Fetal Left Ventricular Apical Aneurysm Progressing to Dilated Cardiomyopathy Due to Glycogen Storage Disease.

Fetal dilated cardiomyopathy is a rare anomaly characterized by ventricular dilation and dysfunction. Its causes are diverse, and its outcomes are generally dismal. We describe a rare case of prenatally diagnosed left ventricular apical aneurysm that progressed rapidly to dilated cardiomyopathy. At age 2 months, the infant underwent heart transplantation. Pathologic examination of the explanted heart revealed that the cause of the dilated cardiomyopathy was glycogen storage disease. This case highlights the crucial roles of timely diagnosis, frequent close monitoring, and multidisciplinary care in achieving a successful postnatal outcome.

Outcomes of infants with pulmonary atresia with intact ventricular septum listed for heart transplantation: A multi-institutional study.

BACKGROUND: Management of infants with pulmonary atresia/intact ventricular septum (PA/IVS) is variable. Because of higher mortality in more severe forms, heart transplant (HT) is an acceptable approach, but waitlist and post-transplant outcomes are unclear. This study compared outcomes of infants with PA/IVS vs. other single ventricle (SV) anatomies listed for HT. METHODS: Data from the Pediatric Heart Transplant Society (1993-2018) were analyzed for survival and risk factors for mortality. RESULTS: Of 1617 SV infants, 300 had PA/IVS (19%) and 1317 had other SV (81%). Overall, 1-, 5-, and 10-year survival was higher among PA/IVS (74%, 65%, 61%) versus other SV infants (62%, 54%, 50%, p = .004). While waitlist mortality was similar between groups (p = .09), PA/IVS was an independent predictor of improved waitlist survival (HR 0.68, p = .03), and PA/IVS infants had higher incidence of waitlist removal (8% vs. 5.5%, p = .03), most commonly for being "too well." Post-transplant survival was superior among PA/IVS versus other SV infants (1- and 5-year survival 93% and 81% vs. 80% and 71%, p < .0001). Risk factors for PA/IVS waitlist mortality (2008-2018) included extracorporeal membrane oxygenation and mechanical ventilation. Prior aortopulmonary (AP) shunt among PA/IVS infants was associated with improved waitlist survival. CONCLUSIONS: Overall survival among PA/IVS infants listed for HT exceeds that of other SV infants with PA/IVS identified as an independent predictor of improved waitlist and post-transplant survival. Prior AP shunt among listed PA/IVS infants was associated with improved waitlist outcomes, though, which may reflect a listing selection bias.

Significance of pre and post-implant MELD-XI score on survival in children undergoing VAD implantation.

BACKGROUND: Derangements in liver and renal function often accompany end-stage heart failure. We sought to assess the utility of an objective risk assessment tool, the Model for End-stage Liver Disease eXcluding INR (MELD-XI), to identify pediatric patients at increased risk for adverse outcomes post-ventricular assist device (VAD) implantation. METHODS: The Pedimacs database was queried for all pediatric patients who underwent VAD implantation from September 19, 2012 to December 31, 2019. Pre-implant and early (1-week) post-implant MELD-XI scores were used to stratify patients into low, intermediate and high score cohorts. Comparison of pre-implant characteristics and post-implant outcomes were conducted across groups. Multiphase parametric hazard modeling was utilized to identify independent predictors of post-implant mortality. RESULTS: A total of 742 patients had a calculable MELD-XI score pre-implant. When stratified by MELD-XI scores pre-implant, patients in the high MELD-XI score cohort (score >13.6) had inferior survival and increased bleeding, renal dysfunction and respiratory failure post-implant compared to intermediate and low score cohorts. Risk factors for mortality post-VAD implantation were: increasing MELD-XI scores (HR 1.1 per 1 unit rise), Pedimacs profile 1 (HR 1.6), congenital heart disease (HR 2.3) and being on a percutaneous VAD (HR 2.7). Importantly, MELD-XI score was a better predictor of post-VAD implant mortality than bilirubin or creatinine alone, neither of which were significant in the final model. Patients with increasing or continued high MELD-XI scores early post-implant had the worst survival. CONCLUSION: The MELD-XI is an easily calculated score that serves as a promising risk assessment tool in identifying children at risk for poor outcomes post VAD implantation.

Arrhythmias and fasciculoventricular pathways in patients with Danon disease: A single center experience.

BACKGROUND: Danon disease is a rare X-linked storage disorder characterized by hypertrophic cardiomyopathy leading to arrhythmias and heart failure. A preexcitation pattern on electrocardiogram (ECG) has been described in these patients, however, invasive studies to distinguish between Wolff-Parkinson-White syndrome syndrome and fasciculoventricular pathways (FVP) are limited. OBJECTIVES: The purpose of this study was to delineate the electrophysiological cardiac abnormalities in patients with Danon disease and to describe the presence of FVP in this population. METHODS: We performed a retrospective study of all patients with a confirmed diagnosis of Danon disease presenting to a single center from May 2005 to May 2018. Baseline demographics, clinical characteristics, ECG findings, and electrophysiology study (EPS) results were collected. RESULTS: Ten patients with Danon disease (30% male, average age 17.4 years) were identified. Seven patients (70%) had tachyarrhythmias including five with atrial arrhythmias and six with nonsustained ventricular tachycardia. Preexcitation pattern on ECG was found in four (40%) patients. Of these, two underwent an EPS which confirmed the presence of an FVP. One patient underwent an adenosine challenge which supported a FVP. Implantable cardioverter defibrillator was placed in five patients for primary prevention with no patients receiving an appropriate discharge. Over a follow-up of 5.3 years, five underwent heart transplantation. CONCLUSIONS: This study reports a high incidence of FVP in patients with Danon disease and preexcitation. It underscores an alternate etiology of preexcitation in this population which can potentially be diagnosed without invasive EPS testing. Future multicenter studies are needed to expand this experience.

When a Child Needs a Transplant but Lacks Familial Social Support.

We present the case of a 19-month-old boy with complex congenital heart disease. His single father is skeptical of traditional medicine and does not offer the social support needed to make heart transplantation successful for his son. After the father demonstrates commitment to transplant success and provides enhanced social support, doctors place the child on a Berlin Heart (a biventricular assist device) as a bridge to transplantation and list him for transplant. When the child is matched to a donor heart, the father refuses transplantation, despite that it is the child's only chance for survival. His doctors report the case to child protective services, but they decline to take protective custody. The father then changes his mind and asks that the child be put back on the waiting list for transplant. By this time, the social supports the father implemented are no longer in place. This case raises a number of issues. First, should courts order heart transplantation when doctors believe that it is in the child's best interest and parents do not consent? Second, once parents refuse a transplant, can they change their minds? Third, if there are uncertainties regarding whether the child has the social support to make transplantation successful, should the child be relisted? Finally, should a child who is not currently a transplant candidate but who may become one in the future be supported with ventricular assist devices?

Radiation Reduction in the Pediatric Catheterization Laboratory Using a Novel Imaging System.

OBJECTIVES: Radiation dose was compared between two modern imaging systems with different x-ray tube technology (Megalix vs Gigalix) and detector type (amorphous vs crystalline silicon) at the same institution. BACKGROUND: Further reduction in radiation dose than currently reported may be achievable with advances in x-ray tube and detector technology. METHODS: Radiation dose (air kerma, dose-area product [DAP]) was retrospectively compared for post-transplant pediatric patients undergoing right heart catheterization/biopsy (fluoroscopy only) or "annual" catheterization with coronary angiography in one of two imaging systems between January 2014 and December 2016. Comparisons were also made with published radiation doses. RESULTS: A total of 122 right heart catheterizations with biopsy were performed in the Megalix/amorphous silicon (Si) lab and 168 in the Gigalix/crystalline Si lab. Age and weight were not statistically different for the two groups. There was a 50% decrease in median air kerma (2.2 mGy vs 1.1 mGy; P<.001) and 66% decrease in median DAP (52.2 µGy•m² vs 18.0 µGy•m²; P<.001) for the Gigalix/crystalline Si lab. A total of 24 "annual" catheterizations were performed in the Megalix/amorphous Si lab and 22 were performed in the Gigalix/crystalline Si lab. There was a 57% reduction in median air kerma (458.6 mGy vs 198.6 mGy; P<.001) and a 46% reduction in median DAP (2548.0 µGy•m² vs 1367.1 µGy•m²; P<.01) for the Gigalix/crystalline Si lab. Similar reductions were found on comparison with published doses. CONCLUSION: The Gigalix tube and crystalline Si detector decrease radiation dose by 50%-60% for fluoroscopy and cine acquisition in pediatric patients.

Characteristics of Clinically Diagnosed Pediatric Myocarditis in a Contemporary Multi-Center Cohort.

The objective of this study was to describe a contemporary cohort of pediatric patients hospitalized for clinically suspected myocarditis. A retrospective chart review was performed at seven tertiary pediatric hospitals. Electronic medical records were searched between 2008 and 2012 for patients ≤18 years admitted with an ICD-9 code consistent with myocarditis. Patients were excluded if the admitting or consulting cardiologist did not suspect myocarditis during the admission or an alternative diagnosis was determined. One hundred seventy-one patients were discharged or died with a primary diagnosis of myocarditis. Median age was 13.1 years (IQR 2.1, 15.9), with a bimodal distribution; 24% <2 years and 46% between 13 and 18 years. Patients with moderate or severe systolic dysfunction were younger, had higher BNPs at admission, but had lower troponin. Mortality, heart transplantation, and readmission did not differ between patients who received only IVIG, only steroids, IVIG and steroids, and no immunotherapy. Ninety-four patients (55%) were discharged on heart failure medications, 16 were transplanted, and seven died. The presence at the time of admission of gastrointestinal (GI) symptoms (p = 0.01) and lower echo shortening fraction (SF) (p < 0.01) was associated with death/transplant. Within one year 16% had a readmission, one underwent heart transplant, and 39% received heart failure therapy. Pediatric myocarditis has a bimodal age distribution. The use of IVIG and steroids is not associated with mortality/heart transplantation. The presence of GI symptoms and lower echo SF may identify patients at risk for death and/or transplantation during the admission.

Cancer recurrence and mortality after pediatric heart transplantation for anthracycline cardiomyopathy: A report from the Pediatric Heart Transplant Study (PHTS) group.

We aimed to determine whether malignancy after pediatric HTx for ACM affects overall post-HTx survival. Patients <18y listed for HTx for ACM in the PHTS database between 1993 and 2014 were compared to those with DCM. A 2:1 matched DCM cohort was also compared. Wait-list and post-HTx survival, along with freedom from common HTx complications, were compared. Eighty subjects were listed due to ACM, whereas 1985 were listed for DCM. Although wait-list survival was higher in the ACM group, post-HTx survival was lower for the ACM cohort. Neither difference persisted in the matched cohort analysis. Primary cause of death in the ACM group was infection, which was higher than the DCM group. Malignancy rates were not different. All ACM malignancies were due to PTLD without primary cancer recurrence or SMN. Long-term graft survival after pediatric HTx for ACM is no different than for matched DCM peers, nor is there an increased risk of any malignancy. However, risk of infection and death from infection after HTx are higher in the ACM group. Further studies are needed to assess the effects of prior chemotherapy on susceptibility to infection in this group.

Protein Losing Enteropathy After Cardiac Transplantation Successfully Treated by Stent Implantation.

Protein losing enteropathy (PLE) is a severe consequence of Fontan physiology that sometimes requires heart transplantation for definitive treatment. We describe transplant refractory PLE in a patient with heterotaxia and complex systemic and hepatic venous connections, successfully treated by transcatheter relief of multiple venous obstructions.

Implantable cardioverter-defibrillator and wait-list outcomes in pediatric patients awaiting heart transplantation.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) reduce the incidence of sudden cardiac death (SCD) in adults with end-stage heart failure; however, their efficacy in pediatric patients awaiting heart transplantation is not well established. OBJECTIVES: This study sought to investigate the role of ICDs in preventing SCD and waiting list mortality as well as to determine risk factors for SCD in pediatric patients listed for heart transplantation. METHODS: We queried the United Network for Organ Sharing database for all pediatric patients (age ≤18 years) listed for heart transplantation (2005-2014). The Cox proportional hazards model was used to identify risk factors for SCD and all-cause mortality. RESULTS: A total of 5072 mostly White (55%) male (55%) patients (mean age 6.2 ± 6.5 years) were identified, of whom 426 (8.3%) had ICD at listing. At 6 months, 65% underwent heart transplantation, 15% died (4% died of SCD), and 20% were alive. In a multivariable model, United Network for Organ Sharing status 1B (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.29-0.95; P = .03), myocarditis (HR 0.19; 95% CI 0.05-0.77; P = .02), restrictive cardiomyopathy (HR 0.19; 95% CI 0.05-0.76; P = .02), and dilated cardiomyopathy (HR 0.32; 95% CI 0.20-0.52; P < .001) were associated with lower SCD risk, while younger age at listing (HR 0.94 per year; 95% CI 0.90-0.98; P = .003) was associated with higher SCD risk. ICD at listing was not associated with reduced SCD (P = .12), all-cause mortality, or delisting (P = .57). CONCLUSION: In pediatric patients listed for heart transplantation, the risk of SCD remains low and does not differ between patients with and without an ICD at listing.

Pacemaker implantation in pediatric heart transplant recipients: Predictors, outcomes, and impact on survival.

BACKGROUND: Little is known about the incidence of permanent pacemaker (PPM) implantation after heart transplantation (HTx) in the pediatric population. OBJECTIVE: The purpose of this study was to investigate the incidence, predictors, and outcomes of acute need for PPM implantation in pediatric HTx recipients. METHODS: We queried the United Network for Organ Sharing (UNOS) database for all pediatric (age <18 years) patients who received HTx (1994-2014). Regression models are reported for prediction of PPM implantation. RESULTS: A total of 6156 patients were analyzed, of whom 69 (1.1%) required posttransplant PPM implantation acutely. PPM use decreased over the study period (hazard ratio [HR] 0.95, P = .01). Compared with the non-PPM group, PPM group was more likely to be older (10 vs 5.0 years, P <.001), used antiarrhythmics (35.6% vs 18.3%, P = .006), required intraaortic balloon pump (2.9% vs 0.5%, P = .049), and had undergone biatrial anastomosis (68.1% vs 48.2%, P = .007). In a multivariable model, PPM implantation was predicted by higher donor age (HR 1.05, P = .002), biatrial anastomosis (HR 2.53, P = .04) and antiarrhythmic use (HR 2.12, P = .02). After adjusting for baseline characteristics, PPM recipients were at increased risk for posttransplant infection (47.8% vs 26.4%, P = .001) and dialysis (15.9% vs 6.6%, P = .003). Adjusted graft survival did not differ between the 2 groups (P = .78). CONCLUSION: Acute postoperative PPM implantation in pediatric HTx recipients is rare and has decreased over time. Acute PPM use is associated with biatrial anastomosis, antiarrhythmic use, and older donor age. Although PPM recipients had higher incidences of infections and dialysis, PPM implantation did not adversely impact survival.

Unusual cause of myocardial ischemia in an infant.

Abnormal coronary artery anatomy should be ruled out in any patient with myocardial dysfunction and an abnormal electrocardiogram. The reported etiologies of infantile myocardial ischemia are abnormalities of coronary arteries, perinatal asphyxia, umbilical catheterization, and myocarditis. Generalized arterial calcification of infancy, although rare, should be considered in the differential diagnosis of infantile myocardial ischemia if coronary artery origin is found to be normal on echocardiography.

Left ventricular systolic dyssynchrony in pediatric and adolescent patients with congestive heart failure.

BACKGROUND: Echocardiographic measures of left ventricular (LV) dyssynchrony in pediatric patients with heart failure (HF) have not been adequately evaluated. The aim of this study was to evaluate LV systolic dyssynchrony in pediatric patients with HF and normal children. METHODS: Among a total of 68 patients, 22 had HF and 46 were normal. Doppler tissue imaging, M-mode echocardiography, and pulsed-wave Doppler echocardiography were performed. Intraventricular dyssynchrony using the maximal difference in time to peak myocardial systolic contraction (Ts), the standard deviation of Ts of 12 LV segments, septal-to-posterior wall motion delay, and interventricular dyssynchrony by measuring aortic and pulmonary pre-ejection delays were obtained. RESULTS: The maximal difference in Ts (patients with HF, 91.27 ± 31.18 msec; controls, 45.93 ± 21.29 msec; P < .001), the standard deviation of Ts (patients with HF, 31.05 ± 10.68 msec; controls, 15.60 ± 7.70 msec; P < .001), septal-to-posterior wall motion delay (patients with HF, 117.14 ± 45.18 msec; controls, 48.69 ± 16.63 msec; P < .001) and interventricular dyssynchrony (patients with HF, 21.60 ± 16.27 msec; controls, 11.56 ± 9.38 msec; P = .03) were significantly prolonged in the HF group. Defining systolic dyssynchrony as a standard deviation of Ts > 31 msec (+2 standard deviations of normal controls) and a maximal difference in Ts > 89 msec in normal controls and 18 patients with HF due to dilated cardiomyopathy was included for analysis of systolic dyssynchrony; it was present in three (6.5%) and two (4.3%) controls and in nine (50%) and 10 (55%) patients with HF due to dilated cardiomyopathy, respectively. Low ejection fraction, elevated LV end-diastolic volume, and elevated LV end-systolic volume had significant correlations with systolic dyssynchrony. QRS duration was not significantly correlated with measures of dyssynchrony. CONCLUSIONS: Systolic mechanical dyssynchrony is common in pediatric patients with HF. QRS duration is not a determinant of systolic dyssynchrony in pediatric patients. Echocardiographic measurements of systolic dyssynchrony are feasible in pediatric patients.

Early survival after heart transplant in young infants is lowest after failed single-ventricle palliation: a multi-institutional study.

BACKGROUND: Infant heart transplant (HT) recipients have the best long-term survival of any age group, but the small donor pool and high early mortality limit the therapeutic effectiveness. We sought to determine the relationship between pre-HT diagnosis and early HT outcome to better define the mortality risk associated with a diagnosis of congenital heart disease (CHD) and to examine differences between early and current HT eras. METHODS: The Pediatric Heart Transplant Study (PHTS) database was used to identify 739 infant HT recipients at age ≤ 6 months between 1993 and 2008 divided into the following etiologic groups: cardiomyopathy (CM), 18%; hypoplastic left heart syndrome (HLHS) without surgery, 41%; HLHS with surgery, 9%; other CHD without surgery, 16%; and other CHD with surgery, 15%. Severity of illness at HT, post-HT survival, and era effects were compared. RESULTS: At 1 year after HT, survival was 89% for the CM group, which was the best, 79% for CHD without surgery, 82% for CHD with surgery, 79% for HLHS without surgery, and 70% for HLHS with surgery, which was the worst outcome. Hazard function analysis demonstrated the difference occurred within the first 3 months after HT. After adjusting for illness severity, differences in mortality risk persisted across etiologic groups. HT survival was similar in the current surgical era for HLHS with surgery, 71% (1993-1998) vs 70% (1999-2008). CONCLUSIONS: Infant HT recipients with different pre-HT diagnoses have significantly different post-HT outcomes. HLHS infants with surgery have the lowest survival and their outcome is unchanged in the current era.

Safety and early outcomes using a corticosteroid-avoidance immunosuppression protocol in pediatric heart transplant recipients.

BACKGROUND: Long-term oral corticosteroids have been a mainstay of maintenance immunosuppression in pediatric heart transplantation. In this study, we report early clinical outcomes in a cohort of pediatric heart transplant recipients managed using a steroid-avoidance protocol. METHODS: Of the 70 patients who underwent heart transplantation during the study period, 55 eligible recipients, including 49 non-sensitized and 6 sensitized (all 55 with negative crossmatch) patients, entered a steroid-avoidance immunosuppression protocol consisting of thymoglobin induction followed by a 2-drug, tacrolimus-based, corticosteroid-free regimen. The primary outcome variable was freedom from moderate rejection (International Society for Heart and Lung Transplantation [ISHLT] Grade 2R/3A or antibody-mediated rejection). RESULTS: The median age at transplant was 7.1 years (range 2 weeks to 22 years) and median follow-up was 19 months (range 2 to 46 months). Fifty patients survived to discharge after transplantation. Of these patients, 2 (4%) were discharged on steroids and 8 (16%) started on maintenance steroids at follow-up. Rejection was diagnosed in 8 patients (Grade 2R cellular rejection in 3 and antibody-mediated rejection in 5). Freedom from rejection was 92% at 6 months (95% confidence interval [CI] 80% to 97%) and 87% at 1 year (CI 73% to 94%). Post-transplant survival was 91% at 6 months (CI 79% to 96%) and 88% at 12 and 24 months (CI 75% to 95%). There was 1 death due to rejection (antibody-mediated) 8 months after transplantation. CONCLUSIONS: An immunosuppression protocol consisting of induction followed by corticosteroid avoidance appears to achieve acceptable rejection rates during the first year post-transplant in pediatric heart transplant recipients.

Lipid profiles in pediatric thoracic transplant recipients are determined by their immunosuppressive regimens.

BACKGROUND: Controversy exists over the pattern of lipidemic effects from calcineurin inhibitors and prednisone. We report an extensive longitudinal study of lipid profiles in pediatric thoracic transplant recipients. METHODS: Serial fasting lipids of subjects from a single pediatric center, along with their immunosuppressive regimens, were examined. Groups were analyzed according to cyclosporine- or tacrolimus-based immunosuppression in addition to whether prednisone was used as adjunctive therapy. RESULTS: Of a total of 119 subjects, 85 were and remained on tacrolimus (TAC), 13 remained on cyclosporine (CSA), 4 switched from TAC to CSA, and 17 switched from CSA to TAC. The median age at transplant was 100 months, and the latest follow-up was 48 months. The CSA Group had higher lipid levels than the TAC Group, and levels changed minimally over time. At 1 year, TAC vs CSA total cholesterol was 153 vs 186 mg/dl (p = 0.002), low-density lipoprotein (LDL) cholesterol was 92 vs 117 (p = 0.09), and high-density lipoprotein (HDL) cholesterol was 42 vs 48 (p = NS), respectively. At the latest follow-up, the TAC vs CSA cholesterol was 143 vs 180 mg/dl (p = 0.001), LDL was 84 vs 115 (p = 0.001), and HDL was 42 vs 41 (p = NS). Profiles of subjects that switched agents reflected the agent used (e.g., higher total cholesterol, LDL, and HDL while on cyclosporine). Sub-group analysis showed prednisone augmented the hyperlipidemic effects. CONCLUSION: Hyperlipidemia is common in pediatric thoracic transplant patients and persists over time. It is more pronounced in cyclosporine subjects and is further elevated with prednisone. These findings indicate the need for close monitoring, and consideration for intervention, especially in high-risk sub-groups.

Impact of ELISA-detected anti-HLA antibodies on pediatric cardiac allograft outcome.

In this study, we determine whether the presence of enzyme-linked immunosorbent assay (ELISA) detected anti-human leukocyte antigen (HLA) antibodies correlates with acute and chronic rejection in pediatric heart transplantation (Tx). Forty-five patients, who had serial ELISA pre- and posttransplantation, were studied. Age at Tx was 8.2 +/- 7.2 years. Acute rejection (AR) was defined as International Society for Heart and Lung Transplantation Grade > or =3a. Patients were defined as rejectors (22 cases) if they had recurrent AR or steroid-resistant AR within the first year post-Tx; the other cases (23) were defined as nonrejectors. Overall, 219 samples were analyzed. Twenty-two of the 45 had pre- or post-Tx anti-HLA antibodies: 77% in rejectors (17/22) and only 22% in nonrejectors (5/23), p = 0.0002. Pre-Tx HLA antibodies were present in 12 cases (27%). Presensitization was more frequent in rejectors (11/22, 50%) than in nonrejectors (1/23, 4%, p = 0.0005). Nineteen cases retained (9 cases) or developed (10 cases) anti-HLA antibodies post-Tx: 14 in rejectors (63.6%) and 5 in nonrejectors (21.7%), p = 0.003. Four of eight cases with coronary artery disease (50%) had preformed anti-HLA antibodies compared with 8 of 37 without coronary artery disease (25.6%) (p = 0.09). Preformed, persistent, and de novo ELISA-detected anti-HLA antibodies were correlated with first-year acute rejection profile.

Impact of TGFbeta1 gene polymorphisms on late renal function in pediatric heart transplantation.

Late renal dysfunction may affect long-term outcome of nonrenal transplant recipients. We hypothesized that transforming growth factor beta1 (TGFbeta1) might play a role in the fibrogenic mechanisms leading to renal dysfunction. The aim was to determine whether TGFbeta1 gene polymorphisms are associated with renal outcome in pediatric heart recipients. Eighty-eight patients underwent a first heart transplantation at the age of 7.1 +/- 6.5 years, received tacrolimus-based immunosuppression, and were followed for > or =1 year (6.7 +/- 3.2 years). Creatinine clearance (CrCl; ml/mn/1.73 m2) was calculated (Schwartz) before transplant, then at 1 month, 6 months, and 1 year, and yearly up to 7 years. Impaired function was defined as CrCl <80 ml/mn/1.73 m2. Mean CrCl decreased from 120 +/- 53 ml/mn/1.73 m2 before transplant to 98 +/- 40, 96 +/- 37, 102 +/- 30, and 101 +/- 38 ml/mn/1.73 m2 at, respectively, 6 months and 1, 5 (n = 58), and 7 years (n = 33). The TGFbeta1 high-producer genotype had worse CrCl than intermediate and low producers at every time point, despite similar pretransplant CrCl (pretransplant = 120 +/- 53 vs 118 +/- 55 ml/mn/1.73 m2 [p = 0.8], 1 year = 92 +/- 38 vs 113 +/- 30 ml/mn/1.73 m2 [p = 0.03]) and similar tacrolimus levels. The TGFbeta1 high-producer genotype was associated with CrCl < 80 ml/mn/1.73 m2. The TGFbeta1 high-producer genotype is associated with renal dysfunction in pediatric heart recipients.

Usefulness of plasma B-type natriuretic peptide to identify ventricular dysfunction in pediatric and adult patients with congenital heart disease.

The usefulness of B-type natriuretic peptide (BNP) levels to assess ventricular dysfunction in children and the congenital heart disease population remains largely unknown. We retrospectively analyzed 62 patients with or without known heart disease who had plasma BNP measured for the investigation of new or severity grading of known ventricular dysfunction. BNP levels were significantly higher in patients with ventricular dysfunction (mean 623 +/- 146 pg/ml, range 5 to 5,000) than in patients without ventricular dysfunction (mean 22 +/- 5 pg/ml, range 5 to 63; p <0.01). Using a cutoff of 40 pg/ml, BNP levels detected heart disease associated with ventricular dysfunction at a sensitivity of 85%, specificity of 81%, positive predictive value of 92%, and negative predictive value of 68%. The degree of BNP elevation was also associated with the severity of heart failure and high ventricular filling pressures. Plasma BNP elevation can be a reliable test in children and young adults with various kinds of congenital heart disease resulting in ventricular dysfunction.