Arrhythmogenic cardiomyopathy: pathogenesis, pro-arrhythmic remodelling, and novel approaches for risk stratification and therapy

Stephanie M van der Voorn; Anneline S J M Te Riele; Cristina Basso; Hugh Calkins; Carol Ann Remme; Toon A B van Veen

doi:10.1093/cvr/cvaa084

Arrhythmogenic cardiomyopathy: pathogenesis, pro-arrhythmic remodelling, and novel approaches for risk stratification and therapy

Cardiovasc Res. 2020 Jul 15;116(9):1571-1584. doi: 10.1093/cvr/cvaa084.

Authors

Stephanie M van der Voorn¹, Anneline S J M Te Riele², Cristina Basso³, Hugh Calkins⁴, Carol Ann Remme⁵, Toon A B van Veen¹

Affiliations

¹ Division of Heart and Lungs, Department of Medical Physiology, University Medical Center Utrecht, PO Box 85060, Utrecht 3508 AB, The Netherlands.
² Division of Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, PO Box 85060, Utrecht 3508 AB, The Netherlands.
³ Cardiovascular Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua Medical School, Via A. Gabelli, 61 35121 Padova, Italy.
⁴ Johns Hopkins Hospital, Sheikh Zayed Tower 7125R, Baltimore, MD 21287, USA.
⁵ Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam 1105AZ, The Netherlands.

Abstract

Arrhythmogenic cardiomyopathy (ACM) is a life-threatening cardiac disease caused by mutations in genes predominantly encoding for desmosomal proteins that lead to alterations in the molecular composition of the intercalated disc. ACM is characterized by progressive replacement of cardiomyocytes by fibrofatty tissue, ventricular dilatation, cardiac dysfunction, and heart failure but mostly dominated by the occurrence of life-threatening arrhythmias and sudden cardiac death (SCD). As SCD appears mostly in apparently healthy young individuals, there is a demand for better risk stratification of suspected ACM mutation carriers. Moreover, disease severity, progression, and outcome are highly variable in patients with ACM. In this review, we discuss the aetiology of ACM with a focus on pro-arrhythmic disease mechanisms in the early concealed phase of the disease. We summarize potential new biomarkers which might be useful for risk stratification and prediction of disease course. Finally, we explore novel therapeutic strategies to prevent arrhythmias and SCD in the early stages of ACM.

Keywords: Arrhythmia; Cardiomyopathy.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Action Potentials*
Animals
Arrhythmogenic Right Ventricular Dysplasia / genetics
Arrhythmogenic Right Ventricular Dysplasia / mortality
Arrhythmogenic Right Ventricular Dysplasia / physiopathology*
Arrhythmogenic Right Ventricular Dysplasia / therapy
Death, Sudden, Cardiac / etiology
Death, Sudden, Cardiac / prevention & control
Genetic Predisposition to Disease
Heart Rate*
Humans
Mutation
Phenotype
Prevalence
Prognosis
Risk Assessment
Risk Factors
Ventricular Remodeling*