Atrial functional mitral regurgitation (AFMR) is independently associated with adverse outcomes in patients with heart failure with preserved ejection fraction (HFpEF) when it is moderate or severe at rest, a new study shows. Additionally, exercised-induced increases are valuable for prognosis and evaluating the differences between resting and active AFMR assessment. Sebastiaan Dhont, MD, from the Zienkenhuis Oost-Limburg, Genk, and Hasselt University, Belgium; Wouter L’Hoyes, MD, from the Jessa Hospital, Hasselt, and Imelda Hospital, Bonheiden, Belgium; and colleagues, reported these results in a manuscript published online in JACC: Cardiovascular Imaging on Wednesday. “AFMR is increasingly recognized, as also reflected in the new European valvular guidelines. In HFpEF, both the valve and the myocardium contribute to symptoms,” lead author Dr. Dhont told CRTonline. “Our study shows that mild AFMR mainly reflects left atrial disease, while moderate or greater AFMR directly drives pathophysiology and is linked to worse outcomes.” AFMR in HFpEF often leads to adverse health outcomes, including higher rates of hospitalization and increased risk of death. The investigators in this trial evaluated the significance of AFMR in patients with HFpEF and compared the differences between patients at rest versus exercising. A total of 429 patients (mean age=74 years, 65% female) with HFpEF underwent cardiopulmonary exercise testing with echocardiography in this multicenter, cohort study. Outcomes at follow-up included cardiovascular hospitalization and all-cause death. Echocardiography primarily focused on MR. At rest, 35% of patients had AFMR (24% mild, 11% ≥ moderate). As AFMR increased in severity, patients were more likely to have atrial fibrillation, larger left atrium volumes, reduced function in the left atrium, lower peak oxygen consumption and greater exercise-incuded pulmonary hypertension. The investigators adjusted for age, sex and ventricular and atrial volume and function and found that moderate or severe MR was linked to worse outcomes (hazard ratio [HR]=4.03, 95% confidence interval [CI]=2.26-7.21, p<0.001). The severity of MR increased in 12% of patients during exercise, the investigators reported. Also independently predictive of adverse outcomes was an absolute increase in effective regurgitant orifice area ≥ 5 mm2 (HR=2.43, 95% CI=1.34-4.41, p=0.004). The investigators noted that quantifying MR continues to be difficult, especially during exercise, which was a major limitation in this study. Overall, patients with HFpEF who have AFMR have higher rates of adverse events, and this should be evaluated both at rest and during exercise for the best comprehensive overview of a patient’s condition. “Even subtle exercise-induced increases add prognostic value and can simultaneously reveal HFpEF,” Dr. Dhont told CRTonline. “The next step to move from association to causation will be interventional studies — not only testing transcatheter edge-to-edge or surgical valve repair, but also rhythm control and pharmacological strategies in this underexplored population.” Source: Dhont S, L’Hoyes W, Ferreira SM, et al. Atrial functional mitral regurgitation and exercise-incuded changes in heart failure with preserved ejection fraction. JACC Cardiovasc Imag. 2025 Septmeber 17 (Article in press). Image Credit: LIGHTFIELD STUDIOS – stock.adobe.com