Redefining response to cardiac resynchronization therapy: a post hoc analysis of the MORE-CRT MPP trial

Cardiac resynchronization therapy (CRT) response is commonly assessed at 6 months using left ventricular end-systolic volume (LVESV) and clinical endpoints. However, response may continue to evolve beyond this time point, with some initial non-responders subsequently improving or stabilizing. This study aimed to characterize changes in echocardiographic response from 6 to 12 months, identify predictors of these trajectories, and assess their relationship with longer-term clinical outcomes.

This post hoc analysis of the MORE-CRT MPP trial included patients receiving conventional biventricular pacing only. Patients were classified as non-responders (<15% LVESV reduction at 6 and 12 months), early responders (>15% reduction at 6 months), or delayed responders (<15% reduction at 6 months but >15% at 12 months). Six-month non-responders were further classified as stabilized (LVESV reduction at 12 months) or deteriorated (LVESV increase at 12 months). Heart failure hospitalization or death was analysed using restricted mean survival time and adjusted accelerated failure time models. Among 2732 patients (69.4% male; 62.8% non-ischaemic), event-free survival differed between early, delayed, and non-responders (P < 0.001). Non-responders had 52% shorter event-free survival than early responders (P < 0.001), and 38% shorter than delayed responders (P = 0.025). Early and delayed responders had similar outcomes (P = 0.221). Among non-responders, 39.0% stabilized and 61.0% deteriorated; outcomes diverged after 6 months (P < 0.001). The deterioration group had 59% shorter event-free survival (P < 0.001). Ischaemic aetiology, non-LBBB, and lower baseline LVEF predicted delayed response.

Delayed responders demonstrated similarly favourable clinical outcomes to early responders over the duration of follow-up. These findings support 12-month assessment and trajectory-based definitions of CRT response.