LVAD, healer of broken hearts? Heart failure biomarkers suggest yes

A look into cardiomyocytes and DNA damage response may offer new hope for patients with heart failure. Long-term use of left ventricular assist devices (LVADs) may encourage the heart to repair itself at a cellular level.

Ten heart failure patients referred to the University of Texas Southwestern Medical Center in Dallas for LVAD or heart transplantation provided heart tissue samples. Samples were paired at initial LVAD implantation and at the time of subsequent removal for heart transplant. Tissue samples were then analyzed for mitochondrial content, DNA damage response and cardiomyocyte proliferation.

While LVAD is generally a bridge of last resort for heart failure patients in need of a transplant, in a few documented cases, some devices were later removed without heart transplant. Diana C. Canseco, PhD, and colleagues at the center theorized that cells may be repairing themselves while patients are on the devices. The team determined biomarkers may hold the key to why this happens and how to replicate that response in other patients.

Their work builds on earlier investigations into mammalian cardiac regenerative response to injury.

They found mitochondrial content decreased by up to 60 percent and cardiomyocyte size up to 45 percent between post- and pre-LVAD hearts. The most statistically significant change occurred when LVAD was used longer than six months. Phosphorylated ataxia telangiectasia mutated protein foci also decreased significantly in patients with longer ventricular unloading. Canseco et al noted that DNA damage response may be deactivated after longer periods on LVAD.

“This result shows that patients with mechanical assist devices have the ability to make their muscle cells divide,” said senior author Hesham A. Sadek, MD, PhD, in a press release. Sadek asked whether this was the heart regenerating and if prolonged LVAD might be the key to healing heart failure.

“Putting in a mechanical pump rests the heart and apparently sends a signal to make new cells. This is the first time that this phenomenon has been shown to occur in human heart failure,” said Pradeep P.A. Mammen, MD, co-senior author.

Future work will look at whether this observation produces viable heart muscle tissue, improves heart function, and whether this effect produces improved outcomes in a greater number of patients.

The study was published online Jan. 21 in the Journal of the American College of Cardiology.