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BACKGROUND: Restrictive cardiomyopathy (RCM) has been associated with poor prognosis in childhood. The goal of the present analysis was to use the Pediatric Cardiomyopathy Registry to analyze outcomes of childhood RCM, with a focus on the impact of phenotype comparing pure RCM with cases that have additional features of hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: We analyzed the Pediatric Cardiomyopathy Registry database (1990-2008; N=3375) for cases of RCM. Cases were defined as pure when RCM was the only assigned diagnosis. Additional documentation of HCM at any time was used as the criterion for RCM/HCM phenotype. RCM accounted for 4.5% of cases of cardiomyopathy. In 101 (66%), pure RCM was diagnosed; in 51 (34%), there was a mixed phenotype. Age at diagnosis was not different between groups, but 10% of the pure RCM group was diagnosed in infancy versus 24% of the RCM/HCM group. Freedom from death was comparable between groups with 1-, 2-, and 5-year survival of RCM 82%, 80%, and 68% versus RCM/HCM 77%, 74%, and 68%. Transplant-free survival was 48%, 34%, and 22% and 65%, 53%, and 43%, respectively (P=0.011). Independent risk factors at diagnosis for lower transplant-free survival were heart failure (hazard ratio 2.20, P=0.005), lower fractional shortening z score (hazard ratio 1.12 per 1 SD decrease in z score, P=0.014), and higher posterior wall thickness in the RCM/HCM group only (hazard ratio 1.32, P<0.001). Overall, outcomes were worse than for all other forms of cardiomyopathy. CONCLUSIONS: Transplant-free survival is poor for RCM in childhood. Survival is independent of phenotype; however, the RCM/HCM phenotype has significantly better transplant-free survival. CLINICAL TRIALS REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00005391. [ABSTRACT FROM AUTHOR]

The increase in time waiting for appropriate pediatric allografts for heart transplantation has mandated the use of long-term mechanical assistance in the pediatric population. Extracorporeal membrane oxygenation support has been routinely used but is limited by both its inability to provide support without life-threatening complications for longer than 2 to 3 weeks as well as the inability of patients to achieve mobility. For the past 10 years, pediatric programs have increasing experience with the use of ventricular assist devices (VADs) to bridge patients to heart transplant. This retrospective study analyzed the clinical features and outcomes of 99 pediatric patients who underwent VAD implant as a bridge to heart transplant. METHODS: Between 1993 and 2003, the Pediatric Heart Transplant Study Group enrolled 2,375 patients (age 1 day-17.9 years) listed for heart transplant from 23 participating centers. Four percent (99 patients) of those listed received VAD support as a bridge to transplantation. Seventy-seven (77%) patients survived to transplant with a mean time on support of 57 days. There were 17 deaths on support and 5 bridged to recovery. Overall incidence of adverse events was similar to the adult data with a 19% risk of stroke. There was no difference in 5-year survival after transplant for patients on VAD at time of transplant compared with those (n = 2,293) not requiring VAD (77% vs 73%, P = .8). These data suggest that despite the lack of pediatric specific devices and relatively high adverse event rate, VADs may be used as a bridge to transplant therapy in appropriate-sized children with the expectation of a successful outcome in most patients. [ABSTRACT FROM AUTHOR]

Background: Research comparing the survival of children with familial dilated cardiomyopathy (FDCM) to that of children with idiopathic dilated cardiomyopathy (IDCM) has produced conflicting results., Methods and Results: We analyzed data from children with FDCM or IDCM using the National Heart, Lung, and Blood Institute-funded Pediatric Cardiomyopathy Registry. Compared to children with IDCM (n=647), children with FDCM (n=223) were older (mean 6.2 versus 4.5 years, P <0.001), less often had heart failure (64% versus 78%, P <0.001), had less-depressed mean left ventricular fractional shortening z scores (-7.85±3.98 versus -9.06±3.89, P <0.001) and lower end-diastolic dimension z scores (4.12±2.61 versus 4.91±2.57, P <0.001) at diagnosis. The cumulative incidence of death was lower for patients with FDCM compared with IDCM ( P =0.04; hazard ratio 0.64, P =0.06), but no difference in risk of transplant or the combined death or transplant outcome. There was no difference in the proportion of children with echocardiographic normalization at 3 years of follow-up (FDCM, 30% versus IDCM, 26%; P =0.33). Multivariable analysis showed no difference in outcomes between FDCM and IDCM but for both groups older age, congestive heart failure, and increased left ventricular end-systolic dimension z score at diagnosis were independently associated with an increased risk of death or heart transplantation (all P s<0.001)., Conclusions: There was no survival difference between FDCM and IDCM after adjustment for other factors. Older age, congestive heart failure, and greater left ventricular dilation at diagnosis were independently associated with increased risk of the combined end point of death or transplantation., Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00005391., (© 2017 American Heart Association, Inc.)

Background: Current organ allocation algorithms direct hearts to the sickest recipients to mitigate death while waiting. This may result in lower post-transplant (Tx) survival for high-risk candidates mandating close examination to determine the appropriateness of different technologies as a bridge to Tx., Methods and Results: We analyzed all patients (<18 years old) from the Pediatric Heart Transplant Study (PHTS) database listed for heart Tx (1993-2013) to determine the effect of extracorporeal membrane oxygenation (ECMO) support at the time of listing and the time of Tx on waitlist mortality and post-Tx outcomes. Eight percent of patients were listed on ECMO, and within 12 months, 49% had undergone Tx, 35% were deceased, and 16% were alive waiting. Survival at 12 months after listing (censored at Tx) was worse in patients on ECMO at listing (50%) compared with ventricular assist device at listing (76%) or not on ECMO or ventricular assist device at listing (76%; P<0.0001). Two hundred three (5%) patients underwent Tx from ECMO; 135 (67%) had been on ECMO since listing, and 67 (33%) had deteriorated to ECMO support while waiting. Survival after Tx was worse in patients who underwent Tx from ECMO (3 years: 64%) versus on ventricular assist device at Tx (3 years: 84%) or not on ECMO/ventricular assist device at Tx (3 years: 85%; P<0.0001). Patients transplanted from ECMO at age <1 year had the worst survival., Conclusions: Pediatric patients requiring ECMO support before heart Tx have poor outcomes. Prioritization of donor hearts to children waitlisted on ECMO warrants careful consideration because of ECMO's high pre- and post-Tx mortality., (© 2015 American Heart Association, Inc.)

Background: Pediatric dilated cardiomyopathy (DCM) is the leading indication for heart transplantation after 1 year of age. Risk factors by etiology at clinical presentation have not been determined separately for death and transplantation in population-based studies. Competing risks analysis may inform patient prioritization for transplantation listing., Methods and Results: The Pediatric Cardiomyopathy Registry enrolled 1731 children diagnosed with DCM from 1990 to 2007. Etiologic, demographic, and echocardiographic data collected at diagnosis were analyzed with competing risks methods stratified by DCM etiology to identify predictors of death and transplantation. For idiopathic DCM (n=1192), diagnosis after 6 years of age, congestive heart failure, and lower left ventricular (LV) fractional shortening z score were independently associated with both death and transplantation equally. In contrast, increased LV end-diastolic dimension z score was associated only with transplantation, whereas lower height-for-age z score was associated only with death. For neuromuscular disease (n=139), lower LV fractional shortening was associated equally with both end points, but increased LV end-diastolic dimension was associated only with transplantation. The risks of death and transplantation were increased equally for older age at diagnosis, congestive heart failure, and increased LV end-diastolic dimension among those with myocarditis (n=272) and for congestive heart failure and decreased LV fractional shortening among those with familial DCM (n=79)., Conclusions: Risk factors for death and transplantation in children varied by DCM etiology. For idiopathic DCM, increased LV end-diastolic dimension was associated with increased transplantation risk but not mortality. Conversely, short stature was significantly related to death but not transplantation. These findings may present an opportunity to improve the transplantation selection algorithm.

Background: Rejection with hemodynamic compromise (RHC) is associated with high mortality in heart recipients. This study investigates the association between genetic polymorphisms and RHC in pediatric heart recipients., Methods: Data from 532 pediatric heart recipients from six centers in the Pediatric Heart Transplant Study were analyzed for time to RHC by recipient race, age at transplantation, and genotype at 13 genetic polymorphisms (TNF-α A-308G, IL-6 G-174C, INF-γ T+874A, IL-10 G-1082A, C-819T, and C-592A; FAS A-670G, FASL C-843T, and ACE I/D; and VEGF A-2578C, C-1451T, C+405G, and -2549 I/D)., Results: RHC occurred in 126 (23.7%) patients during the study period. Adjusting for age and race, IL-10 G-1082A, FAS A-670G, and ACE I/D genotypes were associated with RHC. IL-10 G-1082A GG genotype was associated with decreased risk of RHC with an adjusted hazard ratio (HR) of 0.49 (95% confidence interval [CI], 0.27-0.90; P=0.020). FAS A-670G AA genotype was associated with increased risk of RHC with an adjusted HR of 1.84 (95% CI, 1.25-2.69; P=0.002). ACE II genotype was associated with decreased risk of RHC with an adjusted HR of 0.58 (95% CI, 0.36-0.95; P=0.031)., Conclusions: Recipients with a high anti-inflammatory and immune-regulatory genetic profile (high interleukin-10) were protected from RHC. Conversely, recipients with a pro-apoptotic genetic profile (high Fas) or high angiotensin-1-converting enzyme producing genotype were at increased risk of RHC. This represents progress toward understanding the genetic risk factors of posttransplantation outcomes in pediatric heart recipients.

Background: Myocarditis is a cause of a new-onset dilated cardiomyopathy phenotype in children, with small studies reporting high rates of recovery of left ventricular (LV) function., Methods and Results: The presenting characteristics and outcomes of children with myocarditis diagnosed clinically and with biopsy confirmation (n=119) or with probable myocarditis diagnosed clinically or by biopsy alone (n=253) were compared with children with idiopathic dilated cardiomyopathy (n=1123). Characteristics at presentation were assessed as possible predictors of outcomes. The distributions of time to death, transplantation, and echocardiographic normalization in the biopsy-confirmed myocarditis and probable myocarditis groups did not differ (P≥0.5), but both groups differed significantly from the idiopathic dilated cardiomyopathy group (all P≤0.003). In children with myocarditis, lower LV fractional shortening z-score at presentation predicted greater mortality (hazard ratio, 0.85; 95% confidence interval, 0.73 to 0.98; P=0.03) and greater LV posterior wall thickness predicted transplantation (hazard ratio, 1.17; 95% confidence interval, 1.02 to 1.35; P=0.03). In those with decreased LV fractional shortening at presentation, independent predictors of echocardiographic normalization were presentation with an LV end-diastolic dimension z-score >2 (hazard ratio, 0.36; 95% confidence interval, 0.22 to 0.58; P<0.001) and greater septal wall thickness (hazard ratio, 1.16; 95% confidence interval, 1.01 to 1.34; P=0.04)., Conclusions: Children with biopsy-confirmed or probable myocarditis had similar proportions of death, transplantation, and echocardiographic normalization 3 years after presentation and better outcomes than those of children with idiopathic dilated cardiomyopathy. In children with myocarditis who had impaired LV ejection at presentation, rates of echocardiographic normalization were greater in those without LV dilation and in those with greater septal wall thickness at presentation. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005391.

Background: In patients with dilated cardiomyopathy, the magnitude of cardiac remodeling often correlates with the clinical severity of heart failure. We sought to determine whether measures of left ventricular (LV) dilation and systolic dysfunction in children with dilated cardiomyopathy at the time of listing for cardiac transplantation are associated with survival while waiting for and early after transplant., Methods and Results: We analyzed echocardiographic data obtained within 6 months of listing for heart transplant and clinical data from 261 children with dilated cardiomyopathy who were included in both the Pediatric Cardiomyopathy Registry and the Pediatric Heart Transplant Study. Median time to listing after diagnosis was 1.9 months and to transplant after listing was 0.8 months. There were 42 deaths (29 waiting and 13 within 6 months after transplant). We found a significant age-dependent association of LV end-diastolic dimension z score (n=204, 31 deaths) with death controlling for race, transplant status, and medical insurance. The association was strongest for infants younger than 6 months at diagnosis (hazard ratio 1.47, P=0.008) and was not significant in children older than 5 years at diagnosis. A similar interaction was identified between age and LV end-systolic dimension z score (P=0.04). Neither LV function nor mass was associated with death, overall, or in subgroups., Conclusions: The severity of LV dilation at listing for heart transplant is associated with outcome in infants and young children with dilated cardiomyopathy, whereas the severity of LV systolic dysfunction is not. These findings should be considered in risk stratification of these children at listing.

Background: Granzyme B has been associated with allograft rejection in solid organ transplantation. Single nucleotide polymorphisms (SNPs) in the granzyme B gene might impact its expression. The aims of this study were (1) to establish the frequency of two granzyme B SNPs (A-295G; Q-55R) in pediatric heart transplant (PHTx) recipients and (2) to determine their phenotypic expression in healthy individuals., Methods: Three hundred ninety-six PHTx patients (245 white non-Hispanic, 49 black non-Hispanic, 82 Hispanics, and 20 others) and 52 healthy controls were screened for Q-55R and A-295G. For the control samples, we assessed the frequency of granzyme B positive cells by ELISPOT assay after mitogen stimulation., Results: Among the PHTx recipients, 57% percent of the population carried the Q/Q genotype, whereas 6% were R/R homozygotes. Seven of 49 (14%) black non-Hispanics were R/R homozygotes, whereas 13 of 245 (5%) of white non-Hispanics and 5 of 82 (6%) Hispanics carried the R/R genotype (P=0.02). The A allele frequency of granzyme B A-295G (49.6%) was similar to that of the G allele (50.4%). However, 80% of Black non-Hispanics were A allele carriers compared with 68% of White non-Hispanics (P<0.0001). After mitogen stimulation, the frequency of granzyme B positive cells was higher in the Q/Q homozygotes compared with R/R carriers (P=0.006), whereas a similar frequency of granzyme B positive cells was noticed among the genotypes of A-295G SNP., Conclusions: These data indicate that 55 Q/Q genotype is associated with increased in vitro expression of granzyme B.

Objective: The objective of this study was to determine the association between the genetic polymorphisms of proinflammatory and regulatory cytokines and long-term rates of repeat and late acute rejection episodes in pediatric heart transplant (PHTx) recipients., Methods: Three hundred twenty-three PHTx recipients: 205 White non-Hispanic, 43 Black non-Hispanic, and 75 Hispanic were analyzed for time to first repeat and late acute rejection episodes by race, age at transplantation, and gene polymorphism (interleukin [IL]-6, -174 G/C, IL-10, -1082 G/A, -819 C/T, 592 C/A; vascular endothelial growth factor (VEGF) -2578 C/A, -460 C/T, +405 C/G; tumor necrosis factor alpha (TNF-alpha)-308 G/A)., Results: Recipient black race and older age at transplant were risk factors for both repeat and late rejections, though black race was more significantly related to late rejection (P=0.006). Individually, TNF-alpha high, IL-6 high, VEGF high, and IL-10 low phenotypes did not impact the risk of repeat or late rejection. However, the combination VEGF high/IL-6 high and IL-10 low was associated with increased estimated risk of late rejection (P=0.0004) and only marginally with repeat rejection (P=0.051). In a multivariate analysis, adjusting for age and race, VEGF high/IL-6 high and IL-10 low still remained an independent risk factor for late acute rejection (RR=1.91, P<0.001)., Conclusion: This is the largest multicenter study to document the impact of genetic polymorphism combinations on PHTx recipients' outcome. The high proinflammatory (VEGF high/IL-6 high) and lower regulatory (IL-10 low) cytokine gene polymorphism profile exhibited increased risk for late rejection, irrespective of age and race/ethnicity.

Background: Allograft failure in African-Americans remains higher than in Caucasians. Single nucleotide polymorphisms (SNPs) have been associated with altered allograft outcomes., Methods: In this multi-center study we compared SNP frequencies in 364 pediatric heart recipients from three ethnic/racial groups: Caucasian (n = 243), African-American (n = 39), and Hispanic (n = 82). The target genes were: tumor necrosis factor-alpha, interleukin (IL)-10, IL-6, interferon (IFN)-gamma, vascular endothelial growth factor (VEGF), transforming growth factor-beta1, Fas, FasL, granzyme B, ABCB1, CYP3A5., Results: Compared to Caucasians, African-Americans exhibited a higher prevalence of genotypes associated with low expression of IFN-gamma (24% vs. 45.7%, P < 0.001) and IL-10 (33% vs. 57.1%, P = 0.052). African-Americans also exhibited an increased prevalence of high IL-6 (82.9% vs. 38.1%; P < 0.001). VEGF -2578 C/C and -460 C/C genotypes were found more frequently in African-Americans and Hispanics as compared to Caucasians (P < 0.001). G/G genotype of Fas and T/T genotype of FasL were expressed more often by African-American recipients. The prevalence of Granzyme B (-295A/G) genotype was differentially distributed in the three groups. Compared with Caucasians, African-Americans were twice as likely to carry the ABCB1 2677 G/G genotype (78.6% vs. 33.7%, P < 0.0025), and they were more frequent carriers of the CYP3A5 *1/*1 genotype (35.7% vs. 0.6% in Caucasians and 7.2% in Hispanics; P < 0.001)., Conclusion: African-Americans have a genetic background that may predispose to proinflammatory/lower regulatory environment, reduced drug exposure and immunosuppressive efficacy. In this ongoing multicenter study, these gene polymorphisms differences among ethnic/racial groups are being documented so that therapeutic strategies can be devised to optimize outcomes for pediatric transplant recipients.

The design of mechanical circulatory support devices typically requires a priori knowledge of the hemodynamic requirements of their intended use. These requirements are difficult to determine because of limited clinical experience. This is especially true for the pediatric population, for whom there is a dearth of longitudinal data. This report aims to provide both engineers and physicians with benchmarks for determining the optimal flow requirements and settings for pediatric ventricular assist devices that are currently being developed. Criteria were developed on the basis of estimates derived from various sources. The potential patient population was estimated by using the prevalence of children on the heart transplant waiting list and those placed on extracorporeal membrane oxygenation. Cardiac outputs were determined for individual weights and body surface areas, using published values for healthy and sick pediatric patients. The recommended pump range was optimized to include the most patients, while considering the design constraints. This study identifies a significant population of patients who would benefit from a device providing 0.52 to 1.92 l/min.

Background: The aim of this study was to assess the influence of IL-10 and TGFbeta1 gene polymorphisms on the development of acute rejection and coronary disease in pediatric heart transplant recipients., Methods: Patients were classified as either Rejectors or Nonrejectors. Coronary artery disease (CAD) was diagnosed by angiography or on macroscopic examination. Genotyping PCR-SSP were performed for IL-10 and TGFbeta1 (codon 10 and 25) in 111 patients. Thirty-nine were Rejectors and 31 developed CAD., Results: The proportion of IL-10 low-producers was higher in Rejectors than in Nonrejectors (respectively 46% versus 22%, P=0.009). IL-10 gene polymorphism was not associated with CAD. TGFbeta1-codon10-25 high-producers were 92.3% in Rejectors and 75% in Nonrejectors (P=0.026), 93.5% in patients with CAD and 76.2% in patients free from CAD (P=0.037). TGFbeta1-codon25 high-production separately analyzed correlated with CAD (31/31 high-producers in CAD=100% versus 69/80 in noCAD patients=86.2%, P=0.03). TGFbeta1-codon10 gene polymorphisms were not associated with CAD., Conclusion: IL-10 low-producers have an increased risk of acute rejection. High-expressors of TGFbeta1-codon10-25 have an increased risk of acute rejection and CAD, while TGFbeta1-codon25 high-production is associated with coronary disease. Genetic polymorphism may reveal patients at high-risk in whom therapies and monitoring should be adjusted.

Children with heart failure unresponsive to medical therapy are left with few options for survival. Pulsatile paracorporeal ventricular assist devices are life-saving options for such patients, allowing for bridge to transplantation or cardiac recovery. From March 1997 to July 2004, 12 patients underwent implantation of Thoratec biventricular assist devices (BVADs) for refractory heart failure. Mean age was 14.9 (range 7-20) and mean BSA was 1.7 (range 1.1-1.9). Indications for support included end-stage cardiomyopathy (n=10), myocarditis (n=1), and postcardiotomy heart failure (n=1). Preimplant variables included 50% of patients requiring mechanical ventilation (mean 4.2 days), hyperbilirubinemia in 58%, and acute renal failure in 50%. Mean duration of support was 64.5 (range 2-175) days. Overall survival was 83%, with nine patients successfully bridged to transplantation (75%). One patient exhibited recovery allowing for device explantation, and two patients died while on BVADs. Complications included bleeding requiring reoperation in 25% (n=3), stroke in 8% (n=1), driveline infections in 17% (n=2), and device malfunction in one patient. Pulsatile paracorporeal BVADs can be used successfully in children and adolescents with heart failure. These results warrant consideration of using available miniaturized technology in the United States for the support of smaller children with intractable biventricular failure.

Background: This study was performed to determine whether a preoperative hemodynamic evaluation with oxygen and inhaled nitric oxide identifies patients with pulmonary hypertension who are appropriate candidates for corrective cardiac surgery or transplantation more accurately than an evaluation with oxygen alone., Methods and Results: At 10 institutions, 124 patients with heart disease and severe pulmonary hypertension underwent cardiac catheterization to determine operability. The ratio of pulmonary and systemic vascular resistance (Rp:Rs) was determined at baseline while breathing approximately 21% to 30% oxygen, and in approximately 100% oxygen and approximately 100% oxygen with 10 to 80 parts per million nitric oxide to evaluate pulmonary vascular reactivity. Surgery was performed in 74 patients. Twelve patients died or developed right heart failure secondary to pulmonary hypertension following surgery. Rp:Rs<0.33 and a 20% decrease in Rp:Rs from baseline were chosen as 2 criteria for operability to determine, in retrospect, the efficacy of preoperative testing in patient selection. In comparison to an evaluation with oxygen alone, sensitivity (64% versus 97%) and accuracy (68% versus 90%) were increased by an evaluation with oxygen and nitric oxide when Rp:Rs<0.33 was used as the criterion for operability. Specificity was only 8% when a 20% decrease in Rp:Rs from baseline was used as the criterion for operability., Conclusion: By using a combination of oxygen and inhaled nitric oxide, a greater number of appropriate candidates for corrective cardiac surgery or transplantation can be identified during preoperative testing when a specific value of Rp:Rs is used as a criterion for operability.

We present the youngest successful patient with combined heart-lung-liver transplantation. The patient was a 2.5-year-old child with Alagille syndrome suffering from tetralogy of Fallot with pulmonary atresia and multiple aortopulmonary collaterals and familial cholestasis.

Background: Cytokine genetic polymorphisms have been associated with transplant outcome in some experimental and clinical studies, but the cytokine profile of patients who are clinically tolerant has not been investigated., Aim: Allelic variations in tumor necrosis factor (TNF)-alpha, interferon (INF)-gamma, transforming growth factor (TGF)-beta1, interleukin (IL)-6, and IL-10 were evaluated in patients successfully withdrawn from immunosuppression., Methods: Pediatric liver transplant recipients who were successfully withdrawn from immunosuppression (n=12) or who are on minimal immunosuppression (n=7) were genotyped. A control group of liver recipients who required maintenance immunosuppression served as a control group (n=37)., Results: Compared to the control group, low TNF- alpha and high/intermediate IL-10 profiles were seen in all 12 children maintained off immunosuppression and in 6 of 7 children requiring minimal immunosuppression., Conclusion: Children successfully maintained off immunosuppression are more likely to have a genetic predisposition toward low TNF-alpha and high/intermediate IL-10 production. Children maintained on minimal immunosuppression exhibit a similar cytokine profile to those successfully weaned.

Background: Posttransplantation diabetes mellitus (PTDM) is a well-known complication of tacrolimus-based immunosuppression in both adult and pediatric solid organ recipients. The "natural history" of diabetes in the pediatric thoracic transplant population has not yet been described., Methods: We identified all pediatric thoracic transplant patients receiving tacrolimus-based immunosuppression who developed PTDM. Medical records were reviewed, with a particular focus on the clinical course of PTDM and its relationship to drug weaning., Results: Diabetes developed in 24 of 143 (17%) 30-day survivors of heart (12/96, 13%) and heart-lung/lung (12/ 47, 26%) transplantation. In 17 (71%) patients, the immunosuppressive regimen at the onset of PTDM also included maintenance corticosteroids. Seventeen patients demonstrated glucose intolerance before the onset of diabetes. Nine patients (38%) developed diabetes during pulsed corticosteroid therapy. Median time of onset after transplantation was 9.0 months. All patients required s.c. insulin for glucose control. The median follow-up from transplant was 49.9 months. There was a significant decrease in mean tacrolimus dosage (P<0.01), tacrolimus level (P<0.04), and steroid dosage (P<0.02) from onset of PTDM to most recent follow-up. Despite this significant reduction in immunosuppression, only 3/24 (13%) patients were successfully weaned off insulin., Conclusions: Diabetes mellitus is a common complication in pediatric thoracic transplant patients receiving tacrolimus-based immunosuppression. Insulin dependence in our population rarely resolved, even after lowering tacrolimus and steroid doses. Discontinuation of steroids did not guarantee resolution of diabetes.

Background: Fetal echocardiography is widely established in the United Kingdom for prenatal diagnosis of congenital heart disease. This may result in a substantial reduction in incidence at birth because of selected termination of pregnancy. The objective of this population-based study was to determine the incidence of pulmonary atresia with intact ventricular septum (PAIVS) at birth, the impact of fetal echocardiography on this incidence, and to compare the outcome of cases with and those without prenatal diagnosis., Methods and Results: From 1991 to 1995, all infants born with PAIVS and all fetal diagnoses in the United Kingdom and Eire were studied. There were 183 live births (incidence 4.5/100,000 live births). The incidence was 4.1 cases per 100,000 live births in England and Wales, 4.7 in Scotland, 6.8 in Eire, and 9.6 in Northern Ireland (P=0.01). There were 86 fetal diagnoses made at a mean of 22.0 weeks of gestation leading to 53 terminations of pregnancy (61%), 4 intrauterine deaths (5%), and 29 live births (34%). The incidence at birth would be 5.6 per 100,000 births in England and Wales, 5.3 in Scotland, and unchanged in Eire and Northern Ireland, if there were no terminations of pregnancy and assuming no further spontaneous fetal deaths (P=0.28). An initial diagnosis of critical pulmonary stenosis was made in 6 cases, at a mean of 22.3 weeks of gestation with progression to PAIVS by 31.4 weeks. Probability of survival at 1 year was 65% and was the same for live-born infants whether or not a fetal diagnosis had been made., Conclusions: PAIVS is rare, occurring in 1 in 22,000 live births in the United Kingdom and Eire. Termination of pregnancy has resulted in an important reduction in the live-born incidence in mainland Britain.

Background: It is common practice to interrupt all alternative sources of pulmonary blood flow ("competitive flow") at the time of a bidirectional superior cavopulmonary anastomosis (BCPA), although the merits of this have not been systematically studied., Methods and Results: We reviewed the early and medium-term clinical and hemodynamic findings in 108 consecutive patients 3 weeks to 25 years old (median, 1.9 years) undergoing BCPA at one of three institutions. Preoperatively, pulmonary blood flow was dependent on antegrade ventricular flow (n = 50), systemic-to-pulmonary shunts (n = 33), or mixed sources (n = 25). Postoperatively, competitive sources of pulmonary blood flow were left patent in 43 of 108 patients (40%). There were four early (3.7%) and four late deaths, none related to persistence of competitive flow. After BCPA, patients with competitive flow had significantly higher systemic oxygen saturations at 1 hour (85% versus 79%), 24 hours (84% versus 78%), and at hospital discharge (84% versus 78%) and required a shorter period of artificial ventilation (median, 9 versus 24 hours) and intensive care (median, 2 versus 4 days). Oxygen saturations at late follow-up (median, 2.8 years; range, 1 to 7) did not differ (83% versus 82%). No patient developed pulmonary arteriovenous malformations., Conclusions: Competitive flow is well tolerated in the short and medium term after BCPA, and early postoperative systemic oxygen saturations are improved. The long-term influence of competitive flow on pulmonary arterial growth, arteriovenous malformation development, and ventricular function warrants investigation.