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Introduction to the ISHLT e-monograph on the History of International Heart and Lung Transplantation

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James K. Kirklin, MD
University of Alabama at Birmingham
Birmingham, AL, USA

First HTX TIME CoverThe developmental history of human heart transplantation is laced with innovation, prescient persuasion, intense competition and courageous convictions. When all is written and the controversies laid to rest, Norman Shumway will always rise above the rest as the true Father of Heart Transplantation. But he wasn't the first. That landmark event in the history of medicine is inexorably linked to Christian Barnard, the charismatic cardiac surgeon from Cape Town, South Africa, who on December 3, 1967 took the heart from Denise Darvall, the deceased victim of a hit-and-run motor vehicle tragedy. The recipient was Louis Washkansky, a 53-year-old former sports enthusiast in the terminal phase of heart failure. The simple recognition of this amazing and historic accomplishment belies the intensely competitive struggle involving four heart surgeons and their teams, each of whom would be acclaimed in the early history of heart transplantation.

The experimental prelude and surgical preparations, shrouded in the drama of human ambition and quest for immortality, is a beautifully woven story written by the widely acclaimed writer Donald McRae in the first chapter of this monograph. Norman Shumway, Richard Lower, Adrian Kantrowitz and Christian Barnard became the principle antagonists in this fascinating race to perform the first human heart transplant. With all of his monumental contributions to the field, Norman Shumway, with his usual grace and good humor, accepted his shared place in history as he reflected about the journey in his final interview with Donald McRae (see Chapter 1): "Maybe, in the end, it all worked out for the best...yeah, I think it worked out just fine..." It was fitting that he was selected Honorary Life President of the International Society for Heart Transplantation in 1981.

Nevertheless, long before Shumway, Alexis Carrel planted the seeds for future heart transplantation in the early 1900's. An experimental surgeon, Carrel was inspired to provide surgical solutions to prevent fatal hemorrhage from wounds such as the lacerated portal vein in the assassination of French President Carnot in 1894. Carrel would later win the Nobel Prize in Medicine (1912) for his work with Charles Guthrie on vascular anastomoses.

Vladimir Demikhov staked the Russian claim to relevance in developing this field with his pioneering experimental work in canine heart and heart-lung transplants. The surgical techniques evolved with the experimental work of Webb, Goldberg, Akman and Reemtsma in the 1950's and 60's. In 1964, James Hardy at the University of Mississippi etched his name in the historical annals with his ill-fated xenotransplant of a chimpanzee heart into a dying 68-year-old man.

Shumway and Lower provided the critical experiments that paved the path for a rational approach to heart transplantation. In 1960, they first demonstrated that an animal could recover with its circulation entirely supported by a transplanted heart. Kantrowitz extended these experiments to puppies and achieved survival exceeding 100 days. Following eight years of experimental work with Richard Lower and the Stanford research team, Shumway was quoted in a JAMA article in the late fall of 1967, "We think the way is clear for human heart transplantation." Two weeks later, Christian Barnard shocked the world.

The chronology of those first few heart transplants is fascinating. Three days after the first transplant, Adrian Kantrowitz performed the first infant heart transplant on baby Jamie Scudero, dying from Ebstein malformation. Like Shumway and Lower, Kantrowitz had a strong experimental background in heart transplantation, but it was not enough for this baby. The donor heart failed and the baby died eight hours after the transplant. Louis Washkansky began showing signs of infection at the end of his second week, later dying of pneumonia 18 days after his historic transplant.

The year 1968 began with great optimism in the transplant world, but it would be short-lived. Barnard performed the world's third human heart transplant on January 2nd, and the recipient, Philip Blaiberg, became the first long term survivor, succumbing after 18 months. Shumway performed his first (the world's fourth) on January 5. Kantrowitz completed the fifth on January 9. Two weeks later, four of the first 5 heart transplants were dead, then the dark epoch shrouded heart transplantation. These three pioneers were followed by Cabrol, Ross, and Cooley. By the end of 1968, 102 heart transplants had been performed in 50 different institutions in 17 countries. The mortality was 60% by the eighth postoperative day, with a mean patient survival of only 29 days! With the sobering reality that available immunosuppression modalities were not reliably controlling rejection and infection, the global experience in cardiac transplantation fell to 17 during 1969, 13 of which were in the U.S.

By 1970, nearly all centers worldwide, with the exception of Shumway's group at Stanford and Lower's team at Medical College of Virginia, had declared a moratorium on heart transplantation because of dismal survival. Shumway's group quietly worked away during the dark decade of the 70's, gradually improving outcomes and increasing the science and knowledge of heart transplantation. During this enshrouded time frame, many events occurred that provided the scaffolding for later success. Even before Barnard's first heart transplant, Debakey successfully supported a patient with a left ventricular assist device in 1966. In 1968, JAMA published a recommended definition of brain death from the Ad Hoc Committee of Harvard Medical School, setting in motion establishment of a legal definition of brain death. Cooley implanted the first total artificial heart in 1969, just a few months after man walked on the moon. In the early 1970's, Phillip Caves built on contributions of Sakakibara and Konno to develop endomyocardial biopsy of the transplanted heart. With allograft tissue provided by this technique, Margaret Billingham, also at Stanford, established pathologic criteria for the diagnosis for cellular rejection. Distant procurement of donor hearts began in 1973 at Stanford.

The 50 years that have elapsed since the first Cape Town transplant are really demarcated into 2 epochs by the availability of cyclosporine in 1983. Prior to the introduction of cyclosporine, heart transplantation had descended into an abyss by a public splash in the late 1960's to an irrelevancy during the 1970's. Despite important ongoing activity at a few centers, in 1980, less than 10 centers worldwide had active heart transplant programs.

As a young cardiac surgeon just 2 years out of training, I was fortunate enough to be in at the beginning of the second epoch of heart transplantation. The University of Alabama at Birmingham (UAB), like most institutions, was discouraged at the unpredictable and frequently poor outcomes in the late 1970's and early 1980's. The heart transplant program had been shut down, joining the nearly worldwide moratorium on heart transplantation while awaiting more effective immunotherapy. With the first availability of cyclosporine, we were poised to re-engage, and I jumped into the heart transplant world with our first cyclosporine heart transplant in 1983. Soon thereafter, the field exploded. Centers throughout the U.S. and Europe rapidly joined the fray. The International Society for Heart Transplantation had been established in 1981, but was a small niche organization until the unveiling and rebirth of the field in 1983. Soon the Society [later renamed the International Society for Heart and Lung Transplantation (ISHLT)] flourished - mirroring, recording and facilitating the dynamic evolution of the field.

Yes, the ISHLT has showcased the incredible evolution of this revolution, providing the world's dominant platform for scientific and clinical progress, education, innovation and analytics in heart and lung transplantation and mechanical circulatory support. ■

Disclosure Statement: The author has no conflicts of interest to disclose.

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