Jamieson Sw

TWENTY-EIGHT CASES OF HUMAN HEART-LUNG TRANSPLANTATION

Between March, 1981, and August, 1985, twenty-eight heart-lung transplant operations were done in 27 patients at a single institution. 8 patients died in the perioperative period and adhesions related to previous thoracic surgery proved to be a major risk factor for postoperative haemorrhage. Obliterative bronchiolitis developed in half of the 20 long-term survivors, a mean of 11.2 months (range 2-35 months) after surgery: 4 of these patients died, 3 are functionally limited, 2 were successfully treated with corticosteroids, and the remaining patient was successfully retransplanted. The other 10 long-term survivors returned to a normal life with essentially normal pulmonary function measured at a mean of 22.6 months (range 4-42 months) after transplantation. All the surviving patients have evidence of renal impairment related to cyclosporin nephrotoxicity. The results indicate that, although heart-lung transplantation is compatible with essentially normal long-term pulmonary function, the procedure should not yet be regarded as a routine clinical intervention.

Determinants of Operative Mortality for Patients Undergoing Aortic Valve Replacement

The influence of 35 preoperative and intraoperative characteristics on operative mortality risk after 1,479 isolated aortic valve replacement procedures (1967 to 1981) was investigated utilizing univariate and multivariate logistic regression analyses. Mean age at operation was 58 +/- 13 years; 72% of patients were men. Physiology was classified as aortic stenosis (58%), regurgitation (30%), or both (9%). The overall operative mortality rate was 7% +/- 1%, but there were substantial differences in operative mortality rates among physiological subgroups (aortic regurgitation, 10% +/- 2%; aortic stenosis, 6% +/- 1%; stenosis/regurgitation, 5% +/- 2%). Independent determinants of operative mortality rate in the entire group were advanced New York Heart Association functional class, renal dysfunction, physiological subgroup, atrial fibrillation, and older age. In the aortic regurgitation subgroup, functional class, atrial fibrillation, and operative year were independent predictors. In the aortic stenosis subgroup, the significant determinants were functional class, renal dysfunction, age, prosthetic valve dysfunction, and absence of angina. Concomitant coronary bypass grafting, previous operation, endocarditis, and ascending aortic replacement had no independent predictive effect on operative mortality rate. Thus, the early results of aortic valve replacement can be related to several specific variables describing the functional and physiological status of the patient. Operative mortality rate is not independently related to previous operation or concomitant operative procedures. Specific differences in risk factors exist among the various physiological subgroups, probably reflecting the pathophysiology of the different hemodynamic lesions. This information should provide for a more rational approach to aortic valve replacement, at least in terms of early risk/benefit deliberations.

Long-term results, hemodynamics, and complications after combined heart and lung transplantation.

During the first 31/2 years of the Stanford heart-lung transplant program, 23 transplants have been carried out in 22 patients with severe pulmonary vascular disease. Actuarial survival curves predict 1 and 2 year survival rates of 71% and 57%, respectively, for all patients. As a result of increasing experience, the early mortality of 26% has been reduced, with only one early death occurring in the last eight patients; prior cardiac surgery was a contributing factor in three of the six patients suffering early deaths. Two late deaths occurred in the series 14 and 15 months after operation. One patient died suddenly as a result of an acute myocardial infarct and the other patient died because of respiratory failure. At autopsy, both patients had severe proliferative coronary atherosclerosis with obliterative bronchiolitis affecting the lungs. An additional patient required a retransplant for obliterative bronchiolitis 37 months after the initial procedure, and he too was found to have severe coronary artery disease. Hemodynamics and left ventricular function were normal in patients studied 1 and 2 years after undergoing the transplantation procedure. Thus, the early mortality and morbidity of combined heart and lung transplantation has been significantly reduced, but the long-term complications, particularly graft atherosclerosis and obliterative bronchiolitis, are yet to be fully controlled.

Heart-Lung Transplantation for Irreversible Pulmonary Hypertension

Combined heart and lung transplantation was carried out in 17 patients at Stanford University between March, 1981, and December, 1983. The recipients were between 22 and 45 years old. All patients had end-stage pulmonary hypertension; 10 had Eisenmengers syndrome and the remaining 7, primary pulmonary hypertension. Five patients died within the first few postoperative weeks. The remainder are well between four weeks and 33 months from operation. The immunosuppressive protocol has consisted of cyclosporine with an initial course of rabbit antithymocyte globulin. Azathioprine also was given for the first two weeks and then was replaced with prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with high doses of methylprednisolone. Modifications of technique that have developed include the removal of the recipient heart and lungs separately, and preservation of the lungs with a modified Collins solution instead of a cardioplegic solution. Rejection occurred in 6 of the 12 survivors. Infections developed in 9 patients, but only one resulted in a fatal outcome (Legionella). Thus, the results of clinical heart-lung transplantation have been considerably superior to clinical efforts in lung transplantation. It is suggested that the combined operation is preferable for the following reasons: (1) all diseased tissue is removed, thus eliminating recurrent infection and ventilation/perfusion disparity; (2) transplantation of the entire heart-lung block preserves coronary-bronchial vascular anastomoses and makes airway dehiscence less likely; and (3) to date, diagnosis of rejection by cardiac biopsy has appeared to be a satisfactory method of diagnosing and treating pulmonary rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

COMBINED HEART AND LUNG TRANSPLANTATION

Combined heart-lung transplantation has now been carried out in 27 patients at Stanford University Medical Center. All recipients had suffered from pulmonary hypertension, either primary or the result of Eisenmengers syndrome. The one-year survival has been approximately 70%. All survivors returned to normal activity, though later respiratory difficulty has been encountered in some of these patients and has required retransplantation in one. These late occurrences are likely the result of inadequate control of rejection. Heart and lung transplantation has been shown to be an effective therapy for otherwise progressively fatal pulmonary conditions, and, in the case of Eisenmengers syndrome, has presented a therapeutic avenue for the first time. The late complications encountered in some of these patients can probably be averted with increased experience.

Lymphoma in Cardiac Transplant Recipients Associated with Cyclosporin A, Prednisone and Anti-Thymocyte Globulin (ATG)

Cardiac transplantation has been used since 1968 to restore cardiac function in selected patients with otherwise unmanageable heart disease. In these recipients successful outcome of the procedure has been highly dependent upon effective management of allograft rejection using immunosuppressive agents. Prior to 1980 these agents included Azathioprine, corticosteroids and antithymocyte globulin — ATG (conventional therapy). In 1980 cyclosporin A, a fungal product whose therapeutic effect appears to result from its ability to block allograft directed T cell cytotoxic responses while leaving intact T cell suppressoV responses, was substituted for azathioprine in the conventional therapy regimen (cyclosporin A therapy) (1,2). Although outcome of transplantation has been favorably effected in patients treated with cyclosporin A (79% one year survival vs. 63% in conventionally treated recipients) morbidity due to lymphoma has increased.

Current management of cardiac transplant recipients.

Changes in the management of cardiac transplant recipients over the past 10 years have resulted in a substantial improvement in the outlook for survival. Imuran and prednisone remain the primary immunosuppressive agents, but rabbit antihuman thymocyte globulin is used initially and reinstituted during rejection. Endomyocardial biopsy has allowed more precise diagnosis and management of rejection, and more recently immunological monitoring has been introduced to provide more frequent assessment of the host immune response. Infection is the major cause of death, and its diagnosis and treatment is managed aggressively. Current survival figures justify the use of cardiac transplantation, by an experienced team, when other measures have been exhausted.

Minimal lung pathology in long-term primate survivors of heart-lung transplantation

Etude de 2 singes Rhesus ayant survecu longtemps (+ de 5 ans et + de 7 ans) a une transplantation cœur-poumons. Les alterations pulmonaires sont peu importantes; on note une fibrose pulmonaire progressive, probablement due a la toxicite de la cyclosporine, un epaississement de la plevre, mais pas de bronchiolite obliterante (complication frequente chez lhomme)

SURVIVAL OF HEART ALLOGRAFTS IN RATS TREATED WITH AZATHIOPRINE AND SODIUM SALICYLATE

In a rat heart transplant model representing a severe mismatch, median survival time (M.S.T.) with no treatment was 6 days. M.S.T. with azathioprine was 6 days, and with azathioprine and methylprednisolone 7 days. Azathioprine with promethazine hydrochloride gave an M.S.T. of 15 days. In rats treated with sodium salicylate alone M.S.T. was 16 days, and when azathioprine was administered for 12 days in a group continuously treated with sodium salicylate, all hearts were beating normally at 50 days.