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To examine the independent prognostic role of functional mitral regurgitation (FMR) and its impact across the severity of chronic heart failure (CHF) in a large population of outpatients with systolic CHF followed at two multidisciplinary clinics.Echocardiography was performed upon enrolment in 469 CHF patients. Follow-up for death and heart transplant was updated on January 2007. Five-year transplant-free survival was 82.7% in patients with no or Grade I FMR, 64.4% in Grade II, 58.5% in Grade III, and 46.5% in Grade IV (P < 0.0001). There was a strong graded association between FMR and the long-term risk of death and heart transplant, which remained significant after multivariable adjustment (P = 0.0003). The association between FMR and events was strong and independent in patients with less severe symptoms and in those at lower overall risk based on a propensity score analysis, while it was not significant in patients with more advanced CHF or in the high-risk subgroup (P < 0.0001 for interactions).This study clarifies previous apparently discrepant results by demonstrating that FMR is an independent determinant of death and heart transplantation only in less severe CHF and in patients with a lower risk profile. This finding indicates that FMR plays a major role in the early phase of CHF, suggesting that this should be the focus of strategies attempting to reduce it.