A research team co-led by a physician-scientist at the University of Arizona College of Medicine, Tucson’s Sarver Heart Center, found that a subset of artificial heart patients can regenerate heart muscle, which may open the door to new ways to treat and perhaps one day cure heart failure. The results were published in the journal. Circulation.
According to the Centers for Disease Control and Prevention, heart failure affects nearly 7 million American adults and is responsible for 14% of deaths annually. There is no cure for heart failure, although medications can slow its progression. The only treatment for advanced heart failure, other than transplant, is pump replacement through an artificial heart, called a left ventricular assist device, which can help the heart pump blood.
“Skeletal muscle has a significant ability to regenerate after an injury. If you’re playing soccer and you tear a muscle, you need to rest it and it will heal,” said Hesham Sadek, MD, PhD, director of the Sarver Heart Center and chief of the Division of U of A College of Medicine Cardiology, Tucson Department of Medicine. “When a heart muscle is injured, it doesn’t grow back. We have nothing to reverse the loss of heart muscle.”
Sadek led a collaboration among international experts to investigate whether heart muscles can regenerate. The study was funded through a grant awarded to Sadek by the Leducq Foundation’s Transatlantic Networks of Excellence Program, which brings together American and European researchers to tackle big problems.
The project began with tissue from artificial heart patients provided by colleagues at the University of Utah School of Medicine and Health, led by Stavros Drakos, MD, PhD, a pioneer in left ventricular assist device-mediated recovery.
Jonas Frisén, MD, PhD, and Olaf Bergmann, MD, PhD, of the Karolinska Institute in Stockholm, led teams in Sweden and Germany and used their own innovative method of carbon dating human heart tissue to track whether these samples contained newly generated cells. .
The researchers found that patients with artificial hearts regenerated muscle cells at a rate more than six times greater than healthy hearts.
“This is the strongest evidence we have, so far, that human heart muscle cells can actually regenerate, which is really exciting, because it solidifies the notion that there is an intrinsic ability of the human heart to regenerate,” Sadek said. . “It also strongly supports the hypothesis that the inability of the heart muscle to ‘rest’ is an important factor in the loss of the heart’s ability to regenerate soon after birth. It may be possible to target molecular pathways involved in cell division to improve the function of the heart.
Finding better ways to treat heart failure is a top priority for Sadek and Sarver Heart Center. This study builds on Sadek’s previous research on rest and regeneration of heart muscle.
In 2011, Sadek published a paper in Science showing that while heart muscle cells actively divide in the womb, they stop dividing shortly after birth to devote their energy to pumping blood around the body non-stop, with no time to stop. breaks.
In 2014, he published evidence of cell division in patients with artificial hearts, hinting that heart muscle cells may have been regenerating.
These findings, combined with observations by other research teams that a minority of artificial heart patients could have the device removed after experiencing a reversal of symptoms, led him to question whether the artificial heart provides cardiac muscles with the equivalent of bed rest for a person recovering from a soccer injury.
“The pump pushes blood into the aorta, bypassing the heart,” he said. “The heart is essentially resting.”
Sadek’s previous studies indicated that this rest could be beneficial for heart muscle cells, but he needed to design an experiment to determine whether patients with artificial hearts were actually regenerating muscles.
“Irrefutable evidence of cardiac muscle regeneration in humans has never before been shown,” he said. “This study provided direct evidence.”
Next, Sadek wants to find out why only about 25% of patients “respond” to artificial hearts, that is, their heart muscle regenerates.
“It’s not clear why some patients respond and others don’t, but it is very clear that those who respond have the ability to regenerate heart muscle,” he said. “The exciting thing now is determining how we can get everyone to respond, because if you can, you can essentially cure heart failure. The good thing about this is that a mechanical heart is not a therapy that we hope to provide our patients in the future. “These devices are tried and true, and we’ve been using them for years.”