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Despite major advances in the treatment of end-stage heart disease, a sizable number of patients with refractory heart failure (HF), progressive angina, or uncontrolled ventricular arrhythmias cannot be stabilized with medical or interventional/surgical therapy and suffer significant morbidity and mortality.1 In these patients, biological replacement of the heart (cardiac transplantation) has become standard therapy and is widely accepted to improve quality and quantity of life in carefully selected patients. As technologic and engineering advances occur, support or replacement of the heart by mechanical devices (mechanical circulatory support [MCS]) offers additional options for patients with end-stage heart disease as a bridge to recovery, bridge to transplantation, or destination therapy.

Early efforts to implant a functioning donor’s heart into a recipient’s circulation date back to the early part of the twentieth century. In 1905, Carrel and Guthrie2 described the heterotopic transplantation of a functioning donor heart into the neck of a dog. The heart in that model functioned together with the recipient’s heart in the circulation but was not capable of supporting the circulation. Although the exact anatomic connections were not described in detail in the original publication, this model of heterotopic transplantation beat regularly for approximately 2 hours before the blood clotted in all of the chambers. Carrel and Guthrie developed innovative surgical techniques for vascular anastomosis at the University of Chicago, and those advances set the stage for future organ transplantation.3 These techniques included using ever-finer needles and sutures made slick with petroleum jelly, developing the triangulation method of small vessel anastomosis, and perfecting the everting anastomosis technique.4 This work was partially responsible for Carrel’s Nobel Prize for Physiology or Medicine in 1912.

It was not until 1933 that Mann and coworkers5 at the Mayo Clinic published their seminal report of a technique for heterotopic heart transplantation. Because this was a canine working model, the chambers did not clot immediately, and the hearts beat for a mean of 4 days. Mann and coworkers established several important surgical principles or tenets, including the importance of avoiding ventricular distention and air embolism and the prevention of thrombosis by heparin. Their most incisive observation was that failure of a transplanted heart was not always caused by faulty surgical technique “but to some biologic factor which is probably identical to that which prevents survival of other homotransplanted tissues and organs.”5 In what was undoubtedly the first description of acute allograft rejection, Mann and coworkers recount: “When the heart was removed just before it became quiescent … the surface of the heart was covered with mottled areas of ecchymoses … histologically, the heart was completely infiltrated by large mononuclears and polymorphonuclears.”5 It took another 30 years to understand and manipulate the “biologic factor” these authors had described as limiting the survival of allograft organs.

In 1960, Lower and Shumway6 performed orthotopic heart transplants in ...

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