5 Diagnostic yield of arrhythmogenic right ventricular cardiomyopathy (ARVC) in paediatric relatives of probands with sads versus non-diagnostic post-mortems

Background and Purpose Following a Sudden Cardiac Death (SCD) where no cause can be found, evaluation at a specialist centre is indicated for first-degree relatives in order to screen for Inherited Cardiac Conditions (ICCs). Cardiomyopathies, including arrhythmogenic right ventricular cardiomyopathy (ARVC), may represent a proportion of inconclusive SCD, but this has not been previously studied in a paediatric population. This study aimed to describe the prevalence of ARVC 2010 Task Force Criteria (TFC) abnormalities in paediatric first-degree relatives of individuals who have died suddenly with a sudden arrhythmic death syndrome (SADS) or non-diagnostic post-mortem (PM). Methods Retrospective clinical records from a single paediatric tertiary referral centre were reviewed from 2005 to 2023. 361 individuals attending ICC clinics were identified as first-degree relatives of probands who had either SADS or a non-diagnostic PM. Standard cardiovascular pathology criteria were used to classify non-diagnostic findings. Cardiac investigations, including 12-lead and ambulatory electrocardiogram (ECG), echocardiogram and cardiac magnetic resonance (CMR) imaging were reviewed in relation to the ARVC 2010 TFC at baseline and during follow-up. Results 37 individuals (10.2%) from 34 families (14.3%) fulfilled ≥1 criteria from the ARVC TFC. Age at first clinical review was 11.7±4.5 years and median follow-up time was 4 years (IQR 2.5 – 6.5). Probands were mostly a parent (n=30, 90%) and male (n=22, 66.6%), with a mean age of 33.85 years at time of death. The most common findings from non-diagnostic post-mortems (n=19, 57%) were left ventricular hypertrophy macroscopically (n=6, 31.57%) and left ventricular fibrosis microscopically (n=7, 36.8%). The SADS probands (n=15, 44%) were significantly more likely to have had a cardiac specialist post-mortem, 78.5% compared to 36.8%, [p=0.017]. The most commonly fulfilled TFC was a positive Signal Averaged ECG (SAECG) in at least one vector (n=22, 57.9%). Seven patients (18.9%) had documented ventricular tachycardia (VT) during follow-up. Six patients (16.2%) fulfilled criteria for a possible (n=4); borderline (n=2); or definite (n=1) diagnosis of ARVC. Patients had higher numbers of electrographic abnormalities compared to structural changes in-keeping with the literature on ARVC presentation in children. Conclusions This study demonstrates that paediatric first-degree relatives of probands with unascertained SCD fulfil diagnostic TFC for ARVC and, in addition, 10% fulfilled at least one criterion. This suggests that this patient group should be comprehensively screened for both inherited arrhythmia syndromes and cardiomyopathies. Importantly, VT was found in a proportion of patients during follow-up. The high number of patients demonstrating a positive SAECG in ≥1 vector potentially indicates low specificity of this investigation. This study also highlights the importance of a specialist cardiac post-mortem and histology in cases of SCD to guide family screening. Conflict of Interest None known.