nice summary of the surgical technique required for BAT. CrossRefGoogle Scholar
- 30.Barostim Neo - Baroreflex Activation Therapy for Heart Failure (BeAT-HF) Trial. Available at: https://clinicaltrials.gov/ct2/show/NCT02627196?term=Barostim+Neo+-+Baroreflex+Activation+Therapy+for+Heart+Failure+%28BeAT-HF%29+Trial&rank=1. Accessed June 6, 2018.
- 31.U.S. Food and Drug Administration Expidited Access Pathway Program. Available at: https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/ucm441467.htm. Accessed June 11, 2018.
- 32.• Gronda E, Francis D, Zannad F, Hamm C, Brugada J, Vanoli E. Baroreflex activation therapy: a new approach to the management of advanced heart failure with reduced ejection fraction. J Cardiovasc Med (Hagerstown). 2017;18(9):641–9 This review is a thoughtful summary of BAT including the benefits and challenges. CrossRefGoogle Scholar
- 33.•• Abraham WT, Zile MR, Weaver FA, Butter C, Ducharme A, Halbach M, et al. Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction. JACC: Heart Fail. 2015;3(6):487–96 This paper is central to the body of evidence supporting the incorporation of BAT into common treatment for patients with HFrEF. Google Scholar
- 34.• Zile MR, Abraham WT, Weaver FA, Butter C, Ducharme A, Halbach M, et al. Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction: safety and efficacy in patients with and without cardiac resynchronization therapy. Eur J Heart Fail. 2015;17(10):1066–74 Safety results for BAT and demonstration of better effects in patients without CRT. CrossRefGoogle Scholar
- 37.• Dell’Oro R, Gronda E, Seravalle G, Costantino G, Alberti L, Baronio B, et al. Restoration of normal sympathetic neural function in heart failure following baroreflex activation therapy: final 43-month study report. J Hypertens. 2017;35(12):2532–6 The positive effects of BAT are maintained at long-term follow-up. CrossRefGoogle Scholar