Atrial Functional Mitral Regurgitation and Exercise-Induced Changes in Heart Failure With Preserved Ejection Fraction

Abstract

BACKGROUND Atrial functional mitral regurgitation (AFMR) is prevalent among patients with heart failure with preserved ejection fraction (HFpEF) and associated with adverse outcome, yet this bidirectional association remains underexplored. OBJECTIVES The purpose of this study was to elucidate the pathophysiological and prognostic significance of AFMR in HFpEF, both at rest and during exercise. METHODS In this multicenter cohort study, consecutive patients with HFpEF underwent cardiopulmonary exercise testing with echocardiography, with a particular focus on mitral regurgitation (MR) severity assessment in rest and during exercise. Longitudinal follow-up included cardiovascular hospitalizations and all-cause mortality. RESULTS The study involved 429 patients with HFpEF (age 74 +/- 8 years, 65% female). AFMR was observed in 35% of patients at rest (24% mild, 11% >= moderate). Increasing AFMR severity correlated with atrial fibrillation, larger left atrium volumes, reduced left atrial function, lower peak oxygen consumption, and increased exercise-induced pulmonary hypertension. After adjusting for age, sex, ventricular and atrial volume and function, moderate or severe MR remained linked with worse outcomes (HR: 4.03; 95% CI: 2.26-7.21; P < 0.001). During exercise, MR severity increased in 12% of patients based on guideline-based thresholds. Notably, even in patients without formal reclassification, an absolute increase in effective regurgitant orifice area >= 5 mm(2) during exercise was independently predictive of adverse outcomes (HR: 2.43; 95% CI 1.34-4.41; P = 0.004). This increase was not related to systemic blood pressure, chronotropic incompetence, or left ventricular dysfunction. CONCLUSIONS AFMR is common in HFpEF and independently associated with adverse outcomes when moderate or severe at rest. Even mild, exercise-induced increases carry additional prognostic value, underscoring the relevance of both resting and dynamic AFMR assessment. (JACC Cardiovasc Imaging. 2025;18:1285-1296) (c) 2025 by the American College of Cardiology Foundation.