Exercise assessment of right ventricular–pulmonary artery (RV–PA) coupling improves prognostic stratification in secondary mitral regurgitation

J. Glasmacher (Berlin)¹, P. Wilke (Düsseldorf)², S. Angendohr (Düsseldorf)², J. Haschemi (Düsseldorf)², E. Zweck (Düsseldorf)², F. Voß (Düsseldorf)², J. Haurand (Düsseldorf)², A. G. Bejinariu (Düsseldorf)², O. R. Rana (Düsseldorf)², M. Kelm (Düsseldorf)², A. Polzin (Düsseldorf)², M. Spieker (Düsseldorf)^2
1Charité - Universitätsmedizin Berlin CC 11: Med. Klinik für Kardiologie Berlin, Deutschland; ²Universitätsklinikum Düsseldorf Klinik für Kardiologie, Pneumologie und Angiologie Düsseldorf, Deutschland

Background:
Right ventricular–pulmonary artery (RV–PA) uncoupling has emerged as a powerful determinant of outcomes in heart failure (HF) with secondary mitral regurgitation (SMR). Conventional resting echocardiography may underestimate disease burden, whereas exercise echocardiography can unmask latent hemodynamic compromise and dynamic MR progression. We sought to evaluate the prognostic value of exercise-derived RV–PA coupling in symptomatic HF patients with SMR.

Methods:
We prospectively enrolled 151 symptomatic HF patients with at least mild SMR at rest who underwent standardized exercise echocardiography. RV–PA coupling was quantified using the TAPSE/SPAP ratio at rest and peak exercise. Patients were dichotomized into low versus preserved coupling (TAPSE/SPAP <0.405 vs. ≥ 0.405 at rest; <0.34 vs. ≥0.34 during exercise). The primary endpoint was all-cause mortality and HF hospitalization; secondary endpoints included mitral valve (MV) interventions at 12 months.

Results:
Patients were elderly (median age 75 years), 36% female, with prevalent coronary disease (75%). TAPSE/SPAP declined significantly from rest to exercise (0.47±0.20 to 0.37±0.15; p<0.001). Dynamic MR progression was observed in 15% and correlated with worsening RV–PA coupling (r = –0.263; p=0.001). At 1-year, 56.5% experienced death or HF hospitalization. Resting uncoupling predicted adverse outcomes (χ² 4.05; p=0.041) and was associated with greater MV intervention rates (p=0.060). Exercise-defined uncoupling demonstrated a markedly stronger association with the primary endpoint (χ² 12.95; p<0.001) and showed a trend toward increased MV procedures (p=0.074). Discrimination improved with exercise versus rest (AUC 0.65 vs. 0.60).

Conclusions:
Exercise-induced RV–PA uncoupling identifies high-risk HF patients with SMR, correlates with dynamic MR severity and offers superior prognostic value compared to resting evaluation alone. Incorporating exercise echocardiography into routine assessment may refine risk stratification and guide timely mitral valve intervention in this vulnerable patient population.