Risk of Sudden Death with Early Repolarization
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville Dr. DiMarco is a consultant for Novartis, and does research for Medtronic and Guidant.
Source: Haissaguerre M, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med. 2008;358: 2016-2023.
Haissaguerre and his colleagues from twenty-two world-wide arrhythmia referral centers collected 206 patients with idiopathic ventricular fibrillation. They then examined baseline electrocardiograms for the presence of early repolarization. For this report, they defined early repolarization as an elevation of a QRS-ST junction visible in at least two leads. The J point elevation had to be at least 1 mm above the baseline level, and could be seen as either QRS slurring or as notching in the inferior leads, lateral leads, or both. Case subjects were excluded if they had either a short QT interval (QTc less than 340 m/sec) or a long-QT interval (QTc greater than 440 m/sec) syndrome. Cases with idiopathic ventricular fibrillation were matched to a control group of 412 subjects. These control subjects were healthcare professionals with normal cardiac function and no history of syncope or arrhythmias. The control group was matched for the distribution of known compounding factors that included age, sex, race, and level of physical activity.
The cases and controls were compared with regard to the following clinical data: history of syncope, circumstances of sudden cardiac arrest, family history of unexplained sudden death, level of physical activity, signal-averaged electrocardiography, pharmacologic testing, and invasive electrophysiologic testing. All case subjects received an implantable cardioverter defibrillator that was used to document recurrence of ventricular fibrillation.
The series included 206 subjects with idiopathic fibrillation. The mean age was 36 ± 11 years, and there were 123 men and 83 women in the case group. The control group included 412 subjects matched for age, sex, race, and level of physical activity. Early repolarization was noted in 64 case subjects (31%), as compared to 21 control subjects (5%), (P < 0.01). Case subjects with early repolarization were more likely to be male, to have unexplained syncope or cardiac arrest during sleep, and to have a shorter QTc interval. Early repolarization was noted in the inferior leads in 28, in the lateral leads in 6, and in both inferior and lateral leads in 30 patients. In a subset of 18 patients who had frequent ventricular ectopy and episodes of ventricular fibrillation during monitoring, there was a consistent increase in the amplitude of early repolarization during periods of high arrhythmic activity.
Exercise testing and isoproterenol infusions reduced or eliminated early repolarization. In contrast, beta blockers accentuated repolarization abnormalities and were ineffective when used for chronic therapy. Endocardial mapping was performed in 8 subjects. In 6 of these, all ectopy originated from the inferior left ventricular wall corresponding to the early repolarization pattern on the surface electrocardiogram. Catheter ablation was attempted in 8 patients and was successful in eliminating ectopy in 5. During long-term follow-up, arrhythmia recurrences were more frequent in subjects with early repolarization than in those without repolarization. Three subjects with extreme J point elevations had frequent episodes of recurrent ventricular fibrillation. Quinidine was the only antiarrhythmic drug with significant efficacy in preventing recurrences.
Haissaguerre et al conclude that early repolarization has increased prevalence among survivors of idiopathic ventricular fibrillation. The mechanism responsible for this association is currently unknown.
Commentary
In most surveys, between 5%-15% of patients resuscitated from a sudden cardiac arrest have no known associated structural heart disease and have no known cause for their cardiac arrest. In this paper, Haissaguerre et al from 22 centers collected a series of patients resuscitated from an episode of ventricular fibrillation and found them to have no important structural heart disease and did not meet criteria for the known arrhythmic syndromes such as long QT, Brugada, short QT, or catecholaminergic polymorphic ventricular tachycardia. Among the patients collected from these centers, early repolarization was more common than it was in a case controlled group. However, it must be remembered that idiopathic ventricular fibrillation is a rare clinical occurrence, and early repolarization is fairly common in the general population. Therefore, even among patients with known early repolarization, their risk for ventricular fibrillation must be extremely low. This paper, however, does suggest that there may be a mechanism in some individuals with early repolarization that can increase the risk for sudden death. At this point, the mechanism remains unexplained. The fact that quinidine alone, of the antiarrhythmic drugs tested, seems to be effective suggests that it may be related to an abnormality in Ito. That this is the case here remains unproven.
Early repolarization remains a benign finding in most individuals. This paper, however, highlights that there are rare cases where early repolarization on a standard electrocardiogram may be a marker for arrhythmic risk. The challenges facing us in the future are to identify the mechanism responsible for the increased risk. Once we do that, we should be able to differentiate between benign and malignant forms of early repolarization.
Haissaguerre and his colleagues from twenty-two world-wide arrhythmia referral centers collected 206 patients with idiopathic ventricular fibrillation.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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