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:

New hope for treating heart failure
Heart failure patients who are getting by on existing drug therapies can look forward to a far more effective medicine in the next five years or so, thanks to University of Alberta researchers.
Activated T-cells drive post-heart attack heart failure
Chronic inflammation after a heart attack can promote heart failure and death.
ICU care for COPD, heart failure and heart attack may not be better
Does a stay in the intensive care unit give patients a better chance of surviving a chronic obstructive pulmonary disease (COPD) or heart failure flare-up or even a heart attack, compared with care in another type of hospital unit?
Tissue engineering advance reduces heart failure in model of heart attack
Researchers have grown heart tissue by seeding a mix of human cells onto a 1-micron-resolution scaffold made with a 3-D printer.
Smoking may lead to heart failure by thickening the heart wall
Smokers without obvious signs of heart disease were more likely than nonsmokers and former smokers to have thickened heart walls and reduced heart pumping ability.
After the heart attack: Injectable gels could prevent future heart failure (video)
During a heart attack, clots or narrowed arteries block blood flow, harming or killing cells in the heart.
Heart failure after first heart attack may increase cancer risk
People who develop heart failure after their first heart attack have a greater risk of developing cancer when compared to first-time heart attack survivors without heart failure, according to a study today in the Journal of the American College of Cardiology.
Scientists use 'virtual heart' to model heart failure
A team of researchers have created a detailed computational model of the electrophysiology of congestive heart failure, a leading cause of death.
Increase in biomarker linked with increased risk of heart disease, heart failure, death
In a study published online by JAMA Cardiology, Elizabeth Selvin, Ph.D., M.P.H., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues examined the association of six-year change in high-sensitivity cardiac troponin T with incident coronary heart disease, heart failure and all-cause mortality.
1 in 4 patients develop heart failure within 4 years of first heart attack
One in four patients develop heart failure within four years of a first heart attack, according to a study in nearly 25,000 patients presented today at Heart Failure 2016 and the 3rd World Congress on Acute Heart Failure by Dr.

Related Heart Failure Reading:

Heart Failure: A Companion to Braunwald's Heart Disease
by Douglas L. Mann MD (Author), G. Michael Felker MD MHS FACC FAHA (Author)

The 4 Stages of Heart Failure
by Brian Jaski (Author)

100 Questions & Answers About Congestive Heart Failure (100 Questions and Answers About...)
by Campion E. Quinn (Author)

Heart Failure: One Day at a Time

Oxford Textbook of Advanced Heart Failure and Cardiac Transplantation (Oxford Textbooks in Cardiology)
by Michael Domanski (Editor), Mandeep R. Mehra (Editor), Marc Pfeffer (Editor)

Living Well with Heart Failure, the Misnamed, Misunderstood Condition
by Edward K. Kasper (Author), Mary Knudson (Author)

Heart Failure
by Thomas Nelson

MemoCharts Pharmacology: Drug Therapy for Congestive Heart Failure (Review chart)
by Howard Shen (Author)

Heart Failure: A Comprehensive Guide to Pathophysiology and Clinical Care
by Howard Eisen (Editor)

The No-Salt, Lowest-Sodium Cookbook: Hundreds of Favorite Recipes Created to Combat Congestive Heart Failure and Dangerous Hypertension
by Thomas Dunne Books

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

Bias And Perception
How does bias distort our thinking, our listening, our beliefs... and even our search results? How can we fight it? This hour, TED speakers explore ideas about the unconscious biases that shape us. Guests include writer and broadcaster Yassmin Abdel-Magied, climatologist J. Marshall Shepherd, journalist Andreas Ekström, and experimental psychologist Tony Salvador.
Now Playing: Science for the People

#514 Arctic Energy (Rebroadcast)
This week we're looking at how alternative energy works in the arctic. We speak to Louie Azzolini and Linda Todd from the Arctic Energy Alliance, a non-profit helping communities reduce their energy usage and transition to more affordable and sustainable forms of energy. And the lessons they're learning along the way can help those of us further south.