Commented article: Highly malignant disease in childhood-onset arrhythmogenic right ventricular cardiomyopathy (ARVC)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder of the cardiac muscle, characterised by ventricular arrhythmias, dilation and dysfunction of the right ventricle, and, histologically, by fibrofatty replacement of the myocardium (1).  

In the past, there was a common misconception regarding ARVC being primarily a young adult disease. This belief stemmed from family cohort studies, which indicated that ARVC seldom appears during childhood, and instances of sudden death among pediatric relatives were infrequently reported (2,3). 

Smedsrud et al.'s study, "Highly malignant disease in childhood-onset arrhythmogenic right ventricular cardiomyopathy," focuses on the incidence, severity of cardiac events and the penetrance of ARVC in paediatric patients and their relatives, breaking the previous miss concept. The study monitored paediatric patients and genotype-positive relatives under 18 for severe cardiac events, such as cardiac death, heart transplantation, or malignant arrhythmias, defining ARVC penetrance according to the 2010 International Modified Task Force criteria. Childhood-onset ARVC was identified when criteria were met by age 12 (4). Indeed, in this study, nearly 90% of patients were harbouring a PKP2 variant, and all patients presenting with RV disease (with or without LV involvement), making them represent the classical ARVC and fulfilling the criteria of the new European Society of Cardiology (ESC) guidelines 2023 guidelines on cardiomyopathies (5). 

This cohort included 62 pediatric patients from a single national referral centre. Of these, 20 (32%) fulfilled the definite ARVC diagnosis, with 8 (40%) having childhood-onset disease. The study found that 23% of the cohort experienced severe cardiac events, half of them occurring in patients aged 12 or younger. Among those with childhood-onset ARVC, 40% showed a highly malignant phenotype, which included severe ventricular arrhythmias and biventricular cardiac involvement leading to heart failure. Significantly, five out of the eight children with childhood-onset ARVC required heart transplants, underlining the disease's severity. Additionally, the study observed an 18% penetrance rate of ARVC in paediatric relatives by the end of the follow-up, suggesting the necessity for early screening and clinical evaluation of relatives starting from a young age (4,6).  

Traditionally, ARVC, except for rare recessive autosomal diseases like Naxos and Carvajal disease, was considered a disease of young adults, with cardiac screening typically not initiated before the age of 10-12 years in first-degree relatives. However, Smedsrud et al.'s study, along with other recent reports, have identified pediatric-onset ARVC associated with cardiac death and cardiac transplantation. In addition, myocarditis, a relatively common presentation in pediatric age, has been found to be an initial manifestation of ARVC. 

The study, while limited by its small number of patients, retrospective nature, one national center focus, lack of age-specific normative ECG data, potential problems with the 2010 Task Force criteria, and absence of full cardiovascular magnetic resonance data, aligns with other data in the literature. It highlights the importance of early identification of ARVC, which could lead to improved outcomes and new therapeutic avenues (5-10).   

The study concludes by emphasizing the need for increased awareness of the aggressive nature of childhood-onset ARVC. It advocates for a reevaluation of current screening guidelines to begin at a younger age, critical for better management and potentially life-saving interventions in pediatric patients at risk of ARVC anticipating what the new ESC guidelines are mentioning (5-10). 

Indeed, the recent ESC Guidelines are breaking the habit of seeing cardiomyopathies in children as separate from those in adolescents and adults, each having distinct causes, progression, and treatment approaches.  Pediatric-onset cardiomyopathies typically represent two extremes: either severe, early-onset diseases with rapid progression and poor prognosis, similar to the most serious adult cases, or early manifestations of adult cardiomyopathy phenotypes, increasingly identified through family screenings (5). Therefore, it is advised to consider cardiomyopathies across all age groups as a continuum, with guidelines applicable to pediatric and adult populations. In the particular case of ARVC phenotype, infants are rarely affected, and are most commonly autosomal recessive forms associated with cutaneous manifestations (e.g. Naxos disease and Carvajal syndrome), although this may reflect a lack of systematic clinical screening for these conditions in early childhood (3).