Redefining response to Cardiac Resynchronisation Therapy: A Post-hoc Analysis of the MORE-CRT MPP trial.

BACKGROUND: Cardiac resynchronization therapy (CRT) response is commonly assessed at 6 months using left ventricular end-systolic volume (LVESV) and clinical endpoints. Some initial non-responders may improve or stabilize by 12 months. OBJECTIVES: To determine outcomes and predictors of echocardiographic response trajectories and evaluate the clinical course of patients who stabilised or deteriorated after 6 months. METHODS: 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 stabilised (LVESV reduction at 12 months) or deteriorated (LVESV increase at 12 months). Heart failure hospitalization (HFH) or death was analysed using restricted mean survival time and adjusted accelerated failure time models. RESULTS: Among 2,732 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% stabilised 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. CONCLUSIONS: 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.