Impact of left atrial size on outcomes in patients with atrial functional mitral regurgitation

Abstract Background Atrial functional mitral regurgitation (AFMR) is caused by mitral annular enlargement following left atrium (LA) enlargement because of atrial fibrillation and/or heart failure with preserved ejection fraction. However, the distribution and clinical impact of LA size are unknown. Purpose To assess the impact of LA volume index (LAVI) on clinical outcomes in patients with AFMR. Methods We investigated patients with ≥moderate AFMR from the REVEAL-AFMR registry. Patients with ≥moderate aortic valve diseases and/or missing LAVI were excluded. The primary endpoint was a composite of cardiovascular death and heart failure hospitalization. Results Of total 871 patients with AFMR (age 78 ± 9 years, men 45%, atrial fibrillation 80%, severe MR 28%), median LAVI was 75 [58-110] mL/m². LAVI <50, 50-99, 100-149, 150-199 and ≥200 mL/m² were present in 117 (13%), 48 (55%), 162 (19%), 61 (7%) and 48 (6%), respectively. In these subgroups, severe MR was present in 10%, 20%, 38%, 61%, and 69% (Figure A), and NYHA III or IV in 8%, 8%, 13%, 13% and 23%, respectively. During the median follow up of 2.9 [2.0-3.2] years, LAVI ≥200 and 150-199 mL/m² were associated with lower event-free survival compared with <50 mL/m² (Figure B) . In the multivariable analysis, LAVI ≥150 mL/m² was an independent risk factor of adverse events (adjusted hazard ratio [HR] 1.69; 95% CI 1.05-2.73, p=0.030), adjusted for age, sex, body mass index, severe symptoms, chronic kidney disease, anemia, severe MR and tricuspid regurgitation (TR). Variables associated with LAVI ≥150 mL/m² were atrial fibrillation (adjusted OR 5.95; 95% CI 1.79-19.8, p<0.01), severe MR (OR 3.99; 95% 2.49-6.39, p<0.01) , elevated PASP (OR 3.10; 95% 1.80-5.33, p<0.01) and TR (OR; 2.46 95% 1.43-4.21, p<0.01), left ventricular end-diastolic volume (adjusted OR 1.26 per 10mL; 95% 1.17-1.36, p<0.01). Conclusion LAVI was 50-99 mL/m² in nearly a half of patients with AFMR, but enlarged to ≥150 mL/m² in 13%. Patients with larger LAVI more frequently had severe symptoms. LAVI ≥150 mL/m² was associated with worse outcomes, independent of MR severity. Severe MR and left ventricular size were strongly associated with LA enlargement other than atrial fibrillation.Figure AFigure B