Cardiac contractility modulation improves long-term survival and hospitalizations in heart failure with reduced ejection fraction

Stefan D Anker, Martin Borggrefe, Hans Neuser, Marc-Alexander Ohlow, Susanne Röger, Andreas Goette, Bjoern A Remppis, Karl-Heinz Kuck, Kevin B Najarian, David D Gutterman, Benny Rousso, Daniel Burkhoff, Gerd Hasenfuss, Stefan D Anker, Martin Borggrefe, Hans Neuser, Marc-Alexander Ohlow, Susanne Röger, Andreas Goette, Bjoern A Remppis, Karl-Heinz Kuck, Kevin B Najarian, David D Gutterman, Benny Rousso, Daniel Burkhoff, Gerd Hasenfuss

Abstract

Aims: Cardiac contractility modulation (CCM) improves symptoms and exercise tolerance and reduces heart failure (HF) hospitalizations over 6-month follow-up in patients with New York Heart Association (NYHA) class III or IV symptoms, QRS < 130 ms and 25% ≤ left ventricular ejection fraction (LVEF) ≤ 45% (FIX-HF-5C study). The current prospective registry study (CCM-REG) aimed to assess the longer-term impact of CCM on hospitalizations and mortality in real-world experience in this same population.

Methods and results: A total of 140 patients with 25% ≤ LVEF ≤ 45% receiving CCM therapy (CCM-REG25-45 ) for clinical indications were included. Cardiovascular and HF hospitalizations, Minnesota Living with Heart Failure Questionnaire (MLHFQ) and NYHA class were assessed over 2 years. Mortality was tracked through 3 years and compared with predictions by the Seattle Heart Failure Model (SHFM). A separate analysis was performed on patients with 35% ≤ LVEF ≤ 45% (CCM-REG35-45 ) and 25% ≤ LVEF < 35% (CCM-REG25-34 ). Hospitalizations decreased by 75% (from 1.2/patient-year the year before, to 0.35/patient-year during the 2 years following CCM, P < 0.0001) in CCM-REG25-45 and by a similar amount in CCM-REG35-45 (P < 0.0001) and CCM-REG25-34 . MLHFQ and NYHA class improved in all three cohorts, with progressive improvements over time (P < 0.002). Three-year survival in CCM-REG25-45 (82.8%) and CCM-REG24-34 (79.4%) were similar to those predicted by SHFM (76.7%, P = 0.16; 78.0%, P = 0.81, respectively) and was better than predicted in CCM-REG35-45 (88.0% vs. 74.7%, P = 0.046).

Conclusion: In real-world experience, CCM produces results similar to those of previous studies in subjects with 25% ≤ LVEF ≤ 45% and QRS < 130 ms; cardiovascular and HF hospitalizations are reduced and MLHFQ and NYHA class are improved. Overall mortality was comparable to that predicted by the SHFM but was lower than predicted in patients with 35% ≤ LVEF ≤ 45%.

Keywords: Hospitalizations; Left ventricular ejection fraction; Minnesota Living with Heart Failure Questionnaire; Survival.

© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.

References

    1. Ambrosy AP, Fonarow GC, Butler J, Chioncel O, Greene SJ, Vaduganathan M, Nodari S, Lam CS, Sato N, Shah AN, Gheorghiade M. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol 2014;63:1123-1133.
    1. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P. 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;18:891-975.
    1. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, PE MB, Peterson PN, Stevenson LW, Westlake C. 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 Am Coll Cardiol 2017;70:776-803.
    1. Tschope C, Birner C, Bohm M, Bruder O, Frantz S, Luchner A, Maier L, Stork S, Kherad B, Laufs U. Heart failure with preserved ejection fraction: current management and future strategies: expert opinion on the behalf of the Nucleus of the “Heart Failure Working Group” of the German Society of Cardiology (DKG). Clin Res Cardiol 2018;107:1-19.
    1. Kadish A, Nademanee K, Volosin K, Krueger S, Neelagaru S, Raval N, Obel O, Weiner S, Wish M, Carson P, Ellenbogen K, Bourge R, Parides M, Chiacchierini RP, Goldsmith R, Goldstein S, Mika Y, Burkhoff D, Abraham WT. A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. Am Heart J 2011;161:329-337.e1-2.
    1. Borggrefe MM, Lawo T, Butter C, Schmidinger H, Lunati M, Pieske B, Misier AR, Curnis A, Böcker D, Remppis A, Kautzner J, Stühlinger M, Leclerq C, Táborsky M, Frigerio M, Parides M, Burkhoff D, Hindricks G. Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses for symptomatic heart failure. Eur Heart J 2008;29:1019-1028.
    1. Abraham WT, Kuck KH, Goldsmith RL, Lindenfeld J, Reddy VY, Carson PE, Mann DL, Saville B, Parise H, Chan R, Wiegn P, Hastings JL, Kaplan AJ, Edelmann F, Luthje L, Kahwash R, Tomassoni GF, Gutterman DD, Stagg A, Burkhoff D, Hasenfuß G. A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation. JACC Heart Fail 2018;6:874-883.
    1. Abraham WT, Lindenfeld J, Reddy VY, Hasenfuss G, Kuck KH, Boscardin J, Gibbons R, Burkhoff D; 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;21:16-23.
    1. Borggrefe M, Burkhoff D. Clinical effects of cardiac contractility modulation (CCM) as a treatment for chronic heart failure. Eur J Heart Fail 2012;14:703-712.
    1. Levy WC, Mozaffarian D, Linker DT, Sutradhar SC, Anker SD, Cropp AB, Anand I, Maggioni A, Burton P, Sullivan MD, Pitt B, Poole-Wilson PA, Mann DL, Packer M. The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation 2006;113:1424-1433.
    1. Pocock SJ, Ariti CA, McMurray JJ, Maggioni A, Køber L, Squire IB, Swedberg K, Dobson J, Poppe KK, Whalley GA, Doughty RN, Meta-Analysis Global Group in Chronic Heart Failure. Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies. Eur Heart J 2013;34:1404-1413.
    1. Abi-Samra F, Gutterman D. Cardiac contractility modulation: a novel approach for the treatment of heart failure. Heart Fail Rev 2016;21:645-660.
    1. Wu J. A new one-sample log-rank test. Biometr Biostat 2014;5:1-5.
    1. Yu CM, Chan JY, Zhang Q, Yip GW, Lam YY, Chan A, Burkhoff D, Lee PW, Fung JW. Impact of cardiac contractility modulation on left ventricular global and regional function and remodeling. JACC Cardiovasc Imaging 2009;2:1341-1349.
    1. Muller D, Remppis A, Schauerte P, Schmidt-Schweda S, Burkhoff D, Rousso B, Gutterman D, Senges J, Hindricks G, Kuck KH. Clinical effects of long-term cardiac contractility modulation (CCM) in subjects with heart failure caused by left ventricular systolic dysfunction. Clin Res Cardiol 2017;106:893-904.
    1. Soundarraj D, Singh V, Satija V, Thakur RK. Containing the cost of heart failure management: a focus on reducing readmissions. Heart Fail Clin 2017;13:21-28.
    1. Gillis AM, Kerr CR, Philippon F, Newton G, Talajic M, Froeschl M, Froeschl S, Swiggum E, Yetisir E, Wells GA, Tang AS. Impact of cardiac resynchronization therapy on hospitalizations in the Resynchronization-Defibrillation for Ambulatory Heart Failure trial. Circulation 2014;129:2021-2030.
    1. Liu M, Fang F, Luo XX, Shlomo BH, Burkhoff D, Chan JY, Chan CP, Cheung L, Rousso B, Gutterman D, Yu CM. Improvement of long-term survival by cardiac contractility modulation in heart failure patients: a case-control study. Int J Cardiol 2016;206:122-126.
    1. Schau T, Seifert M, Meyhofer J, Neuss M, Butter C. Long-term outcome of cardiac contractility modulation in patients with severe congestive heart failure. Europace 2011;13:1436-1444.
    1. Kuschyk J, Roeger S, Schneider R, Streitner F, Stach K, Rudic B, Weiß C, Schimpf R, Papavasilliu T, Rousso B, Burkhoff D, Borggrefe M. Efficacy and survival in patients with cardiac contractility modulation: long-term single center experience in 81 patients. Int J Cardiol 2015;183:76-81.
    1. Kloppe A, Lawo T, Mijic D, Schiedat F, Muegge A, Lemke B. Long-term survival with cardiac contractility modulation in patients with NYHA II or III symptoms and normal QRS duration. Int J Cardiol 2016;209:291-295.
    1. Sartipy U, Dahlstrom U, Edner M, Lund LH. Predicting survival in heart failure: validation of the MAGGIC heart failure risk score in 51,043 patients from the Swedish Heart Failure Registry. Eur J Heart Fail 2014;16:173-179.
    1. Freitas P, Aguiar C, Ferreira A, Tralhao A, Ventosa A, Mendes M. Comparative analysis of four scores to stratify patients with heart failure and reduced ejection fraction. Am J Cardiol 2017;120:443-449.
    1. Popescu BA, Beladan CC, Popescu AC. Mechanical dyssynchrony in heart failure with preserved ejection fraction: a treatment target or a dead end? Eur J Heart Fail 2017;19:1053-1055.
    1. Dickstein K. Early clinical benefit after cardiac resynchronization therapy: fortunately, QRS width and ejection fraction are still the best predictors. Eur J Heart Fail 2017;19:1064-1066.
    1. Steen T, Dickstein K. Do real world data support and extend our ability to predict reverse remodelling following cardiac resynchronization therapy based on QRS morphology and width? Eur J Heart Fail 2017;19:1152-1153.
    1. Tavazzi L. A brief overview of cardiac resynchronization therapy and its current use in clinical practice. Eur J Heart Fail 2017;19:1280-1283.
    1. Tsuji K, Sakata Y, Nochioka K, Miura M, Yamauchi T, Onose T, Abe R, Oikawa T, Kasahara S, Sato M, Shiroto T, Takahashi J, Miyata S, Shimokawa H, CHART-2 Investigators. Characterization of heart failure patients with mid-range left ventricular ejection fraction - a report from the CHART-2 Study. Eur J Heart Fail 2017;19:1258-1269.
    1. Koh AS, Tay WT, Teng TH, Vedin O, Benson L, Dahlstrom U, Savarese G, Lam CS, Lund LH. A comprehensive population-based characterization of heart failure with mid-range ejection fraction. Eur J Heart Fail 2017;19:1624-1634.
    1. Rastogi A, Novak E, Platts AE, Mann DL. Epidemiology, pathophysiology and clinical outcomes for heart failure patients with a mid-range ejection fraction. Eur J Heart Fail 2017;19:1597-1605.
    1. Nauta JF, Hummel YM, van Melle JP, van der Meer P, Lam CS, Ponikowski P, Voors AA. What have we learned about heart failure with mid-range ejection fraction one year after its introduction? Eur J Heart Fail 2017;19:1569-1573.
    1. Abraham WT, Nademanee K, Volosin K, Krueger S, Neelagaru S, Raval N, Obel O, Weiner S, Wish M, Carson P, Ellenbogen K, Bourge R, Parides M, Chiacchierini RP, Goldsmith R, Goldstein S, Mika Y, Burkhoff D, Kadish A; 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;17:710-717.
    1. Imai M, Rastogi S, Gupta RC, Mishra S, Sharov VG, Stanley WC, Mika Y, Rousso B, Burkhoff D, Ben-Haim S, Sabbah HN. Therapy with cardiac contractility modulation electrical signals improves left ventricular function and remodeling in dogs with chronic heart failure. J Am Coll Cardiol 2007;49:2120-2128.
    1. Butter C, Rastogi S, Minden HH, Meyhofer J, Burkhoff D, Sabbah HN. Cardiac contractility modulation electrical signals improve myocardial gene expression in patients with heart failure. J Am Coll Cardiol 2008;51:1784-1789.

Source: PubMed

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