Honoring 50 Years of Clinical Heart Transplantation in Circulation: In-Depth State-of-the-Art Review

Josef Stehlik, MD, MPH; Jon Kobashigawa, MD; Sharon A. Hunt, MD; Hermann Reichenspurner, MD, PhD; James K. Kirklin, MD


Circulation. 2018;137(1):71-87. 

In This Article

Development of Surgical Technique

After migrating to North America, his seminal collaboration with Charles Guthrie at the University of Chicago began in 1905. Together, they described the technique of transplanting a donor heart within the neck of dogs.[2] Their work on vascular anastomoses resulted in the Nobel Prize in Medicine for Carrel in 1912.

Russian scientist Vladimir Demikhov performed pioneering transplantation experiments in the 1940s and 1950s, including canine heart and heart-lung transplants.[3] Experimental orthotopic (homologous) heart transplantation techniques were reported by Webb et al[4] and Golberg et al[5] in the 1950s. Webb et al[4] initially used anastomotic couplers for pulmonary venous connection; Goldberg et al[5] described a left atrial anastomosis; and Cass and Brock[6] added a right atrial technique.

Others, including Reemtsma and colleagues[7,8] at Tulane University, demonstrated prolonged survival after orthotopic heart transplantation. Stimulated by Reemtsma group's foray into kidney xenotransplantation, James Hardy at the University of Mississippi attempted an ill-fated xenotransplantation of a chimpanzee heart into a dying 68-year-old man in 1964.

The landmark experiments of Richard Lower and Norman Shumway at Stanford, first with canine autotransplantation and then allotransplantation, demonstrated for the first time (1959) that an animal could return to normal recovery with its circulation supported entirely by a transplanted heart.[9]

Kondo and colleagues[10] at Maimonides Medical Center in New York extended canine survival by focusing on puppies. Taking advantage of the immature immune system, they achieved survival in 1 puppy of >100 days after orthotopic heart transplantation. Shumway and Kantrowitz were poised for clinical application of heart transplantation when Christiaan Barnard electrified the world with the first human heart transplantation in Cape Town, South Africa, on December 3, 1967 (Figure 1A). Three days later, Adrian Kantrowitz performed the world's first infant heart transplantation on an 18-day-old infant with Ebstein anomaly using the heart of an anencephalic infant. The baby died of acute cardiac failure shortly after the transplantation. Barnard performed the third heart transplantation on January 2, 1968, resulting in the first long-term survivor (18 months). Shumway performed the fourth heart transplantation 4 days later (Figure 1B). Years later, the original technique of biatrial anastomoses (Figure 2A) would be largely replaced by the bicaval method in which the recipient's right atrium is fully excised and the recipient vena cavae are anastomosed to the donor venae cavae. This modification of the transplantation technique resulted in a lower incidence of tricuspid insufficiency and fewer atrial arrhythmias.

Figure 1.

The pioneers of first human heart transplantations.
A, Dr Christiaan Barnard. Figure courtesy of Heart of Cape Town Museum, Cape Town, South Africa. B, Dr Norman Shumway. Figure courtesy of Stanford Medical History Center, Stanford, CA.

Figure 2.

Anatomy of heart transplantation.
A, Orthotopic heart transplantation. The recipient heart is excised except for the cuffs of the recipient's right and left atria. The donor heart is transplanted into the correct anatomic position by anastomosing the donor and recipient right atrium/right atrial cuff, left atrium/left atrial cuff, aorta, and pulmonary artery (PA). A later refinement introduces a bicaval technique whereby the recipient right atrium is fully excised and the recipient vena cavae are anastomosed to the donor right atrium. B, Heterotopic heart transplantation. The recipient native heart remains in situ while the donor heart is transplanted into the thoracic cavity. The donor and recipient atria are anastomosed; the donor aorta is anastomosed to the recipient aorta; and the donor PA is anastomosed to the recipient PA. Adapted from Reichart et al11 with permission. Copyright © 1987, RS Schulz Verlag.

Although heterotopic heart transplantation had a long history in the experimental laboratory, it was first used clinically in 1974 by Losman and Barnard. The donor heart was transplanted into the thoracic cavity with the native heart remaining in place.[12] Initially, the donor heart essentially served as a permanent biological left ventricular assist device (LVAD); the technique was later modified to a biventricular support[13,14] (Figure 2B). Heterotopic heart transplantation was used primarily in the 1970s and 1980s, but it is rarely used today because of inferior long-term survival.