Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Boston Scientific and Abbott Background One of the presumed advantages of leadless pacemaker (LP) therapy is that tricuspid regurgitation (TR) occurrence and severity would be less than with conventional pacemakers due to the absence of leads. However, TR and mitral regurgitation (MR) may also worsen due to chronic right ventricular (RV) pacing per se. Purpose To determine whether a novel LP is associated with increased TR and MR severity in a chronic canine model and to evaluate predictors of TR and MR worsening. Methods Healthy canine subjects were implanted with a novel LP programmed at a lower rate of 80/min. TR and MR were assessed by transthoracic echocardiography (TTE) prior to implant, at 90 days and at 18 months after implant. Further were assessed percentage of pacing, presence of pacing during TTE, and wall motion abnormalities (WMA) observed during TTE, indicating ventriculo-ventricular dyssynchronous pacing. Paired t-tests were performed to compare TR and MR severity before and after implant. Univariable and multivariable generalized estimating equation (GEE) models were used to evaluate factors predictive of increased TR and MR severity. Paired t-tests were used to evaluate whether the increase of TR and MR differed between subgroups where pacing or WMA were observed or not. Results An LP was implanted in 73 subjects. TR and MR severity at 90 days (n = 55) were significantly increased from baseline (p = 0.02 and 0.001, confidence intervals [CIs] 0.05-0.64 and 0.20-0.75, respectively); at 18 months (n = 37) TR severity remained significantly increased but MR did not (p = 0.01 and 0.62, CI [0.09, 0.69] and [-0.15, 0.25], respectively). Multivariable GEE (figure) showed that WMA and absence of TR at baseline are significant predictors for increased TR, while WMA and a shorter RV long axis are significant predictors for increased MR. Subgroup analysis demonstrated that TR and MR at day 90 were only significantly increased in subjects with observed pacing or WMA (n = 29; p = 0.0014 and p < 0.0001 respectively), but not in subjects without observed pacing or WMA (n = 26; p = 0.56 and 0.16, respectively). At 18 months, the same observation was found for TR but not MR (pacing or WMA [n = 15], p < 0.0001 and p = 0.33 respectively: no pacing or WMA [n = 26], p = 0.23 and 1, respectively). Conclusion In absence of pacing, the novel EMPOWER LP was not associated with increased TR and MR severity in a canine model. When pacing was observed TR and MR did increase. Increased MR severity did not persist at 18 months. Abstract Figure 1