Researchers pinpoint genetic defects that cause heart failure, pointing way to more targeted treatments

An international research team has identified individual genetic defects that lead to heart failure, opening the door to more targeted diagnosis, prevention and treatment.

In research published today in the academic journal Science, the team analyzed cells from 61 failing and 18 healthy hearts using single-cell genetic sequencing. 

“For the first time, we were able to map out in great detail the genotype basis for cardiomyopathy and heart failure,” says lead Canadian investigator Gavin Oudit, cardiologist in the Faculty of Medicine & Dentistry and Canada Research Chair in Heart Failure.

“We’re really trying to understand how genetic problems can lead to cardiomyopathy and heart failure,” says Oudit. “By understanding it, we can start to think about how we can fix it.”

The team, based in London, Cambridge, Boston, Berlin and Edmonton, examined 880,000 cells from hearts donated in Germany, the United States and Western Canada. The diseased hearts all showed signs of dilated cardiomyopathy, which occurs in one in 250 Canadians and is the most common reason for heart transplant. It leaves the heart muscle weak and leads to heart failure or arrhythmia, and can also cause sudden death.

The same research group recently published an atlas of healthy human heart cells, laying the groundwork for the new research. 

“This discovery allows us now to understand the pathophysiology of these different types of cardiomyopathies and really go after novel therapies that are likely to be very effective, and that can be used in an early stage of this disease before it can progress into heart failure or arrhythmias,” says Oudit, who is also director of the Heart Function Clinic at the Mazankowski Alberta Heart Institute.

“Altruism in its truest form”

Oudit says the research could not have been carried out without the generosity of organ donors from Alberta and western Canada.Oudit runs the Human Explanted Heart Program (HELP), the largest research-integrated human heart transplant program in Canada, through which heart transplant recipients can donate their diseased organs for research. Healthy organs are donated by deceased individuals and their families through the Human Organ Procurement and Exchange Program (HOPE) program. 

“One of our major contributions to this manuscript was to systematically collect tissue from non-failing controls and failing human hearts, which we perform in association with the Mazankowski Alberta Health Institute and the University of Alberta Hospital,” says Oudit. “Our biobank contains samples obtained from 500 patients.”

“I wish to express gratitude to our patients and their families for signing up for this,” he says. “Our ultimate aim here is to come up with better therapies to treat them and their families. Their donation is altruism in its truest form.”

The Oudit lab’s contributions to the collaboration were funded by the Heart and Stroke Foundation, the Canadian Institute of Health Research, the Canada Research Chairs program and the University Hospital Foundation. Oudit is also a member of the Women and Children’s Health Research Institute.

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