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EPIDEMIOLOGY OF CARDIOVASCULAR DISEASE

Epidemiology of inherited arrhythmias

Abstract

The primary electrical disorders are a group of inherited cardiac ventricular arrhythmias that are a major cause of sudden cardiac death in young individuals. Inherited ventricular arrhythmias result from mutations in genes encoding cardiac ion channels or their modulatory subunits. Advances in genetic screening in the past three decades have led to the assembly of large patient cohorts with these disorders. Studies in these patients, as well as in the general population, have striven to define the prevalence of these inherited arrhythmias and the characteristics of patients with different genetic subtypes of the disease. In this Review, we provide a comprehensive update on the epidemiology of inherited ventricular arrhythmias, focusing on natural history, prevalence and patient demographics. In addition, we summarize the various founder populations (groups of individuals with a disease that is caused by a genetic defect inherited from a common ancestor) that have been identified for some of these disorders and which lead to increased prevalence in some geographical regions. To date, although numerous studies have markedly increased our understanding of the epidemiology of these disorders, demographic data, especially from non-Western countries, remain scarce. Furthermore, defining the true prevalence of these disorders remains challenging. International collaboration will undoubtedly accelerate the collection of demographic information and improve the accuracy of prevalence data.

Key points

  • The primary electrical disorders, which are a common cause of sudden cardiac death in young individuals, result from mutations in genes encoding ion channels or their regulatory proteins.

  • Genetic testing has become an integral part of the management of patients with these disorders, although debate is ongoing about the causality of some genes that have been implicated in these disorders by candidate-gene studies.

  • Multiple, large cohorts of patients have facilitated studies on the natural history of these disorders and on proarrhythmic risk factors, although very few proarrhythmic risk factors have been described for short QT syndrome, idiopathic ventricular fibrillation and early repolarization syndrome.

  • The prevalence of these primary electrical disorders is hard to establish, given their rarity; the prevalence of long QT syndrome has been established through prospective studies whereas, for the other diseases, prevalence is based on electrocardiogram features or is merely an estimation.

  • In geographical regions with founder populations, the prevalence of the primary electrical disorders is likely to be much higher than currently assumed.

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Fig. 1: Clinical overview of inherited primary rhythm disorders.
Fig. 2: Country-specific prevalence data for the primary rhythm disorders combined from different studies.

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Acknowledgements

A.A.M.W. and C.R.B acknowledge the support of the Leducq Foundation (17CVD02), the Netherlands Heart Foundation (PREDICT2, CVON2018–30) and the Netherlands Organization for Scientific Research (VICI fellowship, 016.150.610, to C.R.B.).

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J.A.O. wrote the manuscript and researched data for the article. C.R.B and A.A.M.W. discussed the content of the manuscript, and reviewed and edited the manuscript before submission.

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Offerhaus, J.A., Bezzina, C.R. & Wilde, A.A.M. Epidemiology of inherited arrhythmias. Nat Rev Cardiol 17, 205–215 (2020). https://doi.org/10.1038/s41569-019-0266-2

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