Therapeutic mycophenolic acid monitoring by means of limited sampling strategy in orthotopic heart transplant patients.

Therapeutic drug monitoring (TDM) is essential to maintain the efficacy of many immunosuppressant drugs while minimizing their toxicity. TDM of mycophenolate mofetil requires area under the curve AUC determinations but appears laborious, costly, and clinically impractical. To overcome these problems, limited sampling strategies (LSS) have been proposed in adult and pediatric renal transplant patients. The purpose of this study was to develop an LSS in heart transplant patients. Forty-four mycophenolic acid (MPA) full AUC(0-12h) profiles were generated by high-performance liquid chromatography in nine heart transplant patients during the first 12 weeks posttransplant. Each patient received concomitant cyclosporine and prednisone therapy. Multiple stepwise regression analysis was used to define the time points of MPA levels to explain the MPA AUC(0-12h). Agreement between abbreviated AUC and the full AUC(0-12h) was tested by means of a Bland and Altman analysis. The highest coefficient of determination r(2) among MPA AUC and single concentrations (r(2) = .610) was observed with C(2), while C(12) provided the lowest one (r(2) = .003). Stepwise linear regression showed that the minimal model with the best estimation of MPA AUC(0-12h) was obtained at timed values of 1.25, 2, and 6 hours. The corresponding estimated model was AUC = 5.568 + 0.902 * C(1.25) + 2.022 * C(2) + 4.594 * C(6) (r(2) = .926). Bland and Altman analysis revealed good agreement between predicted AUC and full AUC. A further interesting model equation obtained by four samples was AUC = 3.800 + 1.015 * C(1.25) + 1.819 * C(2) + 1.566 * C(4) + 3.479 * C(6) (r(2) = .948).

Carotenoids co-localize with hydroxyapatite, cholesterol, and other lipids in calcified stenotic aortic valves. Ex vivo Raman maps compared to histological patterns.

Unlike its application for atherosclerotic plaque analysis, Raman microspectroscopy was sporadically used to check the sole nature of bioapatite deposits in stenotic aortic valves, neglecting the involvement of accumulated lipids/lipoproteins in the calcific process. Here, Raman microspectroscopy was employed for examination of stenotic aortic valve leaflets to add information on nature and distribution of accumulated lipids and their correlation with mineralization in the light of its potential precocious diagnostic use. Cryosections from surgically explanted stenotic aortic valves (n=4) were studied matching Raman maps against specific histological patterns. Raman maps revealed the presence of phospholipids/triglycerides and cholesterol, which showed spatial overlapping with one another and Raman-identified hydroxyapatite. Moreover, the Raman patterns correlated with those displayed by both von-Kossa-calcium- and Nile-blue-stained serial cryosections. Raman analysis also provided the first identification of carotenoids, which co-localized with the identified lipid moieties. Additional fit concerned the distribution of collagen and elastin. The good correlation of Raman maps with high-affinity staining patterns proved that Raman microspectroscopy is a reliable tool in evaluating calcification degree, alteration/displacement of extracellular matrix components, and accumulation rate of different lipid forms in calcified heart valves. In addition, the novel identification of carotenoids supports the concept that valve stenosis is an atherosclerosis-like valve lesion, consistently with their previous Raman microspectroscopical identification inside atherosclerotic plaques.

Cardiac transplantation in a Duchenne muscular dystrophy carrier.

We report here for the first time the case of a symptomatic DMD carrier, who had a heart transplant for a severe dilated cardiomyopathy. Dystrophin immunohistochemistry, western blot and analysis of X-chromosome inactivation on leucocytes, and skeletal and cardiac muscle biopsies on the explanted heart were performed. The patient was a heterozygote for exons 50-52 deletion in the dystrophin gene. The number of dystrophin-deficient fibres in the heart was much higher than in skeletal muscle. On the other hand, the explanted heart showed a non-skewed pattern of X-chromosome inactivation, as in leukocytes and skeletal muscle. The adverse cardiac course may be explained by the absence of regeneration among cardiomyocytes.

Impairment of fibrinolytic potential in long-term steroid treatment after heart transplantation.

Thrombotic complications constitute an important risk in transplant recipients, in whom a hypercoagulable state and hypofibrinolysis have been associated with immunosuppressive treatment, especially with cyclosporine. In no case have clotting and fibrinolytic abnormalities been correlated with steroid immunosuppression, even though steroids were always administered. Previous studies found a relationship between hypercorticism and hypofibrinolysis both in Cushing's disease and after renal transplantation. The aim of this investigation was to compare fibrinolytic potential using the venous occlusion test in two similar groups of heart transplant patients treated with or without steroids. Euglobulin lysis time, tissue-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) activities, and antigens were determined before and after the venous occlusion test. A reduced fibrinolytic potential (significant prolongation of lysis time) due to a significant increase in PAI-1 activity and antigen levels was found in heart transplant patients treated with steroids, as compared with patients without steroid treatment and control subjects. The prevalence of reduced fibrinolytic potential was 69.2% (18 cases) in the steroid-treated group and 34.8% (8 cases) in the non-steroid-treated group. In every case, the impaired fibrinolytic potential was due to high basal PAI-1 levels. Our results are compatible with the presence of a hypofibrinolytic state secondary to long-term steroid treatment. In heart transplant recipients, steroid-induced hypofibrinolysis may constitute a further risk factor for thrombotic disease.

Extracorporeal photochemotherapy as adjuvant treatment of heart transplant recipients with recurrent rejection.

Recurrent rejection is an uncommon, severe complication after heart transplantation that is associated with a poor long-term prognosis. Photopheresis (ECP), a new form of extracorporeal photo-chemotherapy used for the treatment of cutaneous T cell lymphoma and several autoimmune diseases, has also been used for prevention and treatment of acute rejection in heart transplant recipients. It seems to induce specific suppression of both cellular and humoral rejection. In this study, we evaluated whether ECP added to standard therapies allowed better control of rejection and reduction of conventional immunosuppressive drugs in patients with repeated rejection episodes. Eight heart transplant recipients (6 men and 2 women, mean age 48 yr), with recurrent rejection were treated with ECP for 6 months. Endomyocardial biopsies (EMB) were performed monthly. As a result of treatment, 7 patients on ECP experienced a reduction of the number and severity of rejection episodes. The fraction of EMB negative for rejection increased from 13 to 41%, whereas the fraction of specimens with multifocal and/or diffuse moderate lymphocytes infiltration (grades 3A and 3B) decreased from 41 to 21%. ECP allowed reductions of daily immunosuppressive therapy: prednisone by 44% (16.9 vs. 9.4 mg), cyclosporine by 21% (366 vs. 291 mg), and azathioprine by 29% (137 vs. 97 mg). No major side effects were observed. We conclude that, although the number of patients is small, the use of ECP was safe and associated with improved control of recurrent rejection. This allowed tapering of immunosuppressive drugs, which was particularly useful in two patients with insulin-dependent diabetes and one with sternal wound osteomyelitis.

Histologic findings in the conduction system after cardiac transplantation and correlation with electrocardiographic findings.

The study of the sinus node and the specialized atrioventricular junction by serial sections in cardiac transplantation revealed that acute rejection involving the conduction system was equally severe as the working myocardium, with the exception of the His bundle. During acute rejection, the sudden appearance of a first-degree atrioventricular block may suggest severe involvement of the conduction system with impending cardiac arrest.

Morphologic spectrum of primary restrictive cardiomyopathy.

A restrictive hemodynamic profile with left ventricular (LV) end-diastolic volume < 100 ml/m2 and LV end-diastolic pressure > 18 mm Hg, in the absence of endomyocardial, pericardial, and specific cardiomyopathy, is a peculiar feature of primary restrictive cardiomyopathy. From 1985 to 1994, 7 hearts of patients who met the above hemodynamic criteria and underwent endomyocardial biopsy because of heart failure, were studied through gross (5 cardiectomies and 2 autopsies), histologic, and electron microscopic investigations. Ages ranged from 9 to 48 years (mean age 29 +/- 13). Four patients (57%) had a positive family history: 2 for hypertrophic and 2 for restrictive cardiomyopathy. Three patterns were identified in the 7 hearts: (1) pure restrictive form in 4 cases with mass/volume ratio 1.2 +/- 0.5 g/ml, ejection fraction 58 +/- 5%, LV end-diastolic volume 67.5 +/- 12.6 ml/m2, LV end-diastolic pressure 26.7 +/- 3.5 mm Hg; (2) hypertrophic-restrictive form in 2 cases with mass/volume ratio 1.5 +/- 0.07 g/ml, ejection fraction 62 +/- 1%, LV end-diastolic volume 69 +/- 10 ml/m2, LV end-diastolic pressure 30 +/- 7 mm Hg; and (3) mildly dilated restrictive form in 1 case with mass/volume ratio 0.9 g/ml, ejection fraction 25%, LV end-diastolic volume 98 ml/m2, LV end-diastolic pressure 40 mm Hg. Histology and electron microscopy disclosed myocardial and myofibrillar disarray and endoperimysial interstitial fibrosis in each pattern. The familial forms suggest the presence of a genetic abnormality. Primary restrictive cardiomyopathy may present with or without hypertrophy and shares similar microscopic pictures with hypertrophic cardiomyopathy. The 2 entities may represent a different phenotypic expression of the same genetic disease.

Donor shortage in heart transplantation. Is extension of donor age limits justified?

Chronic shortage of donor organs for heart transplantation led us to extend donor age limits. To verify the effectiveness of such a policy we have compared the results of heart transplantation in 45 patients with donors more than 40 years of age (group 1) with those of 72 patients older than 50 years of age who had heart transplantation with younger donors (group 2) between November 1985 and December 1992. The two groups were comparable in terms of mean recipient age, recipient and donor sex, and indication for heart transplantation. Mean donor age was 46 +/- 4 years (range 41 to 59 years) in group 1 and 23 +/- 7 years (range 8 to 39 years) in group 2 (p < 0.001). In group 1 cerebrovascular accidents were more common as the cause of donor death (60% versus 16%, p = 0.001), and no difference was found in ischemic time (144 +/- 47 minutes versus 140 +/- 48 minutes, p = not significant). There were 6 early (< 30 days) deaths in group 1 (13%) and 10 in group 2 (14%; p = not significant). Fatal acute graft failure was more prevalent, but not significantly so, in group 1 (10% versus 5.5%, p = not significant). Mean follow-up was 29 +/- 20 months (range 3 to 78 months) in group 1 and 30 +/- 20 months (range 3 to 80 months) in group 2 (p = not significant). At 5 years actuarial survival was 80% +/- 6% in both groups with comparable graft performance at echocardiographic and hemodynamic control studies. A significant difference was found in freedom from any type of coronary artery abnormality between group 1 (49% +/- 13%) and group 2 (77% +/- 8%) at 5 years (p < 0.05); however, freedom from coronary stenotic lesions only was similar. Major conduction disturbances have occurred more frequently in patients of group 1 (37% versus 12%; p = 0.003) without any difference in the need for permanent pacing. Donors older than 40 years of age can be accepted for heart transplantation with early and long-term results comparable with those obtained with younger donors. The impact of a higher incidence of coronary abnormalities on late performance of older grafts must be assessed at longer follow-up. Our results indicate that, because of the current organ shortage, extension of donor age limits is justified, even up to the sixth decade of life in selected cases.

Repair of congenitally malformed mitral valve in children.

We report our experience with 30 children under 15 years of age treated surgically for congenital mitral valve disease from March 1972 to July 1986. Valve reconstruction was possible in 26 patients (87%), whereas in four the valve was replaced with a mechanical prosthesis. Five patients died in the hospital (16.6%), four after conservative operations and one after mitral valve replacement. There was only one late death in a child in chronic congestive heart failure. Three patients, treated conservatively, required valve replacement 2, 22, and 24 months, respectively, after the operation. Follow-up data reveal that 22 of 24 patients are asymptomatic 5 months to 15 years after operation. Two-dimensional echocardiographic studies were performed in 19 patients treated conservatively, 17 of whom are asymptomatic. Eleven of them have no signs of mitral regurgitation or stenosis, six show only mild mitral incompetence, and two have moderate mitral regurgitation or stenosis. Peak pulmonary artery pressure is within normal limits in all. Our results indicate that mitral valve reconstructive procedures for congenital valve dysplasia may be effective and reliable in children despite the frequent severity of valve malformation. Although no major prosthesis-related complications were observed in the present series, we believe that mitral valve repair should always be attempted in the pediatric population to avoid the drawbacks of the currently available prostheses.

Viability and morphology of aortic and pulmonary homografts. A comparative study.

In view of possible clinical use of the pulmonary homograft for right ventricular outflow tract reconstruction a comparative study with the aortic counterpart was performed. Samples of aortic and pulmonary walls from 10 cadaveric hearts were assessed for viability and morphologic characteristics before and after storage in nutrient-antibiotic solution. The viability, as evaluated by an autoradiographic technique, was similar in both aortic and pulmonary specimens at the time of dissection, after 2 weeks, and after 4 weeks of storage. The histologic examination showed no changes in the structure of the media in all samples up to 4 weeks of storage. The total calcium content per gram of tissue in the pulmonary media was on an average less than half of that in the aortic counterpart. We conclude that the pulmonary homograft is preserved the same as the aortic homograft and, accordingly, it becomes available for clinical application. Moreover, a lesser content of elastic tissue and a lower amount of total calcium may, in all likelihood, make the pulmonary wall less prone to calcification.

Cardiac fibroma and heart transplantation.

Successful orthotopic heart transplantation was performed in a 38-day-old child with a fetal echocardiographic diagnosis of a left ventricular mass and in a 40-year-old woman with cardiac murmur since childhood and an echocardiographic diagnosis of asymmetric septal hypertrophy. Pathologic examination of the removed hearts, consisting of gross, histologic, immunohistochemical, and ultrastructural studies, led to the final diagnosis of cardiac fibroma. Both patients were alive and in good condition at 35 and 28 months, respectively, after operation.

Surgical management of double-outlet right ventricle.

From 1977 to 1983, 32 consecutive patients, ranging in age from 15 days to 24 years, underwent operations for double-outlet right ventricle. Twenty patients had a palliative operation either to increase (12 cases) or to reduce (eight cases) pulmonary blood flow: Ten of them have subsequently undergone total repair, and in another six correction was delayed because of possible incremental operative risk factors, such as multiple ventricular septal defects or the need for an extracardiac conduit. Four patients with multiple, complex associated intracardiac anomalies are currently considered to have uncorrectable defects. A total of 22 patients underwent correction either primarily (12) or after palliation (10). Intraventricular tunneling was performed in 16 patients with a subaortic ventricular septal defect and in one with a doubly committed ventricular septal defect. Seven of these had pulmonary stenosis and five had reconstruction of the right ventricular outflow by means of a patch (three) or a conduit (two); among this group, five also had enlargement of the ventricular septal defect. In three patients with a subpulmonary defect and in one with a remote ventricular septal defect, all of them without pulmonary stenosis, total repair was achieved by a Senning, a Mustard, or an arterial switch operation. Finally, the only patient with atrioventricular discordance and pulmonary stenosis had insertion of a left ventricle-pulmonary artery conduit. No operative deaths were observed after palliation, but one patient died of intrapulmonary hemorrhage after total repair (4.5%). Major postoperative complications included detachment of the ventricular septal defect patch in one patient and late progression of pulmonary vascular obstructive disease in another. No late deaths have been recorded. Surgical repair of double-outlet right ventricle can be accomplished with gratifying early and late results, the risk of operative death being below 5%. The outcome in patients with subaortic ventricular septal defect appears particularly favorable, despite the extensive intracardiac procedures required for total correction. An early intervention is recommended to prevent development of pulmonary vascular obstructive disease and to avoid massive cardiac hypertrophy and fibrosis, which may cause late rhythm disturbances and impede the intracardiac repair.

Tricuspid atresia versus other complex lesions. Comparison of results with a modified Fontan procedure.

Several modifications of the Fontan principle are currently applied to the treatment of tricuspid atresia with low mortality. The use of these modifications in other malformations has most frequently been associated with less satisfactory results. At our institution, from June 1977 to October 1986, 35 consecutive patients, whose ages ranged from 8 months to 20 years (median age 3.4 years), underwent a modified Fontan procedure. Twenty patients with a median age of 3.2 years (group I) having tricuspid atresia (16 patients) or hypoplastic right heart syndrome (four patients) were treated by means of a right atrium-pulmonary artery anastomosis (12 patients) or right atrium-subpulmonary chamber connection (eight patients). Fifteen patients (group II) with a median age of 3.6 years, having a single left ventricle (10 patients), left atrioventricular valve hypoplasia or atresia (three patients), or double-outlet right ventricle (two patients), underwent right atrium-pulmonary artery anastomosis, together with a repositioning of the atrial septum to the right of the right atrioventricular valve, which thus left intact the inlet to the ventricle(s). The operative mortality rate was 25% in group I and 0% in group II. One patient in group I and one in group II died late postoperatively. All the 28 survivors are free of symptoms 3 months to 9 years after correction. According to our results, low risk can be associated with modified Fontan procedures in the treatment of complex heart malformations other than tricuspid or pulmonary atresia. Preserving the integrity of the entire inlet to the ventricle(s) by repositioning the interatrial septum, as done in group II malformations, might be helpful in improving the quality of the repair.

HIV infection in the first heart transplantation in Italy: fatal outcome. Case report.

A 46-year-old man with alcoholic dilated cardiomyopathy underwent heart transplantation on November 14, 1985. It was the first cardiac transplant in Italy and at that time no HIV antibody screening test was available in this country. The patient remained in good health for 6 years postoperatively, with only one episode of rejection (type 3A). In June 1992 he died of fulminant complications of AIDS and severe chronic rejection. Neither the patient nor the organ donor belonged to any of the known risk groups for HIV infection; a retrospective analysis revealed that perioperative blood transfusions had been the vectors of transmission.

Clinical results of heart transplantation in recipients over 55 years of age with donors over 40 years of age.

Between November 1985 and November 1991, 180 patients underwent heart transplantation at our institution; 55 of these patients (31%) were over 55 years of age. Eighteen patients (10%) received hearts from donors who were over 40 years of age (mean age, 47 years; range, 40 to 55 years); (group 1); 37 hearts (21%) were from donors who were under 40 years of age (mean age, 23 years; range, 8 to 38 years). Mean recipient age was 59 years (range, 55 to 64 years) and 57 years (range, 55 to 68 years) in groups 1 and 2, respectively. The main indication for transplantation was ischemic heart disease in group 1 and dilated cardiomyopathy in group 2. Perioperative mortality and intensive care assistance were similar in the two groups. Survival was 88% versus 84% at 1 year and 81% versus 80% at 4 years in groups 1 and 2, respectively. Although infections were more frequent in group 1 (0.27 versus 0.11 episode/patient), the incidence of acute rejection was comparable in the two groups (1.50 versus 1.65 episode/patient). Angiographic and echocardiographic controls showed normal graft function up to 4 years, with low incidence of chronic rejection in both groups. We conclude that heart transplantation in patients over 55 years of age with donors over 40 years of age offers excellent short-term and mid-term results. The consideration of older donors makes heart transplantation a valid therapeutic option for selected patients in the sixth and seventh decade of life, in spite of chronic donor shortage.

Use of prostaglandin E1 in the treatment of sexual impotence after heart transplantation: initial clinical experience.

Many patients report problems of impotence after heart transplantation, which definitely impairs their quality of life. Ten men, with a mean age of 41 years, were evaluated for persistent erection problems after heart transplantation by measurement of nocturnal penile tumescence using a Rigiscan. Three men had a positive response, and their disturbances were therefore considered to have a psychological basis; seven men had a negative or only weakly positive response, and their impotence was attributed to organic causes. To all patients, intracavernous injections of an initial dose of 10 to 20 micrograms of prostaglandin E1 were administered as first-choice treatment. Nine patients obtained a firm, lasting erection 2 to 5 minutes after injection, with no relevant side effects. The patients were then instructed to self-administer the drug before intercourse, and some were able to return to spontaneous sexual activity at various intervals. Intracavernous injection of prostaglandin E1 seems to be an effective treatment of erectile impotence in heart transplant recipients; it is well tolerated with no side effects and considerably improves the patient's quality of life.

Evolution of focal moderate (International Society for Heart and Lung Transplantation grade 2) rejection of the cardiac allograft.

BACKGROUND: In the absence of clinical evidence of cardiac allograft rejection, it is still poorly defined whether the International Society for Heart and Lung Transplantation biopsy grade 2 (e.g., focal moderate rejection) should be treated. Aim of the present study was to retrospectively investigate the evolution of focal moderate rejection, diagnosed during the first postoperative year in patients who had undergone orthotopic heart transplantation. METHODS: A retrospective analysis was conducted on 256 International Society for Heart and Lung Transplantation grade 2 biopsies from 110 orthotopic heart transplantations; 125 episodes occurred within the first 3 months (group 1), 131 later (group 2). For each grade 2 diagnosis, two biopsies, one immediately before and one after, were analyzed and classified as follows: lower (grade 0 or 1), equal (grade 2), or higher (grade 3 or 4). RESULTS: Evolution of grade 2 rejection was to a lower grade in 66% of cases, an equal grade in 16.8%, and a higher grade in 17.2%, with differences between group 1 and 2 (higher: 25% versus 10%, respectively, p = 0.005). Episodes which progressed into higher grades occurred earlier compared with those which persisted or resolved (9.2 +/- 8.6 weeks versus 20.0 +/- 15.6, p < 0.001). Five-year actuarial survival and incidence of graft coronary disease were similar in patients whose conditions progressed and those whose conditions did not. However, left ventricular ejection fraction at 1 and 2 years was lower in patients whose conditions progressed compared with those whose conditions persisted or resolved (56% +/- 4% versus 66% +/- 2%, p = 0.004; 56% +/- 10% versus 64% +/- 8%, p = 0.02, respectively). CONCLUSIONS: Progression of grade 2 rejection occurred in a minority of cases and did not affect 5-year survival or incidence of coronary disease, but its relationship with long-term cardiac allograft dysfunction warrants further investigation.

HBV and HCV infections in heart transplant recipients.

BACKGROUND: Heart transplant (HTx) recipients risk acquiring hepatotropic viral infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV), and the impact of these infections on post-HTx survival remains unclear. The aim of the present study was to define the prevalence, clinical features, and natural history of HBV and HCV infections in a cohort of HTx recipients. METHODS: We retrospectively studied 360 consecutive patients who had undergone HTx. Clinical picture, hepatic injury indexes, and HBV/HCV viral serology were followed post-transplant. RESULTS: During follow-up (average, 8 +/- 3.1 years), 49 (16.5%) of the HTx recipients tested positive for at least 1 of the 2 viruses (3.1% HBV, 12% HCV, 0.5% concomitant infection). The prevalence of HCV infection in heart transplant recipients transplanted before and after 1990 was 28% and 4.2%, respectively, the latter being markedly lower (p < 0.001) than in earlier series of HTx recipients and much lower than expected in the age- and sex-matched general population. All HBV-positive and 58% of HCV-positive recipients developed chronic liver disease. Sixteen percent of patients developed cirrhosis during follow-up, and 8% died of end-stage liver disease. CONCLUSIONS: The prevalence of HBV and HCV in a large population of HTx recipients is not very different from that reported in the general population. Active viral replication of HBV and an aggressive natural history of both infections are seen in HTx recipients, however. The low prevalence of HBV- and HCV-related infection in recent series probably reflects current viral screening and vaccination policies.

Prognostic determinants of six-month morbidity and mortality in heart transplant recipients. The Italian Study Group on Infection in Heart Transplantation.

BACKGROUND: Knowledge of time course and risk factors for morbidity and mortality may allow better cardiac graft allocation, surveillance timing, and planning of immunosuppressive strategies. METHODS: Six-month morbidity and mortality were retrospectively analyzed in a multiinstitutional series of 645 heart transplant recipients. RESULTS: During a 3432 patient-months follow-up, 87 patients died of infection (n = 11), rejection (n = 11), multiorgan failure (n = 9) and other transplant-related causes (n = 56); six-month survival rate was 86%. Three hundred thirty-seven recipients had 967 treated rejection episodes (2.87 episodes/patient with rejection, lethality 3.2%); 223 major infectious episodes occurred in 162 patients (1.38 episodes/infected patient, lethality 7%). Six-month rejection and infection-free survival rates were 44% and 73%. Total mortality and cause-specific morbidity sharply declined after the first month; 160 patients (25%) had no events during follow-up. At multivariable analysis, significant risk factors for mortality were postoperative acute kidney failure, prolonged cardiopulmonary bypass time, and previous cardiac surgery. Rejection was associated with steroid-free and globulin-free immunosuppression and infection was associated with steroid immunosuppression, cytolytic treatment, venous lines placement greater than 7 days, and mechanical ventilation time. No single or combination of variables was able to discriminate patients with an event-free course. CONCLUSIONS: Morbidity and mortality have the highest incidence during the early posttransplantation phase. Preoperative variables are of limited value with respect to immunosuppressive treatment in predicting outcome. Infection is far less frequent than rejection but, in view of the higher lethality rate, deserves a vigorous effort for prevention, which is best addressed by appropriate modulation of immunosuppressive strategies.