Genetic profiling as a marker for risk of sudden cardiac death.
OBJECTIVE
Clinical trials provide evidence that an empirical approach of implantable cardioverter-defibrillator implantation in all heart failure patients (ejection fraction </= 35%) with mild to moderate symptoms effectively reduces mortality rate as compared to the best available medical therapy. At least 50% of patients, however, will succumb to a non-arrhythmic demise and over half of all patients will not require device therapy over long-term follow-up. Thus, the approach of empiric implantable cardioverter-defibrillator implantation is costly in light of the considerable expense of device cost, implantation, and patient follow-up. This review discusses the prospect of genomic medicine as an approach to assess genetic susceptibility to sudden arrhythmic death in at-risk populations.


RESULTS
Through the past 10 years of primary prevention implantable cardioverter-defibrillator trials, the number of patients needed to treat to prevent a sudden death has risen from one in four patients to one in 14. Although numerous clinical tests exist for stratification, they are of low positive predictive value in assessing arrhythmic risk, and have not been prospectively validated as effective strategies in identifying arrhythmia-prone patients. Recent data from genetic studies identifying genes responsible for sudden cardiac death have compiled a list of relatively common genetic variations (polymorphisms). These polymorphisms, encoding for proteins known to be involved in cardiac electrophysiology, may contribute to arrhythmic risk in the milieu of heart failure.


CONCLUSIONS
Current clinical indications for implantable cardioverter-defibrillator implantation in primary prophylaxis of sudden cardiac death necessarily include a significant number of patients who may not benefit. The identification of common genetic variations causing an increased risk of vulnerability to ventricular arrhythmia in heart failure patients may optimize the use of medical resources through rapid identification of sub-populations at highest risk.
Gollob
Michael H
MH
Arrhythmia Research Laboratory and Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. mgollob@ottawaheart.ca
D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000628:therapy; D016757:Death, Sudden, Cardiac / Q000209:etiology* / Q000517:prevention & control; D017147:Defibrillators, Implantable; D004554:Electric Countershock / Q000295:instrumentation; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic; D012307:Risk Factors
D005819:Genetic Markers