Artificial Intelligence-Derived Computed Tomography Phenotyping for Cardiovascular Risk Stratification in Transcatheter Mitral Valve Replacement.

Background: Despite high procedural success of transcatheter mitral valve replacement (TMVR), mortality remains substantial, and conventional risk scores inadequately reflect the specific risk profile of this high-risk population. Artificial intelligence (AI)-derived analysis may enable TMVR-specific risk assessment using routinely acquired computed tomography (CT). Methods: In a retrospective European multicenter registry, AI-based segmentation of harmonized real-world pre-procedural cardiac CT with variable thoracic and upper-abdominal coverage was applied in patients undergoing TMVR with the TendyneTM system (134 patients; 346 CT-derived variables retained for high-dimensional screening). One-year cardiovascular mortality was assessed using Cox proportional hazards models with Benjamini-Hochberg false discovery rate correction. STS- and EuroSCORE II-adjusted analyses and a targeted coronary-ventricular coupling analysis were performed. Results: In the STS-adjusted Cox analysis, nine AI-derived CT parameters met the 10% FDR discovery threshold for cardiovascular mortality, spanning skeletal (n = 3), muscular (n = 1), and cardiopulmonary phenotypes (n = 5), whereas three parameters met this threshold in CT-only analyses. Coronary-ventricular coupling, defined as coronary artery volume relative to left ventricular end-diastolic volume, was significantly associated with lower 1-year cardiovascular mortality in the CT-only analysis (HR per IQR 0.47, 95% CI 0.22-1.00; p = 0.049) and after EuroSCORE II adjustment (HR 0.47, 95% CI 0.22-0.99; p = 0.046), while the STS-adjusted estimate remained directionally consistent but did not reach statistical significance (HR 0.49, 95% CI 0.23-1.05; p = 0.067). Conclusions: AI-based CT phenotyping identifies imaging-derived markers associated with cardiovascular mortality beyond information captured by conventional surgical risk scores in TMVR patients. Coronary-ventricular coupling emerges as a promising automated CT-derived imaging marker with a biologically plausible pathophysiological basis, linking coronary arterial volume to ventricular size in mitral valve disease.