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Background: Children undergoing orthotopic heart transplant (OHT) may require complex reconstruction of superior vena cava (SVC) anomalies. SVC anatomy and mode of reconstruction are potential risk factors for SVC obstruction., Methods: A retrospective single-center review was conducted of patients undergoing initial OHT between January 1, 1990, and July 1, 2021. Simple SVC anatomy included a single right SVC to the right atrium or bilateral SVCs with a left SVC to an intact coronary sinus, without prior superior cavopulmonary connection. Presence of anomalous SVC anatomy, superior cavopulmonary connection, or previous atrial switch operation defined complex anatomy. Reconstructive strategies included atrial anastomosis; direct SVC-to-SVC anastomosis; and augmented SVC anastomosis using innominate vein, patch, cavopulmonary connection, or interposition graft. The primary outcome was reintervention for SVC obstruction., Results: Of 288 patients, pretransplant diagnoses included congenital heart disease (n = 155 [54%]), cardiomyopathy (n = 125 [43%]), and other (n = 8 [3%]). Most (n = 208 [72%]) had simple SVC anatomy compared with complex SVC anatomy (80 [28%]). Reintervention for SVC obstruction occurred in 15 of 80 (19%) with complex anatomy and 1 of 208 (0.5%) with simple anatomy (P = .0001). Reintervention was more common when innominate vein or a patch was used (9/25 [36%]) compared with an interposition graft (1/7 [14%]) or direct anastomosis (6/82 [7%]; χ 2  = 13.1; P = .001). Most reinterventions occurred within 30 days of OHT (14/16 [88%])., Conclusions: Patients with complex SVC anatomy have a higher rate of reintervention for SVC obstruction after OHT compared with those with simple SVC anatomy. In cases of complex SVC anatomy, interposition grafts may be associated with less reintervention compared with complex reconstructions using donor tissue., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: There is a significant incidence of pre-Fontan attrition-defined as failure to undergo Fontan completion-after superior cavopulmonary connection. This study investigated the impact of at least moderate ventricular dysfunction (VD) and atrioventricular valve regurgitation (AVVR) on pre-Fontan attrition., Methods: This single-center retrospective cohort study included all infants who underwent Norwood palliation from 2008 to 2020 and subsequently underwent superior cavopulmonary connection. Pre-Fontan attrition was defined as death, listing for heart transplantation before Fontan completion, or unsuitability for Fontan completion. The study's secondary outcome was transplant-free survival., Results: Pre-Fontan attrition occurred in 34 of 267 patients (12.7%). Isolated VD was not associated with attrition. However, patients with isolated AVVR had 5 times the odds of attrition (odds ratio, 5.4; 95% CI 1.8-16.2), and patients with both VD and AVVR had 20 times the odds of attrition (odds ratio, 20.1; 95% CI 7.7-52.8) compared with patients without VD or AVVR. Only patients with both VD and AVVR had significantly worse transplant-free survival compared with patients without VD or AVVR (hazard ratio, 7.7; 95% CI 2.8-21.6)., Conclusions: The additive effect of VD and AVVR is a powerful contributor to pre-Fontan attrition. Future research investigating therapies that can mitigate the degree of AVVR may help improve Fontan completion rates and long-term outcomes., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Rejection remains a primary cause of graft loss after heart transplant (HT). Recognizing the immunomodulation of multi-organ transplant can enhance our understanding of the mechanisms of cardiac rejection., Methods: This retrospective cohort study identified patients from the UNOS database with isolated heart (H, N = 37 433), heart-kidney (HKi, N = 1516), heart-liver (HLi, N = 286), and heart-lung (HLu, N = 408) transplants from 2004 to 2019. Propensity score matching reduced baseline differences between groups. Outcomes included risk of rejection prior to transplant hospital discharge and within 1 year, and mortality within 1 year of transplant., Results: In the propensity score matched data, the relative risk of being treated for rejection prior to transplant hospital discharge was 61% lower for HKi (RR .39, 95% CI .29, .53) and 87% lower for HLi (RR .13, 95% CI .05, .37) compared to H. Similarly, the probability of being treated for rejection in the first year after transplant remained lower in HKi (RR .45, 95% CI .35, .57) and HLi (RR .13, 95% CI .06, .28) compared to H. The 1-year survival analysis revealed an equivalent risk of death in HKi (HR .84, 95% CI .68, 1.03) and HLi (HR 1.41, 95% CI .83, 2.41) compared to H, while HLu had a higher risk of death in the first year after transplant (HR 1.65, 95% CI 1.17, 2.33)., Conclusions: Recipients of HKi and HLi experience a reduced risk of rejection when compared to H, but an equivalent risk of 1 yr mortality. These findings have important implications for the future of HT medicine., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background Healthcare resource utilization is substantial for single-ventricle cardiac defects ( SVCD ), with effort commencing at time of fetal diagnosis through staged surgical palliation. We sought to characterize and identify variables that influence resource utilization for SVCD from fetal diagnosis through death, completed staged palliation, or cardiac transplant. Methods and Results Patients with a prenatal diagnosis of SVCD at our institution from 2004 to 2011 were screened. Patients delivered with intent to treat who received cardiac care exclusively at our institution were included. Primary end points included the total days hospitalized and the numbers of echocardiograms and cardiac catheterizations. Subanalysis was performed on survivors of completed staged palliation on the basis of Norwood operation, dominant ventricular morphology, and additional risk factors. Of 202 patients born with intent to treat, 136 patients survived to 6 months after completed staged palliation. The median number of days hospitalized per patient-year was 25.1 days, and the median numbers of echocardiograms and catheterizations per patient-year were 7.2 and 0.7, respectively. Mortality is associated with increased resource utilization. Survivors had a cumulative length of stay of 57 days and underwent a median of 21 echocardiograms and 2 catheterizations through staged palliation. Right-ventricle-dominant lesions requiring Norwood operation are associated with increased resource utilization among survivors of staged palliation. Conclusions For fetuses with SVCD , those with dominant right-ventricular morphology requiring Norwood operation demand increased resource utilization regardless of mortality. Our findings provide insight into care for SVCD , facilitate precise prenatal counseling, and provide information about the resources utilized to successfully manage SVCD .

Background: Risk assessment in heart transplantation is critical for candidate selection, but current models inadequately assess individual risk of postoperative mortality. We sought to identify risk factors and develop a scoring system to predict mortality after heart transplantation in children., Methods: The records of patients undergoing heart transplantation at our institution from 2010 through 2016 were reviewed. Clinical characteristics were recorded and compared between survivors and nonsurvivors. We used Cox proportional hazard modeling of factors associated with postoperative mortality to develop a risk factor score., Results: There were 74 patients who underwent heart transplantation at a mean age of 8.8 ± 6.6 years. Congenital heart disease was the most common indication, comprising 48.6% of the cohort. Overall mortality was 18.9%, with 10 of 14 dying within 30 days of the operation or during the initial postoperative admission (early mortality). Preoperative factors associated with overall mortality were single-ventricle congenital heart disease (hazard ratio [HR], 3.2; p = 0.042), biventricular assist device (HR, 4.8; p = 0.043), history of four or more sternotomies (HR, 3.9; p = 0.023), panel reactive antibody exceeding 10% (HR, 4.4; p = 0.013), any previous operation at another institution (HR, 3.2; p = 0.038), and pulmonary vein disease (HR, 4.7; p = 0.045). Each risk factor was assigned a point value, based on similar magnitude of the HRs. A score of 4 or higher predicted mortality with 57% sensitivity and 90% specificity., Conclusions: In this single-center pediatric cohort, postheart transplantation mortality could be predicted using patient-specific risk factors. The cumulative effect of these risk factors predicted mortality with high specificity., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Circulatory failure necessitating cardiac transplantation will ultimately develop in many patients with functional single-ventricle physiology. Interest in the use of mechanical circulatory support (MCS) in this population is growing., Methods: This was a retrospective case series of patients with functional single-ventricle physiology who underwent MCS with a ventricular assist device or a total artificial heart as a bridge to cardiac transplantation between January 2006 and December 2014. Baseline demographics, intraoperative data, postoperative complications, and outcome data were collected from the medical record., Results: MCS was used in 5 patients: HeartWare ventricular assist device (HeartWare International, Framingham, MA) in 1 patient, SynCardia total artificial heart (SynCardia Systems, Tucson, AZ) in 1, Thoratec Paracorporeal ventricular assist device (Thoratec Corp, Pleasanton, CA) in 1, and the Berlin Heart EXCOR (Berlin Heart Inc, The Woodlands, TX) in 2. The mean age at MCS was 12 ± 8 years. There were 2 early deaths at 12 and 28 days after MCS: 1 patient died of multiorgan system failure and 1 of neurologic injury. Overall, neurologic complications occurred in 3 patients (60%), and 1 patient (20%) required renal replacement therapy. Three patients (60%) underwent successful cardiac transplantation. The median time on the waiting list was 59 days (interquartile range, 18 to 126 days), and the median duration of MCS was 60 days (interquartile range, 28 to 93 days). At the time of transplant, all 3 patients were ambulatory, without the need for mechanical ventilation, and end-organ dysfunction had resolved. The 3 patients who received transplants were discharged from the hospital and were alive at an average follow-up of 9 ± 14 months., Conclusions: MCS can be successfully used as a bridge to transplantation in patients with a failing single-ventricle circulation. Use of MCS can allow for resolution of end-organ dysfunction and rehabilitation, leading to improved outcomes in this difficult population., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Copy number variants (CNVs) are duplications or deletions of genomic regions. Large CNVs are potentially pathogenic and are overrepresented in children with congenital heart disease (CHD). We sought to determine the frequency of large CNVs in children with isolated CHD, and to evaluate the relationship of these potentially pathogenic CNVs with transplant-free survival., Methods: These cases are derived from a prospective cohort of patients with nonsyndromic CHD (n = 422) identified before first surgery. Healthy pediatric controls (n = 500) were obtained from the electronic Medical Records and Genetic Epidemiology Network, and CNV frequency was contrasted for CHD cases and controls. CNVs were determined algorithmically; subsequently screened for >95% overlap between 2 methods, size (>300 kb), quality score, overlap with a gene, and novelty (absent from databases of known, benign CNVs); and separately validated by quantitative polymerase chain reaction. Survival likelihoods for cases were calculated using Cox proportional hazards modeling to evaluate the joint effect of CNV burden and known confounders on transplant-free survival., Results: Children with nonsyndromic CHD had a higher burden of potentially pathogenic CNVs compared with pediatric controls (12.1% vs 5.0%; P = .00016). Presence of a CNV was associated with significantly decreased transplant-free survival after surgery (hazard ratio, 3.42; 95% confidence interval, 1.66-7.09; P = .00090) with confounder adjustment., Conclusions: We confirm that children with isolated CHD have a greater burden of rare/large CNVs. We report a novel finding that these CNVs are associated with an adjusted 2.55-fold increased risk of death or transplant. These data suggest that CNV burden is an important modifier of survival after surgery for CHD., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Heart retransplant (HRT) recipients represent a growing number of transplant patients. The impact of concurrent kidney transplants (KTs) in this population has not been well studied. We tested the hypothesis that recipients of HRT with concurrent KT (HRT-KT) would have worse survival than recipients of HRT alone., Methods and Results: A retrospective analysis of the United Network of Organ Sharing database was performed for all patients undergoing HRT from 1987 to 2011. There were 1660 HRT patients, of which 116 (7%) received concurrent KT. Those who received HRT-KT had older age, longer wait-list time, worse kidney function, and more known diabetes. Survival among recipients of HRT-KT was significantly better than that of recipients of HRT alone (P=0.005). A subgroup of 323 HRT patients with severe kidney dysfunction (estimated glomerular filtration rate <30 mL/min per 1.73 m(2) or on dialysis) was studied in more detail, and 76 (24%) received concurrent KT. Those on dialysis at the time of HRT had better survival with versus without concurrent KT (P<0.0001). On multivariable analysis, concurrent KT was independently associated with better outcomes for all patients with HRT and for the subgroup of patients with severe kidney dysfunction., Conclusions: Recipients of HRT-KT have better survival than recipients of HRT alone. Further research is needed to determine which HRT patients may benefit the most from concurrent KT., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Adolescents often fare poorly after heart transplantation. However, whether the effect of age varies according to the etiology of heart failure is unknown. We tested the hypothesis that age-related heart transplantation outcomes are different in patients with myocarditis and congenital heart disease (CHD)., Methods: A retrospective analysis of the United Network of Organ Sharing database was performed for patients with myocarditis (n = 709) and CHD (n = 1,631) undergoing heart transplantation from 1987 to 2011. The effect of age on graft survival was assessed. Age was categorized as children (6-12 years), adolescents (13-18 years), younger adults (19-30 years), and older adults (31-50 years)., Results: For myocarditis, the median graft survival for adolescents was 6.9 years (95% confidence interval [CI], 5.6-9.6), which was significantly lower than other age groups (children: 14.1 [95% CI, 9.8-10.9] years, p = 0.004; younger adults: 11.8 [95% CI, 8.3-15.2] years, p = 0.172; older adults: 12.0 years [95% CI, 10.0-14.3 years], p = 0.033). For CHD, the median graft survival for adolescents was 7.4 years (95% CI, 6.8-8.6), which was not significantly different from other age groups (children: 9.0 [95% CI, 7.9-11.0] years, p = 0.737; younger adults: 11.2 [95% CI, 8.6-13.3] years, p = 0.744; older adults: 11.6 [95% CI, 9.2-15.3] years, p = 0.608). Multivariable analysis showed adolescent age was independently associated with worse graft survival for patients with myocarditis but not for CHD., Conclusions: Adolescents with myocarditis have significantly worse graft survival after heart transplantation, but adolescents with CHD have similar outcomes to other patients with CHD. Further study is needed to improve outcomes in this vulnerable population., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Hypoplastic left ventricle with scimitar syndrome is a rare combination of anatomic lesions. Five patients with this anatomy have been followed up at our institution. Four of these patients are alive: 2 after heart transplant, 1 underwent a Norwood operation, and 1 has survived staged palliation, culminating in a Fontan operation., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Wait-list mortality for children awaiting heart transplantation remains high. Potential donor hearts with depressed ventricular function are often declined. We aimed to test the hypothesis that pediatric heart transplant recipients of grafts with depressed ventricular function would have comparable survival with those with normal function., Methods and Results: A retrospective study was performed for pediatric heart transplants from the United Network of Organ Sharing Database from October 26, 1999, to June 30, 2011. Patients were grouped based on accepted donor left ventricular ejection fraction (LVEF): normal function (LVEF ≥55%), mildly depressed function (LVEF 45%-54%), or moderately-to-severely depressed function (LVEF <45%). During the study period, there were 3672 pediatric heart transplants; 3306 (90%) had a LVEF reported. Ventricular function was mildly depressed in 245 (7%) and moderately-to-severely depressed in 172 (5%). Patients receiving grafts with moderately-to-severely depressed function were more likely to be younger and weigh less (P<0.001 for both) than those receiving grafts with normal function. Median graft survival from accepted donors with normal ventricular function (10.6 years) was similar to survival from accepted donors with mildly depressed ventricular function (9.7 years; P=0.24) and from accepted donors with moderately-to-severely depressed ventricular function (9.1 years; P=0.13). On propensity-matched analysis, donor ventricular function was not associated with graft survival., Conclusions: The use of donors with depressed ventricular function is uncommon in pediatric heart transplantation (<15% of all transplants), yet graft survival does not differ significantly from accepted donors with normal ventricular function. Hearts from donors with depressed ventricular function may be considered in selected patients.

Background: The Norwood procedure with a modified Blalock-Taussig (MBT) shunt, the first palliative stage for single-ventricle lesions with systemic outflow obstruction, is associated with high mortality. The right ventricle-pulmonary artery (RVPA) shunt may improve coronary flow but requires a ventriculotomy. We compared the two shunts in infants with hypoplastic heart syndrome or related anomalies., Methods: Infants undergoing the Norwood procedure were randomly assigned to the MBT shunt (275 infants) or the RVPA shunt (274 infants) at 15 North American centers. The primary outcome was death or cardiac transplantation 12 months after randomization. Secondary outcomes included unintended cardiovascular interventions and right ventricular size and function at 14 months and transplantation-free survival until the last subject reached 14 months of age., Results: Transplantation-free survival 12 months after randomization was higher with the RVPA shunt than with the MBT shunt (74% vs. 64%, P=0.01). However, the RVPA shunt group had more unintended interventions (P=0.003) and complications (P=0.002). Right ventricular size and function at the age of 14 months and the rate of nonfatal serious adverse events at the age of 12 months were similar in the two groups. Data collected over a mean (+/-SD) follow-up period of 32+/-11 months showed a nonsignificant difference in transplantation-free survival between the two groups (P=0.06). On nonproportional-hazards analysis, the size of the treatment effect differed before and after 12 months (P=0.02)., Conclusions: In children undergoing the Norwood procedure, transplantation-free survival at 12 months was better with the RVPA shunt than with the MBT shunt. After 12 months, available data showed no significant difference in transplantation-free survival between the two groups. (ClinicalTrials.gov number, NCT00115934.), (2010 Massachusetts Medical Society)

Background: Ventricular assist devices (VAD) are associated with the formation of antibodies to anti-human leukocyte antigens (HLA) or sensitization. The incidence and effects of VAD-associated anti-HLA sensitization have not been well studied in the pediatric population., Methods: A retrospective review of all patients undergoing VAD implant at our institution from 1998 to 2008 was performed. Panel reactive antibody (PRA) results before VAD implant, after VAD implant, and after orthotopic heart transplantation (OHT) were recorded. Patients who became sensitized (PRA for class I and/or II immunoglobulin G antibodies >or= 10%) on VAD support were compared with non-sensitized patients with regard to demographics, diagnosis, device type, and blood product exposure on VAD support. Outcomes after OHT were also compared between groups., Results: VAD support was initiated in 20 patients (median age, 14.4 years), with 75% survival to OHT or recovery. PRA data before and after VAD implant were available for 17 patients. VAD-associated sensitization developed in 35% of recipients. There were no differences between those sensitized in association with VAD support and non-sensitized patients with regard to age, gender, diagnosis, device type, extracorporeal membrane oxygenation use, or blood product exposure on VAD support. Black race predicted sensitization on VAD (p = 0.02). There were no differences in survival or rejection between groups., Conclusions: VAD therapy was associated with the development of anti-HLA sensitization in 35% of recipients. Black race predicted sensitization, but there were no differences in overall survival or outcomes after OHT., (Copyright (c) 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Risk factors for tricuspid regurgitation (TR) after adult orthotopic heart transplantation (OHT) have been reported, although there are no pediatric data., Methods: This study was a single-center retrospective analysis of patients

Objective: Mechanical cardiorespiratory support is occasionally required before or after pediatric thoracic organ transplantation. Extracorporeal membrane oxygenation is the most commonly used mechanical support technique in children. The goal of this study was to examine the indications for initiation and outcomes after peritransplant use of extracorporeal membrane oxygenation., Methods: A retrospective study was conducted of 65 patients who received peritransplant extracorporeal membrane oxygenation between November 1994 and June 2000. The pretransplant group included 45 patients (average age, 38 months) supported with extracorporeal membrane oxygenation and listed for transplantation (31 heart, 8 lung, and 6 heart-lung), and the post-transplant group included 20 patients (average age, 83 months) who required extracorporeal membrane oxygenation after thoracic organ transplantation (12 heart, 6 lung, and 2 heart-lung transplants). Hospital course and outcomes were evaluated., Results: With regard to pretransplant extracorporeal membrane oxygenation, patients listed for heart transplants were more likely to survive to transplantation than were those listed for lung or heart-lung transplants (12/31 [39%] vs 1/14 [7%], P =.03). There was no difference in long-term survival between heart transplant patients after extracorporeal membrane oxygenation and those without extracorporeal membrane oxygenation (12-month actuarial survival, 83% vs 73%; P =.68). Patients who survived for prolonged periods on extracorporeal membrane oxygenation (>250 hours) typically received heart transplants (7/8 [88%]). With regard to post-transplant extracorporeal membrane oxygenation, patients receiving lung or heart-lung transplants had better short-term outcomes than those receiving heart transplants (63% survived to discharge vs 33%). All 3 patients with early graft dysfunction receiving lung transplants survived to discharge., Conclusions: Long-term outcomes among those undergoing heart transplantation after support with an extracorporeal membrane oxygenator are comparable with those of patients not receiving extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation can be a useful post-transplant support device, particularly in patients undergoing lung transplants.

Survival among recipients of repeat thoracic organ transplantation, particularly in the setting of acute graft failure (AGF), is lower than survival after a primary transplant. This has created controversy over the fair allocation of scarce organs. We reviewed our experience to assess the effectiveness of aggressive therapy and retransplantation in pediatric patients with AGF. Between November 1994 and March 1998, 52 patients aged 49 days to 16.9 years (median age 4.7 years) underwent thoracic organ transplantation (32 primary and 4 repeat heart, 16 primary and 4 repeat lung, and 3 primary heart-lung transplants). Acute graft failure occurred in nine (4 heart, 3 lung, 2 heart-lung transplants), six of whom were supported with extracorporeal membrane oxygenation (ECMO), and four of whom underwent repeat transplant. Six of the nine survived, including all of those who were retransplanted, and five of the nine were alive 1 year later. The average postoperative hospital stay after receiving a second organ was 46.5 days vs. a postoperative 22-day stay in recipients without AGF (p = 0.07). We conclude that the decision to allocate institutional and professional resources to the aggressive support of patients with AGF must be made at the level of the individual transplant center. However, we feel that the outcome of aggressive support and retransplantation justifies the allocation of organs to these patients and suggests that the current policies governing organ allocation for patients with early graft failure should be re-examined.

Cardiac transplantation provides the best option for neonates with congenital heart disease that is not amenable to surgical repair or palliation. The scarcity of suitable organs for this group has resulted in prolonged waiting times; many infants die awaiting transplantation. We present the case of a newborn with severe Ebstein's anomaly and low cardiac output who was supported with extracorporeal membrane oxygenation for 1,126 hours, until an appropriate organ became available.

A 14-year-old girl with congenital heart disease underwent ventricular assist device placement before cardiac transplantation. The inability to close her abdominal fascia necessitated the placement of Prolene mesh, which subsequently became exposed and contaminated when her incision dehisced. Stable closure was obtained with Vicryl mesh and a rectus abdominis turnover flap. Her posttransplant course was notable for compression of the donor heart, necessitating prolonged open sternotomy. She failed an attempt at delayed sternal closure due to compression of the right ventricle by the sternum. In addition to standard pectoralis advancement flaps, a pedicled osseous sternal flap based on her left internal mammary artery was developed to avoid ventricular compression yet still provide some protection to the mediastinum. Alternative uses of this vascularized bone flap to assist with chest wall reconstruction are discussed.

Objective: Heart and lung transplantation has gained acceptance as therapy for end-stage cardiac and pulmonary failure. The early and intermediate survival benefits of one center's 10-year experience with 177 patients undergoing thoracic transplantation were examined., Summary Background Data: As experience in cardiac and pulmonary transplantation has increased, improvements in patient selection, organ preservation, preoperative support, and perioperative care have significantly reduced the early threats to patient survival. Graft dysfunction due to chronic rejection appears to be the main risk for longer-term survival, and data compiled by the United Network for Organ Sharing (UNOS) indicate a 70% 5-year survival for heart transplants and a 50% 5-year survival for lung transplant recipients., Methods: The medical records of 120 heart recipients, 52 lung transplant recipients, and 5 heart-lung recipients were reviewed. Cumulative survival estimates were made using Kaplan-Meier analysis. The etiologies of operative and long-term mortality in each transplant population were identified. A comparison of long-term survival after heart transplantation versus coronary revascularization in a group of patients with ischemic cardiomyopathy was performed., Results: Operative mortality in both the cardiac and pulmonary transplant recipients was 8%. From 1990 to 1995, 70 consecutive adult cardiac transplant procedures were performed without an operative mortality. Three of five patients survived heart-lung transplantation. The extended actuarial survival rate at 5 years was 80% for the cardiac transplant recipients. The 2-year actuarial survival rate for the lung transplant recipients was 88%. Graft dysfunction was the most common cause of operative mortality in the heart transplant group whereas infection was responsible for most of the operative mortality after lung transplantation., Conclusions: Cardiac and pulmonary transplantation can be applied to morbidly ill patients with excellent operative and intermediate-term survival.

Background: The incidence of lymphoproliferative disease, including B-cell lymphomas (BCL) in patients who have undergone heart or combined heart-lung transplants, has been reported to be as high as 15%. The majority of these tumors contain Epstein-Barr virus (EBV) DNA and regress when immunosuppressive agents are discontinued. This tumor regression is thought to be secondary to cytotoxic T lymphocytes (CTL) reactive to EBV-infected cells whose function is impaired in patients receiving immunosuppressive agents. We hypothesize that EBV-CTL expanded in the absence of these agents may demonstrate an antitumor effect against an EBV-expressing human BCL in vitro and in vivo., Methods and Results: An EBV-expressing BCL from a heart transplant recipient was isolated and expanded in culture. EBV-CTL were generated by stimulation of peripheral blood leukocytes with irradiated autologous tumor cells in low-dose interleukin-2. Autologous BCL, HLA-mismatched BCL, lymphokine-activated killer target cell line (Daudi), and the natural killer target cell line (K562) were used in a standard 4-hour cytotoxicity assay using 51CrO4 after 7, 14, and 28 days of stimulation. There was significant percent specific lysis of autologous BCL targets (78%) at an effector-to-target ratio as low as 20:1 as compared with control cells. EBV-CTL were then adoptively transferred into SCID mice (provided by Duke University Vivarium) that had been engrafted with autologous BCL 7 days before. There was a significant survival advantage to those mice engrafted with EBV-CTL as compared with control cells., Conclusions: The results indicate that ex vivo expansion of EBV-CTL in the absence of immunosuppressive agents results in a population that has significant antitumor activity. This strategy may be useful in the generation of EBV-CTL that might be effective antitumor agents in transplant recipients with EBV-associated lymphomas.