Ventricular Arrhythmia Ablation in Inherited Cardiomyopathy: Phenotype Variability and Outcomes Based on Functional Genotypes

Figures

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  Figure 1. Functional genotype‐based classification and the corresponding gene variants observed in our study are shown on the left. On the right, an illustration of a cardiomyocyte shows the subcellular components and the proteins encoded by specific genes (created with BioRender.com). LMNA indicates lamin A/C; and TTN, titin.

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  Figure 2. Distribution of initial clinical manifestation among the functional genotype groups. DSP indicates desmoplakin; LMNA, lamin A/C; MMVT, monomorphic ventricular tachycardia; NSVT, nonsustained ventricular tachycardia; PMVT, polymorphic ventricular tachycardia; PVC, premature ventricular complex; TTN, titin; and VF, ventricular fibrillation.

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  Figure 3. Individual patient trajectories of echocardiographic LVEF among the predominant functional genotype groups from before the first ablation to the latest follow‐up (median interval of 35 months [15–68 months]). Ejection fraction is depicted on the y‐axis (%). DSP indicates desmoplakin; FU, follow‐up; LVEF, left ventricular ejection fraction; and RFCA, radiofrequency catheter ablation.

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  Figure 4. The American Heart Association's 17‐segment heart model is shown to depict the frequency and distribution of LGE on CMR, bipolar and unipolar voltage abnormalities as seen on electro‐anatomical maps of the left ventricle, in the following genotype groups: TTN, LMNA, sarcomeric, and DSP. The color scales represent the percentage of patients affected in each segment, with the CMR section in blue additionally showing transmural involvement (epicardial, midwall, endocardial). CMR indicates cardiac magnetic resonance; DSP, desmoplakin; EAM, electroanatomical mapping; LGE, late gadolinium enhancement; LMNA, lamin A/C; and LVA, low voltage abnormalities.

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  Figure 5. Case examples of phenotype expression among the genotype groups are shown in columns A–E. The first row shows LGE seen on CMR imaging, highlighted by yellow arrowheads. The second and third rows show substrate seen on LV voltage maps. Color‐coded voltage threshold scales are shown on the left for both bipolar and unipolar maps (low bipolar voltage ≤1.5 mV and low unipolar voltage ≤8.3 mV). Column A: DSP variant with subepicardial LGE extending from lateral to inferior LV, bipolar endocardial voltage map is normal, and bipolar epicardial map shows LVAs on the lateral LV. Column B: TTN variant with small area of basal septal LGE, bipolar voltage map shows anteroseptal and perivalvular LVA, unipolar map shows larger area of LVA in the septum. Column C: LMNA variant with midmyocardial ring‐like LGE spanning the entire septum and extending to the inferior LV. Bipolar endocardial map shows patchy septal, perivalvular and lateral LVA, unipolar map shows diffuse LVA. Column D: MYBPC3 variant with ring‐like LGE of the entire septum, extending to the anterior and inferior LV. Bipolar map shows patchy septal LVA but unipolar map shows diffuse LVA of the septum and anterior LV. Column E:…

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  Figure 6. Kaplan–Meier analysis of outcomes by genotype (left column: graphs A–C) and phenotype‐based classification (right column: graphs D–F). Graphs (A) and (D) show VT‐free survival over 3 years in the VT ablation cohort (n=80). Graphs (B) and (E) illustrate freedom from all‐cause mortality, HT, and LVAD. Graphs (C) and (F) display freedom from LVAD and/or HT. ARVC indicates arrhythmogenic right ventricular cardiomyopathy; BiV‐CM, biventricular cardiomyopathy; DCM, dilated cardiomyopathy; HT, heart transplant; LVAD, left ventricular assist device; SCD, sudden cardiac death; VF, ventricular fibrillation; and VT, ventricular tachycardia.