Lamin A/C (LMNA) gene mutation, identified in 10% of familial dilated cardiomyopathy (DCM) patients, is associated with an increased risk of sudden cardiac death (SCD), which may be the first clinical manifestation (1). Myocardial fibrosis (MF) has been identified in the hearts of LMNA mutation carriers experiencing arrhythmias or conduction disturbances, irrespective of left ventricular (LV) dilation and/or dysfunction (2). Thus, MF may be a precocious primary phenomenon responsible for the subsequent development of electrical instability and LV dysfunction. Cardiovascular magnetic resonance (CMR) allows the depiction of gross MF by late gadolinium enhancement (LGE), whereas extracellular/extravascular volume (ECV) fraction of the myocardium by pre-and postcontrast T1 mapping was recently demonstrated to detect interstitial MF (3). We aimed to investigate the incidence and pattern of MF using comprehensive CMR in LMNA mutation carriers.

We prospectively studied 7 families whose probands with the DCM phenotype were referred to our hospital between 2009 and 2011. We found 5 missense, 1 frame, and 1 splicing mutations (Online Appendix). All LMNA mutation carriers underwent biohumoral assays (hematocrit, N-terminal pro–B-type natriuretic peptide, plasma catecholamine, aldosterone, and plasma renin activity [PRA]), 12-lead electrocardiography, 24-h Holter monitoring, a cardiopulmonary exercise test, and CMR. All 6 probands received beta-blocker and/or an angiotensin-converting enzyme inhibitor therapy. A group of 16 age-matched healthy volunteers without a clinical history of cardiovascular disease was recruited as controls and underwent CMR, 12-lead electrocardiography, and blood sampling for hematocrit determination.