Abstract Body (Do not enter title and authors here): Introduction: Tricuspid regurgitation (TR) is increasingly identified on resting echocardiography (TTE). Newly diagnosed severe TR and rate of progression from mild to severe TR are associated with worse mortality. Heart failure with preserved ejection fraction (HFpEF) is a risk for incident TR. The clinical significance of at least moderate TR during evaluation for unexplained dyspnea is unclear. This study described characteristics, exercise hemodynamics, and 5-year outcomes among patients identified with HFpEF by exercise right heart catheterization (RHC) and at least moderate TR.

Hypothesis: We hypothesized patients with exercise HFpEF and ≥ moderate compared to absent-mild TR have worse exercise hemodynamics and outcomes through 5-year follow-up.

Methods: Consecutive patients undergoing exercise RHC for unexplained dyspnea at two academic centers in US and Italy from April 2017-Oct 2024 were included if they met exercise criteria for HFpEF [peak pulmonary artery wedge pressure (PAWP) ≥25 or PAWP-cardiac output (CO) slope ≥2]. Patients were grouped by degree of TR (absent-mild v. ≥ moderate) during resting TTE. Exercise hemodynamics were compared by regression analyses, and 5-year composite heart failure hospitalization (HFH) or death were compared using Cox regression analyses. Models were also adjusted for age and sex.

Results: Of 258 consecutive patients, 192 (74%) met hemodynamic criteria for exercise HFpEF. Forty (21%) had ≥ moderate and 152 (79%) had absent-mild TR. Those with worse TR were older (mean 74.2±7.5 v. 67.5±11.7 years) and had higher natriuretic peptide levels (234±197 v. 125±170 pg/mL). Those with worse TR had modestly higher resting mean pulmonary artery pressure (PAP) and PAWP, but lower CO (Table); after adjustment, worse TR was associated with lower max CO (6.7±2.0 v. 8.8±2.8 L/min; p=0.007) and higher PAP-CO slope (8.1±8.5 v. 5.5±5.0; p=0.041) despite similar exercise time (3.3±0.6 v. 5.2±2.9 min; p=0.2). Worse TR group had higher 5-year composite events [12 (30%) v. 16 (10%); p=0.009]; adjusted HR 2.46 (1.12, 5.40; p=0.025).

Conclusion: In patients with unexplained dyspnea identified to have exercise HFpEF, the presence of ≥ moderate compared to absent-mild TR at rest was associated with worse cardiac reserve despite similar exercise time and worse 5-year composite HFH or death. These data provide hemodynamic insights and potential consideration for valvular intervention timing in those with ≥ moderate TR and exercise HFpEF.