Aims: Cardiac resynchronization therapy (CRT) via biventricular (BIV) pacing is indicated in patients with heart failure (HF), reduced ejection fraction, and prolonged QRS duration. Quadripolar leads and multipoint pacing (MPP) allow multiple left ventricle (LV) sites pacing. We aimed to assess the clinical benefit of MPP in patients who do not respond to standard BIV pacing.

Methods and results: Overall, 3724 patients were treated with standard BIV pacing. After 6 months, 1639 patients were considered as CRT non-responders (echo-measured relative reduction in LV end-systolic volume (LVESV) < 15%) and randomized to MPP or BIV. We analysed 593 randomized patients (291 MPP, 302 BIV), who had BIV pacing >97% of the time before randomization and complete 12 months of clinical and echocardiographic data. The endpoint composed of freedom from cardiac death and HF hospitalizations and by LVESV relative reduction ≥15% between randomization and 12 months occurred more frequently in MPP [96/291 (33.0%)] vs. BIV [71/302 (23.5%), P = 0.0103], which was also confirmed at multivariate analysis (hazard ratio = 1.55, 95% confidence interval = 1.02-2.34, P = 0.0402 vs. BIV). HF hospitalizations occurred less frequently in MPP [14/291 (4.81%)] vs. BIV [29/302 (9.60%), incidence rate ratio = 50%, P = 0.0245]. Selecting patients with a large (>30 ms) dispersion of interventricular electrical delay among the four LV lead dipoles, reverse remodelling was more frequent in MPP [18/51 (35.3%)] vs. BIV [11/62 (17.7%), P = 0.0335].

Conclusion: In patients who do not respond to standard CRT despite the high BIV pacing percentage, MPP is associated with lower occurrence of HF hospitalizations and higher probability of reverse LV remodelling compared with BIV pacing.