Sep. 18, 2006 Fainting during childhood, and whether a teen is going through the male or female changes of puberty, are among the factors that predict whether a genetic defect will suddenly stop the teen's heartbeat, according to a study published today in the Journal of the American Medical Association (JAMA). The study also found that treating teens at the highest risk for fatal arrhythmias with widely used blood pressure drugs reduced their risk by 64 percent.
Cardiac arrhythmias are electrical malfunctions that throw the heart out of rhythm, causing many of the 330,000 sudden cardiac deaths each year in the United States. Most fatal arrhythmias occur in aging patients when scar tissue left by a heart attack interferes with the heart's electrical system. As many as 1,000 of the deaths, however, are caused by a genetic disorder called Long QT Syndrome (LQTS), which occurs mostly in teens with otherwise healthy hearts.
The QT interval is part of the heart's electrical signature as recorded by an electrocardiogram (ECG). It represents the time it takes for the heart's lower chambers to "reset" electrically after each heartbeat. In LQTS patients, the QT reset time is prolonged, which makes the heart more susceptible to fatal arrhythmias. The condition may go unnoticed until sports, strong emotions or even loud noises knock the heart out of rhythm, causing loss of pulse and consciousness (syncope). Sudden death often results if the heart is not restarted with a defibrillator.
"LQTS shocks communities across the nation each year as teens die during sporting events," said Arthur Moss, M.D., professor of Medicine in the Department of Medicine at the University of Rochester Medical Center and an author of the JAMA paper. "It runs in families and can remain undiagnosed until the victim's brother or sister dies as well. New research has made clear the factors that accurately predict which kids are at high risk, factors that can be easily be monitored during routine office visits. We have the power to save more children through vigilance."
In 1979, Moss helped to launch the International Long QT Syndrome (LQTS) Registry, a database of families with the LQTS trait. By following generations of sufferers, gene hunters used the registry to track down more than 300 genetic mutations involving seven genes that cause versions of LQTS. By following the outcomes of patients in the registry over many years, researchers are now drawing accurate conclusions about risk.
In current study, researchers went back and looked at 2,772 subjects from the LQTS Registry who were alive at age 10 and who were monitored by a physician until age 20. This is the largest LQTS study to date, and it is study the first to look at which risk factors are associated only with life-threatening events in teens, both those that ended in sudden cardiac death, and those where cardiac arrest was stopped by emergency treatment. Researchers found three significant predictors of life-threatening events in these patients: timing of prior fainting spells (syncope), the degree to which the QT interval was prolonged as measured by an ECG, and the patient's sex.
Statistical analysis revealed that children with two or more fainting spells in the two years prior to the study period were about 18 times more likely to experience a life-threatening event than children with no history of fainting spells in the previous ten years. Children with a recent history of a single fainting spell in the two years prior to the study period proved to be at nearly 12 time greater risk.
The second clearly identified risk factor was the length of a child's QTc, which is QT corrected for heart rate, a more accurate measure. Results confirm that patients QTc of greater than or equal to 530 milliseconds in length were twice as likely to experience a life-threatening cardiac event as those with a shorter QTc.
Thirdly, the study found that male children were at four times greater risk than females between the ages of 10 and 12, but there was no significant risk difference between males and females 13 to 20 years of age. One theory is that shifting levels of androgens in males and estrogens in females, the hormones associated with the changes of puberty, may change QTc during adolescence to create different risk levels at different stages. Further research is needed to clarify these complex relationships.
Perhaps most surprisingly, the current analysis found no significant association between the genetic type of LQTS a patient had, and their likelihood of facing a life-threatening event, despite the findings of previous publications to the contrary. The author's argue that clinical factors provide a more accurate representation of disease severity than genotype.
Lastly, researchers found that beta-blocker therapy reduced risk by 64 percent among children with syncope in the two years prior to the study period (those at highest risk). The use of beta-blockers for all LQTS patients, especially the LQT1 and LQT2 subtypes, remains prudent, according to the study authors. In addition, implantable cardioverter defibrillators (ICDs), devices designed to correct arrhythmias, should be considered given that landmark studies have found that the devices can drastically reduce sudden death.
"Between beta-blocker therapy, ICDs and preventive monitoring, we should be able to prevent many of these tragedies," said Jenny B. Hobbs, M.D., first author on the JAMA paper and a recent graduate of the University of Rochester School of Medicine and Dentistry. "Perhaps we can alleviate the suffering of these at-risk families and help to solve a major worldwide health threat with the same line of research."
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