Washington: Scientists for the first time has unravelled how genetic defects can help predict the risk of sudden cardiac death in individuals.
This knowledge could guide treatment and potentially lessen the occurrence of sudden cardiac death in patients with Long QT syndrome, a rare, inherited heart rhythm disorder. It could also provide insight into the assessment and treatment of the millions of people who experience cardiac arrhythmias – irregular heart rhythms that cause the heart to beat too fast or too slow and can lead to sudden death if not corrected.
The new study showed that the function of specific genetic mutations – namely, the defects these mutations cause – are strong predictors of risk of sudden death and other cardiac events in patients with Long QT.
The finding is especially relevant for individuals who have the condition but don’t have particularly pronounced clinical risk factors, such as a very prolonged QT interval – the time it takes for the heart’s electrical system to recharge after each heartbeat and get ready for the next (hence, the name “Long QT” syndrome). When the QT interval is prolonged, the heart is more susceptible to arrhythmias.
These tricky, in-between patients, who make up about 70 percent of the Long QT syndrome population, often fall into a treatment gray area. In the future, lead study author Coeli Lopes, hopes that physicians may be able to use mutation-specific information to better identify high-risk individuals in this group who should be followed more carefully and treated more aggressively.
“To our knowledge, this is the first time anyone’s linked the activity of specific mutations to actual risk in patients,” said Lopes, assistant professor at the Aab Cardiovascular Research Institute at the University of Rochester Medical Center.
“We’re literally going from studying mutant proteins in cells in the lab to risk assessment in the clinic, which is an exciting and very promising concept,” added Lopes.
In the study, researchers looked at the most frequent mutations found in patients with Long QT syndrome type 1, one of the most common forms of the disease, and analyzed their influence on ion channels – small pores or holes on the surface of each heart muscle cell. These channels open and close to let electrically charged particles flow into and out of the cell, generating the signal the heart needs to stop contracting and relax after pumping blood throughout the body.
When they compared the results with patient outcomes, they discovered that mutations that cause ion channels to open more slowly than they should were strongly associated with increased risk for cardiac events. Patients with these slow activating channels were twice as likely as patients with other mutations to die before the age of 30 or experience serious symptoms.
The study is detailed in the journal Science Translational Medicine.