https://doi.org/10.4081/monaldi.2026.4191
Dissociation between structural reverse remodeling and clinical outcomes in ischemic cardiomyopathy undergoing cardiac resynchronization therapy: a real-world analysis
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Accepted: 12 October 2026
Published: 28 October 2026
Patients with non-ischemic cardiomyopathy (NICM) generally exhibit better responses to cardiac resynchronization therapy (CRT) due to more pronounced reverse remodeling compared to ischemic cardiomyopathy (ICM) patients. However, the prognostic impact of CRT in ICM patients remains uncertain. This study aimed to evaluate the impact of heart failure (HF) etiology on reverse remodeling, clinical outcomes, and survival following CRT in a real-world population.
We conducted a retrospective observational study including patients who underwent CRT-P (pacing)/CRT-D (defibrillator) implantation. Patients were stratified according to HF etiology (ICM vs. NICM). The primary composite endpoint was the occurrence of all-cause mortality and HF hospitalization. Secondary outcomes focused on echocardiographic measures of left ventricular reverse remodeling. Survival analysis was performed using Kaplan-Meier curves and Cox regression models.
Of the 95 patients initially screened, 83 were included in the final analysis, of whom 38 (45.8%) had ICM. The mean age was 69.5±10.4 years, and 75.8% were male. Both groups received similar medical therapy. NICM patients demonstrated a significant improvement in reverse remodeling after CRT [left ventricular ejection fraction (LVEF): 32.3±11.5% to 44.0±13.2%, p=0.001); end-diastolic volume (LVEDV): 189.6±74.3 mL to 143.9±48.9 mL, p=0.010] with post-CRT LVEF being higher than in ICM patients (44.0±13.2% vs. 35.5±13.5%, p=0.003). NICM patients were more likely to be super-responders (58.1% vs. 25.0%, p=0.014). No significant differences were observed between groups in the primary composite endpoint (27.3% vs. 42.1%, p=0.171) or overall survival over a mean follow-up of 35 months (log-rank p=0.733).
Although ICM patients showed less pronounced reverse remodeling following CRT, long-term clinical outcomes and survival were comparable to those observed in NICM. These findings reinforce the role of CRT as a disease-modifying therapy that prevents disease progression irrespective of HF etiology and support its systematic use in all eligible patients.
Downloads
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;42:3599-726.
Glikson M, Nielsen JC, Leclercq C, et al. 2021 ESC guidelines on cardiac pacing and cardiac resynchronization therapy. Eur Heart J 2021;42:3427-520.
Mullens W, Auricchio A, Martens P, et al. Optimized implementation of cardiac resynchronization therapy: a call for action for referral and optimization of care: A joint position statement from the Heart Failure Association (HFA), European Heart Rhythm Association (EHRA), and European Association of Cardiovascular Imaging (EACVI) of the European Society of Cardiology. Eur J Heart Fail 2020;22:2349-69.
Gerra L, Bonini N, Mei DA, et al. Cardiac resynchronization therapy (CRT) nonresponders in the contemporary era: a state-of-the-art review. Hear Rhythm 2025;22:159-69.
Stătescu C, Ureche C, Enachi Ș, et al. Cardiac resynchronization therapy in non-ischemic cardiomyopathy: Role of multimodality imaging. Diagnostics 2021;11:625.
Cleland J, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:1539-49.
Abraham WT, Fisher W, Smith A, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002;346:1845-53.
Bristow M, Saxon L, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-50.
Steffel J, Ruschitzka F. Superresponse to cardiac resynchronization therapy. Circulation 2014;130:87-90.
Yokoshiki H, Mitsuyama H, Watanabe M, et al. Cardiac resynchronization therapy in ischemic and non-ischemic cardiomyopathy. J Arrhythmia 2017;33:410-6.
Moss AJ, Hall J, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 2009;361:1329-38.
Tang A, Wells G, Talajic M, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 2010;363:2385-95.
Solomon SD, Foster E, Bourgoun M, et al. Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: Multicenter automatic defibrillator implantation trial: Cardiac resynchronization therapy. Circulation 2010;122:985-92.
St John Sutton MG, Plappert T, Hilpisch KE, et al. Sustained reverse left ventricular structural remodeling with cardiac resynchronization at one year is a function of etiology: Quantitative Doppler echocardiographic evidence from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE). Circulation 2006;113:266-72.
Yu CM, Bleeker GB, Fung JWH, et al. Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation 2005;112:1580-6.
Martens P, Nijst P, Verbrugge FH, et al. Profound differences in prognostic impact of left ventricular reverse remodeling after cardiac resynchronization therapy relate to heart failure etiology. Hear Rhythm 2018;15:130-6.
Braunschweig F, Sörensen J, Von Bibra H, et al. Effects of biventricular pacing on myocardial blood flow and oxygen consumption using carbon-11 acetate positron emission tomography in patients with heart failure. Am J Cardiol 2003;92:95-9.
Varma N, Boehmer J, Bhargava K, et al. Evaluation, management, and outcomes of patients poorly responsive to cardiac resynchronization device therapy. J Am Coll Cardiol 2019;74:2588-603.
Mullens W, Verga T, Grimm RA, et al. Persistent hemodynamic benefits of cardiac resynchronization therapy with disease progression in advanced heart failure. J Am Coll Cardiol 2009;53:600-7.
Ethics Approval
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.