A research team co-led by a physician-scientist at the University of Arizona's Sarver Heart Center in Tucson has discovered that a subset of artificial heart patients can regenerate heart muscle, which could 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 a transplant, is replacing a pump with an artificial heart, called a left ventricular assist device, which can help the heart pump blood.
Skeletal muscle has a significant capacity to regenerate after injury. If you're playing football and you tear a muscle, you have to rest it and it heals. When a heart muscle is injured, it does not grow back. We have nothing to reverse the loss of heart muscle. »
Hesham Sadek, MD, PhD, director of the Sarver Heart Center and division chief of cardiology at the U of A College of Medicine – Tucson Department of Medicine
Sadek led a collaboration among international experts to determine whether heart muscles can regenerate. The study was funded by a grant to Sadek from the Fondation Leducq'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 Health College and School of Medicine, led by Stavros Drakos, MD, PhD, a pioneer in recovery mediated by a left ventricular assist device.
Jonas Frisén, MD, PhD, and Olaf Bergmann, MD, PhD, of the Karolinska Institutet in Stockholm, led teams in Sweden and Germany and used their own innovative method of carbon dating human heart tissue to determine whether these samples contained newly generated cells.
Investigators found that patients with artificial hearts regenerate their muscle cells at a rate six times higher 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 reinforces the idea that there is an intrinsic capacity of the human heart to regenerate,” Sadek said. “It also strongly supports the hypothesis that the inability of the heart muscle to 'rest' is a major factor in the heart's loss of ability to regenerate shortly after birth. It may be possible to target the molecular pathways involved in cell division to improve heart function. ability to regenerate. »
Finding better ways to treat heart failure is a top priority for Sadek and the 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 although heart muscle cells actively divide in utero, they stop dividing shortly after birth to devote their energy to continually pumping blood around the body, without any pause.
In 2014, he published evidence of cell division in patients with artificial hearts, suggesting that their heart muscle cells could regenerate.
These results, combined with observations from other research teams that a minority of artificial heart patients might have their devices removed after seeing a reversal of symptoms, led him to question whether the artificial heart provides the heart muscles with the equivalent of bed rest in a convalescing person. football injury.
“The pump pushes blood into the aorta, bypassing the heart,” he explained. “The heart is essentially at rest. »
Sadek's previous studies indicated that this rest might benefit heart muscle cells, but he needed to design an experiment to determine whether patients with artificial hearts actually regenerated their muscles.
“Compelling evidence for heart muscle regeneration has never been demonstrated before in humans,” he said. “This study provided direct evidence. »
Sadek next wants to understand why only about 25% of patients respond to artificial hearts, meaning their heart muscle regenerates.
“It is not clear why some patients respond and others do not, but it is very clear that those who respond have the ability to regenerate heart muscle,” he said. “The exciting part now is figuring out how we can get everyone to respond, because if you can, you can essentially cure heart failure.” The beauty of this is that a mechanical heart is not a therapy we hope to offer our patients in the future. the future – these devices are proven and we have been using them for years.
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