Sudden Death Associated with Short QT Syndrome linked to Mutations in HERG
December 16, 2003
A study linking a new clinical entity responsible for sudden cardiac death, termed the Short QT Syndrome, to an ion channel defect in the heart was published in Circulation today. Senior authors Ramon Brugada, M.D. and Charles Antzelevitch, Ph.D. indicate that these findings have opened a new door in our understanding of causes of abnormal heart rhythms, known as cardiac arrhythmias, and their role in the sudden death of infants, children and young adults.
The Long QT syndrome has long been associated with a risk for life-threatening cardiac arrhythmias. However, little is known about prognostic implications of the reverse; the short QT interval, a disease that had been highlighted only in the last three years. These new findings describe the genetic basis for the Short QT syndrome, which can causes sudden death in otherwise healthy individuals. The study is the result of a collaboration among investigators in Europe and the United States. The team at the Masonic Medical Research Laboratory (MMRL) in Utica, NY discovered the mutation responsible for the disease in a gene that encodes for a potassium channel in the heart. Hyperactivity of this ion channel was found to alter electrical activity within the cells of the heart causing it to beat at very fast rates that could lead to sudden death.
The electrocardiogram of affected patients displays a very short QT interval and tall symmetrical T waves. Clinicians need to be aware of this deadly ECG pattern as it portends a high risk of sudden death in otherwise healthy subjects.
The identification of the genetic basis for the disease permits investigators at the MMRL to pinpoint drugs that may be candidates for the specific treatment of this syndrome. One of the great benefits of genetic identification of disease is that it provides us an understanding of the disease at its root cause, thus providing a better means to diagnose, treat and someday cure the congenital dysfunction. Working with their clinical colleagues in Europe, MMRL investigators are well on their way to identifying appropriate therapies for patients who inherit the disease from their parents. Until now, the implantation of an automatic cardioverter defibrillator was the only option in preventing sudden premature death.
Sudden cardiac death in individuals with structurally normal hearts accounts for approximately 20% of all forms of sudden cardiac death. The past decade has witnessed a revolution in the understanding of inherited syndromes. Genetic screening will one day soon became a routine aid to the physician in the identification of specific disease syndromes. Previously unknown cardiac death syndromes are gradually coming into focus as forms of inherited ion channel diseases as a result of the great advances in genetic research.
The internationally renowned Masonic Medical Research Laboratory in Utica, NY is a leading center of study for cardiac arrhythmias and sudden death. It has rapidly become a haven for clinical investigators to obtain training in basic science and then translate those basic findings into clinically applicable treatments. The facility recently erected a new wing dedicated to molecular genetics and is studying DNA samples from patients worldwide afflicted with many forms of inherited electrical diseases of the heart.
