Abstract

Introduction: Multipoint pacing (MPP) delivers sequential stimuli from multiple left‐ventricular electrodes, potentially improving cardiac resynchronization therapy (CRT) response versus conventional biventricular pacing (BiV). We performed an updated systematic review and meta‐analysis to synthesize contemporary evidence. Methods: Following PRISMA 2020 (PROSPERO CRD420261293273), MEDLINE, EMBASE, and CENTRAL were searched to January 2026 for comparative studies of MPP versus conventional BiV in adults receiving CRT. Primary outcomes were all‐cause mortality and heart failure (HF)‐related hospitalization. Secondary outcomes included echocardiographic response, NYHA class improvement, and absolute change in left‐ventricular ejection fraction (LVEF). Random‐effects models produced pooled odds ratios (OR) or mean differences (MD). Results: Eight studies (n = 2430; 1190 MPP, 1240 BiV), including five randomized and three observational studies, were analyzed. All‐cause mortality showed no significant difference between groups (OR = 1.46, 95% CI 0.76–2.80; p = 0.25; I2 = 0%). HF‐related hospitalization was significantly reduced with MPP in the largest trial (5.4% vs. 8.9%; p = 0.015), corresponding to a 39% relative risk reduction. MPP was associated with significantly higher echocardiographic response (OR = 0.43, 95% CI 0.29–0.64; p < 0.0001; I2 = 0%), greater NYHA class improvement (OR = 0.38, 95% CI 0.20–0.73; p = 0.004; I2 = 3%), and greater absolute LVEF (MD = −4.67, 95% CI −6.70 to −2.64; p < 0.00001; I2 = 0%). Conclusions: Compared with conventional CRT, MPP was associated with improved functional and echocardiographic outcomes and reduced HF hospitalization, without a demonstrated mortality benefit. Larger prospective studies with longer follow‐up are required to assess long‐term prognostic effects.