Abstract 12125: Distribution of Myocardial Fibrosis in Patients With Non-Ischemic Cardiomyopathy and Ventricular Tachycardia Based on Genetic Variant

Introduction: Patients with non-ischemic cardiomyopathy (NICM) have an increased propensity to develop arrythmias such as ventricular tachycardia (VT). A significant subset of patients with NICM have an underlying inherited genetic component.

Hypothesis: This study evaluated the location of substrate for ventricular tachycardia in patients with NICM with proven genetic variants. We sought to characterize patterns of substrate location based on specific genetic variants.

Methods: Patients referred for VT ablation between October 2018 and November 2022 at a single medical center were evaluated for pathologic genetic variants of known cardiomyopathy-related genes. Electro-anatomic mapping was reviewed for substrate localization.

Results: Thirty-two patients with pathologic variants were evaluated (age 55 +/- 16 years, 94% male, left ventricular ejection fraction 34 +/- 13%). Mutations in TTN (n=11 of 32), LMNA (n=6 of 32), PKP2 (n=5 of 32), MYBPC3 (n=3 of 32), DSP (n=2 of 32), TTR (n=1 of 32), FNLC (n=1 of 32), AGL (n=1 of 32), DES (n=1 of 32), DSG2 (n=1 of 32), were observed. Mutations in TTN were associated with substrate in the basal periaortic region (100%) and basal septum (50%) (Figure 1). LMNA mutations were associated with mid inferolateral (60%) and apical inferolateral (60%) substrate. Substrate location for individuals with mutations associated with PKP2 were solely observed in the right ventricle.

Conclusion: Certain genetic variants are associated with reproducible patterns of fibrosis in NICM. Understanding expected patterns of fibrosis based on genetic variants in NICM may facilitate ablation planning.