Study shows unexpected electrical changes in the first successful transplant of a genetically modified pig heart

Study shows unexpected electrical changes in the first successful transplant of a genetically modified pig heart

Ten months after transplanting the first genetically modified pig heart into a human patient, researchers at the University of Maryland School of Medicine (UMSOM) continue to report new insights from the groundbreaking transplant. Their latest study shows for the first time that unexpected electrical changes occurred in the pig heart transplanted to patient David Bennett. The results were presented last weekend at the American Heart Association (AHA) meeting.

The unexpected cardiac conduction measurements, as seen on an electrocardiogram (ECG), did not contribute to the heart failure at two months but will help inform future cardiac xenotransplantation.

Electrical signals in a pig heart normally travel very quickly, faster than in a human heart, but we found that electrical signals in a transplanted pig heart in Mr. Bennett traveled much slower. Sometimes these signals even moved slower than we would expect from a human heart. To be clear, his heart rhythm was normal, only the time it took for the current to flow through the heart was prolonged.”

Timm Dickfeld, MD, PhD, study leader, professor of medicine and head of electrophysiological research at UMSOM

He and his colleagues used an EKG to monitor the patient daily after his transplant. Monitoring the heart with ECG post-transplant is one way to assess the electrical conduction system after a heart transplant. A 12-lead ECG measures electrical conduction in 12 different electrical angles of the heart.

Specifically, UMSOM researchers reviewed two ECG measures: the PR interval/QRS complex and the QT interval. The PR interval and QRS complex measure the time it takes for current to travel from the upper chamber to the lower chamber and through the lower chambers, ultimately pumping blood throughout the heart. The QT interval measures the time it takes for the lower chambers of the heart to complete a complete electrical cycle associated with a heartbeat.

“These findings do not appear to be associated with a pathologic outcome such as heart failure or signs of rejection,” said study co-author Bartley Griffith, MD, Professor of Surgery and Thomas E. and Alice Marie Hales Distinguished Professor of Transplantation at UMSOM. He performed Mr. Bennett's transplant.

“Genetic modifications to the pig heart designed to reduce the likelihood of an immune system response were not responsible for the unexpected ECG results,” said study co-author Muhammad M. Mohiuddin, MD, professor of surgery and scientific/program director of UMSOM's Cardiac Xenotransplantation Program, whose research led to this historic transplant.

Other faculty members have analyzed cardiac imaging studies, which are used to monitor heart function and check for signs of transplant rejection. Manjula Ananthram, MD, assistant professor of medicine at UMSOM, and her colleagues presented a research excerpt at the heart association meeting showing that echocardiography works well to measure the volume of blood pumped from the pig's heart to the rest of the body compared to the more invasive "gold standard" procedure, cardiac catheterization. “This was reassuring news and could ultimately mean that we may not need to do as much invasive monitoring in future patients receiving xenografts,” said Dr. Ananthram. “We are still carefully reviewing our data to determine the best way to monitor the function of the transplanted pig heart.”

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The historic xenotransplantation surgery was performed on January 7, 2022 by faculty at the University of Maryland School of Medicine (UMSOM) at the University of Maryland Medical Center (UMMC), collectively known as University of Maryland Medicine. Surgery was the only treatment option available for patient David Bennett, who did not qualify for a traditional heart transplant and was in end-stage heart failure nearing the end of his life. The procedure was approved by the US Food and Drug Administration under its Expanded Compassionate Use provision.

Before the transplant, Mr Bennett was bedridden for eight weeks with a life-threatening heart arrhythmia and was placed on a heart-lung bypass machine called extracorporeal membrane oxygenation (ECMO) to stay alive. Within days of the transplant, he was weaned from ECMO and participated in active rehabilitation for nearly two months. He regularly visited family members and sang along to “America the Beautiful” while watching the Super Bowl with his physical therapist in February.

The research team published its initial findings about the transplant last June in the New England Journal of Medicine.

"The transplanted pig heart was exposed to numerous variables in its new environment of the human body. One or more of these may have affected the electrical conduction system," said UMSOM Dean Mark T. Gladwin, MD, vice president for medical affairs at the University of Maryland, Baltimore, and John Z. and Akiko K. Bowers Distinguished Professor. “We need to continue to examine the data and share our findings with the medical community.”

Dr. Griffith was selected by the AHA to deliver the annual William WL Glenn Lecture at this year's AHA meeting for his cardiothoracic achievements. In addition to his recent achievements in advancing the field of cardiac xenotransplantation, in 1983 he performed the first double lung transplant on a young man with cystic fibrosis. He was also one of the early pioneers who tested the artificial heart as a bridging device while waiting for a donor heart to become available.

Source:

University of Maryland School of Medicine

Reference:

Kagan, C., et al. (2022) Abstract 12072: ECG Appearance and Evolution of Baseline ECG Characteristics in the Worldwide First Genetically Modified Porcine-to-Human Xenotransplant. Traffic. https://www.ahajournals.org/doi/10.1161/circ.146.suppl_1.12072.

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