Arrhythmogenic right ventricular cardiomyopathy - A still underrecognized clinic entity

Arrhythmogenic right ventricular cardiomyopathy is a new morbid entity that was discovered thanks to the study of sudden death in the young. This heart muscle disease is characterized by myocardial atrophy, mostly of the right ventricle, with massive fibro-fatty infiltration, accounting for ventricular electrical instability at risk of severe arrhythmias and even cardiac arrest. The disease was found to be the major cause of sudden death in young people and athletes in the Veneto Region, Italy. A familial occurrence with autosomal dominant transmission was then discovered, and the prevalence was estimated to be higher than 1 in 5000. The disease is genetically heterogeneous: Linkage analysis, carried out in a large family with recurrence of sudden deaths, led to map the gene to chromosome 14q23-q24. Linkage analysis in a second family allowed mapping of another gene to chromosome 1q42-q43. Clinical diagnosis can be achieved through electrocardiography, echocardiography, angiocardiography, magnetic resonance imaging, and endomyocardial biopsy. Diagnostic criteria have been put forward by a committee of the International Society and Federation of Cardiology. The disease was recently included among the cardiomyopathies in the revised World Health Organization (WHO) classification. Study of the natural history allowed us to distinguish (a) a covert phase in apparently normal subjects who have a risk of abrupt electrical instability and sudden death, (b) an overt arrhythmic phase with palpitations and impending cardiac arrest, (c) congestive heart failure with pump depression, sometimes so severe as to require heart transplantation. Both the etiology and pathogenesis of the disease are unknown. In particular, the mechanisms leading to progressive loss of myocardium and fibro-fatty replacement are still speculative. Apoptosis in the right ventricle occurring not only in infancy, as in the normal heart, but also in childhood and adulthood might account for the progressive disappearance of myocardial tissue.