Skip to main content

Advertisement

SpringerLink
Log in

Should HFrEF patients with NYHA class II expect benefit from CCM therapy? Results from the MAINTAINED observational study

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Background

Cardiac contractility modulation (CCM) is an FDA-approved device therapy for patients with refractory systolic heart failure and normal QRS width. Randomized trials demonstrated benefits of CCM primarily for patients with severe heart failure (> NYHA class II).

Purpose

To better understand individualized indication in clinical practice, we compared the effect of CCM in patients with baseline NYHA class II vs. NYHA class III or ambulatory IV over the 5-year period in our large clinical registry (MAINTAINED Observational Study).

Methods

Changes in NYHA class, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), NT-proBNP level, and KDIGO chronic kidney disease stage were compared as functional parameters. In addition, mortality within 3 years was compared with the prediction of the Meta-Analysis Global Group in Chronic heart failure risk score.

Results

A total of 172 patients were included in the analyses (10% with NYHA class II). Only patients with NYHA class III/IV showed a significant improvement in NYHA class over 5 years of CCM (II: 0.1 ± 0.6; p = 0.96 vs. III/IV: − 0.6 ± 0.6; p < 0.0001). In both groups, LVEF improved significantly (II: 4.7 ± 8.3; p = 0.0072 vs. III/IV: 7.0 ± 10.7%; p < 0.0001), while TAPSE improved significantly only in NYHA class III/IV patients (II: 2.2 ± 1.6; p = 0.20 vs. III/IV: 1.8 ± 5.2 mm; p = 0.0397). LVEF improvement was comparable in both groups over 5 years of CCM (p = 0.83). NYHA class II patients had significantly lower NT-proBNP levels at baseline (858 [175/6887] vs. 2632 [17/28830] ng/L; p = 0.0044), which was offset under therapy (399 [323/1497] vs. 901 [13/18155] ng/L; p = 0.61). Actual 3-year mortality was 17 and 26% vs. a predicted mortality of 31 and 42%, respectively (p = 0.0038 for NYHA class III/IV patients).

Conclusions

NYHA class III/IV patients experienced more direct and extensive functional improvements with CCM and a survival benefit compared with the predicted risk. However, our data suggest that NYHA class II patients may also benefit from the sustained positive effects of LVEF improvement.

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

Access this article

Log in via an institution

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

Similar content being viewed by others

Abbreviations

CCM:

Cardiac contractility modulation

CKD:

Chronic kidney disease

CRT:

Cardiac resynchronization therapy

ESC:

European society of cardiology

FDA:

Food and drug administration

IPG:

Implanted pulse generator

KDIGO:

Kidney disease improving global Outcomes

(LV) EF:

(Left ventricular) ejection fraction

MAGGIC:

Meta-analysis global group in chronic [heart failure]

MAINTAINED:

Mannheim cardiac contractility modulation observational study

NT-proBNP:

NT-proB-type natriuretic peptides

NYHA:

New York heart association

OMT:

Optimal medical therapy

RV:

Right ventricular

TAPSE:

Tricuspid annular plane systolic excursion

vs.:

Versus

References

  1. Rao IV, Burkhoff D (2021) Cardiac contractility modulation for the treatment of moderate to severe HF. Expert Rev Med Devices 18(1):15–21. https://doi.org/10.1080/17434440.2020.1853525

    Article  PubMed  CAS  Google Scholar 

  2. Tschöpe C, Kherad B, Klein O, Lipp A, Blaschke F, Gutterman D, Burkhoff D, Hamdani N, Spillmann F, Van Linthout S (2019) Cardiac contractility modulation: mechanisms of action in heart failure with reduced ejection fraction and beyond. Eur J Heart Fail 21(1):14–22. https://doi.org/10.1002/ejhf.1349

    Article  PubMed  Google Scholar 

  3. 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 (2008) Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses for symptomatic heart failure. Eur Heart J 29(8):1019–1028. https://doi.org/10.1093/eurheartj/ehn020

    Article  PubMed  Google Scholar 

  4. 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 (2011) A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. Am Heart J 161(2):329-337.e321–322. https://doi.org/10.1016/j.ahj.2010.10.025

    Article  PubMed  Google Scholar 

  5. 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 (2011) Subgroup analysis of a randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. J Card Fail 17(9):710–717. https://doi.org/10.1016/j.cardfail.2011.05.006

    Article  PubMed  Google Scholar 

  6. 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 (2018) A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation. JACC Heart Fail 6(10):874–883. https://doi.org/10.1016/j.jchf.2018.04.010

    Article  PubMed  Google Scholar 

  7. Kuschyk J, Roeger S, Schneider R, Streitner F, Stach K, Rudic B, Weiss C, Schimpf R, Papavasilliu T, Rousso B, Burkhoff D, Borggrefe M (2015) Efficacy and survival in patients with cardiac contractility modulation: long-term single center experience in 81 patients. Int J Cardiol 183:76–81. https://doi.org/10.1016/j.ijcard.2014.12.178

    Article  PubMed  Google Scholar 

  8. Anker SD, Borggrefe M, Neuser H, Ohlow MA, Röger S, Goette A, Remppis BA, Kuck KH, Najarian KB, Gutterman DD, Rousso B, Burkhoff D, Hasenfuss G (2019) Cardiac contractility modulation improves long-term survival and hospitalizations in heart failure with reduced ejection fraction. Eur J Heart Fail 21(9):1103–1113. https://doi.org/10.1002/ejhf.1374

    Article  PubMed  Google Scholar 

  9. Kuschyk J, Falk P, Demming T, Marx O, Morley D, Rao I, Burkhoff D (2021) Long-term clinical experience with cardiac contractility modulation therapy delivered by the optimizer smart system. Eur J Heart Fail. https://doi.org/10.1002/ejhf.2202

    Article  PubMed  Google Scholar 

  10. Fastner C, Yuecel G, Rudic B, Schmiel G, Toepel M, Burkhoff D, Liebe V, Kruska M, Hetjens S, Borggrefe M, Akin I, Kuschyk J (2021) Cardiac contractility modulation in patients with ischemic versus non-ischemic cardiomyopathy: results from the MAINTAINED observational study. Int J Cardiol 342:49–55. https://doi.org/10.1016/j.ijcard.2021.07.048

    Article  PubMed  Google Scholar 

  11. Wiegn P, Chan R, Jost C, Saville BR, Parise H, Prutchi D, Carson PE, Stagg A, Goldsmith RL, Burkhoff D (2020) Safety, performance, and efficacy of cardiac contractility modulation delivered by the 2-lead optimizer smart system: the FIX-HF-5C2 study. Circ Heart Fail 13(4):e006512. https://doi.org/10.1161/circheartfailure.119.006512

    Article  PubMed  CAS  Google Scholar 

  12. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A (2021) 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 42(36):3599–3726. https://doi.org/10.1093/eurheartj/ehab368

    Article  PubMed  CAS  Google Scholar 

  13. Kuschyk J, Nägele H, Heinz-Kuck K, Butter C, Lawo T, Wietholt D, Roeger S, Gutterman D, Burkhoff D, Rousso B, Borggrefe M (2019) Cardiac contractility modulation treatment in patients with symptomatic heart failure despite optimal medical therapy and cardiac resynchronization therapy (CRT). Int J Cardiol 277:173–177. https://doi.org/10.1016/j.ijcard.2018.10.086

    Article  PubMed  Google Scholar 

  14. Kuschyk J, Kloppe A, Schmidt-Schweda S, Bonnemeier H, Rousso B, Röger S (2017) Cardiac contractility modulation: a technical guide for device implantation. Rev Cardiovasc Med 18(1):1–13

    Article  PubMed  Google Scholar 

  15. Rich JD, Burns J, Freed BH, Maurer MS, Burkhoff D, Shah SJ (2018) Meta-analysis global group in chronic (MAGGIC) heart failure risk score: validation of a simple tool for the prediction of morbidity and mortality in heart failure with preserved ejection fraction. J Am Heart Assoc 7(20):e009594. https://doi.org/10.1161/jaha.118.009594

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Bao J, Kan R, Chen J, Xuan H, Wang C, Li D, Xu T (2021) Combination pharmacotherapies for cardiac reverse remodeling in heart failure patients with reduced ejection fraction: a systematic review and network meta-analysis of randomized clinical trials. Pharmacol Res 169:105573. https://doi.org/10.1016/j.phrs.2021.105573

    Article  PubMed  CAS  Google Scholar 

  17. Imai M, Rastogi S, Gupta RC, Mishra S, Sharov VG, Stanley WC, Mika Y, Rousso B, Burkhoff D, Ben-Haim S, Sabbah HN (2007) Therapy with cardiac contractility modulation electrical signals improves left ventricular function and remodeling in dogs with chronic heart failure. J Am Coll Cardiol 49(21):2120–2128. https://doi.org/10.1016/j.jacc.2006.10.082

    Article  PubMed  Google Scholar 

  18. Zhang F, Dang Y, Li Y, Hao Q, Li R, Qi X (2016) Cardiac contractility modulation attenuate myocardial fibrosis by inhibiting TGF-beta1/Smad3 signaling pathway in a rabbit model of chronic heart failure. Cell Physiol Biochem 39(1):294–302. https://doi.org/10.1159/000445624

    Article  PubMed  CAS  Google Scholar 

  19. Cappannoli L, Scacciavillani R, Rocco E, Perna F, Narducci ML, Vaccarella M, D’Amario D, Pelargonio G, Massetti M, Crea F, Aspromonte N (2021) Cardiac contractility modulation for patient with refractory heart failure: an updated evidence-based review. Heart Fail Rev 26(2):227–235. https://doi.org/10.1007/s10741-020-10030-4

    Article  PubMed  Google Scholar 

  20. Gorter TM, van Veldhuisen DJ, Bauersachs J, Borlaug BA, Celutkiene J, Coats AJS, Crespo-Leiro MG, Guazzi M, Harjola VP, Heymans S, Hill L, Lainscak M, Lam CSP, Lund LH, Lyon AR, Mebazaa A, Mueller C, Paulus WJ, Pieske B, Piepoli MF, Ruschitzka F, Rutten FH, Seferovic PM, Solomon SD, Shah SJ, Triposkiadis F, Wachter R, Tschöpe C, de Boer RA (2018) Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the heart failure association of the European society of cardiology. Eur J Heart Fail 20(1):16–37. https://doi.org/10.1002/ejhf.1029

    Article  PubMed  Google Scholar 

  21. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB, American Heart Association Statistics C, Stroke Statistics S (2013) Heart disease and stroke statistics–2013 update: a report from the American heart association. Circulation 127(1):e6–e245. https://doi.org/10.1161/CIR.0b013e31828124ad

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim (UMM), Medical Faculty Mannheim, Heidelberg University, European Center for AngioScience (ECAS), and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Christian Fastner, Goekhan Yuecel, Boris Rudic, Gereon Schmiel, Matthias Toepel, Volker Liebe, Mathieu Kruska, Martin Borggrefe, Ibrahim Akin, Daniel Duerschmied & Juergen Kuschyk

  2. Department of Geriatrics, University Medical Centre Mannheim (UMM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Christian Fastner

  3. Department of Medical Statistics and Biomathematics, University Medical Centre Mannheim (UMM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Svetlana Hetjens

  4. Cardiovascular Research Foundation, New York City, NY, USA

    Daniel Burkhoff

Authors
  1. Christian Fastner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Goekhan Yuecel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Svetlana Hetjens
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Boris Rudic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gereon Schmiel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Matthias Toepel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Volker Liebe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mathieu Kruska
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Martin Borggrefe
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Daniel Burkhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ibrahim Akin
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Daniel Duerschmied
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Juergen Kuschyk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juergen Kuschyk.

Ethics declarations

Conflict of interest

BR received lecture fees from Impulse Dynamics Germany GmbH (Stuttgart, Germany). CF received travel allowance and lecture fees from Impulse Dynamics Germany GmbH (Stuttgart, Germany). DB is a paid consultant to Impulse Dynamics (Marlton, NJ, USA). JK works as a consultant for Impulse Dynamics (Marlton, NJ, USA) and received honoraria and lecture fees from this company.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (JPG 705 KB)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fastner, C., Yuecel, G., Hetjens, S. et al. Should HFrEF patients with NYHA class II expect benefit from CCM therapy? Results from the MAINTAINED observational study. Clin Res Cardiol 111, 1286–1294 (2022). https://doi.org/10.1007/s00392-022-02089-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-022-02089-w

Keywords

Search

Navigation