Decoding the Complexity of Tricuspid Regurgitation Prognostic Drivers Using Explainable Artificial Intelligence

AIMS: Prognosis in tricuspid regurgitation (TR) is shaped by complex clinical and hemodynamic interactions, complicating risk stratification. We aimed to use explainable artificial intelligence (EAI) to model these relationships and identify key predictors of outcomes. METHODS AND RESULTS: We analyzed long-term all-cause mortality in a large prospective registry of patients with native TR across the full severity spectrum. Patients underwent detailed clinical evaluation and quantitative Doppler-echocardiography. Supervised-EAI models were applied to identify and rank predictors of mortality under medical therapy, capturing non-linear associations and interactions among baseline characteristics.Among 9,761 patients (mean age 73 ± 15 years; 56.9% women; EROA 40[30-56]mm2; RVol 39[29-53]mL/beat; 42% severe TR), 2,676 deaths occurred during 3.8 ± 4.6 years of follow-up. EAI identified and ranked 20 prognostic determinants of survival. Hemodynamic measures, led by elevated pulmonary-artery systolic and right-atrial pressures, were strongest, followed by age and comorbidity. TR-related variables ranked next, led by right-ventricular dysfunction and EROA, which outperformed integrative TR grade and TRIScore. Left-ventricular parameters were less influential. Non-linear effects, including those involving ejection fraction, and interactions such as higher EROA-related risk with elevated pulmonary-pressures or lower TRIScore (both p < 0.03) were observed. Proportional-hazards models confirmed EROA as the strongest TR severity marker (p < 0.0001), with excess mortality beginning at 40mm2 and increasing further at 60mm2. CONCLUSIONS: EAI ranked mortality predictors in TR, highlighting patient factors, hemodynamics, TR-specific measures, and left-ventricular function. Among TR-specific measures, EROA and TRIScore were most prognostic. Recognizing their impact can refine risk stratification, guide intervention timing, and inform long-term management.