Arrhythmogenic cardiomyopathy: double, double toil, and trouble

Abstract

Figures

(A) Family tree depicting the members with pathogenic mutations, with and without an ACM phenotype. The patient’s son exhibits a positive ACM phenotype, including RV dilation and systolic dysfunction with biventricular extensive LGE, and has an implantable cardioverter-defibrillator for secondary prevention, following a syncope due to monomorphic ventricular tachycardia with left bundle branch block morphology. (B) ECG of the 70-year-old patient depicting atrial fibrillation (50–60 b.p.m.), complete right bundle branch block, epsilon waves in V1–V3 (arrow), and T-wave inversion in all precordial leads. (C) Cardiac magnetic resonance showing subepicardial LGE in the inferolateral and inferior walls of the left ventricle (asterisk), irregular myocardial contour of the LV lateral wall [‘rat-bite sign’ (arrow)], and dyskinetic movement of the right ventricular apex, and the inflow and outflow tracts [ACM ‘triangle of dysplasia’ (1, 2, 3)].

Full text

Summary

While single genetic variants associated with arrhythmogenic cardiomyopathy (ACM) have a highly variable penetrance and expression, compound heterozygosity increases the likelihood of displaying the ACM phenotype.^1^ We here describe the case of a patient with a positive screening with double mutation and a late-presenting ACM phenotype, emphasizing the importance of a structured systematic cascade screening.

Case description

A 70-year-old man patient with permanent atrial fibrillation, hypertension, and type 2 diabetes was referred to the Cardiomyopathy Clinic following genetic cascade screening for ACM. His son (index case) had symptomatic ACM with two pathogenic variants: PKP2 (c.1170 + 2T > A) and DSC2 [c.2112_2116del p.(Phe708fs14)]. The patient also had both the same mutations. His father had died suddenly at the age of 50 years, of unknown cause, and two other relatives were genotype-positive but phenotype-negative—see the genogram (Figure 1A*).

(A) Family tree depicting the members with pathogenic mutations, with and without an ACM phenotype. The patient’s son exhibits a positive ACM phenotype, including RV dilation and systolic dysfunction with biventricular extensive LGE, and has an implantable cardioverter-defibrillator for secondary prevention, following a syncope due to monomorphic ventricular tachycardia with left bundle branch block morphology. (B) ECG of the 70-year-old patient depicting atrial fibrillation (50–60 b.p.m.), complete right bundle branch block, epsilon waves in V1–V3 (arrow), and T-wave inversion in all precordial leads. (C) Cardiac magnetic resonance showing subepicardial LGE in the inferolateral and inferior walls of the left ventricle (asterisk), irregular myocardial contour of the LV lateral wall [‘rat-bite sign’ (arrow)], and dyskinetic movement of the right ventricular apex, and the inflow and outflow tracts [ACM ‘triangle of dysplasia’ (1, 2, 3)].

He complained of mild fatigue and orthostatic intolerance. The ECG (Figure 1B) showed atrial fibrillation, complete right bundle branch block, and epsilon waves in V_1_–V_3_. The transthoracic echocardiography revealed right ventricular (RV) dilation and moderate systolic dysfunction with free wall akinesia. The cardiac magnetic resonance imaging (Figure 1C; Supplementary Material Supplementary material online, Videos S1-S4) confirmed the reduced RV systolic function (ejection fraction 30%), apical, inflow, and outflow dyskinesia and subepicardial late gadolinium enhancement (LGE) in the so-called triangle of dysplasia. Late gadolinium enhancement was also seen in the left ventricular infero-lateral wall. Notably, both ventricles had myocardial contour irregularities (‘rat-bite sign’), suggestive of adipose infiltration. The 48 h Holter monitor (while on bisoprolol 5 mg) recorded 73 polymorphic premature ventricular contractions.

The diagnosis of biventricular ACM was established (according to the 2020 Padua criteria^2^). The estimated 5 year arrhythmic risk was 17.3% using the ACM risk calculator v3.0.^3^ Accordingly, we recommended an implantable cardioverter-defibrillator, which was placed for the primary prevention of sudden cardiac death. At 1.5 years of follow-up, the patient complains of mild fatigue and has had no cardiovascular events or ICD therapies.

Supplementary Material

ytaf563_Supplementary_Data