Association of Moderate to Severe Tricuspid Regurgitation With Exercise Hemodynamics and Outcomes in Patients With Heart Failure With Preserved Ejection Fraction: Multicenter Study

Background The clinical significance of at least moderate tricuspid regurgitation (TR) during evaluation for unexplained dyspnea is unclear. This study describes the characteristics, exercise hemodynamics, and 5-year outcomes among patients with moderate to severe TR found to have exercise heart failure with preserved ejection fraction (HFpEF). Methods and Results We included 258 consecutive patients undergoing exercise right heart catheterization for unexplained dyspnea at 2 academic centers in the United States and Italy from April 2017 to October 2024 if they met exercise criteria for HFpEF (peak pulmonary artery wedge pressure [PAWP] of ≥25 or PAWP–cardiac output [CO] slope of ≥2). We dichotomized patients by degree of TR (absent or mild vs moderate to severe) during resting echocardiography. We compared hemodynamics by regression analyses and 5-year composite HF hospitalization or death by Cox regression analyses, adjusting for age, sex, and country. There were 206 patients (80%) who met the exercise criteria for HFpEF; 41 (20%) had moderate to severe TR and 165 (80%) had absent or mild TR. Those with worse TR were older (75 years [IQR 68-79 years] vs 70 years [IQR 62-76 years]) and had higher resting mean pulmonary artery pressure and PAWP, but a lower CO; after adjustment, worse TR was associated with lower maximum CO (6.6 L/min [IQR 5.1–8.1 L/min] vs 8.4 L/min [IQR 7.0–11.0 L/min], P < 0.001) and higher mean pulmonary artery pressure–CO slope (5.7 [IQR 3.6–9.0] vs 4.0 [IQR 2.4–5.9], P  = 0.022) despite similar exercise time. The worse TR group had higher 5-year composite events (29% vs 11%) (adjusted hazard ratio 3.33, 95% confidence interval 1.46–7.57, P  = 0.004). Conclusions In patients with exercise HFpEF, the presence of moderate to severe TR was associated with worse cardiac reserve and worse 5-year composite heart failure hospitalization or death.