State-of-the-art paper | July 2013
Impact of Genetics on the Clinical Management of Channelopathies
J Am Coll Cardiol. 2013;62(3):169-180. doi:10.1016/j.jacc.2013.04.044
Abstract | Long QT Syndrome | Updated Genetics | Genetics and Arrhythmia Triggers | Genetics and Risk Stratification | Genetics, Response to Therapy, and Clinical Management | Catecholaminergic Polymorphic Ventricular Tachycardia | Brugada Syndrome | Issues With Genetic Testing in Channelopathies | Conclusions | References
There are few areas in cardiology in which the impact of genetics and genetic testing on clinical management has been as great as in cardiac channelopathies, arrhythmic disorders of genetic origin related to the ionic control of the cardiac action potential. Among the growing number of diseases identified as channelopathies, 3 are sufficiently prevalent to represent significant clinical and societal problems and to warrant adequate understanding by practicing cardiologists: long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and Brugada syndrome. This review will focus selectively on the impact of genetic discoveries on clinical management of these 3 diseases. For each disorder, we will discuss to what extent genetic knowledge and clinical genetic test results modify the way cardiologists should approach and manage affected patients. We will also address the optimal use of genetic testing, including its potential limitations and the potential medico-legal implications when such testing is not performed. We will highlight how important it is to understand the ways that genotype can affect clinical manifestations, risk stratification, and responses to the therapy. We will also illustrate the close bridge between molecular biology and clinical medicine, and will emphasize that consideration of the genetic basis for these heritable arrhythmia syndromes and the proper use and interpretation of clinical genetic testing should remain the standard of care.