Moura-Ferreira S; Department of Cardiology and Jessa & Science, Jessa Hospital, Hasselt, Belgium
Pugliese NR;Milani M; Taddei S; Jacobs A;  De Biase N; Dhont S; Falter M; Bekhuis Y; L’Hoyes W; Hoedemakers S; Droogmans S; Cosyns B; Jasaityte R; Claessen G; Del Punta L; Herbots L; De Carlo M; Mazzola M; Bertrand PB; Falcetta G; Debonnaire P; Masi S; Verwerft J

Circulation [Circulation] 2025 Nov 03.
Date of Electronic Publication: 2025 Nov 03.Publication Model:Ahead of Print

Background: Managing clinically significant primary mitral regurgitation is challenging. Right ventricular-pulmonary arterial coupling, assessed with tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP) ratio, reflects right ventricular adaptability to afterload. This international multicenter cohort study aimed to evaluate the prognostic value of rest TAPSE/sPAP and exercise TAPSE (exTAPSE)/sPAP in primary mitral regurgitation.
Methods: Between January of 2019 and December of 2023, 211 patients assigned to a derivation cohort (64±12 years of age, 40% women) and 146 patients assigned to a validation cohort (66±13 years of age, 39% women), all of whom had moderate or severe primary mitral regurgitation, no or discordant symptoms, and no left ventricular systolic dysfunction or atrial fibrillation, underwent semisupine cycle-ergometry cardiopulmonary exercise testing combined with exercise echocardiography. TAPSE/sPAP was measured at rest and at intermediate (defined as the first ventilatory threshold) and peak exercise. The primary end point was a composite of cardiovascular death, unplanned cardiovascular hospitalizations, and new atrial fibrillation.
Results: In the derivation cohort, 48 patients reached the composite outcome (median follow-up, 24 months [interquartile range, 12-51]). Intermediate and peak exTAPSE/sPAP were strongly correlated ( r =0.84; P <0.001), with intermediate exTAPSE/sPAP offering superior feasibility (98% versus 92%) with comparable prognostic accuracy to peak exTAPSE/sPAP (area under the receiver operating characteristic curve, 0.794 [0.730-0.849] versus 0.765 [0.698-0.823]) and therefore was used as the exercise TAPSE/sPAP measure. Patients with a reduced rest TAPSE/sPAP (cutoff 0.8 mm/mm Hg) and intermediate exTAPSE/sPAP (cutoff 0.6 mm/mm Hg) had a lower event-free survival (log-rank P <0.0001). Intermediate exTAPSE/sPAP and percent-predicted peak VO ₂ were independently associated with the primary end point (hazard ratio, 0.64 [0.51-0.80] per 0.1 mm/mm Hg increase [ P <0.001] and hazard ratio, 2.03 [1.05-3.93] if <80% [ P =0.04], respectively) and had incremental prognostic value beyond age, left atrial volume index, mitral regurgitation severity, rest TAPSE/sPAP, and mitral valve intervention (time-dependent covariable). Similar results were found when rest and intermediate exTAPSE/sPAP were included in the multivariable model as categorical measures. Validation in an independent cohort confirmed the consistent and robust performance of both multivariable models, irrespective of whether TAPSE/sPAP was modeled as a continuous or categorical variable.
Conclusions: Exercise right ventricular-pulmonary arterial coupling, particularly intermediate exTAPSE/sPAP, is a robust and feasible measure independently associated with adverse outcomes, and provides prognostic information beyond resting variables and cardiorespiratory fitness, potentially refining risk stratification and guiding management in patients with primary mitral regurgitation.