Cardiac chamber three-dimensional volumes and deformation predict clinical outcomes in chronic mitral regurgitation

Abstract Background In patients with mitral regurgitation (MR), cardiac remodeling assessed by two-dimensional (2D) echocardiographic linear indexes is highly variable and not suitable for individualized risk assessment. Purpose To evaluate whether measurements of myocardial strain and left atrial (LA), left ventricular (LV) and right ventricular (RV) three-dimensional (3D) volumes improve risk assessment in MR. Methods In the prospective 3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation study (3D-PRIME), 176 patients with significant (moderate or greater) MR were investigated with 2D/3D echocardiography. Referral criteria for mitral intervention followed current guidelines. LA remodeling was assessed by the maximum and minimum 3D LA volume (3D-LAV), peak reservoir strain (LASr), and stiffness (i.e. the ratio: mitral peak E-wave divided by the annular e’ velocity (E/e´) / LASr). LV and RV were considered dilated in case of increased 3D end-diastolic (LV>=86/74 and RV>=87/74ml/m2 in men/women) and end-systolic volumes indexed for body surface area (LV>=41/33 and RV>=44/36ml/m2 in men/women). Peak global longitudinal strain was measured in the LV (LV-GLS) and the RV free wall (RV-FWS). The primary outcome was a composite of mitral valve surgery, percutaneous mitral edge-to-edge repair and death. Results During a 14 [8-24] months follow-up, the patients (70±13 years, 39% women) experienced 73 events including 14 deaths. In univariate survival analyses, LV and RV dilatation, but not LV-GLS and RV-FWS, were associated with the primary outcome (Figure) and had superior predictive value to 2D volumes and diameters (p<0.05). On contrary, both atrial size and function predicted outcome, with 3D-LAV (HR 1.01, 95% CI 1.00-1.01), LASr (HR 1.03, 95% CI 1.01-1.06) and increased LA stiffness (Figure) all significant predictors of events (p<0.05). In multivariate Cox analysis with adjustment for age, sex, body mass index and MR etiology, dilated LV (HR 2.6, 95% CI 1.5-4.4), dilated RV (HR 2.0, 95% CI 1.1-3.6) and increased LA stiffness ((HR 2.4, 95% CI 1.3-4.6) were independently associated with higher rate of events (p<0.05). Conclusion In patients with moderate or greater MR, increased cardiac chamber 3D volumes and LA stiffness, as well as impaired LA reservoir strain are associated with higher risk of disease progression towards mitral valve intervention and death. Our findings indicate that assessment of both cardiac chamber 3D size and LA deformation can contribute to increased diagnostic and prognostic precision in patients with MR.