Tissue characterisation in a male triathlete with a history of sudden cardiac arrest

Abstract

A Caucasian male triathlete and previous soccer player in his early thirties presented for further evaluation post out-of-hospital cardiac arrest and implantation of a transvenous single-chamber implantable cardioverter-defibrillator (ICD) (Figure 1). He originally presented with chest pain and ventricular ectopy with no family history of sudden cardiac death or inherited cardiac disease. Question: The findings were consistent with pathological characteristics of arrhythmogenic cardiomyopathy (ACM) with biventricular involvement. Diagnosis was made considering the 2010 Task Force criteria and the 2020 International criteria (Padua criteria).1, 2 The 12-lead ECG showed sinus bradycardia (50 bpm), T-wave inversion in the inferior leads (II, III, and aVF) with isoelectric J-points and ST segments and low QRS voltage criteria in the limb leads (Figure 1A). Poor anterior R-wave progression and prolonged terminal activation duration (V2) were also present. The transthoracic echocardiogram (ECHO) demonstrated normal left ventricle (LV) size with low normal systolic function (EF 52%) (Video 1). However, strain imaging was abnormal, with reduced LV epicardial and mid layer-specific global longitudinal peak systolic strain (GLPSS) (−11% and −13.2%) (Figure 1C), prolonged mid-wall LV mechanical dispersion (60 ms) and post-systolic shortening in the basal segments (Figure 2—arrows). The right ventricle (RV) was normal in size with reduced systolic function (RV FAC 34%), with a dyskinetic RV apex (Figure 1B) (Video 2). RV deformation patterns showed early systolic lengthening and post-systolic shortening of the apex (Figure 3—arrows). Prior to ICD implantation, cardiac magnetic resonance (CMR) demonstrated extensive circumferential, intramural and subepicardial late gadolinium enhancement (LGE) of the LV (nonischaemic pattern) (Figure 1D). Genotyping revealed a heterozygous pathogenic (ACMG class 5) missense desmin (DES) gene variant: c.1205T>C, p.(IIe402Thr). Family screening of his asymptomatic sister in her late twenties showed a mildly dilated RV with apical dyskinesis on cardiac imaging. ACM is a genetic disease characterised by progressive fibrofatty tissue replacement of the myocardium, with greater exercise exposure associated with LV involvement and systolic dysfunction.2, 3 CMR imaging is considered the gold standard for the characterisation of tissue, with the detection and quantification of myocardial fibrosis (MF) using gadolinium. MF is associated with increased myocardial stiffness, heart failure, a higher incidence of ventricular arrhythmias (VA), and adverse cardiac outcomes such as sudden cardiac death.4 Tissue characterisation with the use of 2D strain imaging on ECHO and CMR can help in the distinction of different ACM phenotypes and identify subclinical disease.5, 6 Studies have shown that 2D strain imaging including layer-specific GLPSS and LV mechanical dispersion may help identify ACM patients with high-risk arrhythmic features such as LGE and VA.3, 6, 7 Valentini et al. also highlighted that low QRS voltages on ECG may provide valuable information regarding suspicion of MF, particularly in isolated LV or biventricular variants.8 ACM has been identified in genes encoding non-desmosomal proteins such as DES, which can be associated with isolated or biventricular phenotypes.5 In a study by James et al., DES was identified as 1 of 8 genes with definitive or moderate evidence for ACM (plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, junction plakoglobin, transmembrane protein 43, phospholamban, and DES), which should yield a major criterion for ACM diagnosis.9 DES is the major intermediate filament protein in the human heart and skeletal muscle, providing mechanical stabilisation and linkage of the cell structures in cardiomyocytes. Cardiac involvement (desminopathy) presents in more than 70% of pathogenic DES variants.10 These are associated with arrhythmogenic, dilated, hypertrophic, restrictive or LV non-compaction cardiomyopathies. Desminopathies typically present with circumferential pattern of LV subepicardial LGE on CMR and during the third decade of life, however onset of the disease can be highly variable.5, 10 The presence of major MF, including nonischaemic and ischaemic patterns should prompt further evaluation and follow-up regarding potential cardiac disease, particularly in young athletes. The author would like to thank Dr. Kegan Moneghetti, Cardiologist at the Baker Heart and Diabetes Institute and St Vincent's Hospital Melbourne for his invaluable input in improving the manuscript. None. Supplemental Video 1. LV triplane imaging. Supplemental Video 2. 3D RV focus view. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.