TY - JOUR
T1 - Arrhythmogenic right ventricular cardiomyopathy
T2 - Progress toward personalized management
AU - James, Cynthia A.
AU - Calkins, Hugh
N1 - Funding Information:
Dr. Calkins is a consultant for Medtronic Inc. and St. Jude Medical/Abbott. Dr. Calkins receives research support from Foundation Leducq (16 CVD 02) and from Boston Scientific Corp. for a study of subcutaneous ICDs in ARVC. Dr. James receives salary support from this grant. Dr. James has received funding for an invited lecture from Abbott.
Funding Information:
The Johns Hopkins ARVD/C Program is supported by the Dr. Francis P. Chiaramonte Private Foundation, the Leyla Erkan Family Fund for ARVD Research, the Dr. Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins, the Bogle Foundation, the Healing Hearts Foundation, the Campanella family, the Patrick J. Harrison Family, the Peter French Memorial Foundation, and the Wilmerding Endowments. We are grateful to the ARVD/C patients and families who have made this work possible.
Funding Information:
The largest ARVC cohort diagnosed according to the 2010 criteria included 1,001 ARVC index cases and at-risk family members identified from the Johns Hopkins and Dutch ARVC Registries (5). Other key data have been derived from cohorts from the Swiss and Nordic Registries, national centers with decades of ARVC expertise, and the North American ARVC Registry supported by the National Institutes of Health (NIH). Taken together, studies from these cohorts have established that ARVC patients typically present between adolescence and mid-adulthood (average age 35.1 ± 14.9). Reports of prepubertal children with ARVC have been rare (14). Among 75 patients with pediatric-onset ARVC in a combined US-Dutch cohort, there was no patient diagnosed prior to 11 years of age (15). Studies have established that the risk of ventricular arrhythmias rises rapidly in adolescence (16), and adolescents are most likely to present with sudden cardiac death (15). At the other end of the age spectrum, one-fifth of ARVC patients in the Johns Hopkins/Dutch cohort presented at age 50 or older, and 3% were diagnosed after age 65 (17). These patients were more likely to present with sustained ventricular tachycardia, but their clinical courses were otherwise indistinguishable from those of younger patients.
Publisher Copyright:
© 2019 by Annual Reviews.
PY - 2019/1/27
Y1 - 2019/1/27
N2 - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease characterized by fibrofatty replacement of the ventricular myocardium, a high risk of ventricular arrhythmias, and progressive ventricular dysfunction. The clinical course is highly variable, and optimal approaches to management remain undefined. ARVC is associated with pathogenic variants in genes encoding the cardiac desmosome. Genetic testing facilitates identification of at-risk family members, but penetrance of ARVC in pathogenic variant carriers is difficult to predict. Participation in endurance exercise is a known key risk factor. However, there remains significant uncertainty about which family member will develop disease and how best to approach longitudinal screening. Our clinically focused review describes how new insights gained from natural history studies, improved understanding of pathogenic mechanisms, and appreciation of genetic and environmental modifiers have set the stage for developing personalized approaches to managing both ARVC patients and their at-risk family members.
AB - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease characterized by fibrofatty replacement of the ventricular myocardium, a high risk of ventricular arrhythmias, and progressive ventricular dysfunction. The clinical course is highly variable, and optimal approaches to management remain undefined. ARVC is associated with pathogenic variants in genes encoding the cardiac desmosome. Genetic testing facilitates identification of at-risk family members, but penetrance of ARVC in pathogenic variant carriers is difficult to predict. Participation in endurance exercise is a known key risk factor. However, there remains significant uncertainty about which family member will develop disease and how best to approach longitudinal screening. Our clinically focused review describes how new insights gained from natural history studies, improved understanding of pathogenic mechanisms, and appreciation of genetic and environmental modifiers have set the stage for developing personalized approaches to managing both ARVC patients and their at-risk family members.
KW - arrhythmogenic right ventricular cardiomyopathy
KW - desmosome
KW - exercise
KW - genetic testing
KW - implantable cardioverter defibrillator
KW - ventricular tachycardia
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U2 - 10.1146/annurev-med-041217-010932
DO - 10.1146/annurev-med-041217-010932
M3 - Review article
C2 - 30355260
AN - SCOPUS:85060639906
VL - 70
SP - 1
EP - 18
JO - Annual Review of Medicine
JF - Annual Review of Medicine
SN - 0066-4219
ER -