A distinctive molecular signature could help doctors predict which patients will recover from heart failure.
As a last resort for people with end-stage heart failure, doctors can implant a device called a left ventricular assist device (LVAD), a mechanical pump that takes the load off the heart muscle. While the device is intended to stay in the body permanently, doctors noticed that, in some patients, the assistance provided by the LVAD allowed the patient’s own heart to regain strength and function.
Why do some hearts recover while others don’t? To answer this question, researchers at University of Utah Health have been studying molecular processes that keep heart cells running. Now, they’ve identified a distinct molecular signature that distinguishes hearts that bounce back from those that don’t. The findings could change the way doctors think about using LVADs. While it’s currently considered a last resort, LVADs could potentially be implanted sooner in patients with a favorable molecular profile, as a temporary intervention that helps the heart heal.
“We identified a very clear panel of molecules that are able to distinguish hearts that are capable of recovery from those that aren't,” says Sarah Franklin, PhD, associate professor in the Division of Cardiovascular Medicine and an investigator at the Nora Eccles Harrison Cardiovascular Research & Training Institute, and senior author on the study. “This is really groundbreaking.” The research published in the journal, Circulation.
Franklin, lead author Stavros Drakos, MD, PhD, professor of cardiovascular medicine and CVRTI investigator, and colleagues, obtained heart tissue samples from 93 heart failure patients who received LVADs. They tested the heart tissue to identify differences in gene expression between the hearts that grew stronger and those that didn’t. Importantly, the researchers weren’t looking for inherited genetic differences between the groups but differences in which genes were active in heart cells at the time the device was implanted.
A person’s genetic makeup doesn’t change much throughout life, but genes can be activated and deactivated at different times depending on what the body needs. When a gene is “activated,” that means the cell is making the protein molecule encoded by that gene. The study found some very reliable differences between the two groups in terms of which proteins were being made.
Having an LVAD implanted is expensive and invasive, and the device can be unwieldy to live with. It would be very helpful to know beforehand whether a patient’s heart is likely to recover after a period of rest with the device. Future research will seek to uncover how, exactly, these protein molecules help the heart heal. “We want to understand a little bit better what the individual proteins are doing, and how you go from a heart that's failing to potentially a heart that's recovering,” Franklin says.
The results also showed that people whose hearts recovered after LVAD implantation were younger, on average, than people who did not regain heart function. This could lead to a shift in how doctors use the device, Franklin says. Current protocol is to wait as long as possible before implanting an LVAD because the device is cumbersome, expensive, and will most likely remain in place forever. “This can help us to identify those individuals that would have the best response to recovery and potentially benefit from implanting the pump earlier, instead of waiting and maybe losing that window,” Franklin says.