ABSTRACT: Background Emerging data suggest important prognostic value to left atrial (LA) characteristics, but the independent impact of LA function on outcome remains unsubstantiated. Thus, we aimed to define the incremental prognostic value of LA coupling index (LACI), coupling volumetric and mechanical LA characteristics and calculated as the ratio of left atrial volume index to tissue Doppler imaging a', in a large cohort of patients with isolated floppy mitral valve. Methods and Results All consecutive 4792 patients (61±16 years, 48% women) with isolated floppy mitral valve in sinus rhythm diagnosed at Mayo Clinic from 2003 to 2011, comprehensively characterized and with prospectively measured left atrial volume index and tissue Doppler imaging a' in routine practice, were enrolled, and their long-term survival analyzed. Overall, LACI was 5.8±3.7 and was <5 in 2422 versus ≥5 in 2370 patients. LACI was independently higher with older age, more mitral regurgitation (no 3.8±2.3, mild 5.1±3.0, moderate 6.5±3.8, and severe 7.8±4.3), and with diastolic (higher E/e') and systolic (higher end-systolic dimension) left ventricular dysfunction (all P≤0.0001). At diagnosis, higher LACI was associated with more severe presentation (more dyspnea, more severe functional tricuspid regurgitation, and elevated pulmonary artery pressure, all P≤0.0001) independently of age, sex, comorbidity index, ventricular function, and mitral regurgitation severity. During 7.0±3.0 years follow-up, 1146 patients underwent mitral valve surgery (94% repair, 6% replacement), and 880 died, 780 under medical management. In spline curve analysis, LACI ≥5 was identified as the threshold for excess mortality, with much reduced 10-year survival under medical management (60±2% versus 85±1% for LACI <5, P<0.0001), even after comprehensive adjustment (adjusted hazard ratio, 1.30 [95% CI, 1.10-1.53] for LACI ≥5; P=0.002). Association of LACI ≥5 with higher mortality persisted, stratifying by mitral regurgitation severity of LA enlargement grade (all P<0.001) and after propensity-score matching (P=0.02). Multiple statistical methods confirmed the significant incremental predictive power of LACI over left atrial volume index (all P<0.0001). Conclusions LA functional assessment by LACI in routine practice is achievable in a large number of patients with floppy mitral valve using conventional Doppler echocardiographic measurements. Higher LACI is associated with worse clinical presentation, but irrespective of baseline characteristics, LACI is strongly, independently, and incrementally determinant of outcome, demonstrating the crucial importance of LA functional response to mitral valve disease.
