Atrial functional mitral regurgitation and exercise-induced changes in heart failure with preserved ejection fraction

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Abstract Background Atrial functional mitral regurgitation (AFMR) is common in patients with heart failure with preserved ejection fraction (HFpEF) and associated with adverse outcome. However, its dynamic nature and pathophysiological significance during exercise remain incompletely understood. Objectives To elucidate the pathophysiological and prognostic significance of AFMR in HFpEF, both at rest and during exercise. Methods In a multicenter cohort study, consecutive patients with HFpEF underwent cardiopulmonary exercise testing with echocardiography (CPETecho), with a particular focus on 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 74years, 65%female). AFMR was observed in 35% of patients at rest (24% mild, 11% ≥moderate). Increasing AFMR severity was associated with atrial fibrillation, larger left atrial (LA) volumes, reduced LA 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 independently 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 (EROA) ≥5 mm² 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 LV dysfunction. Conclusions AFMR is prevalent in HFpEF and independently linked to adverse outcomes when ≥ moderate at rest. Moreover, subtle exercise-induced increases in regurgitant severity—even without formal reclassification—carry significant prognostic implications. These findings highlight the added value of dynamic MR assessment during stress echocardiography in HFpEF.AFMR in HFpEF AFMR assessment in HFpEF

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