Relation of QRS Duration to Clinical Benefit of Cardiac Resynchronization Therapy in Mild Heart Failure Patients Without Left Bundle Branch Block: The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy Substudy

Abstract

Background: There are conflicting data regarding the efficacy of cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and without left bundle branch block.

Methods and results: We evaluated the long-term clinical outcomes of 537 non-left bundle branch block patients with mild HF enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study by QRS duration or morphology further stratified by PR interval. At 7 years of follow-up, the cumulative probability of HF hospitalization or death was 45% versus 56% among patients randomized to implantable cardioverter-defibrillator and CRT with defibrillator (CRT-D), respectively (P=0.209). Multivariable-adjusted subgroup analysis by QRS duration showed that patients from the lower quartile QRS duration group (≤ 134 ms) experienced 2.4-fold (P=0.015) increased risk for HF hospitalization or death with CRT-D versus implantable cardioverter-defibrillator only therapy, whereas the effect of CRT-D in patients from the upper quartiles group (QRS>134 ms) was neutral (hazard ratio [HR] =0.97, P=0.86; P value for interaction =0.024). In a second analysis incorporating PR interval, patients with prolonged QRS (>134 ms) and prolonged PR (>230 ms) were protected with CRT-D (HR=0.31, P=0.003), whereas the association was neutral with prolonged QRS (>134 ms) and shorter PR (≤ 230 ms;, HR=1.19, P=0.386; P value for interaction =0.002). The effect was neutral, regardless of morphology, right bundle branch block (HR=1.01, P=0.975), and intraventricular conduction delay (HR=1.31, P=0.172).

Conclusions: Overall, patients with mild HF but without left bundle branch block morphology did not derive clinical benefit with CRT-D during long-term follow-up. Relatively shorter QRS was associated with a significantly increased risk with CRT-D relative to implantable cardioverter-defibrillator -only.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00180271, NCT01294449, and NCT02060110.

Keywords: bundle-branch block; heart failure; implanted cardioverter–defibrillator; morbidity/mortality; resynchronization.