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

J Am Heart Assoc. 2018 May 27;7(11):e009592. doi: 10.1161/JAHA.118.009592.


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: Unique identifier: NCT00683696.

Keywords: cardiac resynchronization therapy; left ventricle size; narrow QRS.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Aged
  • Cardiac Resynchronization Therapy* / adverse effects
  • Cardiac Resynchronization Therapy* / mortality
  • Echocardiography
  • Electrocardiography
  • Female
  • Heart Conduction System / physiopathology*
  • Heart Failure / diagnosis
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Heart Failure / therapy*
  • Heart Rate
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / physiopathology*
  • Humans
  • Hypertrophy, Left Ventricular / diagnosis
  • Hypertrophy, Left Ventricular / mortality
  • Hypertrophy, Left Ventricular / physiopathology
  • Hypertrophy, Left Ventricular / therapy*
  • Male
  • Middle Aged
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Time Factors
  • Treatment Outcome
  • Ventricular Function, Left*
  • Ventricular Remodeling*

Associated data