Gauging the Risk of Arrhythmic Death by Common Genetic Variants

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The holy grail of personalized medicine in clinical cardiac electrophysiology is to establish a reproducible genetic imprint or the associated intermediate phenotype (“endophenotype”) that would with high accuracy predict arrhythmic death in an individual. Although we are far from it, the study in this issue of Circulation: Cardiovascular Genetics by Noseworthy et al1 is another step in the right direction. It is well established that an abnormal QT interval (ie, too long or too short) is a predictor of arrhythmogenic risk in patients with the rare syndromes caused by ion channel mutations. However, the role of QT in gauging the risk of death in the general population is recent,2 complex,3,4 and laced with fundamental questions that remain unanswered. Noseworthy et al tackle this problem straight on and investigate the value of common genetic variants for predicting QT duration and sudden cardiac death (SCD) risk. Article see p 305 The QT interval is an inexpensive, easily measurable, generally reproducible endophenotype, which makes it attractive for predicting risk of SCD as shown by present and prior studies.2 However, the QT is a “read-out” of complex interactions between multiple genes encoding both ion channel1 and non–ion channel proteins5 and multiple environmental factors (drugs, electrolytes, hormones, body temperature, etc). As a result, the QT duration can fluctuate widely …