TTE was performed using commercially available state-of-the-art ultrasonography machines. Comprehensive TTE examinations were performed according to previously published guidelines. ^, Notably, LA volumes were assessed using the biplane disk summation method in apical 2- and 4-chamber views. As LAD is also a reference for diagnosing left atrial enlargement, we also evaluated LAD values corresponding to the LAVI measurements. LAD was measured as the anteroposterior linear dimension in the parasternal long-axis view. MR severity was evaluated with a multiparametric integrative approach. Valvular heart diseases including mitral regurgitation were considered significant if its grade was moderate or higher.

The primary endpoints were cardiovascular mortality and hospitalization for HF. The first event during follow-up was used to determine event-free survival. Each hospital team obtained information on the possible occurrence and/or cause of death through electronic chart reviews and telephone interviews.

Continuous data are expressed as means ± standard deviations or medians (interquartile ranges), and categorical data are expressed as frequencies or percentages. Continuous variables were compared among the groups using 1-way analysis of variance (ANOVA) and repeated-measures ANOVA with Tukey’s post hoc test, whenever appropriate. Nominal variables were compared between groups using the chi-squared test. Trends in severe MR or symptoms across the LAVI grades were evaluated using the Cochran–Armitage trend test. Survival analysis was performed using the Kaplan–Meier method and log-rank test. In these analyzes, patients who died of no cardiovascular disease or who received MV intervention were censored at the event. The Cox proportional hazards model was used to identify independent predictors of cardiovascular mortality or hospitalization due to HF. The results are presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Age, sex, body mass index, systolic blood pressure, NYHA functional class, previous history of HF hospitalization, serum hemoglobin levels, creatinine levels, and the European System for Cardiac Operative Risk Evaluation II scores were included in the multivariate model in accordance with other studies from this registry. To investigate the relationship between the LAVI and outcomes, a penalized spline model was used. The penalized spline allows for flexible modeling of nonlinear associations. The model included the LAVI as the predictor of interest, whereas the covariates of age, sex, and MR severity were included as adjustment variables. The penalized spline approach was selected to account for potential nonlinear relationships between the LAVI and outcome, ensuring a robust estimation of the association. A multivariate logistic regression analysis was performed to assess independent determinants for a large left atrium; variables with p <0.05 in univariate analysis or key clinical variables of interest were included as candidate variables for the multivariate model. The association between LAD and LAVI was studied using nonlinear regression. Receiver operating characteristic (ROC) curve analysis was performed to assess the accuracy of the LAD for the corresponding LAVI. The Youden index was used to determine the optimal cutoff value. Tests were 2-sided, and p <0.05 was considered statistically significant. Statistical analyzes were performed using JMP Pro 17 (SAS Institute, Cary, North Carolina). Time-dependent ROC curve analyzes for survival data were performed using EZR to evaluate the prognostic significance of LAVI (Omiya, Saitama, Japan). The Fine–Gray model was assessed to consider competing risk of death from no cardiovascular disease using EZR, which is for R. More precisely, it is a modified version of the R commander designed to add statistical functions frequently used in biostatistics.