Opportunity to increase life span in narrow QRS cardiac resynchronization therapy recipients by deactivating ventricular pacing: evidence from randomized controlled trials

Objectives: This study examined the time course of clinical events in cardiac resynchronization therapy (CRT) trials.

Background: Recent randomized controlled trial results suggest that in heart failure with narrow QRS, biventricular pacing (CRT) may increase mortality. The authors proposed implant complications as the cause, rather than a progressive adverse physiological effect.

Methods: The study identified all trials comparing CRT with no CRT, which reported Kaplan-Meier curves in groups defined by QRS: narrow, non-left bundle branch block (LBBB) broad, and LBBB broad. For each trial, the change in life span every 3 months up to 3.5 years (the longest time for which data are available) was calculated and a power law was fitted, that is, ∝ time(n).

Results: Four trials (MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy], RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure Trial], REVERSE [REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction], and EchoCRT [Echocardiography Guided Cardiac Resynchronization Therapy]), totaling 4,717 patients, reported curves for mortality or heart failure-related hospitalization, or for mortality. In patients with LBBB broad QRS (within MADIT-CRT), life span gain increased in proportion to time(1.94). In contrast, in patients with non-LBBB broad QRS (within MADIT-CRT) and patients with narrow QRS (EchoCRT), life span was lost in proportion to time(1.92) and time,(1.96) respectively. Hospitalization-free survival showed similar patterns.

Conclusions: The nonlinear growth of life span gained when a CRT device is implanted in patients with LBBB broad QRS is unfortunately mirrored by a similarly progressive loss in life span in narrow QRS heart failure. This suggests the culprit is a progressive physiological effect of pacing rather than implant complications. If these data are not sufficient, a randomized controlled trial of deactivating CRT in patients with narrow QRS may now be needed, with a primary endpoint of increasing survival.