Effect of Cardiac Resynchronization Therapy on Reverse Left Ventricular Remodeling in Patients with Functional Class II Heart Failure

Introduction. Implantation of a cardioverter-defibrillator reduces the risk of sudden cardiac death caused by the development of ventricular tachycardia (VT) and ventricular fibrillation (VF) of the heart, but implantation of this device does not improve the function of the left ventricle (LV). Modern implantable cardioverter-defibrillators (ICD) with endocardial electrodes allow for optimal treatment of cardiac arrhythmias in heart failure (HF) due to the function of electrical cardiac pacing. Cardiac resynchronization therapy (CRT) is aimed at synchronizing contractions of the opposite walls of the LV, which leads to an improvement in the inotropic function of the heart, and subsequently to reverse remodeling of the LV geometry.

The obtained results of the study made it possible to determine whether there was an improvement in volume changes, cardiac function and shock rate when using CRT in combination with an ICD (CRT-D) in patients with HF accompanied by LV dysfunction and a wide QRS complex.

Aim of Study. To assess whether CRT in combination with ICD has an effect on LV reverse remodeling in patients with functional class (FC) II HF.

Material and Methods. A total of 35 patients with a wide QRS complex >130 ms were included in the study: 15 patients in the CRT-D group and 20 with ICD. The obtained results of the study were interpreted one year after the start of treatment in all patients. Changes in the volumes and contractility of the ventricles of the heart were analyzed in both groups. An assessment was made of the dependence of these changes on the results of treatment in subsequent years.

Results. In patients in the CRT-D group, compared with the ICD group, there was an improvement in the LV end-diastolic volume index (-18.7 vs. 8.6 ml/m²), LV end-systolic volume index (-22.5 vs. 5.2 ml/m²), LV ejection fraction (13.2 vs. 0.4%), left atrial volume index (-16.8 vs. 2.7 ml/m²), and pulmonary artery systolic pressure (-11.4 vs. 1.4 mmHg), p<0.05 for all parameters. The improvement in LV functional parameters 1 year after treatment was reflected in a decrease in mortality and recurrence of HF in these patients in the long-term period (13% in the CRT-D group vs. 50% in the ICD group, p><0.05). During the first year of observation, one to two shocks for VT/VF were administered in two patients with CRT-D and three patients with an implanted ICD. During the subsequent threeyear observation period, the defibrillation function was activated in two more patients in the CRT-D group and in two patients with an implanted ICD. CONCLUSION Cardiac resynchronization therapy combined with an implantable cardioverter -defibrillator improves cardiac performance in patients with class II heart failure. Our study demonstrated a decrease in end-diastolic volume, end-systolic volume, left atrial volume, an increase in left ventricular ejection fraction, and an improvement in right ventricular function in patients treated with combined cardiac resynchronization therapy and an implantable cardioverter -defibrillator compared with those treated with an implantable cardioverter -defibrillator alone. These results were consistent with improved outcomes, and outcomes at 1 year were directly related to the degree of improvement in ventricular volumes and function. Keywords: cardiac resynchronization therapy, left ventricular remodeling, heart failure> < 0.05 for all parameters. The improvement in LV functional parameters 1 year after treatment was reflected in a decrease in mortality and recurrence of HF in these patients in the long-term period (13% in the CRT-D group vs. 50% in the ICD group, p < 0.05). During the first year of observation, one to two shocks for VT/VF were administered in two patients with CRT-D and three patients with an implanted ICD. During the subsequent three-year observation period, the defibrillation function was activated in two more patients in the CRT-D group and in two patients with an implanted ICD.

Conclusion. Cardiac resynchronization therapy combined with an implantable cardioverter -defibrillator improves cardiac performance in patients with class II heart failure. Our study demonstrated a decrease in end-diastolic volume, end-systolic volume, left atrial volume, an increase in left ventricular ejection fraction, and an improvement in right ventricular function in patients treated with combined cardiac resynchronization therapy and an implantable cardioverter -defibrillator compared with those treated with an implantable cardioverter-defibrillator alone. These results were consistent with improved outcomes, and outcomes at 1 year were directly related to the degree of improvement in ventricular volumes and function.

1. Saxon LA, De Marco T, Schafer J, Chatterjee K, Kumar UN, Foster E; VIGOR Congestive Heart Failure Investigators. Effects of long-term biventricular stimulation for resynchronization on echocardiographic measures of remodeling. Circulation. 2002;105(11):1304–1310. PMID: 11901040 https://doi.org/10.1161/hc1102.105730

2. St John Sutton MG, Plappert T, Abraham WT, Smith AL, DeLurgio DB, Leon AR, et al.; Multicenter InSync Randomized Clinical Evaluation (MIRACLE) Study Group. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation. 2003;107(15):1985–1990. PMID: 12668512 https://doi.org/10.1161/01.CIR.0000065226.24159.E9

3. Horwich T, Foster E, De Marco T, Tseng Z, Saxon L. Effects of resynchronization therapy on cardiac function in pacemaker patients “upgraded” to biventricular devices. J Cardiovasc Electrophysiol. 2004;15(11):1284–1289. PMID: 15574179 https://doi.org/10.1046/j.1540-8167.2004.04279.x

4. Rao RK, Kumar UN, Schafer J, Viloria E, De Lurgio D, Foster E. Reduced ventricular volumes and improved systolic function with cardiac resynchronization therapy: a randomized trial comparing simultaneous biventricular pacing, sequential biventricular pacing, and left ventricular pacing. Circulation. 2007;115(16):2136–2144. PMID: 17420340 https://doi.org/10.1161/CIRCULATIONAHA.106.634444

5. Kuznetsov VA, Soldatova AM, Krinochkin DV, Enina TN. Cardiac Resynchronisation Therapy in Patients With Congestive Heart Failure: Whether We Should Expect for an “Early” Response? Russian Heart Failure Journal. 2017;18(3):172–177. (In Russ.) https://doi.org/10.18087/rhfj.2017.3.23411

6. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, et al.; Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350(21):2140–2150. PMID: 15152059 https://doi.org/10.1056/NEJMoa032423

7. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al.; Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352(15):1539–1549. PMID: 15753115 https://doi.org/10.1056/NEJMoa050496

8. Yu CM, Bleeker GB, Fung JW, Schalij MJ, Zhang Q, van der Wall EE, et al. Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation. 2005;112(11):1580–1586. PMID: 16144994 https://doi.org/10.1161/CIRCULATIONAHA.105.538272

9. Ypenberg C, van Bommel RJ, Borleffs CJW, Bleeker GB, Boersma E, Schalij MJ, et al. Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodeling at midterm follow-up. J Am Coll Cardiol. 2009;53(6):483–490. PMID: 19195605 https://doi.org/10.1016/j.jacc.2008.10.032

10. Daubert C, Gold MR, Abraham WT, Ghio S, Hassager C, Goode G, et al.; REVERSE Study Group. Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. J Am Coll Cardiol. 2009;54(20):1837–1846. PMID: 19800193 https://doi.org/10.1016/j.jacc.2009.08.011

11. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al.; Chamber Quantification Writing Group; American Society of Echocardiography’s Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18(12):440–1463. PMID: 16376782 https://doi.org/10.1016/j.echo.2005.10.005

12. Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD, Levine RA, et al.; American Society of Echocardiography. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr. 2003;16(7):777–802. PMID: 12835667 https://doi.org/10.1016/S0894-7317(03)00335-3

13. Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, et al.; MADIT-CRT Trial Investigators. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009;361(14):1329– 1338. PMID: 19723701 https://doi.org/10.1056/NEJMoa0906431

14. Moss AJ, Brown MW, Cannom DS, Daubert JP, Estes M, Foster E, et al. Multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT): design and clinical protocol. Ann Noninvasive Electrocardiol. 2005;10(4 Suppl):34–43. PMID: 16274414 https://doi.org/10.1111/j.1542-474X.2005.00073.x

15. St John Sutton M, Ghio S, Plappert T, Tavazzi L, Scelsi L, Daubert C, et al.; REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) Study Group. Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure. Circulation. 2009;120(19):1858–1865. PMID: 19858419 https://doi.org/10.1161/CIRCULATIONAHA.108.818724

16. Zornoff LA, Skali H, Pfeffer MA, St John Sutton M, Rouleau JL, Lamas GA, et al.; SAVE Investigators. Right ventricular dysfunction and risk of heart failure and mortality after myocardial infarction. J Am Coll Cardiol. 2002;39(9):1450–1455. PMID: 11985906 https://doi.org/10.1016/s0735-1097(02)01804-1

17. Anavekar NS, Skali H, Bourgoun M, Ghali JK, Kober L, Maggioni AP, et al. Usefulness of right ventricular fractional area change to predict death, heart failure, and stroke following myocardial infarction (from the VALIANT ECHO Study). Am J Cardiol. 2008;101(5):607–612. PMID: 18308007 https://doi.org/10.1016/j.amjcard.2007.09.115

18. Meris A, Amigoni M, Uno H, Thune JJ, Verma A, Køber L, et al. Left atrial remodelling in patients with myocardial infarction complicated by heart failure, left ventricular dysfunction, or both: the VALIANT Echo study. Eur Heart J. 2009;30(1):56–65. PMID: 19001474 https://doi.org/10.1093/eurheartj/ehn499

19. Bleeker GB, Schalij MJ, Nihoyannopoulos P, Steendijk P, Molhoek SG, van Erven L, et al. Left ventricular dyssynchrony predicts right ventricular remodeling after cardiac resynchronization therapy. J Am Coll Cardiol. 2005;46(12):2264–2269. PMID: 16360056 https://doi.org/10.1016/j.jacc.2005.04.069

20. Yu CM, Fang F, Zhang Q, Yip GWK, Li CM, Chan JYS, et al. Improvement of atrial function and atrial reverse remodeling after cardiac resynchronization therapy for heart failure. J Am Coll Cardiol. 2007;50(8):778–785. PMID: 17707183 https://doi.org/10.1016/j.jacc.2007.04.073

21. St John Sutton MG, Plappert T, Hilpisch KE, Abraham WT, Hayes DL, Chinchoy E. Sustained reverse left ventricular structural remodeling with cardiac resynchronization at 1 year is a function of etiology: quantitative Doppler echocardiography evidence from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE). Circulation. 2006;113(2):266–272. PMID: 16401777 https://doi.org/10.1161/CIRCULATIONAHA.104.520817