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Methods
A 47-year-old man with end-stage valvular cardiomyopathy underwent orthotopic heart transplantation on December 18, 1991, after being on the waiting list for heart transplantation for 11 months. He had been operated on at another hospital in 1984 for severe aortic regurgitation with a dilated ascending aorta; a composite graft with a Bjork-Shiley mechanical prosthesis had been implanted. His early postoperative course had been complicated by a myocardial infarction, low-output state, and ventricular arrhythmias. Recurrent episodes of ventricular tachycardia were observed one year after surgery, and the patient was treated with amiodarone. During the next few years he had several episodes of left-sided heart failure that required repeated hospitalization, and he became fully disabled in 1990. At the time of transplantation, he was bedridden, with marked dyspnea at rest.
The heart donor was a 20-year-old man in whom brain death was due to a self-inflicted gunshot injury. An uneventful orthotopic heart transplantation was performed with a modified technique involving end-to-end anastomoses of both venae cavae, a procedure we now use routinely, instead of a single right atrial anastomosis. The endotracheal tube was removed on the first postoperative day, and the patient was transferred from the intensive care unit one day later. On the fifth postoperative day, the patient, who had appeared to have made a full recovery, had sudden intracerebral bleeding with right-sided hemiplegia, disorientation, and aphasia. No preceding hypertensive crisis had been recorded. His prothrombin time was 28 percent (therapeutic range, 25 to 35 percent; international normalized ratio, 2.6), the platelet counts were normal, and no other clotting disorders were present. Cerebral angiography ruled out a cerebral aneurysm, and computed tomography revealed an intracerebral hematoma in the region of the left internal capsule with perifocal edema. This hematoma was evacuated through a left frontotemporal craniotomy on the ninth postoperative day.
In spite of aggressive treatment, the patient's intracranial pressure continued to increase until it reached 60 mm Hg. On the 13th postoperative day the neurologic examination showed no brain-stem reflexes; Doppler study and cerebral angiography indicated complete cessation of brain perfusion, and the diagnosis of brain death was made on the 13th postoperative day. The hemodynamic state remained stable, without the need for positive inotropic medication. A myocardial biopsy demonstrated normal findings and an absence of rejection. Echocardiography showed excellent function of the transplanted heart, and the decision was made to reuse this heart in another patient. Before transplantation, the first patient gave his consent for the eventual use of his organs; the second patient was fully informed about the procedure and gave his consent before surgery. The decision was approved by the ethics committee of our institution.
The second recipient of the heart was a 58-year-old man with inoperable three-vessel coronary artery disease and four previous myocardial infarctions, who had dyspnea and angina pectoris at rest. Since December 1990 he had been in New York Heart Association class III or IV, despite intensive medical therapy. He had been considered for heart transplantation since October 1990. On December 31, 1991, after criteria for brain death had been met in the first recipient, the previously transplanted heart was removed with use of standard operative techniques, and a second orthotopic transplantation was performed. The cardiectomy was performed at the previous suture lines, with careful debridement of the previous anastomotic edges. For the second orthotopic transplantation of the heart, we again used a modified technique with end-to-end anastomoses of the venae cavae.
Immunosuppression was induced in both patients by triple-drug therapy: cyclosporine (at a dose sufficient to maintain whole-blood levels of 400 to 600 ng per milliliter), azathioprine (0.5 to 1.5 mg per kilogram of body weight per day), and prednisone (0.8 mg per kilogram per day for the first 10 days, followed by successive dose reductions to 0.3 mg per kilogram per day by the third week). Rabbit antithymocyte globulin (4 mg per kilogram per day) was given intravenously for the first five days after surgery. Both the first and second recipients received intravenous azathioprine (5 mg per kilogram) at the beginning of anesthesia, and 1000 mg of methylprednisolone was given before the removal of the aortic cross-clamp. Before the removal of the transplanted heart from the first recipient, when the diagnosis of brain death had been clearly established but before the confirmatory (second) electroencephalographic study was performed, immunosuppression was intensified and 1000 mg of methylprednisolone and 4 mg of rabbit antithymocyte globulin per kilogram were given.
Results
The postoperative course of the second recipient of the transplanted heart has been uneventful. The donor and the two recipients had ABO compatibility but, as is often the case in heart transplantation, they were mismatched for HLA-A, B, and DR antigens (Table 1). There were no major episodes of rejection. Routine myocardial biopsies performed at weekly intervals in the second recipient showed no evidence of rejection, except for a biopsy sample obtained on the 15th day. This specimen showed multifocal moderate rejection (grade 3A [Quilty A] according to the International Society for Heart Transplantation standardized grading system4); antirejection therapy (1000 mg of prednisolone and 4 mg of rabbit antithymocyte globulin per kilogram per day) was given for five days.
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Discussion
The shortage of donors is the limiting factor in heart transplantation. Recently, a plateau in the number of procedures has been reached, and an increase is now possible only by enlarging the donor pool5. At present, there are not enough donor hearts, and the waiting time is long1,6. This fact is demonstrated by the case of our second recipient, who had been waiting for an appropriate heart for more than 14 months.
A shortage of donor organs has led to new strategies for increasing the availability of hearts for transplantation. Current criteria for donated organs have been liberalized, thus enlarging the donor pool. Extending the permissible ischemic time to more than four to six hours, accepting donors older than 55 years of age, and accepting greater mismatches between donor and recipient in body weight are some of the changes being implemented, evidently without jeopardizing overall results2,7,8. In addition, hearts have been obtained from recipients of heart-lung transplants who do not have end-stage right-sided heart failure (the so-called domino operation)9. The critical lack of donor organs highlights the importance of the appropriate selection of recipients according to narrower indications for transplantation and retransplantation. Because of an increased risk of early and late morbidity and mortality,3,10 early retransplantation in recipients in whom one heart has been rejected seems not to be justified given the current critical shortage of organs11.
This extraordinary case suggests an unorthodox method of alleviating the organ shortage. Because brain death in a heart-transplant recipient is so rare, however, the reuse of transplanted hearts is unlikely to have any appreciable effect on the chronic shortage of donor hearts. Nonetheless, it is interesting to note that this twice transplanted heart functioned well in three people.
Source Information
From the Clinic for Cardiovascular Surgery, University Hospital Zurich, Zurich, Switzerland.
Address reprint requests to Dr. Pasic at the Clinic for Cardiovascular Surgery, University Hospital Zurich, Ramistrasse 100, CH-8091 Zurich, Switzerland.
References
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Related Letters:
Reuse of a Transplanted Kidney
Andres A., Morales J. M., Lloveras J.
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Full Text
N Engl J Med 1993;
328:1644, Jun 3, 1993.
Correspondence
This article has been cited by other articles:
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