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The number of patients with heart failure is growing. End-stage heart failure is associated with significant morbidity, need for recurrent hospitalizations, decrease in quality of life, and increased mortality. Cardiac transplantation has evolved as an effective therapy for many of these patients. Tremendous advancements in the fields of immunosuppression, rejection, and infection have transformed what was once considered an experimental intervention into a routine treatment available worldwide.

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The innovative French surgeon Alexis Carrel performed the first heterotopic canine heart transplant with Charles Guthrie in 1905. Frank Mann at the Mayo Clinic further explored the idea of heterotopic heart transplantation in the 1930s. The neck became the preferred site of implantation in early experimental animal models because of the ease of monitoring the organ, the simplicity of access to major vessels, and because the recipient's native heart could serve as a built-in cardiac assist device for the transplanted organ. Mann also proposed the concept of cardiac allograft rejection, in which biologic incompatibility between donor and recipient was manifested as a leukocytic infiltration of the rejecting myocardium. In 1946, after unsuccessful attempts in the inguinal region, Vladimir Demikhov of the Soviet Union successfully implanted the first intrathoracic heterotopic heart allograft. He later demonstrated that heart-lung and isolated lung transplantation also were technically feasible.

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The use of moderate hypothermia, cardiopulmonary bypass, and an atrial cuff anastomotic technique permitted Norman Shumway (Fig. 64-1) and Richard Lower at Stanford University to further explore orthotopic heart transplantation using a canine model in 1960. The first human cardiac transplant was a chimpanzee xenograft performed at the University of Mississippi by James Hardy in 1964. Although the procedure using Shumway's technique was technically satisfactory, the primate heart was unable to maintain the recipient's circulatory load and the patient succumbed several hours postoperatively. Despite great skepticism that cardiac transplantation ever would be performed successfully in humans, South African Christiaan Barnard surprised the world when he performed the first human-to-human heart transplant on December 3, 1967. Over the next several years, poor early clinical results led to a moratorium on heart transplantation, with only the most dedicated centers continuing experimental and clinical work in the field. The pioneering efforts of Shumway and colleagues at Stanford eventually paved the way for the reemergence of cardiac transplantation in the late 1970s. The introduction of transvenous endomyocardial biopsy by Philip Caves in 1973 finally provided a reliable means for monitoring allograft rejection. Ultimately, however, it was the advent of the immunosuppressive agent cyclosporine that dramatically increased patient survival and marked the beginning of the modern era of successful cardiac transplantation in 1981. Heart transplantation is now a widely accepted therapeutic option for end-stage cardiac failure; however, the annual number of transplants in the United States (approximately 2200 per year) has remained relatively constant over the last decade because of limited donor-organ availability (from United Network for Organ Sharing [UNOS] data, through September 2009).

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