Meta-analysis of the role of cardiac magnetic resonance in laminopathy

Abstract

Lamin A/C (LMNA) cardiomyopathy is an inherited form of dilated cardiomyopathy associated with high rates of arrhythmias, conduction disease and sudden cardiac death, often preceding overt heart failure. Although LMNA mutations account for a minority of dilated cardiomyopathy cases, they portend a particularly malignant course. Cardiac magnetic resonance (CMR) imaging, particularly the detection of late gadolinium enhancement, has emerged as a valuable tool for assessing myocardial fibrosis and risk stratification in laminopathy. This study aims to systematically evaluate the structural, functional and prognostic CMR features in LMNA mutation carriers, and to quantify the diagnostic and clinical implications of myocardial fibrosis. A comprehensive literature search was conducted through June 2025. Studies involving genetically confirmed LMNA mutation carriers with CMR data were included. Outcomes included ventricular variables (left ventricular ejection fraction, left ventricular end-diastolic volume index, left ventricular end-systolic volume index, left ventricular wall mass index), late gadolinium enhancement (LGE) presence and arrhythmic events. Between-group comparisons were made: LMNA cardiomyopathy versus healthy controls; laminopathy with versus without LGE; and LMNA-positive versus LMNA-negative cardiomyopathy. We identified 10 studies involving 847 individuals. The LGE risk ratio for patients with LMNA cardiomyopathy versus healthy controls was 14.39 (P < 0.001); the LGE risk ratio for patients with LMNA-positive versus LMNA-negative cardiomyopathy was 2.14 (P < 0.001). In patients with laminopathy, LGE was associated with an increased risk of atrioventricular block (risk ratio 6.94; P = 0.004) and a trend towards more ventricular tachyarrhythmia (risk ratio 3.32; P = 0.056). Despite these fibrotic changes, left ventricular volumes and wall mass did not differ significantly from controls. CMR imaging identifies a high burden of fibrosis in LMNA cardiomyopathy, even in early disease, with strong prognostic implications. LGE presence is a key risk marker for arrhythmia and conduction disease, supporting early imaging-based risk stratification and possible preventive implantable cardioverter-defibrillator implantation in mutation carriers.