JACC Focus Seminar: Precision Medicine: From Genes to Phenotypes in Cardiovascular Health and Disease
JACC Focus Seminar
Contemporary and Future Approaches to Precision Medicine in Inherited Cardiomyopathies: JACC Focus Seminar 3/5

https://doi.org/10.1016/j.jacc.2020.12.072Get rights and content
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Highlights

  • Despite recognition of genetic causes of inherited cardiomyopathy, translation to patient management is limited.

  • Factors other than single gene mutations often determine the clinical manifestations of inherited cardiomyopathies, and combinations of genetic variation, comorbidities, and lifestyle influence these phenotypes.

  • Addressing the genetic underpinnings of inherited cardiomyopathies could lead to interventions tailored to specific genetic variants or downstream mechanisms.

  • Precision medicine promises to leverage data on the individual patient to implement personalized approaches to disease management.

Abstract

Inherited cardiomyopathies are commonly occurring myocardial disorders that are associated with substantial morbidity and mortality. Clinical management strategies have focused on treatment of heart failure and arrhythmic complications in symptomatic patients according to standardized guidelines. Clinicians are now being urged to implement precision medicine, but what does this involve? Advances in understanding of the genetic underpinnings of inherited cardiomyopathies have brought new possibilities for interventions that are tailored to genes, specific variants, or downstream mechanisms. However, the phenotypic variability that can occur with any given pathogenic variant suggests that factors other than single driver gene mutations are often involved. This is propelling a new imperative to elucidate the nuanced ways in which individual combinations of genetic variation, comorbidities, and lifestyle may influence cardiomyopathy phenotypes. Here, Part 3 of a 5-part precision medicine Focus Seminar series reviews the current status and future opportunities for precision medicine in the inherited cardiomyopathies.

Key Words

arrhythmogenic right ventricular cardiomyopathy
dilated cardiomyopathy
hypertrophic cardiomyopathy
precision medicine

Abbreviations and Acronyms

ACM
arrhythmogenic cardiomyopathy
ARVC
arrhythmogenic right ventricular cardiomyopathy
CMR
cardiac magnetic resonance imaging
DCM
dilated cardiomyopathy
GWAS
genome-wide association studies
HCM
hypertrophic cardiomyopathy
ICD
implantable cardioverter-defibrillator
PRS
polygenic risk score
TTNtv
truncating TTN variant
VUS
variant of uncertain significance

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Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.

David Lanfear, MD, served as Guest Associate Editor for this paper. Javed Butler, MD, MPH, MBA, served as Guest Editor-in-Chief for this paper.

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