Cardiac contractility modulation in patients with heart failure with reduced ejection fraction: a meta-analysis of Russian clinical trials

Aim. To perform a meta-analysis of Russian clinical trials and study the associations of cardiac contractility modulation in patients with heart failure with reduced left ventricular ejection fraction (LVEF).

Material and methods. In the meta-analysis; the following outcome measures were selected: Minnesota Living With Heart Failure Questionnaire (MLWHFQ); 6-minute walk test (6MWT); improvement in heart failure functional class; echocardiography data: LVEF; LV end-systolic and end-diastolic volumes; as well as survival rates at 12 and 24 months.

Results. The results included in the meta-analysis showed a significant improvement in the 6MWT distance (n=216) (mean difference -38;19; 95% confidence interval (CI): -65;46 to -10;91 m; p=0;006); MLWHFQ results (mean difference 7;28; 95% CI: 2;87-11;69; p=0;001); LVEF (mean difference -4;02; 95% CI: from -5;83 to 2;20; p<0;0001) and LV volume parameters (LV end-diastolic volume: mean difference 19;99; 95% CI: 7;56-32;42; p=0;002; LV end-systolic volume: mean difference 22;68; 95% CI: 12;85-32.51; p<0;001) after 24 months in the cardiac contractility modulation group compared to the control group. Survival was assessed after 12 and 24 months of follow-up — the differences were insignificant.

Conclusion. The results of the data from 3 Russian clinical non-randomized studies included in the meta-analysis suggest that cardiac contractility modulation is associated with a significant improvement in quality of life; 6MWT distance; and reverse LV myocardial remodeling. 

1. Polyakov DS, Fomin IV, Belenkov YuN, et al. Chronic heart failure in the Russian Federation: what has changed over 20 years of follow-up? Results of the EPOCH-CHF study. Kardiologiia. 2021;61(4):4-14. (In Russ.) doi:10.18087/cardio.2021.4.n1628.

2. Glikson M, Nielsen JC, Kronborg MB, et al. ESC scientific document group. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization. Eur Heart J. 2021;35(342):3427-520. doi:10.1093/eurheartj/ehab364.

3. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42;36:3599-726. doi:10.1093/eurheartj/ehab368.

4. Zhang Q, Yu C.-M. Could exercise unveil the mystery of non-res¬ponse to cardiac resynchronization therapy? Europace. 2011; 13(6):768-9. doi:10.1093/europace/eur044.

5. Lund LH, Jurga J, Edner M, et al. Prevalence, correlates, and prognostic significance of QRS prolongation in heart failure with reduced and preserved ejection fraction. Eur Heart J. 2013; 34(7):529-39. doi:10.1093/eurheartj/ehs305.

6. Ruschitzka F, Abraham WT, Singh JP, et al. Cardiac-Resyn-chronization Therapy in Heart Failure with a Narrow QRS Complex. N Engl J Med. 2013;369(15):1395-405. doi:10.1056/NEJMoa1306687.

7. Butter C, Rastogi S, Minden HH, et al. Cardiac Contractility Mo-dulation Electrical Signals Improve Myocardial Gene Expression in Patients With Heart Failure. J Am Coll Cardiol. 2008; 51(18):1784-9. doi:10.1016/j.jacc.2008.01.036.

8. Imai M, Rastogi S, Gupta RC, et al. Therapy With Cardiac Con-tractility Modulation Electrical Signals Improves Left Ventricular Function and Remodeling in Dogs With Chronic Heart Failure. J Am Coll Cardiol. 2007;49(21):2120-8. doi:10.1016/j.jacc.2006.10.082.

9. Omelyanovsky VV, Avksentieva MV, Sura MV, et al. Methodological recommendations for conducting a meta-analysis. Federal State Budgetary Institution "Center for Expertise and Quality Control of Medical Care" of the Ministry of Health of the Russian Federation, 2017. 28 р. (In Russ.) EDN PRPXHH.

10. Rebrova OYu, Fedyaeva VK. Questionnaire for assessing the risk of systematic errors in randomized comparative studies: the Russian version of the Newcastle-Ottawa scale. Medical technologies. Assessment and selection. 2016;(3):14-9. (In Russ.)

11. Safiullina AA, Uskach TM, Obraztsov IV, et al. Life expectancy in patients with chronic heart failure, atrial fibrillation and implantable cardiac contractility modulation devices. Russian Cardiology Bulletin. 2023;18(1):38-48. (In Russ.) doi:10.17116/Cardiobulletin20231801138.

12. Safiullina AA, Uskach TM, Sapelnikov OV, et al. The effectiveness of cardiac contractility modulation in patients with chronic heart failure and atrial fibrillation: results of the 12-month follow-up. Terapevticheskii Arkhiv (Ter Arkh.). 2022;94(9):1078-84. (In Russ.) doi:10.26442/00403660.2022.09.201840.

13. Amiraslanov AY, Vaskovskiy VA, Artyukhina E A, et al. Long-term results of cardiac contractility modulation in patients with chronic heart failure. J Arrhythmology. 2022;29(1):17-23. (In Russ.) doi:10.35336/VA-2022-1-03.

14. Chugunov IA, Davtyan KV, Topchyan AH, et al. Cardiac contracti-lity modulation therapy in elderly patients with chronic heart failu¬re: results of the 12-month follow-up. J Arrhythmology. 2021;28(2):5-10. (In Russ.) doi:10.35336/VA-2021-2-5-10.

15. Mamchur SE, Khomenko EA, Chistyukhin OM, et al. Effect of cardiac contractility modulation on contractility synchronization and strain of the left ventricular myocardium: a pilot study. Journal of Arrhythmology. 2018;93:24-9. (In Russ.) doi:10.25760/VA-2018-93-24-29.

16. Mareev VYu, Fomin IV, Ageev FT, et al. Clinical recommendations of the OSSN — RKO — REPAIR. heart failure: chronic (CHF) and acute decompensated (CHF). diagnosis, prevention and treatment. Cardiologiia. 2018;58(6S):8-164. (In Russ.) doi:10.18087/cardio.2475.

17. Kwong JSW, Sanderson JE, Yu C. Cardiac Contractility Modulation for Heart Failure: A Meta‐Analysis of Randomized Control¬led Trials. Pacing Clin Electrophysiol. 2012;35(9):1111-8. doi:10.1111/j.1540-8159.2012.03449.x.

18. Giallauria F, Vigorito C, Piepoli MF, et al. Effects of cardiac con-tractility 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. doi:10.1016/j.ijcard.2014.06.005.

19. Liu X, Yang HJ, Ping HQ, et al. The safety and efficacy of cardiac contractility modulation in heart failure. Herz. 2017;42(8):766-75. doi:10.1007/s00059-016-4514-5.

20. Giallauria F, Cuomo G, Parlato A, et al. A comprehensive individual patient data meta‐analysis of the effects of cardiac contractility modulation on functional capacity and heart failure‐related quality of life. ESC Hear Fail. 2020;7(5):2922-32. doi:10.1002/ehf2.12902.