New preclinical research in animal models finds that infusing a specific protein into scar tissue after a heart attack improves and speeds up the recovery of the heart.
Reperfusion, which is a technique that frees up the flow of oxygen to the heart's tissue, is a common form of treatment after a heart attack. However, up to one-quarter of people who undergo reperfusion develop heart failure within a year.
So, researchers led by James Chong — an associate professor at the University of Sydney in Australia — have explored an alternative treatment that targets the scar tissue that forms after a heart attack.
Chong and colleagues evaluated the therapeutic potential of a protein therapy called recombinant human platelet-derived growth factor-AB (rhPDGF-AB).
As its name suggests, rhPDGF-AB is a recombinant growth factor-AB derived from human platelets. Platelets are small blood cells that rush to an injury site when they are needed to help the blood clot and start the healing process.
The researchers tested the new treatment in a porcine model of heart attack, and their promising results suggest that the therapy may soon help humans recover from heart attack.
The findings appear in the journal Science Translational Medicine.
How rhPDGF-AB improves heart function
The study was a randomized trial. Chong and team assigned 36 pigs to one of three groups:
- one that received a sham procedure (these five pigs did not have a heart attack)
- one that received a balloon occlusion of the coronary artery to mimic a heart attack and took a placebo as "treatment" (11 pigs)
- one that received balloon occlusion and 7 days of intravenous infusion of rhPDGF-AB (11 pigs)
Nine of the pigs who experienced a heart attack died before having the chance to receive any treatment.
A month after the intervention, the researchers used cardiac MRI and other methods to show that their treatment caused more new blood vessels to form, decreased abnormal heart rhythm, and boosted overall heart function.
Specifically, 28 days after the heart attack, the new procedure improved survival by 40% compared with placebo and improved the heart's ejection fraction in the left ventricle — where the heart attack had taken place — by 11.5%.
"By improving cardiac function and scar formation following a heart attack, treatment with rhPDGF-AB led to an overall increase in survival rate in our study," explains Chong.
"While the treatment did not affect overall scar size, importantly, we found that rhPDGF-AB led to increased scar collagen fiber alignment and strength. This improved heart function after a heart attack."
"This is an entirely new approach with no current treatments able to change scar in this way."
Clinical trials in humans to follow very soon
Chong explains how these findings build on the team's previous work, saying, "Our collaborator Prof. Richard Harvey, from the Victor Chang Cardiac Research Institute [in Darlinghurst, Australia], had previously shown that the protein can improve heart function in mouse models following heart attack."
"This project has been developed over more than 10 years, and we now have compelling data in two species for the effectiveness of this treatment."
Chong places the findings in the larger context of the rise of heart disease as a leading cause of death:
"While we have treatment protocols in place, it's clear that there is an urgent, unmet need for additional treatments to improve patient outcomes, particularly after large heart attacks."
"Some further animal studies are required to clarify safety and dosing. Then we can start looking toward clinical trials in humans very soon," says Chong.
"RhPDGF-AB is clearly a promising therapeutic option and could potentially be used alongside existing treatments to improve heart attack patient outcomes and survival rates."
In the future, says Chong, "We […] hope to further investigate the treatment, including whether it could be used in other organ systems impacted by scar tissue, such as the kidneys."