Analysis of time-dependent risks for infection, rejection, and death after pulmonary transplantation.

Infection and rejection remain the greatest threats to the survival of pulmonary allograft recipients. Furthermore, a relationship may exist between these events, because the occurrence of one may predispose to the other. By using multivariate analysis for repeated events, we analyzed the risk factors for bacterial, fungal, and viral infection, grade II or greater acute rejection, and death among 239 lung transplant recipients who received 250 allografts between January 1988 and September 1993. A total of 90 deaths, 491 episodes of acute rejection, and 542 infectious episodes occurred during a follow-up of 6 to 71 months. The hazard or risk patterns of death, infection, and rejection each followed an extremely high risk during the first 100 days after transplantation, a second modest risk period at 800 to 1200 days, and a lower constant risk. Infection and graft failure manifested by diffuse alveolar damage were the major causes of early death (< 100 days), whereas infection and chronic rejection were primary causes of later death after pulmonary transplantation. By multivariate analysis, cytomegalovirus mismatching risk for primary infection was the most significant risk factor for death, rejection, and infection. Absence of cytomegalovirus prophylaxis was also a risk factor for early and late death and late infection. Survival of recipients who received cytomegalovirus prophylaxis was significantly improved. Immunosuppression based on cyclosporine versus FK 506 was a risk factor for late death and late infection. Graft failure manifested by diffuse alveolar damage/adult respiratory distress syndrome was a significant risk for death late after transplantation. These data suggest the following: (1) The hazard for death, infection, and rejection after pulmonary transplantation appears biphasic; (2) lower survival is associated with ischemia-reperfusion lung injury represented by diffuse alveolar damage/adult respiratory distress syndrome; (3) cytomegalovirus mismatch, absence of cytomegalovirus prophylaxis, and development of cytomegalovirus disease are significant threats for death, rejection, and infection after pulmonary transplantation; (4) prevention of cytomegalovirus disease should improve survival by decreasing the prevalence of infection and rejection.

Extracorporeal membrane oxygenation support as a bridge to pediatric heart transplantation.

BACKGROUND: Mechanical circulatory support for intractable heart failure as a bridge to transplantation has been used infrequently in children. The lack of clinically available ventricular assist devices has resulted in the use of conventional extracorporeal circuits with oxygenator as the main modality for circulatory support. In this study we reviewed our experience with extracorporeal membrane oxygenation (ECMO) support in children with irreversible heart failure who were awaiting heart transplantation. METHODS AND RESULTS: Since 1985, 14 children were placed on ECMO support for circulatory failure and were considered candidates for heart transplantation: 8 children had postcardiotomy contractile failure, 3 had dilated cardiomyopathy, and 3 had viral myocarditis. Five of these children had cardiac arrest and were placed on support during cardiopulmonary resuscitation. Mean duration of ECMO support was 109 +/- 20 hours. Eight patients developed pulmonary edema requiring decompression of the left ventricle, 3 by blade atrial septostomy and 5 by left atrial vent cannula. Nine of 14 received a heart transplant, 1 child recovered spontaneously (myocarditis), and 4 died of sepsis on ECMO. Of the children who received transplants, 6 were early survivors with 1 late death (lymphoproliferative disease), for a total of 7 of 14 (50%) early and 6 of 14 (43%) late survivors. CONCLUSIONS: Our experience suggests that ECMO is an effective means of circulatory support as a bridge to transplantation in children. Decompression of the left ventricle is often required to prevent pulmonary edema. Sepsis and bleeding remain a limitation to prolonged mechanical support with ECMO in children.

Anastomotic pitfalls in lung transplantation.

Although airway, arterial, and venous connections required for lung transplantation appear simple, in practice we have encountered morbid early stenosis and obstructions, which are now avoided by technical modifications gradually made since 1985 in 134 cases (60 single lung and 74 double lung). Our initial eight double lung transplant procedures were done with tracheal anastomoses and omental wraps, but ischemic disruption, with a 75% (6 of 8) rate of complications, resulted in the subsequent use of bi-bronchial connections. A total of 192 bronchial anastomoses were reviewed (60 single lung, 66 double lung). Although all anastomoses were constructed between the donor trimmed to one to two rings above the upper lobe origin and the host divided at its emergence from the mediastinum, the suture technique has evolved. Nine (32%) of 28 cases with early bronchial anastomoses with end-to-end suture and intercostal muscle wrap had ischemic or stenotic complications, but the telescoping technique without wrap in 164 bronchial anastomoses reduced the problem to 12% (19 of 164). Twelve anastomoses required temporary intraluminal stenting. Vascular anastomotic obstructions occurred in five arterial (excessive length 2, short allograft artery 1, restrictive suture or clot 2) and two venous (excessive length 1, restrictive suture or clot 1) connections. Suspicion of arterial obstruction was prompted by persisting pulmonary hypertension and reduced flow to the allograft measured by postoperative nuclear scan and hypoxia. Venous obstructions were suggested by persisting radiographic and clinical pulmonary edema. Modifications of earlier techniques have improved our early success in lung transplantation and might be considered by others entering this demanding field.

Experience with pediatric lung transplantation.

Heart-lung transplantation and lung transplantation have become accepted techniques in adult patients with end-stage cardiopulmonary disease. We report here our experience between July 1985 and March 1993 with 34 children (< 20 years) who underwent heart-lung (n = 18) or lung transplantation (n = 17). Indications for transplantation included cystic fibrosis (n = 9), congenital heart disease with Eisenmenger complex (n = 9), primary pulmonary hypertension (n = 8), pulmonary arteriovenous malformations (n = 2), desquamative interstitial pneumonia (n = 2), Proteus syndrome with multicystic pulmonary disease (n = 1), graft-versus-host disease (n = 1), rheumatoid lung disease (n = 1), and bronchiolitis obliterans and emphysema (n = 1). Twenty-six patients (76%) have survived from 1 to 88 months after transplantation; most patients have returned to an active lifestyle. Of the eight deaths, four were due to infections, two to multiorgan failure, 1 to posttransplant lymphoproliferative disease, and one to donor organ failure. Four of the patients who died had cystic fibrosis. Despite considerable morbidity related to infection, rejection, and function of the heart-lung and lung allograft in some patients, our results with this potentially lifesaving procedure in the pediatric population have been encouraging.

A clinical trial comparing University of Wisconsin solution and cold cardioplegic solution with load-independent mechanical parameters.

To evaluate the efficacy of University of Wisconsin solution for clinical heart transplantation, load-independent parameters were used to assess left ventricular function after transplantation. Donor hearts were arrested with and stored in buffered cold cardioplegic solution for control (n = 5) and University of Wisconsin solution for the experimental group (n = 5). Orthotopic transplantations were performed in a routine manner. Mean donor age (cardioplegic solution, 28 +/- 5.2 years; University of Wisconsin solution, 28 +/- 5.1 years) and ischemic times (cardioplegic solution, 181 +/- 27 minutes; University of Wisconsin solution, 224 +/- 23 minutes) were similar. Two hours after reperfusion of the heart, transesophageal echocardiography was used to image the left ventricle at the mid-papillary muscle level, and a high-fidelity catheter-tipped manometer was placed in the left ventricle to record left ventricular pressure simultaneously. These images were digitized during apneic baseline conditions and during an acute reduction in preload from inferior vena caval occlusion. The left ventricular cross-sectional areas were measured and matched with left ventricular pressure from the catheter-tipped manometer to reveal pressure-area relationships. The baseline parameters fractional area change and stroke force were calculated. End-systolic elastance, the slope of end-systolic pressure-area relationship and preload recruitable stroke force, the slope of stroke force versus end-diastolic area were calculated from the inferior vena cava occlusion measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved survival following pediatric cardiac transplantation in high-risk patients.

BACKGROUND: Preoperative hemodynamic support, complex congenital heart disease, and elevated pulmonary vascular resistance present particular challenges for pediatric heart transplantation. This study was performed to identify preoperative factors that influence survival after pediatric heart transplantation over two eras of pediatric heart transplant experience. METHODS AND RESULTS: We retrospectively analyzed demographic, clinical, and hemodynamic data from 67 pediatric patients who underwent heart transplantation between February 1982 and June 1992 and compared survival between two eras (early experience versus late experience). During the early experience (group 1: February 1982 to August 1989), univariate analysis identified congenital heart disease, pretransplant extracorporeal membrane oxygenator (ECMO) support, inotropic and/or ventilatory support (UNOS status I), elevated transpulmonary gradient (at least 15 mm Hg), and elevated pulmonary vascular resistance index (at least 4 Wood units.m2) as preoperative risk factors for early death after pediatric heart transplantation. However, in the late experience (group 2: September 1989 to June 1992), the only risk factor for premature death by univariate analysis was elevated transpulmonary gradient. By multivariate analysis, elevated transpulmonary gradient was the only risk factor for our early, late, and entire experiences. One-year survival after transplantation for congenital heart disease was improved from 46% in group 1 to 73% in group 2 (P < .05). In group 1, only one patient (25%) with pretransplant ECMO support survived 1 year, whereas 66% (four of six) survived more than 1 year in group 2. CONCLUSIONS: Although elevated transpulmonary gradient continues to be a significant risk factor for pediatric heart transplantation, candidates with congenital heart disease, UNOS status I, and pretransplant ECMO support now can be successfully transplanted with reasonable hope for extended survival.

Isolated lung transplantation for patients with Eisenmenger's syndrome.

BACKGROUND: Eisenmenger's syndrome remains one of the greatest challenges in lung transplantation. METHODS AND RESULTS: Since October 1990, seven such patients with Eisenmenger's syndrome received isolated pulmonary grafts (six double lungs and one single lung). Mean patient age was 32 +/- 6 years (two men and five women). The preoperative mean pulmonary arterial pressure was 90.7 +/- 31.2 mm Hg, and the ventriculoscintigram showed markedly enlarged right ventricle and normal left ventricular function with ejection fraction of 0.660 +/- 0.115. Three atrial septal defects and four patent ducti arteriosus were repaired concomitantly. Excised lung histology showed plexogenic pulmonary arteriopathy with Heath-Edwards' grade 4 through 6. One double lung patient who had preexisting systemic vascular collapse died intraoperatively. The other six patients tolerated transplantation, and on the first operative day, mean pulmonary artery pressure decreased to 22.4 +/- 7.3 mm Hg (P < .002) and gas exchange was acceptable with an arterial/alveolar oxygen tension ratio of 0.47 +/- 0.15. Two patients died of mediastinal and pulmonary infection. The follow-up for the four survivors ranged from 13 to 25 months after transplantation. CONCLUSIONS: Our preliminary experience shows that concomitant isolated lung transplantation with cardiac repair could be a viable therapeutic option for patients with Eisenmenger's syndrome and normal left ventricular function. Dynamic right ventricular outflow obstruction is a potential hemodynamic problem in these pulmonary recipients.

Pediatric lung transplantation: expanding indications, 1985 to 1993.

The application of lung transplantation to the pediatric population was a natural extension of the success realized in our adult transplant program, which began in 1982. Thirty-two pediatric patients (age range 1 to 18 years) have undergone heart-lung (n = 16), double-lung (n = 14), and single-lung (n = 2) transplantation procedures. The cause of end-stage lung disease was primary pulmonary hypertension (n = 7), congenital heart disease (n = 7), cystic fibrosis (n = 9), pulmonary arteriovenous malformation (n = 2), desquamative interstitial pneumonitis (n = 2), graft-versus-host disease (n = 1), emphysema (n = 1), rheumatoid lung (n = 1), cardiomyopathy (n = 1), and Proteus syndrome (n = 1). Six patients (19%) underwent pretransplantation thoracic surgical procedures. The survival rate was 78% at a mean follow-up of 1.8 years. The survival rate in the 23 recipients without cystic fibrosis was 87% (95% since 1985). The actuarial 1-year survival rate in the nine recipients with cystic fibrosis was 55%. Immunosuppression was cyclosporine (n = 9) or FK 506 (n = 23)-based therapy with azathioprine and steroids. Children were followed up by spirometry, transbronchial biopsy, and primed lymphocyte testing of bronchoalveolar lavage fluid. The mean number of treated episodes of rejection per patient in the groups treated with cyclosporine and FK 506, respectively, was 1.0 and 1.2 at 30 days, 0.67 and 0.38 at 30 to 90 days, and 2.33 and 0.46 at greater than 90 days (p < 0.001, Fisher exact test).(ABSTRACT TRUNCATED AT 250 WORDS)

A decade of lung transplantation.

OBJECTIVE: The experience accrued at the University of Pittsburgh between March 1982 and December 1992 in the various forms of lung transplantation, including heart-lung, double lung, and single lung, is discussed. SUMMARY BACKGROUND DATA: Heart-lung (n = 97) was the most commonly performed operation followed by double lung (n = 80) and single lung (n = 68). Major indications included primary pulmonary hypertension (n = 76), obstructive lung disease (n = 57), Eisenmenger's syndrome (n = 42), cystic fibrosis (n = 32), and retransplantation (n = 13). Since May 1991, 115 procedures have been performed and heart-lung transplantation has decreased from 61% to 15% of the cases with a corresponding doubling in double lung from 24% to 43% and single lung from 15% to 42%. RESULTS: The 1-, 2-, and 5-year survival rates in all 232 recipients were 61%, 55%, and 44%, respectively. The actuarial survival rate was significantly better for those 107 recent recipients compared to the 125 early recipients (70% vs. 61%). Overall, the 63 single (70%) and 74 double (65%) lung procedures were more successful than heart-lung transplantation (53%). Recently, however, lung transplantation has been associated with an improvement in the survival rate from 48% to 72%. The survival rate has also improved from 53% to 77% for single lung transplant recipients. The causes of death in 106 recipients included infection (n = 40), early allograft dysfunction (n = 23), obliterative bronchiolitis (n = 13), and inoperative bleeding (n = 10). Poor outcomes also included technical problems (n = 6), lymphoma (n = 4), acute rejection (n = 3), diaphragmatic paralysis (n = 2), multisystem organ failure (n = 2), stroke (n = 2), liver failure (n = 1), and airway dehiscence (n = 1). CONCLUSIONS: The long-term outlook for lung transplant recipients has improved. There appears to be significant conservation of organs with single lung and double lung transplantation, finding greater acceptance for diseases once exclusively treated by heart-lung transplantation alone. The improved long-term outlook will be dependent upon better treatment for chronic rejection of the airways that histologically is defined by obliterative bronchiolitis.

A decade (1982 to 1992) of pediatric cardiac transplantation and the impact of FK 506 immunosuppression.

The decade from 1982 through 1992 witnessed tremendous growth in pediatric cardiac transplantation. At Children's Hospital of Pittsburgh 66 cardiac transplants were performed during this period (age range 7 hours to 18 years). The cause of cardiomyopathy was congenital (n = 30), cardiomyopathy (n = 29), myocarditis (n = 2), doxorubicin toxicity (n = 2), ischemic (n = 1), valvular (n = 1), and cardiac angiosarcoma (n = 1). Nine children (14%) required mechanical circulatory support before transplantation: extracorporeal membrane oxygenation (n = 8) and Novacor left ventricular assist system (n = 1) (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.). The mean follow-up time was 2 years (range 4 months to 8 years). The overall survival in the group was 67%. In children with congenital heart disease (> 6 months of age) the perioperative (30 day) mortality was 66% before mid-1988 (n = 10) and 0% since mid-1988 (n = 11). The late mortality (> 30 days) in children with cardiomyopathy transplanted prior to mid-1988 was 66% (n = 14) and 7% since mid-1988 (n = 15). Since mid-1988 1- and 3-year survival was 82% in children with congenital heart disease and 90% in children with cardiomyopathy. Twenty-six children have had FK 506 as their primary immunosuppressive therapy since November 1989. Survival in this group was 82% at 1 and 3 years. The actuarial freedom from grade 3A rejection in the FK group was 60% at 3 and 6 months after transplantation versus 20% and 12%, respectively, in the 15 children operated on before the advent of FK 506, who were treated with cyclosporine-based triple-drug therapy (p < 0.001, Mantel-Cox and Breslow). Twenty of 24 children (83%) in the FK 506 group are receiving no steroids. The prevalence of posttransplantation hypertension was 4% in the FK 506 group versus 70% in the cyclosporine group (p < 0.001, Fisher). Renal toxicity in children treated with FK 506 has been mild. Additionally, eight children have been switched to FK 506 because of refractory rejection and drug toxicity. FK 506 has not produced hirsutism, gingival hyperplasia, or abnormal facial bone growth. The absence of these debilitating side effects, together with the observed immune advantage and steroid-sparing effects of FK 506, hold tremendous promise for the young patient facing cardiac transplantation and a future wedded to immunosuppression.

Motility, chemokinesis, and methylation-independent chemotaxis in Azospirillum brasilense.

Observations of free-swimming and antibody-tethered Azospirillum brasilense cells showed that their polar flagella could rotate in both clockwise and counterclockwise directions. Rotation in a counterclockwise direction caused forward movement of free-swimming cells, whereas the occasional change in the direction of rotation to clockwise caused a brief reversal in swimming direction. The addition of a metabolizable chemoattractant, e.g., malate or proline, had two distinct effects on the swimming behavior of the bacteria: (i) a short-term decrease in reversal frequency from 0.33 to 0.17 s-1 and (ii) a long-term increase in the mean population swimming speed from 13 to 23 microns s-1. A. brasilense therefore shows both chemotaxis and chemokinesis in response to temporal gradients of some chemoeffectors. Chemokinesis was dependent on the growth state of the cells and may depend on an increase in the electrochemical proton gradient above a saturation threshold. Analysis of behavior of a methionine auxotroph, assays of in vivo methylation, and the use of specific antibodies raised against the sensory transducer protein Tar of Escherichia coli all failed to demonstrate the methylation-dependent pathway for chemotaxis in A. brasilense. The range of chemicals to which A. brasilense shows chemotaxis and the lack of true repellents indicate an alternative chemosensory pathway probably based on metabolism of chemoeffectors.

Efficacy of antihypertensive medication in orthotopic heart transplant recipients and its effect on renal function.

The authors looked at 77 patients following orthotopic heart transplant who received a triple immunosuppressive regimen including cyclosporine to see the effect of various antihypertensive medications on mean arterial blood pressure and renal function. There were 62 men and 15 women retrospectively classified into three groups according to the antihypertensive medications they received. Group 1 included 26 patients followed up for 10.7 +/- 2.7 months who received hydralazine therapy. Group 2 included 32 patients followed up for 9.0 +/- 3.4 months who received angiotensin-converting enzyme inhibition therapy. Group 3 included 19 patients followed up for 10.1 +/- 3.3 months who received beta-adrenergic blocking agents. Mean arterial pressure (MAP), serum blood urea nitrogen (BUN), and serum creatinine (CR) were determined for each group at the start and end of the follow-up period. The MAP at the start of the study was 107 +/- 14 in group 1, 110 +/- 13 in group 2, and 100 +/- 11 in group 3. It was not statistically significantly different in any of the groups. At the end of the follow-up period, MAP was 112 +/- 10, 111 +/- 10, and 106 +/- 12 for the three groups respectively, and it was not significantly different in any group. The serum BUN in group 3 was 25 +/- 8 mg/dL at the start of the study, and it was not significantly lower than that in group 1, 28 +/- 6, but it was significantly different from that in group 2, 34 +/- 9, P less than 0.05. At the end of the follow-up period, the difference was still maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Donor-transmitted pneumonia in experimental lung allografts. Successful prevention with donor antibiotic therapy.

Bacterial pneumonia is the most common cause of early morbidity and mortality (less than 2 weeks) after heart-lung transplantation. The majority (76%) of cultures taken from human donor tracheas at the time of explant grew bacteria. The abnormal immune response of the lung allograft and the common finding of bacterial contamination of lung donors led us to hypothesize that clinically silent bacterial contamination of the donor lung progresses to pneumonia in the recipient and that antibiotic treatment of donors will prevent the development of pneumonia in the recipient. Inocula of Streptococcus pneumoniae were instilled into the left middle lobe of normal and donor dogs to identify the number of bacteria that would result in pneumonia in a normal animal and the amount that, when given to a donor, would result in pneumonia in the recipient. Initial studies established that inocula of 10(4) colony-forming units of S. pneumoniae did not result in pneumonia in normal or immunosuppressed animals. When 10(4) colony-forming units or as few as 10(2) were instilled into the left middle lobe of donors 24 hours before explantation and use of the lung for transplantation, severe acute bronchopneumonia developed in all 18 recipients. Treatment of donors with aerosol and intravenous antibiotics, but not with either alone, prevented pneumonia in the recipients. We conclude that bacterial contamination of the donor lung leads to pneumonia in recipients. Intravenous and aerosol antibiotic treatment of donors with bacterial contamination prevents pneumonia in canine lung recipients. Treatment of human donors with this antibiotic regimen may decrease the prevalence of early bacterial pneumonia.

Donor cerebral emboli as a cause of acute graft dysfunction in lung transplantation.

Early graft dysfunction in lung transplantation has many causes, most commonly preservation injury. This report details a more unusual cause of graft failure and respiratory decompensation in the early postoperative period donor cerebral emboli occluding segments of the pulmonary arterial tree in the implanted lung allografts of two patients who had received single lung implants from a common donor in whom massive cerebral trauma had been incurred in a motor vehicle accident. The incidence, complications, and clinical manifestations of cerebral emboli are discussed.

Influence of panel-reactive antibody and lymphocytotoxic crossmatch on survival after heart transplantation.

Review of 463 heart transplants was undertaken to examine the relationship between level of panel-reactive antibody (PRA) and a standard donor-specific lymphocytotoxic crossmatch (LXM) on the incidence of death from hyperacute, acute, and chronic rejection. Death from chronic rejection was defined as being caused by graft atherosclerosis. Hyperacute rejection was diagnosed in 18 allografts, and only two recipients had PRA greater than 10% and another two a positive LXM. Five-year actuarial freedom from death caused by all forms of rejection correlated with PRA values as follows: PRA 0% to 10% (415 patients), 85%; PRA 11% to 25% (29 patients), 68%; PRA greater than 25% (19 patients), 57% (p less than 0.005). Additionally, there was a positive linear relationship between PRA and duration of acute rejection episodes in the first 3 months after transplantation. A positive retrospective donor-specific LXM was present in 42 of 401 patients; most of them (32 patients) were low positive (10% to 50% cell death), and none could be correlated with antibody specificity toward donor HLA antigens. Five-year actuarial freedom from death caused by rejection was 83% in those with a negative LXM, 74% in those with low-positive, and 79% in those with high-positive LXM (p = NS). Negative LXM result did not reduce the risk of death caused by rejection in any of the PRA subgroups. While PRA greater than 10% is a risk factor for rejection-related events, a negative LXM in patients with an elevated PRA does not reduce the risk of death resulting from acute or chronic rejection.

Posttransplant lymphoproliferative disease in thoracic organ transplant patients: ten years of cyclosporine-based immunosuppression.

Lymphoproliferative disease developed in 15 heart and five lung transplant recipients during a decade of heart and lung transplantation from 1980 through 1989. The overall incidence of posttransplant lymphoproliferative disease in patients who survived more than 30 days is 4%. The incidence after heart transplantation is 3.4% and after lung transplantation is 7.9% (p = 0.08). The peak occurrence of posttransplant lymphoproliferative disease is 3 to 4 months after transplantation. However, posttransplant lymphoproliferative disease occurring early versus late (defined as before or after 1 year after transplantation) appears to have different clinical outcomes. The mortality of early onset of posttransplant lymphoproliferative disease as a result of lymphoma is 36%; response to reduction in immunotherapy occurs in 89% and presentation with disseminated disease occurs in 23%. The mortality of late onset of posttransplant lymphoproliferative disease as a result of lymphoma is 70%; no patient responded to reduction in immunotherapy and presentation with disseminated disease occurs in 86% of patients. Epstein-Barr virus primary infection was present in 14 and secondary Epstein-Barr virus infection was present in three of the 20 patients with posttransplant lymphoproliferative disease. The other three patients were positive for Epstein-Barr virus also but had no pretransplant sera for comparison. There is no correlation with immunoprophylaxis or maintenance immunosuppression and the development of posttransplant lymphoproliferative disease in our series.

Heart transplantation in patients with malignant disease.

We have traditionally pushed the limits of conservative candidate criteria for heart transplantation. We have been gratified by our results in the aged, the diabetic, and the mortally ill. Our inclusion of patients with malignant disease underscores our philosophy to include patients as candidates for transplantation for whom the procedure has reasonable expectation of success. We report here our early results of heart transplantation in 11 patients with malignant disease. Our survival rate in this group is 100%, and all patients are leading active lives with no evidence of recurrent or metastatic tumor. Immunosuppression protocols were adjusted on an individual basis determined by the chemotherapy dosage, duration, and relation to transplantation. Whenever possible a 1-year disease-free interval after completion of adequate cancer therapy is desired before transplantation.

Coronary arteriosclerosis in pediatric heart transplant survivors: limitation of long-term survival.

Because coronary atherosclerosis after heart transplantation has been a limiting problem in long-term survival of adults, we reviewed the coronary angiograms, and autopsy data when available, from 21 of 30 children who underwent orthotopic heart transplantation and survived the perioperative period. Six patients had coronary atherosclerosis, and five of these patients died 6 months to 3 years after heart transplantation. The late deaths were sudden and unexpected. Coronary angiography demonstrated several types of lesions, including concentric narrowing, tubular segmental lesions, and abrupt obliteration of major coronary vessels. Risk factors assessed included hypertension, hyperlipidemia, cytomegalovirus infection, type of immunosuppressive regimen, number of rejection episodes, and major histocompatibility antigen mismatches. Only the frequency and duration of rejection episodes seemed to be more prevalent in the patients in whom coronary atherosclerosis developed. Despite the benefits of heart transplantation in treating children with end-stage heart disease, coronary atherosclerosis may limit long-term survival. We suggest that these children should undergo serial coronary angiography to identify those at risk for subsequent events related to coronary artery disease.