Sex Differences in Long-Term Outcomes With Cardiac Resynchronization Therapy in Mild Heart Failure Patients With Left Bundle Branch Block

Abstract

Background: Previous studies have shown conflicting results regarding the benefit of cardiac resynchronization therapy (CRT) by sex and QRS duration.

Methods and results: In the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), we evaluated long-term clinical outcome of heart failure (HF) or death, death, and HF alone by sex and QRS duration (dichotomized at 150 ms) in left bundle-branch block patients with CRT with defibrillator backup (CRT-D) versus implantable cardioverter-defibrillator (ICD) only. There were 394 women (31%) and 887 men with left bundle-branch block. During the median follow-up of 5.6 years, women derived greater clinical benefit from CRT-D compared with implantable cardioverter-defibrillator only, with a significant 71% reduction in HF or death (hazard ratio [HR] 0.29, P<0.001) and a 77% reduction in HF alone (HR 0.23, P<0.001) compared with men, who had a 41% reduction in HF or death (HR 0.59, P<0.001) and a 50% reduction in HF alone (HR 0.50, P<0.001) (all sex-by-treatment interaction P<0.05). Men and women had similar reduction in long-term mortality with CRT-D versus implantable cardioverter-defibrillator only (men: HR 0.70, P=0.03; women: HR 0.59, P=0.04). The incremental benefit of CRT-D in women for HF or death and HF alone was consistent with QRS <150 or >150 ms.

Conclusions: During long-term follow-up of mild HF patients with left ventricular dysfunction and wide QRS, both women and men with left bundle-branch block derived sustained benefit from CRT-D versus implantable cardioverter-defibrillator only, with significant reduction in HF or death, HF alone, and all-cause mortality regardless of QRS duration. There is an incremental benefit with CRT-D in women for the end points of HF or death and HF alone.

Clinical trial registration: URL: https://ichgcp.net/clinical-trials-registry/NCT00180271" title="See in ClinicalTrials.gov">NCT00180271, NCT01294449, and NCT02060110.

Keywords: QRS duration; cardiac resynchronization therapy with defibrillator; clinical outcomes; implantable cardioverter‐defibrillator; long‐term survival; mild heart failure; mortality; sex.

© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1

Cumulative probability of death by treatment arm in women (A) and men (B). The numbers in the parentheses indicates Kaplan–Meier event rates. CRT-D indicates cardiac resynchronization therapy with defibrillator; ICD, implantable cardioverter-defibrillator.

Figure 2

Cumulative probability of HF or death by treatment arm in women (A) and men (B). The numbers in the parentheses indicates Kaplan–Meier event rates. CRT-D indicates cardiac resynchronization therapy with defibrillator; HF, heart failure; ICD, implantable cardioverter-defibrillator.

Figure 3

Forest plot shows risk of heart failure or death event by sex according to treatment group in subgroups of patients. CRT-D indicates cardiac resynchronization therapy with defibrillator; HR, hazard ratio; ICD, implantable cardioverter-defibrillator; LBBB, left bundle-branch block.