Mechanical hearts encourage dormant regions of failing hearts to regenerate

According to a UT Southwestern pilot scale study, mechanical hearts stimulate regeneration in latent areas of failing hearts, paving the way for the development of regenerative heart therapies.

"This is a small study," said lead author Hesham Sadek, M.D., Ph.D., Professor of Internal Medicine, Biophysics, and Molecular Biology, "but it represents the first evidence that mechanical hearts, which are tried and true, approved treatments for end-stage heart failure patients, can generate new muscle tissue in the failing human heart."

His findings, which were published in the American Heart Association's flagship journal Circulation, found that left ventricular assist devices (LVADs), which are widely accepted in cardiology as life-saving devices, showed metabolic reactivation in myocardial areas that had little or no activity previously.

"Now we need to reproduce these findings in larger research," Dr. Sadek explained. "If larger studies confirm this, artificial hearts could emerge as a regenerative therapy for reversing heart failure, which is the holy grail of heart failure treatment."

Dr. Sadek's studies of heart regeneration in mice, which were published in the journals Nature and Science, broke new ground in this field of cardiology research. According to Cell, oxygen metabolism causes DNA damage in cardiac cells, which prevents them from regenerating.

The study was co-led by Vlad Zaha, M.D., Ph.D., Assistant Professor of Internal Medicine, and Dr. Sadek.

"This study discovered signs of regeneration in areas of the heart that were previously thought to be dead," Dr. Zaha said. "It's a hopeful finding that will prompt more research to replicate the findings on a wider scale and, if confirmed, to investigate potential new medicines to magnify this process in the setting of LVAD support."

The metabolic activity of four heart failure patients, aged 39 to 59, was assessed in a pilot research by tracking a radiolabeled sugar molecule termed F-fluorodeoxyglucose (FDG) in the heart. This FDG signal is thought to be an indicator of "living" cardiac tissue.

PET imaging, which followed FDG uptake every six months for up to 18 months, was used. At baseline, all subjects showed an increase in FDG absorption in areas of past metabolic inactivity, indicating the possibility of cardiac regeneration. The increase in FDG uptake from baseline ranged from 1.87 percent to 23.80 percent among the four patients.

Reference:

Tiberiu A. Pana, Jainy Savla, Ingrid Kepinski, Adam Fairbourn, Aneela Afzal, Pradeep Mammen, Mark Drazner, Rathan M. Subramaniam, Chao Xing, Kathryn A. Morton, Stavros G. Drakos, Vlad G. Zaha, Hesham A. Sadek. Bidirectional Changes in Myocardial 18 F-Fluorodeoxyglucose Uptake After Human Ventricular Unloading. Circulation, 2022; 145 (2): 151 DOI: 10.1161/CIRCULATIONAHA.121.056278