Owner of the broken hearts

They were hearts that seemed unneeded, hearts removed from transplant patients to be replaced by healthy donor organs. Diseased and often enlarged or misshapen, the explanted hearts historically were quickly discarded. That started to change 32 years ago, when Kenneth B. Margulies, MD, asked his hospital's transplant surgery director if he could hold on to the explanted organs. He wanted to know: Can severely failing hearts ever recover?

Today, Margulies is a professor of Cardiovascular Medicine at the Perelman School of Medicine at the University of Pennsylvania, where he's continuing to answer that and many other questions. At the time he began collecting hearts, he was an early-career researcher and cardiologist at Temple University in Philadelphia. He suspected that these hearts, though no longer capable of serving their owners, still had much to give. They could provide knowledge about the biology of cardiac disease, potentially leading to new therapies that could delay or eliminate the need for transplantation.

The heart spends a lifetime cycling through contraction and rest, pushing nutrients and oxygen throughout the body. But this muscular organ can fail. Blocked arteries can stop blood from reaching its cells, high blood pressure can force the heart to work harder than it should, and genetic abnormalities can also play a role.

Most of today’s heart medications treat cardiac disease indirectly, for example by reducing blood pressure or lowering bad cholesterol. These medicines address the factors that cause disease, but do not repair the damage done to the muscle itself.

As heart disease is the leading cause of death worldwide, finding ways to restore cardiac health is an urgent need. About 4,000 heart transplants take place in the United States every year, according to the U.S. Health Resources & Services Agency, but double that number of patients are waiting. Many more don’t qualify for transplantation.

Today, the Penn Human Heart Tissue Bank, started by Margulies when he moved to the University of Pennsylvania in 2004, has swelled to include tissues from more than 1,100 explanted hearts, and the number is growing. Over 150 published studies have drawn on its tissue samples, which are distributed upon request to researchers worldwide.

These findings have contributed directly to a shift in how clinicians view the trajectory of heart disease. Previously, heart failure was viewed as invariably progressive, Margulies said, but researchers now know that heart muscle, or myocardium, can recover its contractile ability, helping people feel better and live longer. Hearts can be saved.

“We went from myocardial improvement being really exceptional and rare, to an expectation that many patients’ hearts will improve with treatment,” said Margulies, who directs Penn Medicine’s Cardiovascular Clinical Research Unit. “I think that's an important paradigm shift over the past three decades.”

Although other heart tissue banks exist, Penn’s bank stands out for lengths to which the researchers go to protect the heart tissue during explantation, providing the same care that donor hearts receive. This level of care preserves the heart’s biology so that research findings are accurate. The bank is among the largest and most well documented in the United States, providing not only the tissue itself, but also data on each patient’s risk factors, prior treatments, and other features that make these tissues especially valuable for research.

The collection has spurred major discoveries, inspired new treatments, and is providing fundamental insights—from understanding how stress damages cardiac muscle cells, to tracking the relationship between heart failure and obesity, to more accurately predicting the risk of organ rejection after transplantation.

What is more, the findings are specific to human biology, and thus may generate new hypotheses and therapeutic directions, said Benjamin Prosser, PhD, a professor of Physiology at Penn Medicine, whose lab studies the heart using a range of modalities, including cell culture, rodent models, and human heart tissues.

“With the kinds of experiments that you can do using the Human Heart Tissue Bank,” Prosser said, “I think this is one way to close that gap between basic science discovery and human application.”

In the late 1990s, Margulies was trying to answer a simple question: Could failing heart muscle improve with help from a mechanical pump? Such pumps, known as left ventricular assist devices, act as stopgaps to keep patients alive until a transplant can be done. But does the pump’s assistance also give damaged muscle cells the chance to heal?

To find out, Margulies and his colleagues decided to look at explanted hearts that had earlier received assist devices.

Margulies arranged for the hospital’s transplant center, first at Temple and then at Penn Medicine, to notify him of upcoming transplants, which happen typically within one to two days of a donor heart becoming available and often in the middle of the night.

He or a colleague would show up with a bucket of ice and whisk away the explanted hearts to the lab for dissection, isolation of heart muscle cells for functional studies, and freezing for future analyses.

As the research progressed, however, Margulies realized that the ice-bucket protocol wasn’t enough. It could not prevent the biochemical degradation that begins immediately after the heart is removed and can distort research findings.

Margulies’ collaborating transplantation surgeon had a suggestion: Why not apply the same heart-preserving techniques that they use for transplanting hearts to the diseased hearts being collected for research?

That process begins with the delivery of a cryopreservation fluid into the heart’s circulatory system, silencing electrical signals and rhythmic beating while cooling it to near freezing and protecting the muscle from damage.

The surgical team then hands the heart out of the sterile field to a waiting researcher, who places it in a container of cold saline. Back in the lab, researchers weigh the heart, record observations, and dissect it, placing samples in bar code-labeled vials. Some tissues are prepared for near-term use, while others are stored in freezers.

By applying the improved preservation techniques and then studying the explanted tissues in hearts that had or had not received the pumps, Margulies’ team showed that the pump-assisted hearts had improved contractility and healthier heart muscle cells than unassisted hearts. Indeed, failing hearts can recover to some extent.

It wasn’t long before the researchers realized there was a deeper story to tell by comparing diseased heart tissue to tissue from non-diseased hearts. But they didn’t have heart tissue samples from healthy patients, who by definition don’t need biopsies or transplants. Donor hearts seemed like a solution.

It turns out that roughly two-thirds of hearts in people who’ve opted into organ donor programs are unsuitable for transplant for various reasons.

In 2006, working with the regional organ donor organization Gift of Life, Margulies and his colleagues began collecting hearts from people who agreed to have their organs used for research.

Through studies of these hearts, the team discovered that some of the “healthy” donor hearts actually show signs of early stage disease. Far from limiting their usefulness, that has made them an incredible resource for studying disease progression, said Eliot G. Peyster, MD, MSc, an advanced heart disease and transplant cardiology specialist and a researcher who trained in the Margulies lab.

“This is a unique opportunity to learn about early mechanisms of heart disease and to uncover early, potentially targetable processes that might allow us to prevent progression,” Peyster said. There's almost no place else to get samples of heart tissue so early in the disease process, he said.

In 2022, Penn Medicine established the Gift of Life Donor Care Center at the Hospital of the University of Pennsylvania, dedicated exclusively to deceased organ donors. Caring for these patients here has shortened the time between the operating room and laboratory.

Often the first person to respond when a heart transplantation or donor heart explantation is scheduled is Kenneth Bedi, project manager for the heart tissue bank. In addition to supervising the program and speeding to the hospital, often at 2 a.m., to receive hearts, Bedi set up the database that enhances the value of Penn’s heart tissue bank for research.

Each explanted heart comes with anonymized information about the patient’s diagnosis, condition of the heart, medications, previous procedures, as well as characteristics such as body mass index, genetic diseases, and other risk factors such as smoking.

“It is so important to capture this information, so that we can find out what might have been going on at the molecular level,” Bedi said. The identification of therapeutic targets, he said, will allow researchers to “translate this back to the real world, to the clinic.”

One area where the Human Heart Tissue Bank is helping scientists advance their understanding is a disorder called heart failure with preserved ejection fraction (HFpEF), where the heart pumps blood, but its muscle becomes so thick and stiff that it eventually fails. It accounts for more than half of all heart failure cases—yet treatment options are limited.

One of the only effective therapies for HFpEF was discovered almost by accident, emerging from FDA-mandated studies of a class of diabetes drugs. New insights into how these drugs function have been provided through research using heart bank tissue by Zoltan Arany, MD, PhD, a professor of Physiology at Penn Medicine and frequent collaborator with Margulies. Arany’s ongoing research is studying how these drugs work—with the goal of refining existing treatments and uncovering new approaches for HFpEF and other forms of heart disease.

Meanwhile, Penn’s Human Heart Tissue Bank has become a leading source for human heart tissues for researchers from around the world, and spurred many collaborations between researchers at Penn and other institutions.

A team led by David Kass, MD, a cardiology professor at Johns Hopkins University School of Medicine, looked at heart biopsies from severely obese patients with HFpEF and identified distinct structural abnormalities. When they submitted the study for publication, however, reviewers raised a key question: Were those changes truly linked to HFpEF, or were they simply the result of severe obesity?

Answering that question required access to a rare control—hearts from people without heart failure but with severe obesity. Because hearts of individuals without signs or symptoms of heart failure are almost never biopsied, Kass turned to Margulies to ask whether such samples might exist in the Penn collection. “And I was stunned when he said, ‘Yeah, yeah, we might have, like, 150 of them now in the freezer,’” Kass said.

Using those donated hearts, the researchers showed that it is the combination of obesity and HFpEF, not obesity alone, that disrupts heart muscle structure and function. They published their findings in Science on April 23, 2026.

After the hearts are collected, the data catalogued, and tissue samples stored for future use, the organs go back to the pathology department for additional examination. Eventually, the hearts are cremated, but they leave a lasting legacy through research that is creating therapies for current and future cardiac patients.

For Margulies, it is gratifying to see that today, several other transplant centers collect explanted hearts for cardiac research, helping move the field forward. It is especially meaningful to see the impact that donor hearts have on making discoveries with the potential to save lives.

“This wouldn’t be possible without the donors and family members who permitted use of their hearts for biomedical research,” he said. “It’s a resource that does make something good come out of a tragedy.”