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. 152(23):1594-1607, 2025 Dec 09.

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 VO2 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.
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