Dynamics of heart failure markers and cardiac reverse remodeling in patients receiving cardiac contractility modulation therapy

Aim. To assess the clinical course and cardiac reverse remodeling in patients with heart failure (HF) with reduced ejection fraction (HFrEF) receiving cardiac contractility modulation (CCM) therapy.

Material and methods. Fifty-five patients (mean age, 53±11 years, 46 males) with NYHA class II-III HFrEF (ischemic etiology in 73% of patients), sinus rhythm, QRS<130 ms or QRS<150 ms of non-LBBB morphology receiving optimal medical therapy were enrolled into the study. CCM devices were implanted to all patients between October 2016 and September 2017. We assessed the following parameters: hospitalizations and mortality due to decompensated HF; changes in HF class, NTproBNP concentration, peak oxygen consumption, six-minute walk test, left ventricular end-systolic and end-diastolic volumes and ejection fraction (EF), atrial and ventricular arrhythmias. A comparative analysis of the studied parameters was carried out depending on the pacing with one and two ventricular leads, on LVEF value (>25% and <25%) and HF etiology.

Results. CCM therapy was associated with a decrease in HF class (p<0,00004001), HF-related hospitalization rate (p<0,0001001), blood NTproBNP concentration (p<0,018), an increase in peak oxygen consumption during the first year (p<0,006011), as well as a decrease in LV volumes and a LVEF increase (p<0,0001001). The direction of these changes did not depend on the number of ventricular leads and LVEF. The presence of ischemic cardiomyopathy and old myocardial infarction did not affect the disease prognosis, but was associated with a lower change in LV volumes and NTproBNP during 24 months of CCM therapy. LVEF values were significantly higher in the group of patients with HFrEF not associated with coronary artery disease after 12 and 24 months of follow-up.

Conclusion. In the group of patients with class II-III HFrEF, CCM therapy in most patients was associated with improved clinical and hemodynamic status, increased exercise tolerance, decreased HF-related hospitalization rate, positive echocardiographic and NTproBNP changes.

1. Mando R, Goel A, Habash F, et al. Outcomes of Cardiac Contractility Modulation: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Cardiovasc Ther. 2019;2019:9769724. doi:10.1155/2019/9769724.

2. Kadish A, Nademanee K, Volosin K, et al. A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. Am Heart J. 2011;161:329-37. doi:10.1016/j.ahj.2010.10.025.

3. Abraham WT, Kuck KH, Goldsmith RL, et al. A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation. JACC Heart Fail. 2018;6:874-83. doi:10.1016/j.jchf.2018.04.010.

4. Vander MA, Lyasnikova EA, Belyakova LA, et al. Two-year outcome analysis of patients with chronic heart failure with reduced ejection fraction receiving cardiac contractility modulation therapy. Russ J Cardiol. 2020;25(7):3853. (In Russ.) doi:10.15829/1560-4071-2020-3853.

5. Winter J, Brack KE, Ng GA. The acute inotropic effects of cardiac contractility modulation (CCM) are associated with action potential duration shortening and mediated by ei-adrenoceptor signalling. J Mol Cell Cardiol. 2011;51:252-62. doi:10.1016/j.yjmcc.2011.04.010.

6. Habecker BA, Anderson ME, Birren SJ, et al. Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease. J Physiol. 2016;594.14:3853-75. doi:10.1113/jp271840.

7. Ponikowski P, Voors AA, Anker SD, 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 Heart J. 2016;37(27):2129-2200. doi:10.1093/eurheartj/ehw128.

8. Mareev VY, Fomin IV, Ageev FT, et al. Russian Heart Failure Society, Russian Society of Cardiology. Russian Scientific Medical Society of Internal Medicine Guidelines for Heart failure: chronic (CHF) and acute decompensated (ADHF). Diagnosis, prevention and treatment. Kardiologiia. 2018;58:8-158. (In Russ.) doi:10.18087/cardio.2475.

9. Roger S, Said S, Kloppe A, et al. Cardiac contractility modulation in heart failure patients: Randomized comparison of signal delivery through one vs. two ventricular leads. J Cardiol. 2017;(1):326-32. doi:10.1016/j.jjcc.2016.06.015.

10. Lyon AR, Samara MA, Feldman DS, et al. Cardiac contractility modulation therapy in advanced systolic heart failure. Nat Rev Cardiol. 2013;10:584-98. doi:10.1038/nrcardio.2013.114.

11. Sitnikova MY, Lyasnikova EA, Yurchenko AV, et al. Results of 3 years work of the Russian hospital register of chronic heart failure (RUssian hoSpital Heart Failure Registry — RUS-HFR): relationship between management and outcomes in patients with chronic heart failure. Kardiologiia. 2018;58(10S):9-19. (In Russ.) doi:10.18087/cardio.2483.

12. Witte K, Hasenfus G, Kloppe A, et al. Cost-effectiveness of a cardiac contractility modulation device in heart failure with normal QRS duration. ESC Heart Failure. 2019;6:1178-87. doi:10.1002/ehf2.12526.