The role of complement-fixing donor-specific antibodies identified by a C1q assay after heart transplantation.

BACKGROUND: The development of donor-specific antibodies (DSA) to human leukocyte antigens (HLA) has been associated with acute rejection and allograft failure after heart transplantation. Not all DSA, however, can fix complement. METHODS: To determine the association between complement-fixing DSA and heart transplant outcomes, we retrospectively analyzed results obtained using the C1q solid-phase assay that specifically detects complement-fixing DSA in parallel with the standard IgG assay in 121 adult heart transplant recipients. RESULTS: The 52 recipients who developed post-transplant DSA had a higher incidence of acute cellular rejection (58% vs 19%, P < .001) and antibody-mediated rejection (29% vs 7%, P < .001) than the 69 recipients without DSA. The 24 recipients with C1q+ DSA had more antibody-mediated rejection than the 28 recipients with C1q- DSA (46% vs 14%, P = .012), but there was no difference in the incidence of acute cellular rejection between these two groups. Patients with post-transplant DSA had higher mortality than patients with no DSA (29% vs 13%, P = .031), mainly due to increased incidence of acute rejection. No differences in survival were found between recipients with C1q+ DSA and C1q- DSA. CONCLUSIONS: Routine monitoring of DSA post-transplant, and their characterization using the C1q assay, may provide prognostic information for acute rejection after heart transplantation.

Impact of cytomegalovirus hyperimmune globulin on outcome after cardiothoracic transplantation: a comparative study of combined prophylaxis with CMV hyperimmune globulin plus ganciclovir versus ganciclovir alone.

BACKGROUND: Cytomegalovirus (CMV) disease was previously shown to be unaltered by a 28-day course of ganciclovir compared with placebo in seronegative recipients of hearts from seropositive donors (D+/R-). This study tests the hypothesis that a combination of ganciclovir plus CMV hyperimmune globulin (CMVIG) is more effective than ganciclovir alone for preventing acute CMV illness and its long-term sequelae. METHODS: The study population receiving CMVIG (n=80) included 27 heart transplant recipients (D+/R-) and 53 heart-lung and lung transplant recipients (R+ and/or D+). Each group was matched with historical controls who underwent transplantation within the preceding 2-3 years. Outcome measures compared were as follows: 3-year incidence of CMV disease; fungal infection; acute rejection; survival; rates and severity of transplant coronary artery disease (in heart patients) defined by intimal thickness (ultrasound) and coronary artery stenosis (angiographic); and incidence and death from obliterative bronchiolitis defined by pathological criteria on endobronchial biopsy specimens (in heart-lung/lung patients). RESULTS: Patients treated with CMVIG had a higher disease-free incidence of CMV, lower rejection incidence, and higher survival rate compared with the patients treated with ganciclovir alone. The coronary artery intimal thickness and the prevalence of intimal thickening were lower in the patients receiving CMVIG. Heart-lung and lung transplant patients treated with CMVIG had lower incidences of obliterative bronchiolitis and death from obliterative bronchiolitis and longer survival compared with the patients treated with ganciclovir alone. CONCLUSIONS: CMVIG plus ganciclovir seems to be more effective that ganciclovir alone for preventing the sequelae of CMV infection. A prospective randomized study is required to confirm these observations.

Characteristics of patients surviving more than ten years after cardiac transplantation.

The clinical status and quality of life of 40 patients who lived or are still alive more than 10 years after transplantation at our institution were reviewed with the use of our transplant database, prospective patient examinations, cardiac catheterization, and exercise testing. Patient-perceived health status was determined with use of the Nottingham Health Profile and General Well Being examinations. Factors associated with longevity were determined by a Cox proportional hazards model. Twenty-six patients are alive and 14 have died. The mean age at transplant was 32.4 +/- 12 years and the current age (or age at death) is 46.1 +/- 12.8 years. Actuarial freedom from rejection was similar to that of patients surviving less than 10 years (p = 0.8), but freedom from all types of infection was less (p = 0.005). Immunosuppressive drugs include cyclosporine (11/26 patients), azathioprine (24/26), and prednisone (26/26, mean dose 12.7 mg/day). Catheterization hemodynamic data show well-preserved graft function at a mean follow-up of 11.7 +/- 3.3 years. Graft coronary artery disease prevalence is 51.0% +/- 8%. Exercise test results are as follows: duration 8.7 +/- 3.5 minutes (range 2 to 16 minutes), maximum heart rate/expected rate 77.3% +/- 11% (50% to 92%), maximum systolic blood pressure 171 +/- 23 mm Hg (140 to 208 mm Hg), and metabolic equivalents 9.2 +/- 2.3 units (5.5 to 12.9 units), or about 84% of predicted. Mean score on the General Well Being examination was 75.3 +/- 21.6 (normal). Nottingham Health Profile scores were nearly normal, except for in the 50- to 64-year-old age group in categories of mobility, pain, sleep quality, and energy level. Causes of death were coronary artery disease in 7 of 14, infection in 4 of 14, lymphoma in 1 of 14, and nonlymphoid cancer in 2 of 14. In the Cox regression, variables most associated with survival (t > 2.0, multivariate p = 0.0005) were age at transplantation (t = 3.26), preoperative duration of illness (t = 3.57), postoperative cytomegalovirus infection (t = 2.16), and ejection fraction at 12 months after operation (t = -2.62). We conclude that cardiac transplantation can provide patients with end-stage cardiac failure an acceptable general medical condition, functional status, and perceived quality of life well into the second decade after operation.

Current trends in lung transplantation. Lobar transplantation and expanded use of single lungs.

Heart-lung transplantation remains the only therapeutic option for patients with combined end-stage cardiopulmonary disease. Because of the scarcity of heart-lung donors, we have been investigating other surgical alternatives for patients with end-stage vascular and parenchymal lung disease. From June 1989 through June 1991, 48 patients underwent pulmonary transplantation. Seventeen of the 48 patients underwent single lung transplantation. Of the 17 patients in the single lung group, eight patients had pulmonary hypertension and nine had parenchymal lung disease. Four of the 17 patients underwent repair of a cardiac defect with single lung transplantation. One-year actuarial survival was 68%. Pulmonary function has been excellent. The forced expiratory volume in 1 second was 79.6 +/- 13.6 (percent predicted), forced expiratory flow 25%-75% was 72.6 +/- 14.5 (percent predicted), and arterial oxygen tension was 82.8 +/- 10.06 mm Hg when measured at annual follow-up in a group of eight patients without obliterative bronchiolitis. Pulmonary artery pressures of systemic level or greater in the group with pulmonary vascular disease were normal at annual catheterization. Most patients had at least one episode of allograft rejection. Actuarial freedom from rejection at the end of 3 months was 30%. Three of the 17 single lung patients receiving lung lobes were children. Two children received living-related lobe transplants and one neonate received a lobe from a 2-year-old cadaver donor. Single lung transplantation is an effective therapeutic option for selected patients with vascular or parenchymal lung disease. Expanding indications will permit more individuals to receive transplants from the existing donor pool. Living-related and cadaver lobe transplantation will also increase the options available to children in need of lung transplantation.

Pediatric cardiac transplantation: management issues.

Pediatric heart transplantation is an effective therapeutic modality for children with end-stage heart disease. The overall survival of young heart recipients is very good: 89% to 92% one year survival. Survival data for the long term indicates that pediatric heart recipients have a very good chance of living for decades. Advances in immunosuppression have lent optimism for the future. There are now alternatives in induction, maintenance, and acute rejection therapy. Immunosuppressants are more specific in action and prevent and treat allograft rejection with less toxic side effects and decreased morbidity. Acute rejection and infection are early complications that reduce in incidence significantly after six months post-transplant. Graft coronary artery disease continues to be the most significant hurdle to long-term survival. Currently there is a plateau in the number of heart transplants performed annually. Lack of available pediatric donors plays a large role in the paucity of pediatric transplants. This review focuses on the key management issues involved in the care of the pediatric heart transplant recipient and incorporates the experiences and protocols of the Stanford University Pediatric Heart Transplant Program.

Heart transplantation in patients over 54 years of age. Mortality, morbidity and quality of life.

AIMS: As a consequence of recent advances in heart transplantation, upper age limits for the procedure have been liberalized in many centres. It was the purpose of this study to compare post-transplant mortality, morbidity and quality of life in a consecutive series of 72 patients > 54 years (mean age, 57.6 +/- 2.7 years) with a control group of 72 adult patients < or = 54 years (mean age, 42.4 +/- 9.5 years) transplanted at one centre between 1985 and 1991. METHODS AND RESULTS: Patients were followed for 41 +/- 27 months post-transplant. Actuarial 1-, 5- and 7-year survival rates were 78 +/- 5%, vs 81 +/- 5%, 52 +/- 7% vs 66 +/- 6% and 46 +/- 8% vs 63 +/- 6% in patients > 54 years and < or = 54 years, respectively (P = ns). Causes of death were not significantly different between the groups. Patients > 54 years experienced significantly fewer rejection episodes after the 6th month post-transplant (0.5 +/- 0.9 vs 0.9 +/- 1.0, P < 0.04), and incidence and treatment of rejection episodes as well as incidence of infection was comparable between the groups. Non-lymphoid malignancies, mainly skin cancer, occurred more often in the older age group (27% vs 13%, P < 0.05). Quality of life, as assessed by the Nottingham Health Profile, was better in 5/6 dimensions of social functioning in older patients and the difference reached statistical significance for the dimensions of emotional reactions (P = 0.005) and sleep (P = 0.0005). CONCLUSION: In conclusion, carefully selected patients > 54 years can undergo heart transplantation with mortality and morbidity comparable to younger patients. Quality of life post-transplant seems even to be slightly better in the older age group.

Clinical outcome of interval cadaveric renal transplantation in cardiac allograft recipients.

The introduction of cyclosporine into widespread clinical use has resulted in improved patient survival following cardiac transplantation. As a result of increased numbers of cardiac transplants, the inherent nephrotoxicity of cyclosporine, and prolonged patient survival, cardiac transplant recipients commonly present with renal dysfunction. In the subgroup who ultimately develop end-stage renal disease (ESRD), therapeutic options include renal transplantation. However, the clinical course associated with this treatment modality is unknown. From 1980 to 1993, 430 cardiac transplants were performed with cyclosporine-based immunosuppression at the Standard University Medical Center. Fourteen (3.3%) patients developed ESRD, requiring chronic dialysis or renal transplantation. The cause of ESRD was cyclosporine nephropathy (13/14; 93%) and glomerulonephritis (1/14; 7%). The average time interval to the development of ESRD was 82 +/- 42 months. Nine patients underwent renal transplantation. During the period of followup (38 +/- 27 months; range 6-89 months) after renal transplantation, cardiac function remained stable. There were no episodes of primary nonfunction of the renal allograft. Patient and renal allograft survival was 89% at both 1 and 3 years after renal transplant. Average serum creatinine was 1.3 +/- 0.6 mg/dl at 1 year and 1.6 +/- 0.8 mg/dl at 3 years post-transplant. The incidence of infectious complications was not statistically different when compared to that of the heart transplant controls and that of a group of cadaveric renal transplant controls (n = 20). Surprisingly, the incidence of renal allograft rejection in the heart transplant patients was 10-fold less than that of the renal transplant controls (0.006 +/- 0.02/patient-year vs. 0.062 +/- 0.05/patient-year; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)