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The aim of the present study was to evaluate the prevalence and extent of myocardial fibrosis in patients with isolated left ventricular non-compaction (LVNC) and to determine its relation to clinical status and LV systolic function.The cardiac magnetic resonance imaging (MRI) database of our institution was searched for all patients with a first diagnosis of isolated LVNC. The diagnosis of isolated LVNC was based on the presence of standard cardiac MRI and clinical criteria. For each patient, cine and contrast-enhanced cardiac MR images were analysed to evaluate LV systolic function and the prevalence and extent of late gadolinium enhancement (LGE), a surrogate of myocardial fibrosis. A total of 42 patients (mean age 46 ± 20 years, 62% male) were identified. Late gadolinium enhancement was observed in 23 (55%) patients with isolated LVNC, occupying 4.8 ± 6.7% of the LV mass. Both the presence and extent of LGE were significantly related to the number of abnormal clinical features (i.e. symptomatic status, resting electrocardiogram abnormalities, and 24 h Holter monitoring abnormalities; P< 0.001 and P= 0.001, respectively). Similarly, LGE was more prevalent and extensive in patients with LV ejection fraction (EF) <50% compared with patients with LVEF ≥50% (90 vs. 23%; P< 0.001 and 8.9 ± 7.6 vs. 1.1 ± 2.4%; P< 0.001, respectively). At multivariate analysis, both the presence and extent of LV LGE were independently related to LVEF (β = −0.63; P< 0.001 and β = −0.62; P< 0.001, respectively).Myocardial fibrosis is related to clinical disease severity and LV systolic dysfunction in isolated LVNC.