Changes in estimated glomerular filtration rate over the first year following repeat heart transplant in children and young adults.

BACKGROUND: Renal function is reduced in patients undergoing heart transplant due to hemodynamic compromise, cardiorenal syndrome, and nephrotoxin exposure. No current studies evaluate renal function in retransplants. METHODS: We reviewed all heart transplants at our center from 1995 to 2021 and matched first-time heart transplants with retransplants, based on age at transplant, sex, and race. Estimated glomerular filtration rate (eGFR) was derived from CKiD-U25 calculator using creatinine and measured prior to transplant, 1-week post-transplant, 1-3, 6, and 12 months post-transplant, and recent follow-up. Changes in eGFR were measured within and between patients using a piecewise linear mixed effect model with matching. Exploratory univariate analysis was performed to evaluate pre-transplant risk factors for decreased eGFR. RESULTS: The unmatched cohort included 393 heart transplant recipients, with 47 being retransplants. Thirty-eight patients in both groups with at least 1 year of follow-up underwent matching. Both retransplants and first-time transplants had an initial decline in eGFR. eGFR rebounded to baseline or above baseline at 1-3 months post-transplant, but eGFR in retransplants remained significantly lower. At 1-year post-transplant, the average eGFR was 67.8 ± 4.3 mL/min/1.73 m2 versus 104.7 ± 4.3 mL/min/1.73 m2 (p < .001) in the retransplants and first-time transplants group, respectively. CONCLUSION: This study provides data on anticipated renal trajectory following retransplantation.

Risk factors associated with post-transplant superior caval vein stenosis in paediatric heart transplantation.

Superior caval vein stenosis is a known complication following paediatric heart transplantation. Herein, we sought to assess the incidence of superior caval vein stenosis and need for intervention in a single centre paediatric heart transplantation programme. A retrospective review was performed to identify variables associated with superior caval vein stenosis and need for intervention. Patients were identified based on angiographic and echocardiographic signs of superior caval vein stenosis. Of 204 paediatric heart transplantation recipients, 49 (24.0%) had evidence of superior caval vein stenosis with no need for catheter intervention and 12 (5.9%) had superior caval vein stenosis requiring catheter intervention. Overall, patients with superior caval vein stenosis with and without intervention had more cavopulmonary anastomosis (41.7%; 20.4%), pre-transplant superior caval vein procedures (41.7%; 28.6%), and bicaval approach (100.0%; 98.0%), compared to the group with no stenosis (11.9% and p = 0.015, 12.6% and p = 0.004, 73.4% and p < 0.001, respectively). Smaller recipients and donors were more likely to need intervention. Intervention was also seen more frequently in recipients who were younger at diagnosis (4.7 years) compared to non-intervention (13.3 years; p = 0.040). Re-intervention was required in 16.7% patients (n = 2) and was not associated with any complications.

Postoperative vasoactive inotropic score is predictive of outcomes in pediatric heart transplantation.

Vasoactive inotrope score (VIS) is scarcely studied in pediatric orthotopic heart transplantation (pOHT). We conducted a retrospective review of pOHT (<21 years) recipients. Max VIS and mean VIS were calculated at 0-24 and 24-48 hours post-pOHT. Patients were divided into groups based on ISHLT guidelines: high (>10) and low (≤10). In our group (n = 104), patients with high max and mean VIS groups at 0-24 and 24-48 hours had longer bypass times (high: >130 minutes; low: <108 minutes; P < .05) and high max and mean VIS groups at 0-24 hours had longer ischemic times (high: >215 minutes; low: <192 minutes; P < .05). Patients with high max and mean VIS at 0-24 and 24-48 hours had longer hospital stay, ventilation, inotrope duration, more cardiac events, and acute kidney injury postoperatively (P < .05). High max VIS at 24-48 hours and high mean VIS at 24-48 hours had higher 3-year mortality (P = .04; P = .02). Multivariate analysis confirmed the association of VIS with short-term outcomes. However, VIS was not identified as an independent predictor of mortality. The ROC curve exhibits 10 as the ideal cutoff with area under the curve >0.8 for primary graft dysfunction (PGD).

Family functioning in pediatric heart transplantation: Variables associated with poor outcomes.

Family functioning is integral in a child's life and is linked to quality of life in health as well as disease. This has been scarcely studied in pediatric orthotopic heart transplantation (pOHT). In this study, we evaluate demographic and clinical factors associated with family functioning in this patient population. Pediatric post-transplant families were recruited in an outpatient setting (n = 71). The PedsQL Family Impact Module was administered, along with the Parent and Adolescent Medication Barriers Scales (PMBS; AMBS) and the McArthur socioeconomic scale. Associations between clinical and demographic variables and scaled scores were evaluated. In our sample, patients with congenital heart disease, developmental delay, and enteral feeding had lower total impact (P = .026; P = .011; P = .008) and parent self-reported HRQL scores (P = .018; P = .012; P = .005). Patients with developmental delay and enteral feeding also had lower family functioning summary scores (P = .025; P = .031). Higher parent educational status was associated with lower total impact scores (P = .043). Higher PMBS scores demonstrated negative correlation with total impact (P < .001), parent self-reported HRQL (P < .001), and family functioning summary scores (P = .003). Multiple linear regression analysis identified developmental delay, parental education, and PMBS as independent variables associated with family functioning. Our study highlights important factors impacting family functioning in pOHT. Developmental delay, higher parental education, and PMBS were associated with poorer family functioning. Our findings emphasize the need for a multi-disciplinary approach including serial psychological assessment and interventions in the management of pOHT patients in order to optimize family functioning.

Thenar Muscle Oxygen Saturation Using Vascular Occlusion Test: A Novel Technique to Study Microcirculatory Abnormalities in Pediatric Heart Failure Patients.

Heart failure (HF) is associated with microcirculatory changes secondary to neuro-humoral imbalance, vascular stiffness and increased sympathetic tone. Near Infra-Red Spectroscopy (NIRS) derived Thenar muscle tissue oxygenation levels (StO2) can provide an estimate of the functional status of microcirculation. There is a paucity of literature regarding evaluation of microcirculation in pediatric subjects with HF. We hypothesized that microcirculation and oxygen saturation dynamics as assessed by Thenar StO2 levels using vascular occlusion test (VOT) would be altered in HF subjects and that these changes may correlate with the severity of heart failure. We prospectively enrolled 60 pediatric subjects (29 healthy control, 31 HF). Baseline StO2 levels were measured using InSpectra™ StO2 probe placed over the Thenar eminence of right hand, followed by a VOT for 3 min, during which the changes in StO2 levels during the occlusion phase and post occlusion phase were recorded. Baseline Thenar StO2 levels (72 ± 8 vs 76 ± 5, p = 0.02) and time to baseline StO2 in seconds (150 ± 70 vs 200 ± 70, p = 0.007) were significantly lower in HF group compared to healthy control (HC). In addition, HF patients had a significantly lower trough StO2 (37 ± 9 vs 42 ± 11%, p = 0.04) and peak StO2 compared to HC (87 ± 8 vs 91 ± 5%, p = 0.01). However, there was no difference in the rate of desaturation, rate of resaturation or time to peak StO2 levels in between the 2 groups. Significant correlation was present between baseline Thenar StO2 levels and NYU Pediatric Heart Failure Index Score (NYU-PHFI) (p = 0.003). This study is the first to report an objective assessment of microcirculation and Thenar tissue oxygen dynamics in pediatric subjects with HF in comparison with HC. Our study suggests altered microcirculation and oxygenation patterns in these subjects as well as correlation with a validated pediatric heart failure clinical score. Large-scale prospective studies are needed to further study the utility of this novel technology in HF subjects.

Anti-LFA-1 induces CD8 T-cell dependent allograft tolerance and augments suppressor phenotype CD8 cells.

The induction of tolerance to transplanted organs is a major objective in transplantation immunology research. Lymphocyte function-associated antigen-1 (LFA-1) interactions have been identified as a key component of the T-cell activation process that may be interrupted to lead to allograft tolerance. In mice, αLFA-1 mAb is a potent monotherapy that leads to the induction of donor-specific transferable tolerance. By interrogating important adaptive and innate immunity pathways, we demonstrate that the induction of tolerance relies on CD8+T-cells. We further demonstrate that αLFA-1 induced tolerance is associated with CD8+CD28-T-cells with a suppressor phenotype, and that while CD8 cells are present, the effector T-cell response is abrogated. A recent publication has shown that CD8+CD28- cells are not diminished by cyclosporine or rapamycin, therefore CD8+CD28- cells represent a clinically relevant population. To our knowledge, this is the first time that a mechanism for αLFA-1 induced tolerance has been described.

Hypoplastic left heart in Turner's syndrome: a primary indication for transplant?

Survival for hypoplastic left heart syndrome patients following the Norwood procedure is 71-90%. Mortality in patients with Turner's syndrome and hypoplastic left heart syndrome after conventional palliation (Norwood operation) has been reported as high as 80%. This questions the approach of traditional staged palliation. Here, we report a patient with hypoplastic left heart syndrome and Turner's syndrome bridged to orthotopic heart transplantation following a hybrid procedure.

Ectopic expression of Fas Ligand on cardiomyocytes renders cardiac allografts resistant to CD4(+) T-cell mediated rejection.

Fas Ligand limits inflammatory injury and permits allograft survival by inducing apoptosis of Fas-bearing lymphocytes. Previous studies have shown that the CD4(+) T-cell is both sufficient and required for murine cardiac allograft rejection. Here, utilizing a transgenic mouse that over-expresses Fas Ligand specifically on cardiomyocytes as heart donors, we sought to determine if Fas Ligand on graft parenchymal cells could resist CD4(+) T-cell mediated rejection. When transplanted into fully immunocompetent BALB/c recipients Fas Ligand transgenic hearts were acutely rejected. However, when transplanted into CD4(+) T-cell reconstituted BALB/c-rag(-/-) recipients, Fas Ligand hearts demonstrated long-term survival. These results indicate that Fas Ligand over-expression on cardiomyocytes can indeed resist CD4(+) T-cell mediated cardiac rejection and suggests contact dependence between Fas Ligand expressing graft parenchymal cells and the effector CD4(+) T-cells.

Early predictors of survival to and after heart transplantation in children with dilated cardiomyopathy.

BACKGROUND: The importance of clinical presentation and pretransplantation course on outcome in children with dilated cardiomyopathy listed for heart transplantation is not well defined. METHODS AND RESULTS: The impact of age, duration of illness, sex, race, ventricular geometry, and diagnosis of myocarditis on outcome in 261 children with dilated cardiomyopathy enrolled in the Pediatric Cardiomyopathy Registry and Pediatric Heart Transplant Study was studied. End points included listing as United Network for Organ Sharing status 1, death while waiting, and death after transplantation. The median age at the time of diagnosis was 3.4 years, and the mean time from diagnosis to listing was 0.62±1.3 years. Risk factors associated with death while waiting were ventilator use and older age at listing in patients not mechanically ventilated (P=0.0006 and P=0.03, respectively). Shorter duration of illness (P=0.04) was associated with listing as United Network for Organ Sharing status 1. Death after transplantation was associated with myocarditis at presentation (P=0.009), nonwhite race (P<0.0001), and a lower left ventricular end-diastolic dimension z score at presentation (P=0.04). In the myocarditis group, 17% (4 of 23) died of acute rejection after transplantation. CONCLUSIONS: Mechanical ventilator use and older age at listing predicted death while waiting, whereas nonwhite race, smaller left ventricular dimension, and myocarditis were associated with death after transplantation. Although 97% of children with clinically or biopsy-diagnosed myocarditis at presentation survived to transplantation, they had significantly higher posttransplantation mortality compared with children without myocarditis, raising the possibility that preexisting viral infection or inflammation adversely affects graft survival.

Assessment of parental decision making in congenital heart disease, cardiomyopathy and heart transplantation: an observational study analysing decisional characteristics and preferences.

OBJECTIVE: We explore shared decision making (DM) in guardians of children with heart disease by assessing the desired weight of influence on DM and factors that may alter the relative weight of parent or medical team influence. METHODS: Guardians of patients <21 years and admitted >1 week in the paediatric cardiac intensive care unit (PCICU) were recruited. Twelve vignettes were designed including technical (antibiotic selection, intubation, peripherally inserted central catheter placement, ventricular assist device placement, heart transplant, organ rejection, heart rhythm abnormalities and resuscitation effort) and non-technical vignettes (cessation of life-sustaining therapies, depression treatment, obesity and palliative care referral). Participants responded to questions on DM characteristics and one question querying preference for relative weight of parent or medical team influence on DM. RESULTS: Of 209 participants approached, 183 were included. Most responded with equal desire of medical team and parental influence on DM in all vignettes (range 41.0%-66.7%). Technical scenarios formed one cluster based on DM characteristics, compared with non-technical scenarios. Factors that increase the relative weight of parental influence on DM include desired input and involvement in big-picture goals (OR 0.274, CI [0.217 to 0.346]; OR 0.794, CI [0.640 to 0.986]). Factors that increase the relative weight of medical team influence on DM include perception of medical expertise needed (OR 1.949 [1.630 to 2.330]), urgency (OR 1.373 [1.138 to 1.658]), benefit (OR 1.415 [1.172 to 1.710]), number of PCICU admissions (OR 1.134 [1.024 to 1.256]) and private insurance (OR 1.921 [1.144 to 3.226]). CONCLUSION: Although factors may alter the weight of influence on DM, most parents desire equal parental and medical team influence on DM.

Outcome of acute graft rejection associated with hemodynamic compromise in pediatric heart transplant recipients.

We sought to analyze the outcome of hemodynamically significant acute graft rejection in pediatric heart transplant recipients from a single-center experience. Acute graft rejection remains a major cause of morbidity and mortality for patients who undergo orthotopic heart transplantation and has been associated with the severity of the rejection episode. A retrospective review of all children experiencing a hemodynamically significant rejection episode after orthotopic heart transplantation was performed. Fifty-three patients with 54 grafts had 70 rejection episodes requiring intravenous inotropic support. Forty-one percent of these patients required high-dose inotropic support, with the remaining 59% of patients requiring less inotropic support. Overall graft survival to hospital discharge was 41% for patients in the high-dose group compared to 94% in the low-dose group. Six-month graft survival in patients who required high-dose inotropes remained at 41% compared to 44% in the low-dose group. Hemodynamically significant acute graft rejection in pediatric heart transplant recipients is a devastating problem with poor short- and long-term outcomes. Survival to hospital discharge is dismal in patients who require high-dose inotropic support. In contrast, survival to discharge is quite good in patients who require only low-dose inotropic support; however, six-month graft survival in this group is low secondary to a high incidence of graft failure related to worsening or aggressive transplant coronary artery disease.

Long-term outcome of palliation with internal pulmonary artery bands after primary heart transplantation for hypoplastic left heart syndrome.

The purpose of this study was to describe the long-term outcome of infants with hypoplastic left heart syndrome (HLHS) who underwent placement of internal pulmonary artery bands as part of a transcatheter palliation procedure followed by primary heart transplantation. Transcatheter palliation included stenting of the ductus arteriosus, decompression of the left atrium by atrial septostomy, and internal pulmonary artery band placement. Cardiac hemodynamics, pulmonary artery architecture, and pulmonary artery growth since transplantation are described. Nine infants with HLHS had internal pulmonary artery bands placed and underwent successful heart transplant. No infant required reconstruction of the pulmonary arteries at the time of transplant. At 1 year after transplant, all of the recipients had normal mean pulmonary artery pressure, pulmonary vascular resistance, and transpulmonary gradient. Pulmonary angiography performed at 1 year after transplant demonstrated no distortion of pulmonary artery anatomy with significant interval growth of the branch pulmonary arteries. There was 100% survival to hospital discharge after transplant in this cohort of infants. Transcatheter placement of internal pulmonary artery bands for HLHS offers protection of the pulmonary vascular bed while preserving pulmonary artery architecture and growth with good long-term outcome.

End-organ recovery post-ventricular assist device can prognosticate survival.

BACKGROUND: This study examines our institutional ventricular assist devices (VADs) experience over two decades to understand trends towards predictors of mortality. METHODS: Retrospective study of patients aged 0-21years supported with a VAD from January 1996 to May 2015. Patient data was examined pre and post-VAD implant among survivors and non-survivors. RESULTS: Thirty-six patients identified (8 supported by Thoratec® VAD and 28 supported by EXCOR Berlin Heart®). Patient's diagnosis included dilated cardiomyopathy (DCM) (n=19,53%), congenital heart disease (CHD) (n=12,33%), and other (n=5,14%). Median age and body surface area (BSA) were 1.0years[0-7years] and 0.41[0.24-0.92], respectively. Survival to discharge was 75% with no deaths with DCM. The survival rate for patients with CHD was 42%. Univariate analysis showed diagnosis of CHD, smaller BSA and respiratory failure post-implant (Intermacs criteria) as risk factors for mortality. Median duration of VAD support was lower in non-survivors, 14 vs 63days (p=0.03). Renal function at time of transplant or death was normal/pRIFLE Risk category in 20(74%) of survivors and 2(22%) of non-survivors (p=0.06). Post-implant, peak total bilirubin in the first week trended lower in survivors (p=0.06). CONCLUSIONS: Persistent end-organ impairment in the first 2weeks after VAD placement could be a useful prognostic marker for survival to transplant.

Spontaneous allograft tolerance in B7-deficient mice independent of preexisting endogenous CD4+CD25+ regulatory T-cells.

BACKGROUND: Acute cardiac allograft rejection requires host, but not donor, expression of B7-1/B7-2 costimulatory molecules. However, acute cardiac rejection requires direct antigen presentation by donor-derived antigen presenting cells to CD4 T-cells and does not require indirect antigen presentation to CD4 T-cells. Given this discrepancy in the literature and that the consequence of allograft exposure in B7-deficient mice is unknown; the goal of the study was to examine the antidonor status of allografted B7-1/B7-2-deficient hosts. METHODS: C57Bl/6 B7-1/B7-2-/- mice were grafted with heterotopic BALB/c hearts. Recipients bearing long-term surviving allografts were used to examine the status of antidonor reactivity in vitro and in vivo. Tolerance was examined in vivo through adoptive transfer of splenocytes from graft-bearing animals to secondary immune-deficient Rag-1-/- hosts bearing donor-type or third-party cardiac allografts and by regulatory T-cell depletion with anti-CD25 antibody. RESULTS: When transferred to B7-replete Rag-1-/- recipients, cells from naïve B7-1/B7-2-/- mice readily initiated cardiac allograft rejection. However, splenocytes transferred from long-term allograft acceptor B7-1/B7-2-/- hosts failed to reject donor-type hearts but acutely rejected third-party allografts. In addition, such cells did not reject (donorxthird-party) F1 allografts. Finally, in vivo depletion of regulatory T-cells did not prevent long-term acceptance. CONCLUSIONS: Results demonstrate that B7-deficient T-cells are capable of acute cardiac allograft rejection in a B7-replete environment. Importantly, results also show that B7-deficient hosts do not simply ignore cardiac allografts, but rather spontaneously develop transferable, donor-specific tolerance and linked suppression in vivo. Interestingly, this tolerant state does not require endogenous CD4+CD25+ regulatory T-cells.

Non-invasive detection of acute allograft rejection in children by tissue Doppler imaging: myocardial velocities and myocardial acceleration during isovolumic contraction.

BACKGROUND: In adults, an acute decrease of regional myocardial velocities is a sensitive marker of rejection. In children, velocities are more variable. A new marker, myocardial acceleration during isovolumic contraction (IVA), appears to be less age-dependent than myocardial velocities. This study therefore compared tissue Doppler (TDI)-derived velocities and IVA as potential rejection markers for children. METHODS: TDI was performed in 15 pediatric heart transplant recipients (age 8.0 +/- 3.6 years) during acute rejection and at baseline without rejection, 50 additional transplant children without rejection (7.8 +/- 5.9 years) and 30 age-matched healthy children (7.5 +/- 5.2 years). Color Doppler cine-loops of 3 cardiac cycles were stored as echocardiographic raw data. Using off-line post-processing, systolic (S) and diastolic (E) myocardial velocities and IVA were measured in 5 basal left ventricular segments. IVA is the peak isovolumic contraction wave velocity divided by acceleration time. RESULTS: Without rejection, transplant children had significantly lower diastolic velocities (basal lateral E 10.4 +/- 2.9 vs 11.9 +/- 2.6 cm/s; p < 0.001) and systolic velocities (S 5.6 +/- 1.4 vs 7.1 +/- 2.0 cm/s; p < 0.001) than normal age-matched controls, but IVA was similar (1.2 +/- 1.4 vs 1.3 +/- 0.5 m/s2). During rejection, all markers decreased significantly compared with age-matched normal control, the non-rejecting transplant group and individual baseline values. CONCLUSIONS: Regional myocardial velocities change significantly during acute allograft rejection in children. However, many children already have wall motion abnormalities at baseline, so results are often difficult to interpret. In contrast, isovolumic acceleration was normal without rejection and selectively decreased during the event. IVA is a promising non-invasive rejection marker for pediatric patients.

Transplantation immunology 2003: simplified approach.

Transplantation has been performed clinically for four decades and has become the standard of care for end-stage organ failure. Understanding of the immunobiology of transplantation has made tremendous advances, but knowledge still lags behind the clinical use. As a result, nonspecific immunosuppression remains the standard therapy. This article presents an overview of current knowledge of the immunobiology of solid organ transplantation, with emphasis on T-cell activation (antigen presentation, CoS) and cellular allograft (transplantation) immunity. The molecular events of T-cell activation, with some emphasis on the sites of action of modern immunosuppression, are reviewed. A simplified approach to understanding the immunobiology and strategy of maintenance immunosuppression is discussed. Key early and late steps in T-cell activation and the sites of action of immunosuppressive agents are reviewed. The required cellular interactions for the alloresponse and the targets of biologic agents used in transplants are reviewed. Special considerations for the immunology in neonates, infants, and children as recipients are provided. Understanding the immunobiology of transplantation is key to making decisions about children with transplants, developing better protocols, and creating tolerance in the future.

Steroid avoidance in pediatric heart transplantation results in excellent graft survival.

BACKGROUND: Maintenance steroid (MS) use in pediatric heart transplantation (HT) varies across centers. The purpose of this study was to evaluate the impact of steroid-free maintenance immunosuppression (SF) on graft outcomes in pediatric HT. METHODS: Patients younger than 18 years in the United States undergoing a first HT during 1990 to 2010 were analyzed for conditional 30-day graft loss (death or repeat HT) and death based on MS use by multivariable analysis. A propensity score was then given to each patient using a logistic model, and propensity matching was performed using pre-HT risk factors, induction therapy, and nonsteroid maintenance immunosuppression. Kaplan-Meier graft and patient survival probabilities by MS use were then calculated. RESULTS: Of 4894 patients, 3962 (81%) were taking MS and 932 (19%) SF. Of the 4530 alive at 30 days after HT, 3694 (82%) and 836 (18%) were in the MS and SF groups, respectively. Unmatched multivariable analysis showed no difference in 30-day conditional graft survival between MS and SF groups (hazard ratio=1.08, 95% confidence interval=0.93-1.24; P=0.33). Propensity matching resulted in 462 patients in each MS and SF group. Propensity-matched Kaplan-Meier survival analysis showed no difference in graft or patient survival between groups (P=0.3 and P=0.16, respectively). CONCLUSIONS: We found no difference in graft survival between SF patients and those taking MS. An SF regimen in pediatric HT avoids potential complications of steroid use without compromising graft survival, even after accounting for pre-HT risk factors.

CD4 T cells mediate cardiac xenograft rejection via host MHC Class II.

BACKGROUND: Previous studies have shown that acute CD4 T-cell-mediated cardiac allograft rejection requires donor major histocompatibility complex (MHC) Class II expression and can be independent of "indirect" antigen presentation. However, other studies suggested that indirect antigen presentation to CD4 T cells may play a primary role in cellular xenograft immunity. Thus, the relative roles of direct/indirect CD4 T cell reactivity against cardiac xenografts are unclear. In this study we set out to determine the role for indirect CD4 T cell reactivity in cardiac xenograft rejection. METHODS: Rat hearts were transplanted heterotopically into wild-type and immunodeficient mice. Recipients were untreated, treated with depleting antibodies, or reconstituted with wild-type cells. RESULTS: Antibody depletion confirmed that rat heart xenograft rejection in C57Bl/6 mice was CD4 T-cell-dependent. Also, heart xenografts survived long term in B6 MHC Class II (C2D)-deficient mice. Graft acceptance in C2D mice was not secondary to CD4 T cell deficiency alone, because transferred B6 CD4 T cells failed to trigger rejection in C2D hosts. Furthermore, purified CD4 T cells were sufficient for acute rejection of rat heart xenografts in immune-deficient B6rag1(-/-) recipients. Importantly, CD4 T cells did not reject rat hearts in C2Drag1(-/-) hosts, in contrast to results using cardiac allografts. "Direct" xenoreactive CD4 T cells were not sufficient to mediate rejection despite vigorous reactivity to rat stimulator cells in vitro. CONCLUSIONS: Taken together, our results show that CD4 T cells are both necessary and sufficient for acute cardiac xenograft rejection and that host MHC Class II is critical in this process.

Graft survival is better without prior surgery in cardiac transplantation for functionally univentricular hearts.

BACKGROUND: The effect of surgical history on graft outcomes in patients with functionally univentricular hearts (UH) is not well understood. We compared graft outcomes after heart transplantation in children with a UH between patients who received allografts without prior cardiac surgery (Group A) and patients who underwent transplantation after prior cardiac surgery (Group B). METHODS: We reviewed all patients who received allografts for UH at our institution from 1990 to 2009. Differences in the probability of acute rejection (AR), incidence of graft vasculopathy (GV), and incidence of death or retransplantation were compared between Group A and Group B. Student's t-test, Mann-Whitney U-test, the log-rank test, logistic regression, and Cox proportional hazards modeling were used as appropriate. RESULTS: During the study period, 180 patients with a UH received allografts: 105 in Group A and 75 in Group B at a median (interquartile range) age of 84 (47-120) days vs 584 (168-2,956) days, respectively (p < 0.001). The odds of AR were higher in Group B (odds ratio, 2.7, 95% confidence interval, 1.3-5.4). Group A had lower univariable risks of GV (p = 0.034) and graft loss (p = 0.003). Median graft survival was 18 years in Group A vs 8 years in Group B. The risk of graft loss after 5 years post-transplant was higher in Group B patients who were aged ≥ 1 year at time of transplant (p < 0.001). CONCLUSIONS: Heart transplantation without prior cardiac surgery in patients with a UH was associated with better graft survival and lower probability of AR. The effect of age is complex and time-dependent, with age affecting outcomes after 5 years.