Exercise-induced disproportionate secondary mitral regurgitation is associated with poor outcome in heart failure patients

Abstract Background Secondary mitral regurgitation (SMR) is associated with adverse outcomes in heart failure (HF) patients. Identifying patients, who benefit from mitral valve (MV) repair is crucial. Exercise testing can reveal exercise-induced worsening of SMR. Proportionality classification helps identifying SMR patients with poor prognosis who may benefit from MV repair. This study is the first to combine exercise echocardiography with proportionality classification in SMR, using exercise-induced changes in SMR severity to analyze the combined endpoint of mortality/HF hospitalization and the need for MV surgery/intervention. Methods Isometric handgrip exercise echocardiography was conducted in patients with at least mild SMR and symptomatic heart failure (HF) at a uiversity hospital, Germany, from 2018 to 2021. SMR severity was classified on individual basis according to the concept of proportionality (Lopes et al EHJ, 2022) at rest and during exercise. Patients were followed for one year to assess a combined endpoint of all-cause mortality, HF hospitalization, MV surgery/interventions, ventricular assist device implantation, and heart transplantation. Results A total of 211 patients with SMR and symptomatic HF were included (mean age: 73 ± 11 years; 33% female; mean LVEF: 41% ± 14%). Based on SMR proportionality at rest, 102 patients (48%) had non-severe SMR, 71 (34%) had proportionate SMR, and 38 (18%) had disproportionate SMR. Handgrip exercise led to SMR re-classification in 115 patients (54.5%). After reclassification, 68 patients (32%) showed non-severe SMR and proportionate SMR during exercise, and 75 patients (35.5%) showed disproportionate SMR. Twenty-one patients (10% of 211) with non-severe SMR at rest, developed exercise-induced disproportionate SMR. Thirty-one patients (15% of 211) with proportionate SMR at rest showed disproportionate SMR during exercise. Patients with disproportionate SMR during exercise revealed adverse outcomes compared to those with non-severe/proportionate SMR (Chi2 7.45; log-rank test p=0.006). After MV surgery/intervention in disproportionate SMR patients, mortality and HF hospitalization did not differ significantly from patients with non-severe and proportionate SMR (Chi2 0.054; log rank test p=0.882). Conclusion Exercise echocardiography unmasks exercise-induced disproportionate SMR in a significant number of patients with non-severe or proportionate SMR at rest. These data may have implications for therapeutic decision-making in patients with non-severe SMR and proportionate SMR at rest.Reclassification of SMR during exercise Mortality and HF hospitalisation