Immunosuppressive therapy, management, and outcome of heart transplant recipients during pregnancy.

To evaluate challenges facing heart transplant recipients who become pregnant, we surveyed 194 heart transplantation centers and reviewed the literature. Thirty-two known pregnancies in heart (n = 29) or heart-lung (n = 3) allograft recipients have resulted in 29 children, including two sets of twins. The method of delivery was most often vaginal (cesarean section rate was 33%), and premature delivery was common (41%). The onset of pregnancy from the time of transplantation was 2.6 +/- 0.3 years, with the age at conception ranging from 19 to 35 years. Hypertension (44%), premature labor (30%), and preeclampsia (22%) were the most frequent maternal complications. Four patients experienced a worsening of ongoing chronic renal insufficiency; four patients experienced infections during pregnancy, and six patients (22%) were successfully treated for rejection episodes during pregnancy by adjustments in standard immunosuppressive agents. No peripartum deaths were reported; three late deaths occurred. Of the 29 children born of heart transplant recipients who became pregnant, no fetal anomalies or neonatal deaths occurred. Prematurity (41%) and low birth weight (17%) were the most common complications. All children are reported in good health at 3.4 +/- 0.4 years of age. Most transplant recipients (59%) were being treated with triple-drug immunosuppression with azathioprine, corticosteroids, and cyclosporine during pregnancy. The most common alteration to immunosuppressive therapy during pregnancy (41%) involved increasing cyclosporine doses caused by decreasing cyclosporine levels during pregnancy. Twenty-two percent of patients underwent empiric lowering of cyclosporine doses during pregnancy; four patients continued with corticosteroid tapering during pregnancy, and four patients increased corticosteroid doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac allograft function with corticosteroid-free maintenance immunosuppression.

Potent prophylactic immunosuppressive protocols promote the safe withdrawal of corticosteroid maintenance. The benefits of corticosteroid-free maintenance immunosuppression include the absence of the cushingoid habitus, fewer infections, less obesity, and lower serum cholesterol. The incidence of allograft coronary artery disease is not increased by corticosteroid-free maintenance. To assess the long-term effects of corticosteroid-free immunosuppression on allograft function, we compared results of hemodynamic study and noninvasive evaluation over the 2-year follow-up of 57 patients on corticosteroid-free maintenance to 40 patients who required corticosteroid. Age and pretransplantation diagnoses were similar, but a greater percentage of those who required corticosteroid maintenance were female (28% versus 2%, p less than 0.001). Indexes of allograft function were similar in both groups and these indexes included ejection fraction, right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac index, left ventricular end-diastolic dimension, and posterior wall thickness. Patient survival was identical in the two groups (98%). These data indicate that corticosteroids can be safely withdrawn with the subsequent early benefits and without compromising long-term allograft function.

A randomized trial of the immunosuppressive efficacy of vincristine in cardiac transplantation.

We evaluated the efficacy of the addition of the lymphoblasticidal agent vincristine to standard immunosuppression in heart transplantation in a prospective randomized study of 92 patients (46 to receive and 46 to not receive vincristine) with a follow-up period of 12 months. Patients received either equine antithymocyte globulin for the first week or OKT3 monoclonal antibody (OKT3) for the first 10 or 14 days after transplantation. Six to eight doses of vincristine were given over 9-12 weeks, beginning 2 days after completion of ATG or OKT3. The number of rejection episodes in the first six months posttransplantation, the percentage of patients corticosteroid maintenance-free at one year, cumulative immunosuppressive drug doses, deaths, infections, and neuropathy were followed. The addition of vincristine resulted in more patients achieving corticosteroid maintenance-free status at one year (vincristine 68%, no vincristine 38%, P = 0.01). In comparing patients at relatively high risk for rejection (those younger than 55 years and all females) with those at relatively low risk (males older than 55 years), only the high-risk vincristine-treated patients showed significantly fewer rejection episodes and a higher corticosteroid maintenance status at one year (66% vs. 32%, P = 0.01). There were no significant differences in survival (vincristine 96%, no vincristine 98%), infection, or amounts of other immunosuppressive agents used. The major side effect was neuropathy, which occurred more frequently in the vincristine-treated group (43% vs. 18%, P less than .001). We conclude that vincristine acts as an immunosuppressive agent in cardiac transplantation, particularly in patients at higher risk for rejection.

Amelioration of weight gain after heart transplantation by corticosteroid-free maintenance immunosuppression. UTAH Cardiac Transplant Program.

After heart transplantation, recipients frequently become obese. Although the cause is undoubtedly multifactorial, administration of corticosteroids may contribute to posttransplant obesity. To test this hypothesis, we retrospectively reviewed the change in body weight with respect to corticosteroid use after transplantation in all 110 recipients surviving 1 year in the UTAH Cardiac Transplant Program. Fifty-two recipients (47%, group 1) were unable to be withdrawn from maintenance corticosteroids, and 58 recipients (53%, group 2) were successfully withdrawn, the latter group requiring only cyclosporine and azathioprine long-term maintenance immunosuppression. The change in weight from the time of transplantation to 1 year after transplantation in group 1 was 8.7 +/- 1.1 kg; group 2 patients gained only 4.9 +/- 0.9 kg (p = 0.009). In conclusion, successful withdrawal of maintenance corticosteroids after heart transplantation decreased posttransplant weight gain, suggesting that posttransplant obesity is in part related to use of corticosteroids.