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This study assessed left atrial (LA) dimension as a potential predictor of outcome in hypertrophic cardiomyopathy (HC). From the Italian Registry for Hypertrophic Cardiomyopathy, 1,491 patients (mean age 47 ± 17 years; 61% men; 19% obstructive), followed for 9.4 ± 7.4 years after the initial echocardiographic evaluation, constituted the study group. The mean LA transverse dimension was 43 ± 9 mm and was larger in patients with severe symptoms (48 ± 9 mm for New York Heart Association classes III and IV vs 42 ± 9 mm for classes I and II, p <0.001), atrial fibrillation (47 ± 9 vs 42 ± 8 mm in sinus rhythm, p <0.001), and left ventricular outflow obstruction (46 ± 9 mm for ≥30 mm Hg at rest vs 42 ± 9 mm for <30 mm Hg at rest, p <0.001). On univariate analysis, each 5-mm increase in LA size was associated with a hazard ratio (HR) of 1.2 for all-cause mortality (p <0.0001). On multivariate analysis, a LA dimension >48 mm (the 75th percentile) had a HR of 1.9 for all-cause mortality (p = 0.008), 2.0 for cardiovascular death (p = 0.014), and 3.1 for death related to heart failure (p = 0.008) but was unassociated with sudden death (p = 0.81). Similar results were obtained after the exclusion of patients with atrial fibrillation (HR 1.7, p = 0.008) or outflow obstruction (HR 1.8, p = 0.003). The predictive power of LA dimension >48 mm was also validated in an independent HC cohort from the United States, with similar HRs (1.8 for all-cause mortality, p = 0.019). In conclusion, in a large cohort of patients with HC from a nationwide registry, a marked increase in LA dimension were predictive of long-term outcome, independent of co-existent atrial fibrillation or outflow obstruction. LA dimension is a novel and independent marker of prognosis in HC, particularly relevant to the identification of patients at risk for death related to heart failure. [Copyright &y& Elsevier]