BackgroundLeadless cardiac resynchronization therapy (CRT) using the WiSE-CRT system is an emerging heart failure treatment. An implanted electrode delivers lateral or septal endocardial left ventricular pacing (LVP) upon detection of a right ventricular pacing (RVP) stimulus from a co-implanted device, thus generating biventricular pacing (BiVP). Electrical efficacy data regarding this therapy, particularly leadless LV septal pacing (LVSP) for potential conduction system capture, is limited. ObjectiveTo evaluate the acute performance of leadless CRT using electrocardiographic imaging (ECGi), and assess the optimal pacing modality (OPM) of LVSP based on RV and LV activation. MethodsTen WiSE-CRT recipients underwent an ECGi study testing: RVP; BiVP; LVP only; and LVP with an optimised atrioventricular delay (LV-OPT). BiV, LV and RV activation times (BIVAT-90, LVAT-95, RVAT-90), plus LV and BiV dyssynchrony index (LVDI, BIVDI) were calculated from reconstructed epicardial electrograms. The individual OPM yielding the greatest improvement from baseline was determined. ResultsBiVP generated a 23.7% improvement in BiVAT-90 (p=0.002). An improvement of 43.3% was observed at OPM (p=0.0001), primarily through reductions in RVAT-90. At OPM, BiVAT-90 improved in patients with lateral (43.3%, p=0.0001, n=5) and septal LV implants (42.4%, p=0.009, n=5). The OPM varied by individual. LVP or LV(OPT) were mostly superior in patients with LVSP, and for those in SR and LBBB (n=4). ConclusionLeadless CRT significantly improves acute ECGi-derived activation and dyssynchrony metrics. Using an individualised OPM improves efficacy in selected patients. Effective LVSP is feasible, with fusion pacing at LV(OPT) mitigating the potential deleterious effects on RV activation.