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Background: Left-sided native valve infective endocarditis (LNVIE) can result in mitral (MP) and aortic (AP) valve perforation, the prognostic significance of which remains poorly defined., Hypothesis: Valvular perforation is associated with worse outcomes., Methods: Retrospective review of patients with LNVIE during 1998-2005 was performed to examine characteristics and outcome predictors of LNVIE complicated by valve perforation. Patients were stratified as: group A: MP or AP detected by transesophageal echocardiography (TEE) or surgery; group B: no TEE evidence of MP or AP., Results: A total of 123 patients were included (group A = 47, group B = 76). In group A, 35 patients (74.5%) had MP alone, 11 (23.4%) had AP alone, and 1 patient had both. Severe valvular insufficiency was encountered more in group A (85.1% versus 59.2%, p = 0.003), so was hemodialysis (40.4% versus 17.1%, p = 0.004) and indications for valvular surgery (93.6% versus 77.6%, p = 0.02). Group A had a higher rate of in-hospital death (31.9% versus 15.8%, p = 0.04). Among patients who had an indication for valvular surgery, the in-hospital mortality rate for those who underwent valvular surgery was 16.7% in group A, and 7.9% in group B (p = 0.4), compared to those who did not undergo surgery (71.4% versus 33.3%, p = 0.04). Amongst survivors, hospital stay was on average 9.2 d longer in group A (38.9 versus 29.7 d, p = 0.05). Univariate analysis revealed association between lower survival and valvular perforation (odds ratio [OR]: 0.4, 95% confidence interval [CI]: 0.17-0.95), that was lost after adjusting for hemodialysis., Conclusions: Valve perforation complicating LNVIE is associated with hemodialysis, severe valvular insufficiency, and significant morbidity and mortality. Compared to conservative management, early surgical intervention is associated with improved survival., (Copyright 2009 Wiley Periodicals, Inc.)