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Background: Previous studies have shown that late post-gadolinium myocardial enhancement by cardiac magnetic resonance (LGE-CMR) can identify areas of cardiac fibrosis, and that the extent of left ventricular (LV) diastolic function is related to severity of LGE in a broad range of cardiac conditions. In this study we evaluated the relationship between location of LGE and diastolic function.Methods and Results: 282 consecutive patients undergoing LGE-CMR and Doppler echocardiography were investigated. Fifty-five subjects (20%) had no evidence of structural heart disease; the remaining patients had various cardiac diagnoses, including idiopathic dilated cardiomyopathy (19%) and ischemic cardiomyopathy (29%). No LGE was detected in the vast majority (75%) of the subjects with entirely normal diastolic function; overall, median LGE score in these subjetcs was 0 (IQR 0.00 – 0.5). In contrast, the majority of patients with abnormal diastolic function had substantial fibrosis (median LGE score 4, IQR 0 – 8; p<0.0001). LGE score progressively increased with increasing LV filling pressure estimated by TDI-derived E/E' (≤10 vs >10, p<0.0001). Univariate analysis confirmed the significant correlations between diastolic dysfunction assessed by E/E' and age, diabetes, hypertension, LV ejection fraction, wall motion score index, and LGE score (p<0.05, for all). After multivariate analysis, only age, diabetes and LGE score remained significantly and independently correlated with the degree of diastolic dysfunction. Regional analysis indicated a significant and independent association between septal LGE and E/E' (p=0.0001).Conclusions: In addition to severity, location of myocardial fibrosis by LGE significantly correlates with the degree of diastolic dysfunction. This finding may underscore the role of septum in LV filling, either directly or as a consequence of altered interventricular dependence, which may affect diastolic function.