Late gadolinium enhancement distribution patterns in non-ischaemic dilated cardiomyopathy: genotype–phenotype correlation

Abstract

Aims Late gadolinium enhancement (LGE) is frequently found in patients with dilated cardiomyopathy (DCM), there is little information about its frequency and distribution pattern according to underlying genetic substrate. We sought to describe LGE patterns according to genotype and to analyze the risk of major ventricular arrhythmias (MVA) according to patterns. Methods and results Cardiac magnetic resonance findings and LGE distribution according to genetics was performed in a cohort of 600 DCM patients followed at 20 Spanish centers. After exclusion of individuals with multiple causative gene variants or with variants in infrequent DCM-causing genes, 577 patients (34% females, mean age 53.5 years, LVEF 36.9 ± 13.9%) conformed the final cohort. A causative genetic variant was identified in 219 (38%) patients and 147 (25.5%) had LGE. Significant differences were found comparing LGE patterns between genes (P < 0.001). LGE was absent or rare in patients with variants in TNNT2, RBM20 and MYH7 (0%, 5% and 20%, respectively). Patients with variants in DMD, DSP and FLNC showed predominance of LGE subepicardial pattern (50%, 41% and 18%, respectively) whereas patients with variants in TTN, BAG3, LMNA and MYBPC3 showed unspecific LGE patterns. Genetic yield differed according to LGE pattern. Patients with subepicardial, lineal midwall, transmural, right ventricular insertion points or with combination of LGE patterns showed increased risk of MVA compared with patients without LGE. Conclusion LGE patterns in DCM has a specific distribution according to the affected gene. Certain LGE patterns are associated with increased risk of MVA and with increased yield of genetic testing.

Imagenetics for Precision Medicine in Dilated Cardiomyopathy

“…37 A prevalent septal midwall LGE can be observed in patients with LMNA variants and may explain conduction abnormalities. 38 In addition, LMNA cardiomyopathy may be associated with atrial standstill. 16,39 Certain markers may identify a subgroup of high-risk LMNA carriers 40 , that is, (1) nonsustained ventricular tachycardia, (2) LVEF <45%, (3) male sex, and (4) nonmissense mutations.…”

“…48 A ring-like subepicardial LGE pattern is frequently identified in carriers of FLNC variants. 38,49 The discordance between symptoms and the degree of disease severity even without systolic impairment, suggest that the optimal mode of familial screening in the setting of FLNC variants may be by ECG and CMR, to detect VAs and subepicardial myocardial fibrosis, respectively, even in the absence of LV systolic dysfunction. 12 RNA Binding Motif Protein 20 RBM20 (RNA binding motif protein 20) variants are detected in ≈3% of patients with DCM, are associated with aggressive forms of cardiomyopathy characterized by early signs and symptoms of heart failure and VAs, as well as, high incidence of morbidity and premature mortality.…”

“…52 LGE detection by CMR is less frequently observed in RBM20 cardiomyopathy and may have different patterns of distribution with septal midwall pattern being the most prevalent. 38 Cases of RBM20-related DCM with a dominant arrhythmogenic presentation, without concomitant structural heart disease, have been reported. 53 Sodium Voltage-Gated Channel Alpha Subunit 5…”

“…48 A ring-like subepicardial LGE pattern is frequently identified in carriers of FLNC variants. 38,49 The discordance between symptoms and the degree of disease severity even without systolic impairment, suggest that the optimal mode of familial screening in the setting of FLNC variants may be by ECG and CMR, to detect VAs and subepicardial myocardial fibrosis, respectively, even in the absence of LV systolic dysfunction. 12…”

“…12,31 Next to systolic function impairment, ≈40% of DCM patients may present with myocardial fibrosis. Notably, myocardial fibrosis and systolic dysfunction are only weakly correlated 22,38 ; for example, extensive fibrosis may be observed with normal LVEF, 49 and vice versa severe biventricular failure can be observed in the absence of fibrosis. 38 The disruption of the normal myocardium integrity with fibrotic tissue is a triggering substrate that facilitates conduction disorders and reentrant circuits.…”