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Background: Multipoint pacing (MPP) in cardiac resynchronization therapy (CRT) activates the left ventricle from two locations, thereby shortening the QRS duration and enabling better resynchronization; however, compared with conventional CRT, MPP reduces battery longevity. On the other hand, electrocardiogram-based optimization using the fusion-optimized intervals (FOI) method achieves more significant reverse remodeling than nominal CRT programming. Our study aimed to determine whether MPP could attain better resynchronization than single-point pacing (SPP) optimized by FOI. Methods: This prospective study included 32 consecutive patients who successfully received CRT devices with MPP capabilities. After implantation, the QRS duration was measured during intrinsic rhythm and with three pacing configurations: MPP, SPP-FOI, and MPP-FOI. In 14 patients, biventricular activation times (by electrocardiographic imaging, ECGI) were obtained during intrinsic rhythm and for each pacing configuration to validate the findings. Device battery longevity was estimated at the 45-day follow-up. Results: The SPP-FOI method achieved greater QRS shortening than MPP (-56±16 vs.-42±17 ms, P<0.001). Adding MPP to the best FOI programming did not result in further shortening (MPP-FOI:-58±14 ms, P=0.69). Furthermore, the biventricular activation time according to ECGI was also shorter with SPP-FOI than with MPP. The estimated battery longevity was longer with SPP than with MPP (8.1±2.3 vs. 6.3±2.0 years, P=0.03). Conclusions: SPP optimized by FOI resulted in better resynchronization and longer battery duration than MPP.

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Funding Acknowledgements Type of funding sources: None. Background Radiofrequency ablation (RF) is a well-established treatment for of premature ventricular complexes (PVCs) It is not uncommon to perform radiofrequency ablation of PVCs arising from epicardial/intramural localization, in particular those arising from the LV summit and aortic sinuses of Valsalva. Purpose The aim is to investigate safety, efficacy, and outcome of PVCs radiofrequency ablation through a non-endocardial approach including high power and long duration RF applications. Methods We defined Non-Endocardial Radiofrequency Ablation (NERA) a procedure in which at least one RF site has been identified into the coronary venous system, aortic sinuses of Valsalva, inter-leaflet triangle or pulmonary cusps. We selected the study population from a series of consecutive patients who underwent radiofrequency ablation of PVCs from January 2017-May 2022, in whom at least one RF application has been realized according to the definition. Results During the study period, 399 patients underwent PVCs RF and 46 fulfilled the inclusion criteria (age: 59±13 years; 33, 72% males; mean LVEF:46±12%, mean PVC burden 26±10 %). The total number of NERA sites was 55: 15(27%) coronary venous system, 9(16%) right coronary cusp, 10(18%) left coronary cusp, 18 (33%) interleaflet triangle between right and left coronary cusp and 3 (5%) left pulmonary cusp. In 18 (39%) patients a multisite ablation was performed. Mean power during RF was 37±9 W (15-50) with median of 40W. Mean duration of single RF was 88±72 seconds (30-304) (median: 58 seconds). In 63% of the patients high power (40W or more) and in 55% long duration (&gt;60 seconds) application was delivered in at least one of the ablation spots. Procedural success was achieved in 37 patients (80%). No complications related with RF site were observed. Multisite RF was significantly associated with procedural failure (OR 8,27; CI 1,48– 46,31; p=0,01). During follow up, mean PVCs burden was 7,3±9%, with a mean and median burden reduction (Δ) of 69±41% and 96%. The rate of event-free survival was 69%. Multisite RF and coronary venous system RF were predictors of recurrence (HR 3,81; 95% CI 1,14–12,66; p=0,02 and HR 3,88; 95% CI 1,23 – 12,27; p=0,01), while procedural success was protective (HR 0.1; CI 0.03 - 0.33, p &lt; 0.001). After multivariate Cox proportional hazard analysis, coronary venous system RF was associated with higher VA recurrences during follow up (HR 2.71, CI 0.83 - 8.85, p= 0,09), while procedural success confirmed his protective role (HR 0.13, CI 0.04-0.42, p &lt; 0,001). Conclusion Radiofrequency ablation from non-endocardial sites is a safe and effective procedure, even using high power and/or long duration RF. Nevertheless long term outcomes are still characterized by a recurrence rate higher than in purely endocardial PVC ablation.