Aortic regurgitation (AR) patients who also have mitral regurgitation (MR) are at increased risk of adverse outcomes compared to those without MR, according to a new U.S. multicenter, observational study. The findings from 915 patients across 4 sites were published Monday in JACC: Cardiovascular Imaging, with authors led by Maan Malahfji, MD, from the Houston Methodist DeBakey Heart & Vascular Center. Management of combined AR and MR is largely based on expert opinion and a tendency to treat the dominant lesion, the authors noted. It is known that patients with combined AR and MR experience left ventricular (LV) pressure and volume overload due to AR and the additional volume overload of MR, they said, while prior studies have suggested a higher risk of adverse outcomes for these patients. Nevertheless, “the degree of MR at which outcomes differ from the general AR population is unclear, and specific MR severity thresholds for guiding the management of patients with combined AR/MR are uncertain,” the authors stressed. In particular, outcomes for patients with moderate forms of both AR and MR under medical surveillance are uncertain, they said, adding that the ageing population means that these patients are increasing. The current study therefore set out to evaluate cardiac remodelling using cardiac magnetic resonance (CMR) in patients with combined AR/MR versus isolated AR, as well as adverse outcomes in relation to MR etiologies and severity. The study also assessed the outcomes of asymptomatic or minimally symptomatic patients with moderate forms of both AR and MR under medical surveillance. The 915 patients — 664 (72.6%) with isolated AR and 251 (27.4%) with combined AR/MR – were recruited across Houston Methodist Hospital, as well as Duke University, Atrium Health and Piedmont Healthcare, all in North Carolina, and followed for a median 3 years. Median age was 60 years in isolated AR vs 64.7 years in combined AR/MR (P = 0.001), while 19.3% vs 23.9%, respectively, were female (P = 0.14) and median body mass index was 27.7kg/m2 vs 26.6 kg/m2 (P = 0.06). Overall among the full 915 patient cohort, 29% had bicuspid aortic valve and the median AR fraction was 38%, the authors said. The majority of patients were in New York Heart Association (NYHA) functional class I (77.3% in isolated AR vs 63.7% in combined AR/MR), with the remainder in class II (17% vs 20.3%, respectively), class III (5.3% vs 13.5%) or class IV (0.5% vs 2.4%). Those with prior valvular surgery, anything more severe than mild valve stenosis, hypertrophic or infiltrative cardiomyopathy, or congenital heart disease (except bicuspid aortic valve), were excluded. In the combined group, the median MR fraction was 24% (interquartile range [IQR] 17% to 35%). Across the entire study population, the presence of concomitant moderate-or-worse MR (seen in a total 14.2%) was associated with a greater increase in ventricular volumes per unit increase in AR severity, as well as a decline in ventricular function (P for interaction ≤0.01). During the median 3-year follow up (IQR: 1.1 to 5.6 years) there were 152 deaths, within which concomitant moderate-or-worse MR was associated with an increased hazard for all-cause death, the primary endpoint (hazard ratio [HR]: 2.77; 95% confidence interval [CI]: 1.91-4.01; P < 0.001). The secondary outcome of death or heart failure was also increased in those with moderate-or-worse MR (HR: 2.62; 95% CI: 1.87-3.67; P < 0.001). In the asymptomatic or minimally symptomatic patients undergoing medical surveillance, the presence of combined moderate AR and moderate MR was independently associated with a higher hazard for the primary (HR: 2.20; 95% CI: 1.31-3.67; P = 0.003) and secondary (HR: 1.76; 95% CI: 1.09 to 2.85; P = 0.02) outcomes compared with isolated severe AR (HR: 1.15; 95% CI: 0.68 to 1.97; P = 0.6 for primary and HR 1.76; 95% CI: 1.09 to 2.85; P = 0.021 for secondary endpoints). This was independent of age, sex, comorbidities, ejection fraction and end-systolic volume, the authors said, adding that the findings were consistent in a propensity matched cohort (P = 0.003 vs 0.008, respectively). “The presence of combined AR and MR on CMR is associated with a greater extent of ventricular remodeling and increased hazard for adverse outcomes, compared with isolated AR. Asymptomatic patients with combined moderate AR and MR under medical surveillance are at higher risk for death and HF, and warrant further study,” Dr. Malahfji and the team concluded. In particular, the investigatorspushed for further research into the course of MR after isolate AR correction and how to best implement medical and surgical therapies, as well as their timing, in combined AR/MR patients. Source: Malahfji M, Saeed M, Nguyen DT, et al. Cardiac Remodeling and Outcomes of Patients With Combined Aortic and Mitral Regurgitation. JACC: Cardiovasc Imag 2025; DOI: 10.1016/j.jcmg.2025.09.022. Image Credit: Damian – stock.adobe.com