Development of significant aortic regurgitation following HeartMate 3 implantation: echocardiographic predictors

Abstract Background Aortic regurgitation (AR) is a clinically significant complication in patients with advanced heart failure supported by left ventricular assist devices (LVADs), contributing to both morbidity and mortality. While predictors of AR have been studied in patients with continuous-flow LVADs (CF-LVADs), specific data on the HeartMate 3 (HM3)—a contemporary device that integrates an artificial pulse into a continuous-flow system—remain limited. Purpose To identify pre-implantation echocardiographic predictors of significant AR after LVAD implantation. Methods Pre-implantation and 24-months post-LVAD implantation echocardiograms of patients who underwent HM3 implantation at our center were re-examined. AR severity was assessed using a multiparametric approach, including novel Doppler-based measurements at the outflow cannula, in accordance with current recommendations. Significant AR was defined as more than mild. Following multiple imputation of baseline echocardiography variables, model building using multivariable logistic regression was performed assessing echocardiographic variables as predictors of significant AR after HM3 implantation. The developed model was internally validated using bootstrapping and multiple imputation for each bootstrap sample. Predictive performance was assessed through discrimination (C-index) and calibration (intercept and slope). Results A total of 91 patients (median age 57 (IQR 45-63) years, 63% male) who underwent HM3 implantation between 2016 and 2023 at the University Medical Center Utrecht, the Netherlands, for whom echocardiographic data has been collected so far were included. During a 24-month follow-up period, 36 patients (39.6%) developed significant aortic regurgitation (AR), including 27 (29.7%) with moderate AR, 6 (6.6%) with moderate-to-severe AR, and 3 (3.3%) with severe AR. The final model contained aortic valve degeneration (OR 2.27, 95% CI: 1.03- 4.97) and indexed ascending aorta diameter (OR 1.99, 95% CI: 1.22-3.24) at baseline as statistically significant independent predictors of significant AR after HM3 implantation. The C-index for the final model was 0.76 (95% CI: 0.64-0.84) before internal validation, and 0.71 (95% CI: 0.69-0.73) after internal validation with a calibration intercept of -0.01 and a calibration slope of 0.82. Conclusions In this preliminary analysis, baseline aortic valve degeneration and indexed ascending aorta diameter were independent predictors of significant AR after LVAD implantation. The developed and internally validated model with a C-statistic of 0.71 was reasonably calibrated. These preliminary findings will support the development of a clinically applicable prognostic model to predict which high risk patients may have the benefit of prophylactic concomitant aortic valve surgery during LVAD implantation or personalized HM3 speed settings after implantation, in order to prevent the development of post-LVAD significant AR and its burden of morbidity.