Evolving deformation patterns in a competitive swimmer with low QRS voltages on 12‐lead electrocardiogram

Arrhythmogenic cardiomyopathy (ARVC) is a familial disease characterised by progressive loss of myocardial tissue and gradual replacement by fibrofatty tissue. It less commonly affects women than men, with age-dependent penetrance and variable expressivity.1 ARVC is inherited in an autosomal dominant pattern, with almost half carrying variants affecting the desmosomal genes. However, arrhythmogenic remodelling of the right or left ventricles may occur in gene elusive athletes, who perform a high volume of high-intensity endurance exercise. A female competitive swimmer in her early twenties presented with episodes of chest tightness, shortness of breath and presyncope. She reported no family history of sudden cardiac death or inherited cardiac disease and had a training volume of 10- to 15-h per week of moderate to high intensity. A thorough baseline evaluation was performed following a systematic approach. A resting 12-lead electrocardiogram (ECG) (Figure 1A), transthoracic echocardiogram (ECHO) with 2D strain imaging (Figures 1B and 2, Video S1) and cardiac magnetic resonance (CMR) imaging (Figure 3, Videos S2 and S3) were performed. Differential diagnosis in this case may include ARVC, myocarditis, cardiac sarcoidosis, hypertrophic cardiomyopathy, and idiopathic dilated cardiomyopathy, which may share similar clinical features. The findings were consistent with the pathological characteristics of ARVC. The diagnosis was made based on the 2010 Task Force criteria.2 However, further evaluation using the 2020 International criteria (Padua criteria), identified a biventricular phenotype.3, 4 The ECG demonstrated sinus bradycardia (40 bpm), extensive T-wave inversion (V1–V6, II, III, aVF) with isoelectric J-points and ST segments and low QRS voltages in the chest and limb leads. Based on the 2017 International criteria for ECG interpretation in athletes, these findings were considered abnormal.5 Further evaluation was warranted, given the athlete's symptoms and abnormal ECG. Unbalanced or asymmetric right heart remodelling was identified by 2D ECHO parameters in the athlete.6 Mild to moderate RV dilatation with reduced systolic function (RV FAC 15%) was present. Interestingly, the LV was normal in size, with low normal systolic function (EF 53%) and hypokinesis of the mid to apical lateral segments. LV regional and global 2D longitudinal strain were normal, although post-systolic shortening and prolonged peak strain dispersion in the lateral apical segments were present (Figure 2A – arrows). RV 2D longitudinal strain showed reduced regional and global values (epicardial layer – 12.6%) (Figure 2B). CMR imaging revealed moderately dilated RV (168 mL/m2) with reduced systolic function (EF 34%) and a dyskinetic RV free wall. The LV was mildly dilated (115 mL/m2) with mild segmental systolic dysfunction (EF 47%) and severely hypokinetic apical lateral segment. Subepicardial and mid-myocardial late gadolinium enhancement were identified in the mid to apical LV lateral segments (Figure 3 – arrows). RV EDV: LV EDV (end-diastolic volume) ratio was 1.46, suggested unbalanced RV remodelling.6 Cardiopulmonary exercise testing (CPET) combined stress echocardiography (SECHO) demonstrated an average exercise capacity (VO2max 36 mL/min/kg), which was very abnormal given her athletic status. There was evidence of acute RV dilatation and dysfunction, with reduced LV contractility with exercise, which has been observed in athletes with ARVC.7, 8 Non-sustained ventricular tachycardia with RVOT and LV apical morphologies were seen (Figure 4). The athlete was referred for a subcutaneous implantable cardioverter-defibrillator (ICD), although this was deemed unsuitable, based on low QRS voltages and an unstable QRS morphology across different postures. A transvenous single-chamber ICD was implanted. Genetic testing was negative. Familial evaluation was unremarkable. Exercise prescription for the athlete included avoiding strenuous exercise.9 Aerobic exercise was reduced to low doses with mild intensity and resistance training, whilst on beta blocker therapy. Exercise parameters were set based on heart rate response, exertional symptoms and ventilatory threshold in the CPET. Studies have shown that at least 1/3 of ARVC cases are gene elusive.1, 10 A high proportion of these patients are high-level endurance athletes with no family history of ARVC, suggesting exercise as a contributing factor.10, 11 Exercise can promote stretching of myocytes, which may lead to disruption of the cell–cell junctions, resulting in myocardial damage, inflammation, and fibrosis, which are key processes in determining the severity of ARVC. There is convincing evidence that exercise is a key factor that is associated with a younger age of onset, more severe phenotypes, and a higher frequency of ventricular arrhythmias in gene elusive ARVC patients.10-12 Exercise intensity rather than duration is strongly linked to an adverse prognosis.12 ECHO can provide insight into structural and functional disease progression. This was evident on the 12-month follow-up ECHO, which revealed further RV dilatation (Video S4) and more prominent hypokinesis of the inferolateral LV wall. RV and LV 2D longitudinal strain parameters showed progression in deformation patterns, particular the lateral apical segments which corresponded to areas of myocardial fibrosis on CMR (Figures 5-7).13-15 CPET combined SECHO confirmed a reduction in cardiac reserve and exercise capacity, with a VO2max 26 mL/min/kg (74% of predicted for age-and-gender). Metoprolol was increased to 50 mg, which was well tolerated. An integrated clinical approach using multimodalities is required for athletes with arrhythmias or myocardial dysfunction, as the diagnosis of ARVC can be difficult. Echocardiography plays a valuable role in the assessment of cardiac structure and function. It can assist in risk stratification of ARVC, identifying subclinical disease and prediction of disease progression using 2D strain deformation patterns. The author would like to thank A/Prof Andre La Gerche, Cardiologist at the Baker Heart and Diabetes Institute and St Vincent's Hospital Melbourne for his invaluable input in improving the manuscript. The author declares no conflict of interest. VIDEO S1. Echo PLAX LV. VIDEO S2. CMR horizontal long axis 3ch. VIDEO S3. CMR horizontal long axis 4ch. VIDEO S4. Echo apical 4ch. 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.