Interaction of left ventricular size and sex on outcome of cardiac resynchronization therapy among patients with a narrow QRS duration in the EchoCRT trial

Abstract

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 CRTON [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 sexspecific 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.