Electromechanical evaluation of conduction system pacing techniques in a patient-specific virtual cohort: an in silico clinical trial

Conduction System (CSys) pacing techniques have emerged as alternatives in Cardiac Resynchronization Therapy (CRT) by physiologically pacing the CSys. Despite numerous clinical and in silico clinical trials assessing their response and safety, a comprehensive understanding of their electromechanical effects remains incomplete. In this study, we present a systematic evaluation of CRT pacing protocols through an in silico clinical trial based on a patient-specific digital twin cohort of Left Bundle Branch Block (LBBB) patients. This virtual electromechanical cohort was constructed using in vivo clinical data to replicate patient-specific cardiac anatomy and electromechanical properties. Each virtual patient underwent 14 distinct CRT combinations, including traditional, CSys, and optimized CSys pacing strategies by varying lead positioning and the degree of CSys capture. This enabled a comprehensive comparison of electromechanical responses across CRT techniques. The fifteen digital twin LBBB models were compared against clinical data, accurately reproducing the physiological behavior of electromechanical dyssynchrony. Our In silico clinical trial results found that CSys pacing significantly improved cardiac function and synchrony compared to traditional pacing. Within CSys pacing procedures, a similar left ventricular ejection fraction was observed regardless of capture selectivity or the specific area paced. Optimized CSys pacing demonstrated robustness to capture failure and predicted favorable long-term remodeling by enhancing myocardial work redistribution compared to other CRT strategies. Overall, this in silico clinical trial demonstrates the electromechanical benefits of CSys pacing for LBBB patients, highlighting the value of patient-specific digital twin cohorts for evaluating and optimizing emerging pacing therapies.