Researchers have confirmed the finding of a long-running Medtronic study linking a specific genetic mutation to a higher risk of sudden cardiac death.
Hundreds of thousands of Americans die from sudden cardiac death each year, and the genetic discovery may someday help physicians treat the condition with gene-manipulation techniques. But in the short term, the first-of-its-kind work should help identify patients who most benefit from getting an implanted cardiac defibrillator like the ones Medtronic makes.
"The defibrillator is a lifesaving device. What we need to get better at is identifying not more patients to implant, not less patients to implant, but the right patients to implant. Meaning, the ones who are most likely to have a cardiac arrest in the future," said Dr. Sumeet Chugh, the Los Angeles cardiologist who founded the independent research study that confirmed the Medtronic results.
Medtronic PLC has long sought to discover the genetic underpinnings of sudden cardiac death, which is the condition in which electrical defects in the heart cause it to suddenly stop beating. The average survival rate is about 10 percent if sudden cardiac arrest happens outside the hospital.
A defibrillator is supposed to detect abnormal rhythms and send shocks to the heart to quickly restore a normal heartbeat before lack of oxygen in the blood harms organs including the brain. But doctors still use a relatively crude measure — the percent of blood in the left ventricle that is pumped with each heart contraction — to decide when to implant the devices.
Seeking a predictor
In 2007 the Medtronic Bakken Research Center announced a company-funded study called Discovery, which sought to learn whether a group of 1,200 European patients with implanted defibrillators had mutations in three genes that could be used to predict sudden cardiac death and other outcomes.
The work on patients who already have implantable cardioverter defibrillators (ICDs) identified two separate variations in a single gene, known as GNAS, that were linked to the ventricular arrhythmia that can give rise to sudden cardiac death.
In the second study, federally funded researchers took the sudden cardiac death variations identified in the Medtronic study and looked for the same mutations in a biobank of genetic information on 1,335 people in the Portland, Ore., metro area who have died from sudden cardiac arrest since 2002.
Data from the Oregon Sudden Unexpected Death survey showed that one of the two genetic variations was associated with a 50 percent increased risk of sudden cardiac death.
"This is the first time a gene has been identified using ICD monitoring and then confirmed to be associated with sudden cardiac death in the general population," said Heiner Wieneke, principal investigator for the Discovery trial and chief cardiologist at Contilia Heart and Vessel Centre at St. Marien-Hospital Mulheim in Germany.
A risk, not a cause
The study results were published Monday at the 2015 European Society of Cardiology Congress in London. Medtronic officials noted that over the weekend, the European cardiology association recommended that DNA analysis be used in young victims of sudden cardiac death, which could help to identify relatives at risk.
Chugh, the Los Angeles doctor who founded the Oregon death survey, noted that the results don't prove that the genetic variation causes sudden cardiac death, nor that people who have the variation will experience cardiac arrest. But a cardiologist doesn't need to know whether the variation directly causes cardiac death to know it's a sign of risk.
"In the big picture, this finding really does two things," he said. "It helps the prediction of sudden cardiac death, and secondly, it focuses a spotlight on this [genetic] pathway. It says, let's home in on this pathway and try to really understand what it is doing in the genesis of fatal heart rhythms that lead to sudden cardiac death."