Hemodynamic and Metabolic-Inflammatory Phenotyping Across the Cardiac Index Spectrum in Moderate and Severe Tricuspid Regurgitation: Prognostic Implications

BACKGROUND: Moderate and severe tricuspid regurgitation (TR) is associated with poor outcomes, yet current grading systems do not fully capture circulatory heterogeneity. We investigate the relationship of cardiac index (CI) with rest-exercise hemodynamics, metabolic and inflammatory profiles, and clinical outcomes in moderate and severe TR. METHODS: We prospectively enrolled 300 outpatients with atrial secondary, nonatrial secondary, and lead-associated moderate and severe TRs without ≥moderate left-sided valve disease. All underwent comprehensive laboratory profiling and ultrasound evaluation at rest and during cardiopulmonary exercise. Patients were stratified by CI tertiles and followed clinically (primary end point: all-cause mortality or heart failure hospitalization). RESULTS: CI decreased with TR severity but showed wide interindividual variability. In patients with low CI, severe forward flow limitation was associated with more advanced right ventricle-pulmonary arterial uncoupling and biatrial dysfunction ( P