Bordeaux-Pessac, France - New data published this week suggest that an early repolarization pattern is not as benign as previously thought, with evidence showing support for the arrhythmogenic potential of the commonly observed electrocardiographic pattern [1]. In a new study, investigators showed a "higher-than-expected" prevalence of early repolarization in patients with idiopathic ventricular fibrillation that caused syncope and sudden cardiac arrest.

"Sudden cardiac arrest from arrhythmia may occur in persons who do not have structural heart disease or evident electrocardiographic abnormalities during sinus rhythm," write lead investigator Dr Michel Haïssaguerre (Université Bordeaux, Bordeaux-Pessac, France) and colleagues in the May 8, 2008 issue of the New England Journal of Medicine. "In our study, such case subjects had a significantly higher prevalence of early repolarization than control subjects, in whom the prevalence was similar to that among healthy subjects in studies reported previously."

Speaking with heartwire, Haïssaguerre noted that early repolarization is not an uncommon electrocardiographic finding, occurring in 2% to 5% of the population, often in men, young adults, blacks, and athletes. The electrocardiographic phenomenon is characterized by a notch that produces a positive hump, known as a J wave, at the end of the QRS complex and beginning of the ST segment. Although thought to be benign, previous experiments have suggested that some forms of early repolarization may be potentially arrhythmogenic.

"It was considered a variant," said Haïssaguerre, "a funny electrocardiographic finding. But there was a sort of discrepancy between this seemingly clinically benign aspect of early repolarization, while experimentally there were papers saying it could create a malignant condition."

With this discrepancy in mind, investigators wanted to determine the prevalence of early repolarization and assess its relationship with observed arrhythmias and the subsequent outcomes. Haïssaguerre and colleagues from 22 hospital centers reviewed data from 206 patients, mean age 36 years, who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation. They defined early repolarization as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, which manifested as QRS "slurring" or "notching." Another 412 subjects without heart disease, matched for age, sex, race, and level of physical activity, served as the control group.

Early repolarization was significantly more prevalent in the case subjects, occurring in 31% of those resuscitated after cardiac arrest and 5% of controls, and was present in the inferior lead in 28 subjects. Haïssaguerre explained that these patients were all treated with an implantable cardioverter defibrillator (ICD), and 18 experienced a second arrhythmic episode aborted by ICD discharge. Upon interrogation of the device, investigators report that early repolarization increased in amplitude before ventricular fibrillation and then receded after termination.

"It's not only more frequent in patients with sudden cardiac death, but it seems to dynamically change before ventricular fibrillation," said Haïssaguerre.

Electrophysiologic mapping in eight subjects showed that the signal initiating the ventricular arrhythmia originated in cardiac regions of early repolarization. Regarding clinical outcomes, during a mean follow-up of 61 months after the initial event, arrhythmic recurrences were more frequent in subjects with early repolarization than in those without, with subjects more than twice as likely as controls to experience another arrhythmia.

"Now the big problem is how to distinguish between early repolarization in the general population and those who would be at risk for sudden cardiac death," said Haïssaguerre, cautiously stating that only a small subset of patients will be at risk. At the present time, there is no way to distinguish between benign early repolarization and early repolarization in at-risk subjects. In patients with syncope or a family history of unexplained sudden death, the electrocardiographic pattern should not be dismissed as benign. It is these patients who could receive an ICD or medication to prevent sudden death, he said.

In an editorial accompanying the published studies, Dr Hein Wellens (Cardiovascular Research Institute, Maastricht, the Netherlands) writes that it would be ideal to have a simple test for asymptomatic patients to identify those in whom an augmentation of the J-wave height results in ventricular ectopic activity [3].

Until there are better data, writes Wellens, clinicians are "left with the observation that in some persons with electrocardiographic changes suggesting early repolarization in the inferolateral area, life-threatening arrhythmia may occur." Since many patients who fit such criteria who do not appear to have excess risk, "we need further data to unravel how to identify patients who are at high risk for a catastrophic arrhythmia," he comments.

In his editorial, Wellens states that with a patient with ventricular tachyarrhythmias or syncope, clinicians must rule out all ischemic and nonischemic causes, including long-QT syndrome, short-QT syndrome, the Brugada syndrome, and arrhythmogenic right ventricular dysplasia.

"Once these conditions have been excluded, it is clear that slurring or notching at the junction between the QRS and the ST segment in inferolateral leads (especially in men) can be an important diagnostic sign to detect high-risk persons with a history of unexplained syncope or a familial incidence of sudden death at a young age."

Haïssaguerre told heartwire that sudden death accounts for 350 000 deaths annually in the US, with similar numbers in Europe, and that as many as 10% of these deaths are unexplained. With these new data, he believes that 30% of these unexplained sudden deaths will be explained by early repolarization. "It is a new breakthrough, and we hope something that can be used to identify people at risk," said Haïssaguerre.