Prevention of Pneumocystis carinii pneumonia in cardiac transplant recipients by trimethoprim sulfamethoxazole.

Pneumocystis carinii pneumonia (PCP) continues to cause significant morbidity in recipients of solid-organ transplants. While some programs administer trimethoprim-sulfamethoxazole (TMP-SMX) prophylactically following transplantation, a prospective determination of the safety and efficacy of TMP-SMX in cardiac transplant recipients has not previously been reported. We therefore prospectively randomized 58 cardiac transplant recipients to receive TMP (160 mg)-SMX (800 mg) twice daily either three days per week (group B), or seven days per week (group C), or to receive no treatment (group A). Treatment began 14 days after transplantation and continued for four months. Age, sex, preexisting pulmonary pathology and immunosuppressive protocols did not differ among the groups. Of 17 patients in the control group (A), 7 developed a clinical syndrome compatible with PCP, with the diagnosis histologically confirmed by bronchoalveolar lavage during the first four months following transplantation. In contrast, no patients in either the daily or intermittent therapy groups developed PCP during the study period (P < 0.005). Both doses of TMP-SMX were well tolerated, and discontinuation of therapy was not necessary in any patient. Total white blood cell count, azathioprine dose, and number of treated episodes of rejection per patient did not differ among the three groups. We conclude that TMP-SMX can safely and effectively be administered to prevent the occurrence of P carinii pneumonia during the first four months following cardiac transplantation.

Quality of life and coping in patients awaiting heart transplantation.

The psychosocial adaptation of patients awaiting heart transplantation has not been defined. Forty-one patients (36 men, 5 women; mean age, 48 years) completed standardized questionnaires before transplantation to assess quality of life, physical symptoms, marital/social adjustment, psychiatric morbidity, coping, and compliance to medical regimens. Also, data were obtained from spouses/partners and the transplantation nurse coordinator. Unlike previously reported findings with patients after transplantation, those awaiting transplantation report moderate dissatisfaction with quality of life. Patients report physical symptoms, functional disabilities, sexual dysfunction, and psychological distress. Nonetheless, reported levels of compliance with the medical regimens and of social support were high, and both patients and spouses/partners provided marital adjustment ratings on the Dyadic Adjustment Scale that were comparable to those of well-adjusted, happily married couples. High levels of coping also were recorded. Having a positive attitude and seeking social support were the most common coping strategies, whereas confrontation, acceptance, and escapism were relatively uncommon. In conclusion, patients awaiting heart transplantation, although dissatisfied with quality of life, maintain positive psychological and social adjustment.

Total lymphoid irradiation in heart transplantation: adjunctive treatment for recurrent rejection.

In the face of recurrent heart transplant graft rejection refractory to all conventional immunotherapy, retransplantation is customary treatment. The case of a heart transplant recipient unsuitable for retransplantation whose recurrent rejection was successfully treated with postoperative total lymphoid irradiation is described.

Clinical significance of mild rejection of the cardiac allograft.

BACKGROUND: The clinical status of heart transplant patients during mild rejection (lymphocytic infiltrate without myocyte necrosis) has not been previously reported. This study examined the frequency and outcome of mild rejection associated with allograft dysfunction sufficient in magnitude to be evident on clinical exam (two or more abnormal findings) and/or two-dimensional echocardiography. METHODS AND RESULTS: The study population consisted of 59 patients, 50 men and nine women 14-61 years old (mean, 1.7 +/- 0.8 years) with a mean follow-up of 1.7 +/- 0.8 years after transplant. All were receiving cyclosporine, azathioprine, and prednisone. A total of 108 episodes of mild rejection were detected (frequency, 1.8 episodes per patient). Detailed records of clinical findings were available for 94 episodes. Thirty-five (37%) of these 94 mild rejections were associated with allograft dysfunction: hypotension, n = 4; elevated jugular venous pressure, n = 14; S3, n = 13; rales, n = 10; sinus rate > or = 110 beats per minute, n = 25; atrial fibrillation, n = 5; bradycardia < 60, n = 1; and systolic dysfunction on echo, n = 14. Treatment with high-dose steroids was clinically indicated in eight mild rejection episodes (9%) with allograft dysfunction. Of the remaining 86 untreated episodes, eight (30%) of 27 with allograft dysfunction versus six (10%) of 53 without allograft dysfunction progressed to moderate rejection on subsequent biopsy (chi 2 = 5.15, p = 0.02). Episodes with allograft dysfunction occurred earlier than those without dysfunction (15.4 +/- 2.8 weeks versus 34.4 +/- 5.5 weeks, p = 0.01) when baseline immunosuppression was higher. CONCLUSIONS: Our findings indicate that 1) mild rejection is frequently associated with cardiac allograft dysfunction; 2) nine percent of mild rejection episodes may be accompanied by severe allograft dysfunction or arrhythmias, requiring aggressive treatment; 3) mild rejection associated with allograft dysfunction occurs earlier than that without allograft rejection; 4) untreated, mild rejection episodes with allograft dysfunction progress to moderate rejection more frequently than those without allograft dysfunction. These episodes require increased surveillance for progression.

Unique antithymocyte serum versus OKT3 for induction immunotherapy after heart transplantation.

To determine the efficacy of a unique polyclonal rabbit antithymocyte serum (ATS), we compared 17 consecutive nonrandomized heart transplant recipients (mean age, 38 +/- 15 years) given a 7-day prophylactic postoperative course of locally produced ATS (whole serum, no Freund's adjuvant, IV) with 19 patients (mean age, 42 +/- 17 years) given 14 days of monoclonal antibody OKT3. Cyclosporine, steroid, and azathioprine dosages were similar. At 30 days the event-free incidence of rejection was 66% +/- 11% for OKT3 (2.3 events/100 patient-days) versus 47% +/- 12% for ATS (1.2 events/100 patient-days). At 60 days and thereafter, however, there was no difference in overall number of cumulative rejection episodes. Overall infection rates were similar in both groups: the ATS group tended to have more bacterial infections, whereas the OKT3 group displayed more viral infections. Antiidiotypic antibodies developed in 29% of the ATS group and in 22% of the OKT3 group. This report demonstrates the efficacy of this polyclonal serum preparation made without Freund's adjuvant when used as an adjunct for induction-prophylactic immunotherapy in heart transplant recipients when compared with OKT3.

Heart transplantation in children.

Orthotopic cardiac transplantation has been performed in 15 consecutive neonates and children since 1987. Diagnoses include hypoplastic left heart syndrome (5 patients), critical aortic stenosis with small left ventricle (1 patient), complex cyanotic heart disease (6 patients), and cardiomyopathy (3 patients). Twelve patients survived operation and have been followed from 1 to 45 months. Patients less than 6 years of age are managed with cyclosporine +/- azathioprine; in older patients steroid weaning is attempted. Monitoring for rejection is performed with serial echocardiography in patients under 6 years of age; older patients undergo serial biopsies. Actuarial freedom from rejection was 26% 3 months after operation; 47% were free of infection 6 months after operation. There have been no late deaths. Actuarial survival at 3 years is 79%. Nine patients have undergone postoperative catheterization. Resting hemodynamics were normal in every patient. All long-term survivors are asymptomatic and fully active. It is concluded that cardiac transplantation in neonates and children is an effective treatment option for end-stage cardiomyopathy or otherwise incurable congenital heart disease. Long-term survivors have excellent potential for full rehabilitation.

Therapy of refractory, recurrent heart rejection with multiple courses of OKT3.

The treatment for recurrent cardiac allograft rejection refractory to conventional immunotherapy is retransplantation. When retransplantation is not possible, alternative approaches must be undertaken. This report reviews the successful management of persistently recurring rejection using five serial 14-day courses of OKT3 in a 35-year-old man after two heart transplantations.