Predicting the reduction of functional mitral regurgitation with optimized medical therapy in HFrEF patients by standard echocardiography and non-invasive pressure–volume loop model

BACKGROUND Predicting the improvement of functional mitral regurgitation (FMR) to medical therapy is an important, yet overlooked, clinical issue. The objective of the study was to evaluate whether echocardiographic assessment of left ventricular (LV) mechanoenergetic parameters and of LV volumes is associated with improvement of FMR in HFrEF patients after optimization of pharmacological therapy. METHODS The study included 662 patients with chronic HFrEF prospectively enrolled in a multicenter, open-label registry before starting sacubitril/valsartan. Echocardiography was performed at baseline and repeated at 6-12 months. A simplified, non-invasive echocardiographic P/V loop model was used, based on brachial arterial pressure and transthoracic two-dimensional Doppler echocardiographic data. RESULTS Patients with FMR improvement showed greater gains in LV function and mechanoenergetics. In the subgroup of 279 patients with moderate/severe FMR, age, ventricular efficiency (VE) and LV end-diastolic volume index (LVEDVi) were independently associated with FMR improvement in the primary model. Individual discrimination was modest. In a post-hoc sensitivity analysis adding baseline E/e', VE was no longer significant (OR 1.11; p = 0.491), whereas E/e' was independently associated with FMR improvement (model AUC 0.704 to 0.762). CONCLUSIONS The combined assessment of echocardiography-derived VE and LVEDVi was associated with FMR improvement in the primary model; however, VE was no longer independently associated after additional adjustment for baseline E/e'. FMR improvement was closely associated with LV reverse remodeling, although a causal direction cannot be established from this observational study.