Revived research into J wave syndromes seeks to unmask potential risks, treatments

Researchers are making progress uncovering links between J wave syndromes and life-threatening MI.

J wave syndromes, once dismissed in clinical practice as insignificant, are now drawing an increasing amount of attention from researchers, electrophysiologists and arrhythmia specialists.

The first description of a J wave came in a 1938 paper that described a hypothermic J wave in an accidentally frozen man. What the researcher saw on the electrocardiogram was a slowly inscribed deflection between the QRS complex and the ST segment. For nearly 50 years, early repolarization syndrome related to J waves was classified as benign. That changed in 1984 when Otto and colleagues presented three cases of ventricular fibrillation manifested during sleep in young southeast Asian male refugees who had structurally normal hearts.

Charles Antzelevitch, PhD, is one of the leaders in the pursuit of better understanding of J wave syndromes. Source: DiNicola Photography

J wave abnormalities were still essentially clinically ignored until a 1996 report elucidated the ionic and cellular bases of the J wave, illuminating its potential role in life-threatening tachyarrhythmias. “In the paper, Charles Antzelevitch, PhD, and I named the Brugada syndrome and believed it was related to J waves,” Gan-Xin Yan, MD, PhD , of the Main Line Health Heart Center in Wynnewood, Pa. and co-author of the report, told Cardiology Today in an interview. “In that time, we did not call them J wave syndromes because we did not know enough about it until recently.”

Eight years later, Yan published a paper in Circulation suggesting that J waves may play an important role in the sudden death of people who experienced acute MI. “This made the significance [of J wave research] much broader because acute MI is very common in the United States,” he said. “Also during that time, I and my collaborators in Xi-An Jiaotong University published a review article in China proposing the use of the J wave syndrome.”

According to Yan, one of the most significant findings took place when researchers publishing results of a study in 2008 demonstrated a definitive association between J waves with an early repolarization pattern and ventricular fibrillation. Experimental data from Antzelevitch’s group, showing that in some cases this pattern in the ECG may be associated with life-threatening ventricular arrhythmias, had also suggested a possible association as far back as 2000.

“In the meantime, Dr. Antzelevitch and colleagues also published several cases of people dying in South Korea with the J wave,” Yan added. “In the same issue of the New England Journal of Medicine, Haissaguerre and colleagues presented a large series of patients with early repolarization patterns who developed ventricular tachycardias or ventricular arrhythmias. More people began paying attention to it.”

Affected population and potential treatments

One of the present gray areas in the field of J wave syndrome study is the total affected population. Because the condition is not yet well-defined and can potentially indicate a number of related conditions of varying severity, information regarding the total number of patients affected by J wave syndromes remains unclear.

“We currently don’t know the incidence of these syndromes,” said Douglas Zipes, MD, editor of the arrhythmia section of Cardiology Today, in an interview. “For years, we called this early repolarization and wrote it off as insignificant. There are many people with a benign form of J wave elevation, so we need to be able to understand who has a potentially malignant form and is at risk for ventricular fibrillation.”

However, certain electrocardiographic manifestations of early repolarization are associated with a higher level of risk, Antzelevitch, executive director and director of research at the Masonic Medical Research Laboratory in Utica, N.Y, told Cardiology Today.

“Based on available data, the higher the J-point elevation and the ST-segment elevation, the higher the risk,” he said. “When we see a distinct J wave rather than just a J-point elevation, different studies have associated this with a higher level of risk as well. The same is true for J waves presenting with relatively short QT intervals.”

In the June 2010 issue of Heart Rhythm, Antzelevitch and Yan published a contemporary review on research about J wave syndromes emphasizing the present need for classifying early repolarization syndrome into three types. A type 1 syndrome displays an early repolarization pattern predominantly in the lateral precordial leads, is prevalent among healthy male athletes and is rarely seen in ventricular fibrillation survivors. Type 2 syndromes show an early repolarization pattern predominantly in the inferior or inferolateral leads and are associated with a higher risk levels. A type 3 syndrome displays an early repolarization pattern globally in the inferior, lateral and right precordial leads, is associated with the highest level of risk for development of malignant arrhythmias and is often associated with ventricular fibrillation storms.

“The fourth type of early repolarization syndrome already has a name that we and others named in 1996; it’s called Brugada syndrome,” Antzelevitch added.

Based on current available data, effective treatments for the Brugada syndrome may also be useful in the treatment of early repolarization syndrome. One such pharmacological treatment being studied, according to Antzelevitch, is quinidine.

“Quinidine was on its way to being phased out, but now it is proving useful in all the J wave syndromes. Its main goal is to diminish the transient outward current, which we believe is at the heart of all of these syndromes,” he said. “In the future, we are looking forward to the development of transient outward current blockers that are more ion channel–specific and cardio-selective.”

J wave syndromes and sudden death

According to Yan, much of the upcoming research regarding J waves will be focused on MI and uncovering the role of the J wave in sudden death related to ACS. “Studies are indicating that acute MI showing J waves in the inferior lead has a high incidence of ventricular fibrillation,” he said. “This has much clinical relevance because many people died before they were able to get to a hospital.”

For Antzelevitch, the purpose of putting the review together was to get practitioners to start thinking about J wave syndromes in a more defined manner, thereby creating a catalyst for future research. Specifically, he is looking to understand more about how these various manifestations are associated with risk so physicians can better diagnose a syndrome and, in the future, learn to unmask the syndromes.

“We hope to be able to better define those individuals who should be treated with ICD, those who might be better treated pharmacologically or those who need to be closely monitored,” he said. “We have a lot to learn and we are slowly making progress in all of these areas.” – by Brian Ellis

For more information:

• Antzelevitch C. Heart Rhythm. 2010;7:549–558.
• Haissaguerre M. N Engl J Med. 2008;358:2016–2023.
• Otto C. Ann Intern Med. 1984;101:45–47.
• Tomaszewski W. Arch Mal Coeur Vaiss. 1938;31:525–528.
• Yan G. Circulation. 1996;93:372–379.