Study seeks answer to whether ventricular-assist device can regenerate heart muscle

By Al Saint Jacques, MDLinx
Published December 7, 2016

Key Takeaways

Could heart muscle that’s been damaged by a heart attack be prompted to repair itself? Researchers at The University of Texas Southwestern Medical Center’s Hamon Center for Regenerative Science and Medicine in Dallas, TX, are launching several clinical trials to find the answer. These trials will look at whether a type of mechanical pump called a ventricular-assist device can create an environment that results in regeneration of heart cells.

“Research at UT Southwestern over the past five years was the first to show that the heart muscle in mammals can actually regrow in the early days of life. This ability stops, in part because of the work load that the heart has to do, and we believe that taking away that load by using ventricular assist devices will reactivate this regenerative ability of the heart,” said Dr. Hesham Sadek, Associate Professor of Internal Medicine and with the Hamon Center for Regenerative Science and Medicine.

Heart disease is the leading cause of death in the United States, according to the Centers for Disease Control and Prevention. An estimated 5.7 million people have heart failure, which is the inability of the heart to pump enough blood to keep up with the demands of the body, but does not mean the heart has stopped working. Currently, there are no treatments to regenerate heart muscle.

We are looking at a specific and accessible strategy to reawaken the regenerative ability of the adult heart,” said Dr. Sadek, who holds the J. Fred Schoellkopf, Jr. Chair in Cardiology.

A ventricular assist device (VAD) is a mechanical pump used to support heart function and blood flow in people who have weakened hearts, according to the National Heart, Lung and Blood Institute (NHLBI), part of the National Institutes of Health. The device takes blood from a lower chamber of the heart and helps pump it to the body and vital organs, just as a healthy heart would, according to the NHLBI. A small tube carries blood out of the heart into a pump, while another tube carries blood from the pump to the blood vessels, which deliver the blood to the body.

According to the researchers, UT Southwestern is establishing a Ventricular Assist Device Program through which the clinical trials will be conducted. The first series of clinical trials will be conducted with patients who currently have or will be getting VADs implanted to treat heart failure. Each trial will use a different measure to assess heart regeneration. The initial trial, which is currently enrolling patients, will use a nuclear imaging modality to assess heart mass. Eventually, the researchers expect to complete six or seven trials that assess the ability of VADs to promote heart regeneration and to discover biomarkers of the process in VAD patients.

The clinical trials build on previous research in Dr. Sadek’s lab that found that heart muscle in newborn mammals is capable of regeneration, much like skin and bone are capable of regeneration throughout an animal’s life. But cardiomyocytes, or heart muscle cells, lose that ability in the days following birth due to the high-oxygen environment of the beating heart.

“Dr. Sadek has brought an exciting new perspective to the clinical problem of heart disease. He has obtained evidence indicating that placing a heart on a VAD can active a regenerative response and create new cardiac muscle cells,” said Dr. Eric Olson, Director of the Hamon Center for Regenerative Science and Medicine and Chairman of Molecular Biology.

“The opportunity to bring cutting-edge advances in science to our patients with advanced heart failure who require LVAD support is truly exciting and we hope will lead to major advances in the care of such patients in the future,” said Dr. Mark Drazner, Medical Director of the Heart Failure, LVAD, and Cardiac Transplant program.

UT Southwestern has played an integral role throughout the relatively short history of VAD therapy and in the devices’ rapidly evolving technology. UT Southwestern participated in the landmark clinical trial (REMATCH) that led to FDA approval of the first left ventricular assist device for destination therapy and was the only North Texas center to participate in the HeartWare Bridge-to-Transplant trial, which was completed in 2012 and led to FDA approval of the device. UT Southwestern was among the first in the nation to implant a new, smaller-sized VAD to help a muscular dystrophy patient.

In 2015, Dr. Sadek, Dr. Pradeep Mammen, Associate Professor of Internal Medicine and Integrative Biology, and others found that long-term use of ventricular assist devices induces regeneration of heart muscle by preventing oxidative damage to cardiomyocytes.

“This work suggests that by reducing the load on the heart, a pathway for myocyte cell division that has been silenced by high demand can be turned back on. These trials are the clinical translation of that finding in the lab,” said Dr. Olson, who holds the Pogue Distinguished Chair in Research on Cardiac Birth Defects, the Robert A. Welch Distinguished Chair in Science, and the Annie and Willie Nelson Professorship in Stem Cell Research.

UT Southwestern established the Hamon Center for Regenerative Science and Medicine in 2014 with a $10 million endowment gift from the Hamon Charitable Foundation to further research into the relatively new field of regenerative medicine. The Center’s goal is to understand the basic mechanisms for tissue and organ formation, and then to use that knowledge to regenerate, repair and replace tissues damaged by aging and injury. The Center for Regenerative Science and Medicine is providing the funding for the VAD heart regeneration studies.

UT Southwestern collaborators include Dr. Mark Drazner, Professor of Internal Medicine and Medical Director of the Heart Failure, LVAD, and Cardiac Transplantation Program, and Clinical Chief of Cardiology, who holds the James M. Wooten Chair in Cardiology; Dr. Mammen, who is with the Hamon Center for Regenerative Science and Medicine; and Dr. Matthias Peltz, Associate Professor of Cardiovascular and Thoracic Surgery. Additionally, the UT Southwestern researchers will be working with Washington University and the University of Utah, two of the largest VAD programs in the country, to recruit patients for the clinical trials.

VAD/Heart Regeneration Timeline

1998-2001: UT Southwestern is one of 20 medical centers in the REMATCH trial comparing ventricular assist devices (VADs) to standard care for heart failure patients. Patients with VADs do significantly better.

  A left ventricular assist device
A left ventricular assist device, or LVAD, is a mechanical pump that can be connected to the heart of patients whose hearts are failing.
Credit: Jose Cabrera

Feb. 2011: Work by Dr. Hesham Sadek, Dr. Eric Olson and others showing the ability of the neonatal mouse heart to regenerate is published in Science.

April 2014:Cell publishes research by the Dr. Sadek and others showing that oxygen metabolism causes damage to DNA in heart cells, which shuts down their ability to regenerate.

May 2014: UT Southwestern announces the formation of the Hamon Center for Regenerative Science and Medicine thanks to a $10 million gift from the Hamon Charitable Foundation to focus on tissue and organ regeneration research.

Jan. 2015: A small study by Dr. Sadek, Dr. Pradeep Mammen and others showing that long-term VAD use leads to heart muscle regeneration is published in the Journal of the American College of Cardiology.

Sept. 2016: The first patient is enrolled in a series of clinical trials at UTSW studying the ability of VADs to lead to heart regeneration.

Share with emailShare to FacebookShare to LinkedInShare to Twitter