Researchers have discovered 10 gene variations that may be the first known indicators of sudden cardiac death, a cardiovascular disorder with no clinical warnings that claims more than 250,000 Americans every year.
Collaborating with an international research team from Sardinia and Munich, scientists at Baltimore's Johns Hopkins University School of Medicine looked at the electrocardiograms (ECGs) of 15,842 patients.
Sudden cardiac death is caused by a malfunctioning heart and is associated with the QT interval - the time between heartbeats when the heart contracts and resets itself for the next beat. Abnormally prolonged or shortened durations increase the risk for irregular heartbeats can predispose a person to sudden cardiac death.
"Essentially you get an abnormal rhythm. The heart goes too fast and that leads to an electrical instability and that's what kills them," said Dan Arking, an assistant professor at the school's Institute of Genetic Medicine who took part in the study, published yesterday in the journal Nature Genetics.
"They don't have any clinical symptoms that would warrant intervention. About two-thirds of the time you really have no idea," said Dr. Arking, adding that people typically die within an hour of symptoms, which can include light-headedness, chest pain and stomach upset.
According to the Canadian SADS Foundation, which assists those who are genetically predisposed to sudden arrhythmia death syndrome, the number of Canadian cases is unknown, but the disorder can affect anyone, including children and young adults.
The international researchers used DNA samples to analyze the participants' genomes. After screening 2.5 million genetic markers for variations that change the QT interval, they found alterations at 10 locations. If a patient exhibits several of the variations together, they may be at risk for the condition, the team said.
"We found [variations on] 10 genes, four of which we had no clue were involved in cardiac biology at all," Dr. Arking said.
Some of the variations were near genes that had been previously associated with the heart's electrical activity. Others were near genes that may impact heart-cell growth and blood-pressure regulation.
Backing up the researchers' findings is a separate study led by Christopher Newton-Cheh of the Massachusetts General Hospital Center for Human Genetic Research. Also released yesterday, this study found similar variations in more than 13,000 individuals.
Although Dr. Arking says it is too early to use the data in clinical practice, eventually, doctors may want to "keep a closer eye on" patients who present "enough of the bad variants." That might include more routine ECG screenings or treating people for the irregular heart palpitations that trigger severe cardiac dysfunction.
He added that currently, the only proven intervention is the insertion of a defibrillator into a patient's body, an expensive surgery often performed after a heart attack. The new findings might help narrow down candidates for the procedure.
"They put these devices in lots of people - it costs $40-billion (U.S.) a year - but only about 10 per cent ever use their device," Dr. Arking says.
"If I could knock that down by using these genetic markers to figure out whose at higher risk, that's fewer people having surgery and the health-care cost goes down dramatically."
