The prevalence and prognosis of severe atrial functional mitral regurgitation varies with its definition: insights from a large clinical database

Abstract Background Severe functional mitral regurgitation (fMR) is associated with impaired quality of life and a poor prognosis. The aetiology of fMR can be categorised as either ventricular- or atrial (AfMR) in origin. The definition of AfMR, however, varies considerably across studies, particularly concerning the echocardiographic parameters and comorbidities used for inclusion. This heterogeneity across definitions poses a significant challenge to the consolidation of research findings, the proper treatment and the establishment of consistent clinical guidelines. Purpose The objective of this study was to consolidate existing definitions of AfMR and to evaluate their distribution across the entire cohort of severe fMR as well as their prognostic significance. Methods All currently used AfMR definitions were applied to our comprehensive clinical database spanning from 2010-2020. This database includes 13,052 patients with fMR, of which 1,163 patients had severe fMR. Survival analysis was performed for each definition with moderate fMR as the comparator group. The primary endpoint was all-cause mortality. Results Overall, 49 different definitions for AfMR were found. In the univariate analysis, 31 definitions demonstrated significantly worse survival, with hazard ratios (HR) ranging from 1.36 (95% CI: 1.00-1.85, p=0.049) to 2.35 (95% CI: 1.56-3.56, p0.001). Adjustment for confounding factors, including age, sex, and NT-proBNP resulted in eight distinct AfMR definitions that differed significantly in size and long-term outcome. Out of these, the definition with the best prognosis (Definition A: ejection fraction 50% and left atrial dilatation) had an HR of 1.33 (95% CI: 1.03-1.71, p=0.029) and included 184 patients. AfMR defined by an ejection fraction 50%, atrial fibrillation, left atrial dilatation, and mitral annular dilatation (Definition H) had the worst survival in the multivariable analysis with an HR of 2.27 (CI 95%: 1.51-3.43, p0.001) and only included 55 patients (Table 1, Figure 1). Conclusion The considerable variation in AfMR definitions across studies has been demonstrated to compromise the comparability of research findings. The results of this study emphasise the necessity for a unified, standardised definition of AfMR in order to enhance consistency in clinical research and practice.Multivariable cox analysis Long-term survival analysis