Late gadolinium enhancement magnetic resonance imaging in hereditary arrhythmogenic right (ARVC) and left ventricular cardiomyopathy (ALVC)

Background: Cardiac magnetic resonance imaging (MRI) is increasingly important in the diagnosis of hereditary arrhythmogenic cardiomyopathy. In particular, the use of late gadolinium enhancement (LGE) allows to visualize the distribution and extent of focal or global fibrosis and, thus, to risk stratify patients with arrhythmogenic cardiomyopathy. Cardiac MRI parameters are established criteria for the diagnosis of ARVC whereas the potential of cardiac MRI in ALVC remains to be exploited.

Purpose: The aim of the study was to evaluate the role of LGE in the diagnosis and risk stratification of patients with ARVC and ALVC  in the context of pathogenic genetic mutations for hereditary arrhythmogenic cardiomyopathies in these patients. 

Patients: In 25 patients (15 male, 46+-14 years) with hereditary arrhythmogenic cardiomyopathy, pathogenic genetic variants (class V according to ACMG) or likely pathogenic variants (class IV) were detected, and LGE-MRI was performed. Among them, 9 patients had the phenotype of ARVC (PKP2 gene mutation, n = 5; DSG2, n = 1; DSP, n = 1) or hereditary syndromal diseases with predominant RV involvement (COL2A1, n = 1; deletion of chromosome 7, n = 1). 16 patients had the phenotype of ALVC or family history for malignant ALVC including hypertrophic cardiomyopathy  (MYBPC3, n =3; MYH7, n = 2; TPM1, n = 1; PKP2, n = 1; RYR2, n = 3) and dilated cardiomyopathy or non-dilated left ventricular cardiomyopathy (TTN, n = 3; LMNA, n = 2; FLNC, n = 1). 11 patients had a secondary prophylactic indication for implantable cardioverter defibrillator (ICD) implantation, 4 had a primary prophylactic ICD indication, 7 had less pronounced cardiomyopathies without ICD indication (according to 2022 ESC guidelines) and 3 were asymptomatic mutation carriers with a family history of malignant ALVC. The distribution and amount of LGE was semi-quantitatively classified as marked, moderate or minimal/ no LGE.

Results: 7 of 9 patients with ARVC had marked LGE in RV, one had predominantly fatty degeneration with low LGE and one had predominantly right atrial LGE with atrial arrhythmias. MRI findings in 16 patients with ALVC  showed that patients with secondary or primary prophylactic ICD indication had more LGE than patients with less pronounced cardiomyopathy without ICD indication. In patients with dilated cardiomyopathy or non-dilated left ventricular cardiomyopathy, marked LGE was also found in 3 patients (with laminopathy or filaminopathy) without or with only mild LV dysfunction. In 3 asymptomatic carriers of pathogenic mutations with family history of  malignant ALVC, no or minimal LGE was found.

Conclusions: First experience with LGE MRI in patients with hereditary ALVC suggests that LGE-MRI may provide an early diagnostic feature and may contribute to risk stratification in these patients.