Nav: Home

Biomarker could identify patients with potential for recovery from advanced heart failure

January 16, 2017

Investigators at the University of Utah have identified distinct differences in the hearts of advanced heart failure patients who have defied the odds and showed signs of recovery from the disease. Published online in the journal Circulation, the new findings could help clinicians identify the best candidates for cardiac recovery therapies.

"Based on everything a doctor would traditionally measure, these patients look equally sick," says co-senior author and cardiologist Stavros Drakos, M.D., Ph.D., an associate professor of internal medicine. "But what we're seeing is that there are differences between them at the biological level, and we can use that information to predict who has a chance to recover."

Less than 10 years ago, advanced heart failure was dubbed "end-stage" for a reason. Aside from receiving a heart transplant, there were no treatment options. Since then, researchers have found that some patients respond differently after implantation of a mechanical heart pump, called a left ventricular assist device (LVAD). The invasive procedure comes with its own risks, but for 15 to 20 percent of these patients something happens that was considered unthinkable a decade prior: the pump unburdens the damaged heart and promotes recovery.

The discovery led Drakos and Frank Sachse, Ph.D., associate professor of bioengineering and co-senior author of this study, to reason that "responders" could provide clues to recovering sick hearts.

Considering the burden of heart failure, it's important to find new answers, says Drakos. One in five American adults over age 40 will develop heart failure within their lifetime, according to the American Heart Association. And half die within five years of diagnosis, an outlook that's worse than for most cancers.

To find what makes responders unique, Drakos, Sachse, and their team examined heart biopsies that were taken at the time of LVAD implantation. 10 were from patients who showed signs of recovery three months later, and 16 were from patients who did not recover.

When Sachse looked at samples from heart failure patients for the first time, he thought something had gone technically wrong. An anatomical structure called the transverse system (t-system) typically extends thin, rounded fingers into heart fibers. In most "nonresponders", advanced three-dimensional imaging showed their t-system instead looked like squashed, flattened sheets.

"That was not what we expected at all," says Sachse, also an investigator at the Nora Eccles Harrison Cardiovascular Research and Training Institute. He had researched heart failure in animal models for over a decade, but had never seen anything like what he saw in these patients. Investigations with human heart samples is uncommon.

In contrast to the nonresponders, the t-system looked relatively intact in samples from responders. In fact, the scientists could retrospectively gauge a patient's potential for recovery based on measurements that calculated how close to normal their t-system was.

"We're seeing that a patient's anatomy can help predict if that person has a high or low chance of recovery at the time of LVAD implantation," says first author Thomas Seidel, M.D., Ph.D., who carried out the project as a postdoctoral fellow with Sachse. "Our vision is that we can one day use this information to identify those patients that finally will not need a heart transplant, but may instead be weaned from the LVAD to go back to a normal life."

At the time of LVAD implantation, all patients' hearts did a poor job of pumping out blood to the rest of the body. A measurement of the heart's squeezing performance, called the ejection fraction (EF), was at 21 to 23 percent on average (normal range is 50 to 70 percent). After three months of pumping assistance with an LVAD, the hearts of patients with severely disrupted t-systems performed about the same, with an EF of 25 percent.

Patients whose heart physiology was not as severely impacted improved significantly over time, with their EF rising to 38 percent on average. While still below normal, the change signals that their hearts were getting stronger, says Drakos.

Additional experiments with explanted heart tissue delved further into explaining why the patients respond diffrently. Tissue with severely abnormal physiology also had asynchronous calcium signaling, a mechanism that ordinarily coordinates contraction of cells in the heart.

Drakos explains that a lot goes awry with the heart during advanced stages of the disease. But studies like this one provides a glimpse into mechanisms behind the disorder, information that could one day lead to new strategies for treatment. "Most therapies are based on knowing what goes wrong in disease," he says. "There's also a lot to be gained from understanding what goes right."
-end-
"Sheet-like Remodeling of the Transverse Tubular System in Human Heart Failure Impairs Excitation-Contraction Coupling and Functional Recovery by Mechanical Unloading" was published in Circulation online on Jan. 10, 2017

In addition to Drakos, Sachse, and Seidel, co-authors are Sutip Navankasattusas, Azmi Ahmad, Nikolaos Diakos, Weining David Xu, Martin Tristani Firouzi, Michael Bonios, Iosif Taleb, Deal Li, and Craig Selzman all from the University of Utah.

The work was supported by grants from the American Heart Association, National Institutes of Health, the Nora Eccles Treadwell Foundation, and the Doris Duke Foundation Clinical Scientist Grant.

University of Utah Health Sciences

Related Heart Failure Articles:

Type 2 diabetes may affect heart structure and increase complications and death among heart failure patients of Asian ethnicity
The combination of heart failure and Type 2 diabetes can lead to structural changes in the heart, poorer quality of life and increased risk of death, according to a multi-country study in Asia.
Preventive drug therapy may increase right-sided heart failure risk in patients who receive heart devices
Patients treated preemptively with drugs to reduce the risk of right-sided heart failure after heart device implantation may experience the opposite effect and develop heart failure and post-operative bleeding more often than patients not receiving the drugs.
How the enzyme lipoxygenase drives heart failure after heart attacks
Heart failure after a heart attack is a global epidemic leading to heart failure pathology.
Novel heart pump shows superior outcomes in advanced heart failure
Severely ill patients with advanced heart failure who received a novel heart pump -- the HeartMate 3 left ventricular assist device (LVAD) -- suffered significantly fewer strokes, pump-related blood clots and bleeding episodes after two years, compared with similar patients who received an older, more established pump, according to research presented at the American College of Cardiology's 68th Annual Scientific Session.
NSAID impairs immune response in heart failure, worsens heart and kidney damage
Non-steroidal anti-inflammatory drugs, or NSAIDs, are widely known as pain-killers and can relieve pain and inflammation.
Heart cell defect identified as possible cause of heart failure in pregnancy
A new Tel Aviv University study reveals that one of the possible primary causes of heart failure in pregnant women is a functional heart cell defect.
In heart failure, a stronger heart could spell worse symptoms
Patients with stronger-pumping hearts have as many physical and cognitive impairments as those with weaker hearts, suggesting the need for better treatment.
Patients with common heart failure more likely to have lethal heart rhythms
New Smidt Heart Institute Research shows that patients with Heart Failure with Preserved Ejection Fraction (HFpEF) are more likely to have lethal heart rhythms.
Why does diabetes cause heart failure?
A Loyola University Chicago Stritch School of Medicine study reveals how, on a cellular level, diabetes can cause heart failure.
Oxygen therapy for patients suffering from a heart attack does not prevent heart failure
Oxygen therapy does not prevent the development of heart failure.
More Heart Failure News and Heart Failure Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.