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What Becomes of the Broken Hearted? Penn Cardiovascular Institute’s Tissue Bank Uses Broken Hearts to Unlock the Mysteries of Heart Failure

To celebrate February as American Heart Month, the News Blog is highlighting some of the latest heart-centric news and stories from all parts of Penn Medicine.

BrokenheartIt may seem thoroughly unromantic, but researchers at Penn Medicine’s Cardiovascular Institute are hoping for some broken hearts this Valentine’s Day.  But these broken hearts could wind up being the unlikely heroes in the ongoing search for new therapies to treat one of the most common health conditions in the world – heart failure.

According to the American Heart Association, about 5.7 million people in the U.S. alone suffer from heart failure. Statistics also show that, each year, 670,000 new cases are diagnosed and more than 277,000 people will die of heart failure.

Physicians working to understand and develop new therapies for heart failure rely on human tissues for their investigations. Many of these valuable tissues come from diseased or “broken” hearts that are replaced by transplantation or repaired by implanting medical devices that help keep the heart going. One of the world’s largest repositories for this type of tissue resides right here in Philadelphia, at the Penn Cardiovascular Institute’s Human Heart Tissue Repository.

The program, led by Kenneth Margulies, MD, professor of Medicine and research director for the Heart Failure and Cardiac Transplantation Program at Penn, allows surgeons, physicians and researchers to work together to understand why certain heart defects, such as heart failure, occur and how they can be more accurately treated.

“In the past, portions of excess heart tissue from a variety of procedures, including heart transplants, were simply discarded,” says Dr. Margulies. “We know now that this tissue is extremely valuable for research purposes and can act as a window looking into the genetic contributors to heart disease and the processes that affect the pace and severity of heart failure.”

Heart failure can result from many different diseases (including atherosclerosis, hypertension, diabetes, gene mutations, infections and others), and typically evolves over many years.  Combine these diverse risk factors with the significant differences between hearts of humans and other species, and researchers are left without a truly adequate animal model of human heart failure.

“These factors make our ability to study human heart tissue directly critical to understanding the complex mechanisms of human heart failure,” says Dr. Margulies.

Deep Roots in Research
Dr. Margulies first initiated a human heart tissue research program 18 years ago. Most of his work has involved studies examining how the heart beats (or regulation of contractility), structural and functional changes of the heart after internal or external damage (or myocardial remodeling and recovery), and how various diseases cause the genetic structure of the heart to change over time.  Through continuous commitment to carefully procuring human heart tissue, Penn’s heart tissue bank now includes over 18,000 human heart specimens from more than 850 hearts. 

Dr. Margulies currently collaborates with Thomas Cappola, MD, associate professor of Medicine, on a large scale analysis that will help identify new targets for heart failure treatment.  “To address a growing heart failure epidemic and critical need for new therapeutics, our ongoing research using human heart tissue seeks a better understanding of how human genetics and risk factors cause changes in heart structure and function and of how native cardiac recovery and repair mechanisms can be exploited for therapeutic purposes,” he says.

Dr. Margulies says that the Penn heart tissue bank has supported extramural research at 35 academic laboratories in the U.S., including 28 outside of Penn, with at least 46 peer-reviewed manuscripts derived from human tissue studies to date. 

One such study, funded by the National Heart, Lung, and Blood, Institute, and spearheaded by researchers at Penn and the Washington University School of Medicine, utilized samples from the tissue bank to help identify a common genetic risk factor for heart failure in Caucasians that is also linked to kidney function. Their results are helping clinicians understand that when  treating  heart failure patients, kidney function is also a major concern and that the heart and kidney should be considered together in exploring genetic predisposition to heart failure.

Another recent study identified increased levels of cardiac stem cells in failing human hearts and found that these cells were capable of forming new heart muscles cells.  Understanding these natural repair mechanisms and where they are insufficient indicates where new approaches are needed to improve the engraftment, maturation and survival of stem cell therapies designed to repair hearts damaged by heart attacks. 

“Our long range goals are to empower a therapeutic shift involving more direct molecular and cellular targeting of diseased myocardium via new heart failure therapeutics,” says Dr. Margulies.

In addition to the heart failure work going on at Penn, researchers from the Penn Cardiovascular Institute are also using tissues for investigations that could lead to better ways to diagnose or treat other conditions such as coronary artery disease and cardiomyopathy. 

Complex Research, Easy Process for Patients
The process is simple for any patient who decides to donate their tissue. They are approached before they go in for a transplant or to have a medical device implanted to consent to have a sample of their heart taken for research purposes. For each heart tissue sample procured, comprehensive information about patient demographics, clinical history, cardiac testing, medications and comorbidities are entered into database that provides essential data for a variety of research projects. All of the patient’s personal information is deidentified, so it’s completely confidential.

“When I first approach a patient to consent them for the heart tissue protocol, I am never sure what kind of reception I am going to get, but as soon as I mention that it is for research I am greeted with an enthusiastic ‘Yes’,” says Christine Malloy, a project manager for the heart tissue bank. “The patients understand that there is no direct benefit to them but are more than happy to help others who are affected by heart disease.  It’s a very rewarding experience for all.”

Penn patient Karl Schumm donated part of his diseased heart when he received a heart transplant at Penn in August 2009. Read Karl’s full transplant story.

“We both have been organ donors for a very long time,” says Karl’s wife, Karen Schumm. “When asked if we would donate Karl's diseased heart we thought it was the right thing to do. Who knows the research done may help prevent heart disease forever.”


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