An FDA-approved drug could prevent valve damage after heart attack

Losartan is shown to prevent thickening of the mitral valve after heart attack, in comparison with an untreated heart
An untreated mitral valve (left) shows much more thickening and fibrosis after heart attack than a mitral valve treated with losartan (right).

On average, one in four people who have a heart attack sustain long-lasting damage to the mitral valve, which has the important job of making sure blood pumps through the heart’s ventricles in the right direction. If the valve is damaged, the heart’s pumping efficiency is reduced and blood can flow backward, which can lead to heart failure and death.

Now, a team of collaborators from Boston Children’s Hospital, Massachusetts General Hospital and Brigham and Women’s Hospital has shown, for the first time, that it’s possible to treat and even prevent mitral valve damage after heart attack with an FDA-approved, anti-hypertension drug called losartan. Their findings are published in the Journal of the American College of Cardiology.

“A heart attack is like a fire in the heart; inflammation triggered by damage to the heart muscle attracts [immune] cells to clear up the damage and form a healed scar,” said one of the study’s co-lead authors, Jacob Dal-Bianco, MD, of MGH, in a press release. “The mitral valve can be caught up as an innocent bystander in this process and become inflamed and scarred, eventually becoming shorter, stiffer and less able to close effectively.”

When heart muscle becomes damaged, immune cells and inflammatory factors flock to the heart. The immune cells release transforming growth factor (TGF)-beta, which plays a role in tissue growth and healing. But too much TGF-beta can trigger scarring and stiffening of the endothelial cells that line the mitral valve.

Could losartan improve heart attack survival?

Knowing that losartan inhibits the effects of TGF-beta, the team of collaborators investigated its impact on the mitral valve in a sheep model of heart attack.

“We found that losartan reduced the number of endothelial cells that were transitioning into potentially fibrotic cells, which we speculate is part of how losartan reduced mitral valve thickness,” says Joyce Bischoff, PhD, of the Boston Children’s Vascular Biology Program, co-senior author on the study.

The collaborators plan to further investigate losartan in animal models of heart attack to determine whether it should be assessed for treating mitral valve disease in humans.

“We also need to test whether treatment during the inflammatory period right after a heart attack is sufficient and whether patients who already have developed mitral valve regurgitation and heart failure can benefit from treatment,” says study co-senior author Robert Levine, MD, of the MGH Heart Valve Program. “A medical treatment to prevent or alleviate these changes could significantly improve patients’ quality of life and, we believe, translate into improved survival with less heart failure.”

Adapted from a press release issued by MGH.

More research from Boston Children’s Vascular Biology Program.