Impact of Cardiac Contractility Modulation on Left Ventricular Ejection Fraction and Clinical Outcomes in Heart Failure: A Systematic Review and Meta-Analysis

  • I Nyoman Wiryawan Department of Cardiology and Vascular Medicine, Universitas Udayana/ Prof. dr. I.G.N.G Ngoerah General Hospital, Denpasar, Bali, Indonesia
  • David Yobel Department of Cardiology and Vascular Medicine, Universitas Udayana/ Prof. dr. I.G.N.G Ngoerah General Hospital, Denpasar, Bali, Indonesia
  • Gusti Ngurah Prana Jagannatha Department of Cardiology and Vascular Medicine, Universitas Udayana/ Prof. dr. I.G.N.G Ngoerah General Hospital, Denpasar, Bali, Indonesia
  • Ni Kadek Aristia Dewi Department of Cardiology and Vascular Medicine, Universitas Udayana/ Prof. dr. I.G.N.G Ngoerah General Hospital, Denpasar, Bali, Indonesia
  • Cindy Amanda Shandy Department of Cardiology and Vascular Medicine, Universitas Udayana/ Prof. dr. I.G.N.G Ngoerah General Hospital, Denpasar, Bali, Indonesia
  • Hendy Wirawan Department of Cardiology and Vascular Medicine, Universitas Udayana/ Prof. dr. I.G.N.G Ngoerah General Hospital, Denpasar, Bali, Indonesia
Keywords: Device based therapy, Cardiac resynchronization therapy,, Cardiac contractility modulation, Heart failure, Optimal medical therapy

Abstract

Patients with heart failure and narrow QRS often remain symptomatic despite Optimal Medical Therapy (OMT), while CRT is usually not indicated. Cardiac Contractility Modulation (CCM) may improve symptoms and quality of life in this population. This systematic review and meta-analysis included studies comparing CCM to either OMT alone or OMT with CRT. Assessed outcomes included improvements in clinical, structural, and physiological domains. Random-effects models were applied for all analyses, and results were reported as Odds Ratios (OR) or Mean Differences (MD) with 95% Confidence Intervals (CI). All statistical analyses were conducted using Review Manager V.5.4 A total of eight studies involving 1,486 patients with heart failure were included in this analysis. In terms of structural outcomes, CCM demonstrated improvements in LVEF comparable to those of CRT, with no statistically significant difference between the two therapies (p>0.05). Compared to the OMT-only group, CCM showed significantly greater improvements in VO₂ max (MD 0.91; 95%CI 0.44-1.37; p<0.001; I²=33%), 6MWD (MD 17.95; 95% CI 5.45-30.45; p=0.005; I²=0%), and MLHFQ (MD -7.56; 95% CI -11.65 to -3.47; p<0.001; I²=39%). Although no significant differences were observed between CCM and control in terms of all-cause mortality, MACE, or rehospitalization (p>0.05), CCM group showed significant improvements in quality of life, as measured by NYHA functional class (MD 2.74; 95%CI 1.47-5.12; p<0.001; I²=76%). CCM is a promising therapy for heart failure, offering structural benefits comparable to CRT in narrow QRS patients and improving function and quality of life beyond OMT, despite no significant reduction in hard clinical outcomes.

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References

1. Skouri H, Girerd N, Monzo L, Petrie MC, Böhm M, Adamo M, et al (2025). Clinical management and therapeutic optimization of patients with heart failure with reduced ejection fraction and low blood pressure. A clinical consensus statement of the Heart Failure Association ( HFA) of the ESC. European J of Heart Fail. doi:10.1002/ejhf.3618.
2. Pipilas DC, Hanley A, Singh JP, Mela T. (2023) Cardiac Contractility Modulation for Heart Failure: Current and Future Directions. Journal of the Society for Cardiovascular Angiography & Interventions. https://doi.org/10.1016/j.jscai.2023.101176.
3. Borggrefe M, Mann DL. (2018) Cardiac Contractility Modulation in 2018. Circulation. doi:10.1093/eurheartj/ehn020.
4. Higgins J. (2024) Cochrane Handbook for Systematic Reviews of Interventions. 6.5.
5. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. DOI: 10.1136/bmj.n71.
6. Yuecel G, Gaasch L, Kodeih A, Hetjens S, Yazdani B, Pfleger S, et al. (2025) Device‐therapy in chronic heart failure: Cardiac contractility modulation versus cardiac resynchronization therapy. ESC Heart Failure. DOI: 10.1002/ehf2.15067.
7. Wiegn P, Chan R, Jost C, Saville BR, Parise H, Prutchi D, et al. (2020) Safety, Performance, and Efficacy of Cardiac Contractility Modulation Delivered by the 2-Lead Optimizer Smart System: The FIX-HF-5C2 Study. Circ: Heart Failure. DOI: 10.1161/CIRCHEARTFAILURE.119.006512.
8. Abraham WT, Kuck KH, Goldsmith RL, Lindenfeld J, Reddy VY, Carson PE, et al. (2018) A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation. JACC: Heart Failure. https://doi.org/10.1016/j.jchf.2018.04.010.
9. Zhang Q, Chan YS, Liang YJ, Fang F, Lam YY, Chan CP, et al. (2013) Comparison of left ventricular reverse remodeling induced by cardiac contractility modulation and cardiac resynchronization therapy in heart failure patients with different QRS durations. International Journal of Cardiology. doi:10.1016/j.ijcard.2012.01.066.
10. Kadish A, Nademanee K, Volosin K, Krueger S, Neelagaru S, Raval N, et al. (2011) A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. American Heart Journal. doi:10.1016/j.ahj.2010.10.025.
11. Borggrefe MM, Lawo T, Butter C, Schmidinger H, Lunati M, Pieske B, et al. (2018) Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses for symptomatic heart failure. European Heart Journal. doi:10.1093/eurheartj/ehn020.
12. Neelagaru SB, Sanchez JE, Lau SK, Greenberg SM, Raval NY, Worley S, et al. (2006)Nonexcitatory, cardiac contractility modulation electrical impulses: Feasibility study for advanced heart failure in patients with normal QRS duration. Heart Rhythm. doi:10.1016/j.hrthm.2006.06.031.
13. Stix G. (2004) Chronic electrical stimulation during the absolute refractory period of the myocardium improves severe heart failure. European Heart Journal. doi:10.1016/j.ehj.2004.02.024.
14. Wehner GJ, Jing L, Haggerty CM, Suever JD, Leader JB, Hartzel DN, et al. (2020) Routinely reported ejection fraction and mortality in clinical practice: where does the nadir of risk lie? Eur Heart J. doi: 10.1093/eurheartj/ehz550.
15. Fastner C, Yuecel G, Rudic B, Schmiel G, Toepel M, Burkhoff D, et al. (2021) Cardiac Contractility Modulation in Patients with Ischemic versus Non-ischemic Cardiomyopathy: Results from the MAINTAINED Observational Study. Int J Cardiol. DOI: 10.1016/j.ijcard.2021.07.048.
16. Tschöpe C, Butler J, Farmakis D, Morley D, Rao I, Filippatos G. (2020) Clinical effects of cardiac contractility modulation in heart failure with mildly reduced systolic function. ESC Heart Failure. DOI: 10.1002/ehf2.13126.
17. Abi-Samra F, Gutterman D. (2016) Cardiac contractility modulation: a novel approach for the treatment of heart failure. Heart Fail Rev. DOI 10.1007/s10741-016-9571-6.
18. Rosalia L, Ozturk C, Shoar S, Fan Y, Malone G, Cheema FH, et al. (2021) Device-Based Solutions to Improve Cardiac Physiology and Hemodynamics in Heart Failure With Preserved Ejection Fraction. JACC Basic Transl Sci. https://doi.org/10.1016/j.jacbts.2021.06.002.
19. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. (2021) 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. doi:10.1093/eurheartj/ehab368.
20. Yu CM, Chan JYS, Zhang Q, Yip GWK, Lam YY, Chan A, et al. (2009)Impact of cardiac contractility modulation on left ventricular global and regional function and remodeling. JACC Cardiovasc Imaging. DOI:10.1016/j.jcmg.2009.07.011.
Published
2026-06-11
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How to Cite
Wiryawan, I. N., Yobel, D., Jagannatha, G. N. P., Dewi, N. K. A., Shandy, C. A., & Wirawan, H. (2026). Impact of Cardiac Contractility Modulation on Left Ventricular Ejection Fraction and Clinical Outcomes in Heart Failure: A Systematic Review and Meta-Analysis. Indonesian Journal of Cardiology, 47(2), 154-167. https://doi.org/10.30701/ijc.2182
Section
Review Article