JACC Focus Seminar: Precision Medicine: From Genes to Phenotypes in Cardiovascular Health and Disease
JACC Focus Seminar
Precision Medicine in Catecholaminergic Polymorphic Ventricular Tachycardia: JACC Focus Seminar 5/5

https://doi.org/10.1016/j.jacc.2020.12.073Get rights and content
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Highlights

  • Two decades after the discovery of a gene mutation associated with CPVT, both typical and atypical forms of this disease have been identified.

  • Recognition of these forms of CPVT can promote more precise approaches to management.

  • Gene transfer, allele silencing, gene editing, and modulation of signaling pathways offer promising approaches to management of patients with CPVT.

Abstract

In this final of a 5-part Focus Seminar series on precision medicine, we focus on catecholaminergic polymorphic ventricular tachycardia (CPVT). This focus on CPVT allows us to take a “deep dive” and explore the full extent of the precision medicine opportunities for a single cardiovascular condition at a level that was not possible in the preceding articles. As a new paradigm presented in this article, it has become clear that CPVT can occur as either a typical or atypical form. Although there is a degree of overlap between the typical and atypical forms, it is notable that they arise due to different underlying genetic changes, likely exhibiting differing mechanisms of action, and presenting with different phenotypic features. The recognition of these differing forms of CPVT and their different etiologies and mechanisms is an important step toward implementing rapidly emerging precision medicine approaches that will tailor novel therapies to specific gene defects.

Key Words

cardiovascular
catecholaminergic polymorphic ventricular tachycardia precision medicine
genetics

Abbreviations and Acronyms

AAV
adeno-associated virus
BB
beta-blockers
bVT
bidirectional ventricular tachycardia
CALM
calmodulin
CaMKII
Ca2+/calmodulin-dependent protein kinase II
Cas9
CRISPR-associated protein 9
CASQ2
calsequestrin 2
CPVT
catecholaminergic polymorphic ventricular tachycardia
CRISPR
clustered regularly interspaced short palindromic repeat
DAD
delayed afterdepolarization
ECG
electrocardiogram
EST
exercise stress test
hiPSC-CM
human induced pluripotent stem cell-derived cardiomyocytes
HRC
histidine-rich Ca2+ binding protein
ICD
implantable cardioverter-defibrillator
jSR
junctional sarcoplasmic reticulum
PVC
premature ventricular contraction
pVT
polymorphic ventricular tachycardia
RYR2
ryanodine receptor 2
SR
sarcoplasmic reticulum
TA
triggered activity
TECRL
trans-2,3-enoyl-CoA reductase-like
TRDN
triadin
VA
ventricular arrhythmias
VF
ventricular fibrillation
VT
ventricular tachycardia
WT
wild-type

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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.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.