A team of researchers from the US has developed a genetic test which can identify the condition hypertrophic cardiomyopathy and pave the way for early diagnosis and possible prevention of the sudden deaths.
Footballer O'Donnell died during a match at Motherwell's Fir Park on December 29, 2007, after he collapsed on the pitch minutes before he was due to be substituted.
It came four years after Cameroon footballer Marc-Vivien Foe died from the condition during a match.
The popular footballer's sudden death at the age of 35 sent shockwaves through Scottish football and led to a programme to be set up to test young athletes for potential heart defects.
Now experts from Stanford University School of Medicine in America claim to have identified the biological basis for the condition, sometimes dubbed "athlete's heart" that led to his death.
Hypertrophic cardiomyopathy, which affects about 0.2% to 0.5% of the population, is a condition in which the muscle of the heart is abnormally thickened without any obvious cause.
Symptoms, including irregular heartbeat and chest pain when exercising, typically emerge in late teenage years or young adulthood, but can occur at any age.
Although doctors have known for some time that the disorder can be caused by any one of several genetic mutations, until now it has not been clear how these mutations cause the thickening and eventual failure of the heart muscle.
To solve the mystery, scientists created stem cells, or IPS cells, from the skin cells of 10 members of a family with a genetic mutation that causes the condition.
The two oldest affected children, aged 21 and 18, displayed slightly enlarged hearts and the youngest, aged 14 and 10, displayed a slight increase in blood volume, which is another symptom of the condition.
The researchers then coaxed the cells to become heart muscle cells so they could closely study the cells' behaviour and responsiveness to the chemical and electrical signals that keep a heart beating normally.
They also used these bioengineered heart cells to quickly pinpoint the drugs most likely to be effective in human patients and to study their potential as preventive medications. To test their theory they compared the IPS-generated heart muscle cells, or cardiomycocytes, from the family members who have the mutation to those without it.
They found that all the cardiomyocytes appeared normal at first, for example and were beating rhythmically in a laboratory dish. But the cells with the mutation began to change after about 30 to 40 days.
Joseph Wu, lead author of the study, said: "Our results indicate that we may need to rethink our current treatment strategy.
"Maybe by the time a person begins to exhibit clinical symptoms, the damage could not be easily undone. Earlier intervention may soon be possible in the near future.
"The hope is to be able to use genetic techniques, such as DNA sequencing, coupled with IPS cell-derived cardiomyocytes to identify potential patients at risk at a much earlier stage.
"We may also be able to treat patients earlier with the right medications to prevent enlargement and damage of the heart muscle from taking place in the first place."
The researchers have started to study IPS cells from patients with other mutations associated with hypertrophic cardiomyopathy, as well as to test known drugs.
Dr Wu added: "Instead of conducting clinical trials on patients, which is a much more costly and painstaking process, we may one day be able to do the first stages of a trial primarily on cells in a dish."
However, doctors still do not know what caused Bolton Wanderers footballer Fabrice Muamba to collapse and almost die during a match against Tottenham last year. Muamba has since recovered, but has been forced to retire from the game.
