Interaction of Left Ventricular Size and Sex on Outcome of Cardiac Resynchronization Therapy Among Patients With a Narrow QRS Duration in the EchoCRT Trial

BACKGROUND: Longer QRS duration (QRSd) improves, but increased left ventricular (LV) end‐diastolic volume (LVEDV) reduces, efficacy of cardiac resynchronization therapy (CRT). QRSd/LVEDV ratios differ between sexes. We hypothesized that in the EchoCRT (Echocardiography Guided Cardiac Resynchronization Therapy) trial enrolling patients with heart failure with QRSd <130 ms, those with larger LVEDV would deteriorate but those with the highest QRSd/LVEDV would improve with CRT. METHODS AND RESULTS: Primary outcome in patients (n=787, 72% men, 93% New York Heart Association class III, QRSd <130 ms, LV ejection fraction ≤35%, LV dilation and dyssynchrony) randomized to CRT‐ON or CRT‐OFF and followed up for 19 months was compared according to LVEDV (height indexed) or QRSd/LVEDV ratio, in multivariable analysis. Structural remodeling was assessed echocardiographically 6 months after implantation. Patients with baseline LVEDV higher than or equal to median worsened with CRT (death/heart failure hospitalization: CRT‐ON versus CRT‐OFF, 35.2% versus 24.5% [hazard ratio, 1.64; 95% confidence interval, 1.11–2.42; P=0.012]), but those with LVEDV lower than median remained unaffected. Patients with the highest QRSd/LVEDV ratio improved with CRT (death/heart failure hospitalization in top quartile: 20.9% in CRT‐ON [n=91] versus 28.3% in CRT‐OFF [n=106] [hazard ratio, 0.64; 95% confidence interval, 0.34–1.24; P=0.188], versus the remaining quartiles: 31.7% in CRT‐ON [n=300] versus 24.8% in CRT‐OFF [n=290] [hazard ratio, 1.47; 95% confidence interval, 1.07–2.02; P=0.016], test for interaction P=0.046). QRSd and dyssynchrony were similar between groups. The 3‐way test for interaction indicated no sex‐specific effects. However, numerically, men with LVEDV higher than or equal to median accounted for worse outcomes of CRT‐ON. Women, with the highest QRSd/LVEDV ratio exhibited significant reverse remodeling. CONCLUSION: CRT has opposite effects among patients with heart failure with QRSd <130 ms according to LV size: worsening outcomes in patients with larger LV, but inducing beneficial effects in those with smaller LV. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00683696.