Left ventricular assist devices can trigger metabolic reactivation in myocardial areas with little to no activity, sparking hope for the development of regenerative heart therapies that could potentially reverse heart failure.
Since almost three decades ago, heart failure has been recognised as an emerging epidemic and a major global health burden. In 2017, about 64.3 million people globally were suffering from heart failure. Today, with the global population rapidly growing and ageing, the number of heart failure patients are expected to increase accordingly. As the number of patients suffering from heart failure requiring circulatory support increases, left ventricular assist devices (LVADs) – mechanical pumps that help the left ventricle pump blood out of the ventricle and to the aorta and rest of the body – become a vital form of life-saving intervention.
Now, a pilot study by researchers at UT Southwestern Medical Center has reported that mechanical hearts can stimulate regeneration in dormant parts of failing hearts, sparking hope for the development of regenerative heart therapies. Their findings revealed LVADs exhibited metabolic reactivation in myocardial areas where previous activity was either scarce or absent.
“This is by all accounts a small study, 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,” said lead author Hesham Sadek, M.D., Ph.D., Professor of Internal Medicine, Biophysics and Molecular Biology.
In his prior work, Dr. Sadek had broken extensive ground with research on heart regeneration in mice. His findings revealed that oxygen metabolism can lead to DNA damage in heart cells, consequently ceasing their ability to regenerate. Past studies have also reported considerable functional recovery in some patients with LVADs, albeit a minor percentage of patients with LVADs make a full recovery.
Hoping to better define the underlying mechanisms of myocardial recovery in support of LVAD, the researchers measured the metabolic activity of four patients aged between 39 to 59 who were taking medications for heart failure. They tracked a radiolabelled sugar molecule known as F-fluorodeoxyglucose (FDG) found in the heart of the patients since this FDG signal is considered to be a marker of “viable” or alive heart tissue.
Leveraging positron emission tomography imaging, the team then monitored their subjects’ FDG uptake every six months for up to 18 months. Their observations showed that all the participants experienced some degree of increase in FDG uptake in areas where metabolic inactivity was originally detected at their baseline. These results indicate the possibility of myocardial regeneration. Across the four patients, the rise in FDG uptake from their baseline ranged from 1.87 per cent to 23.80 per cent.
“This study found evidence of regeneration in the parts of the heart that would be considered dead,” explained Dr. Zaha. “It’s a promising finding that will lead to further investigations to replicate the results at larger scale, and – if confirmed – to explore potential new therapies to amplify this process in the context of LVAD support.”
“What we need to do now is replicate these results in larger studies,” said Dr. Sadek. “If this holds true in larger studies, mechanical hearts might emerge as a regenerative therapy to reverse heart failure, which is the holy grail in heart failure treatment.” [APBN]
Source: Pana et al. (2022). Bidirectional Changes in Myocardial 18F-Fluorodeoxyglucose Uptake After Human Ventricular Unloading. Circulation, 145, 151-154.