The added value of contrast-enhanced cardiac magnetic resonance to predict positive genetic testing in clinically suspected lamin A/C cardiomyopathy

Abstract

Lamin A/C cardiomyopathy (CM) is an inherited disease due to LMNA gene mutation with particular cardiac phenotype. Cardiac magnetic resonance (CMR) studies suggest frequent late gadolinium enhancement (LGE) involving septal mid-myocardium. To assess the added value of CMR to conventional clinical features of Lamin A/C CM for the prediction of a positive LMNA gene testing. We performed a retrospective monocentric study in all index patients referred for genetic testing for a clinical suspicion of Lamin A/C CM. The diagnostic performances of relevant parameters for the prediction of a positive LMNA gene testing were analysed in several logistic regression models. In total, 90 patients were included (55 LMNA+, 35 LMNA−). Fifty-five patients had a CMR (28/55 LMNA+, 27/35 LMNA−). LMNA+ patients had significantly more LGE than LMNA− [20/28 (71%) vs. 9/27 (33%), P = 0.011]. The main differences in LGE features were septal involvement (70% in LMNA+ vs. 11% in LMNA−, P = 0.005) and mid-myocardium localisation (95% vs. 44%, P = 0.005). In a first logistic regression model without CMR data in all 90 patients, V1-V3 R-wave abnormalities, familial history of SCD and sinus node dysfunction were independent predictors of a positive LMNA gene testing (sensitivity 89%, specificity 46%, accuracy 72%). A second model in the 55 patients who had a CMR showed better accuracy (85%), mainly driven by increased specificity (81%) with preserved sensitivity (89%). V1-V3 R-wave abnormalities, premature ventricular contractions, non-depressed LVEF and septal LGE predicted positive LMNA gene testing in this model (septal LGE OR = 31, 95% CI: 4–715; P = 0.005) ( Fig. 1 ). CMR, particularly septal mid-myocardium LGE, carries good diagnostic accuracy to predict a positive LMNA gene testing in clinically suspected Lamin A/C CM with increased specificity when added to conventional red flags.