Abstract Background The possible benefit in terms of cardiac resynchronization therapy (CRT) response using a dynamic automatic algorithm designed to provide triple fusion as compared to conventional optimized biventricular pacing (CBP) is not known. Methods In this randomized, doble blinded, multicentric (13 centers) clinical trial we assigned patients with heart failure, reduced left ventricular ejection fraction and left bundle branch block, who underwent CRT implantation to be optimized using the SyncAV dynamic algorithm or through a conventional method. The primary endpoint was the rate of echocardiographic CRT responders at 6-month follow-up defined as a reduction of the left ventricular end diastolic volume (LVEDV) &amp;gt;15%. Results The study had to be stopped for slow recruitment in the context of the COVID-19 pandemic after enrolling 56 patients; 54 patients were finally analyzed. Patients’ basal characteristics are shown in TABLE. Patients assigned to the SyncAV group presented a narrowest paced QRS (128±16 ms vs. 145±19 ms; p &amp;lt;0.01) and a greater reduction in QRS duration (FIGURE A). Furthermore, more patients in the SyncAV group achieved a paced QRSd &amp;lt;120 mseg (7% vs 35%, p = 0.02). 21 (81%) patients in the SyncAV group and 19 (68%) in the CBP group were classified as CRT responders (OR = 1.99; 95% CI 0.57–7). While patients in the SyncAV group demonstrated a trend towards superior reverse remodeling across all secondary endpoints, statistical significance was not reached (FIGURE B). In the SyncAV group, 2 (8%) patients were categorized as negative responders, and 4 (16%) in the CBP group. A total of 43% of patients improved by at least one category in the NYHA functional classification, while 2 patients experienced worsening, both in the CBP group (clinical negative responders) (FIGURE C). No adverse events directly associated with device programming or the activation of the SyncAV algorithm were reported. Conclusions In this multicenter randomized controlled trial comparing CRT with triple fusion pacing using the SyncAV algorithm to conventional optimized biventricular pacing, there was not reached adequate statistical power to draw a conclusion regarding a potential increase in the CRT response rate. Nevertheless, the use of the SyncAV algorithm resulted in a high proportion of CRT responders. A significant greater reduction of the QRS duration was observed when employing the SyncAV algorithm, leading to a high percentage of cases achieving QRS width normalization. Nonetheless, further investigations are warranted to thoroughly assess the possible clinical benefits associated with triple fusion of LV pacing, RV pacing and intrinsic conduction in HF patients with LBBB.FIGURE

CRT with triple fusion: results of the multicentric, randomized, doble-blinded CRUSTY trial