Early outcomes for low-risk pediatric heart transplant recipients and steroid avoidance: A multicenter cohort study (Clinical Trials in Organ Transplantation in Children - CTOTC-04).

BACKGROUND: Immunosuppression strategies have changed over time in pediatric heart transplantation. Thus, comorbidity profiles may have evolved. Clinical Trials in Organ Transplantation in Children-04 is a multicenter, prospective, cohort study assessing the impact of pre-transplant sensitization on outcomes after pediatric heart transplantation. This sub-study reports 1-year outcomes among recipients without pre-transplant donor-specific antibodies (DSAs). METHODS: We recruited consecutive candidates (<21 years) at 8 centers. Sensitization status was determined by a core laboratory. Immunosuppression was standardized as follows: Thymoglobulin induction with tacrolimus and/or mycophenolate mofetil maintenance. Steroids were not used beyond 1 week. Rejection surveillance was by serial biopsy. RESULTS: There were 240 transplants. Subjects for this sub-study (n = 186) were non-sensitized (n = 108) or had no DSAs (n = 78). Median age was 6 years, 48.4% were male, and 38.2% had congenital heart disease. Patient survival was 94.5% (95% confidence interval, 90.1-97.0%). Freedom from any type of rejection was 67.5%. Risk factors for rejection were older age at transplant and presence of non-DSAs pre-transplant. Freedom from infection requiring hospitalization/intravenous anti-microbials was 75.4%. Freedom from rehospitalization was 40.3%. New-onset diabetes mellitus and post-transplant lymphoproliferative disorder (PTLD) occurred in 1.6% and 1.1% of subjects, respectively. There was no decline in renal function over the first year. Corticosteroids were used in 14.5% at 1 year. CONCLUSIONS: Pediatric heart transplantation recipients without DSAs at transplant and managed with a steroid avoidance regimen have excellent short-term survival and a low risk of first-year diabetes mellitus and PTLD. Rehospitalization remains common. These contemporary observations allow for improved caregiver and/or patient counseling and provide the necessary outcomes data to help design future randomized controlled trials.

Significant mortality, morbidity and resource utilization associated with advanced heart failure in congenital heart disease in children and young adults.

BACKGROUND: Children with congenital heart disease (CHD) are at risk for advanced heart failure (AHF). We sought to define the mortality and resource utilization in CHD-related AHF in children and young adults. METHODS: All hospitalizations in the Pediatric Health Information System database involving patients ≤21 years old with a CHD diagnosis and heart failure requiring at least 7 days of continuous inotropic support between 2004 and 2015 were included. Hospitalizations including CHD surgery were excluded. RESULTS: Of 465,482 CHD hospitalizations, AHF was present in 2,712 (0.6%) [58% infant, 55% male, 30% single ventricle]. AHF therapies frequently used included extracorporeal membrane oxygenation (ECMO) (15%) and cardiac transplant (16%). Ventricular assist device (VAD) support was rare (3%), although VAD use significantly increased from 2004 to 2015 (P < .0010). Hospital mortality in CHD with AHF was 26%, with higher mortality associated with single ventricle heart disease (OR 1.64, 95% CI 1.23-2.19; P = .0009), infancy (OR 1.71, 95% CI 1.17-2.5; P = .0057), non-white race (OR 1.28, 95% CI 1.04-1.59; p=0.0234), and chronic complex comorbidities (OR 1.76, 95% CI 1.34-2.30; P < .0001). Over the 11-year study period, despite the significant increase in CHD-related AHF hospitalizations (P < .0001), hospital mortality improved (P = .0011). Median hospital costs were $252,000, a 6-fold increase above those without AHF, and was primarily driven by hospital length of stay (P < .0001). CONCLUSION: AHF in children with CHD in uncommon but increasing and is associated with significant morbidity, mortality and resource utilization. Approximately 1 in 5 children do not survive to hospital discharge. Many risk factors for mortality may not be modifiable, and further study is needed to identify modifiable risk factors and improve care for this complex population.

Cumulative Effect of Preoperative Risk Factors on Mortality After Pediatric Heart Transplantation.

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

Postoperative management of heart failure in pediatric patients.

Low cardiac output syndrome (LCOS) is a well-described entity occurring in 25-65% of pediatric patients undergoing open-heart surgery. With judicious intensive care management of LCOS, most patients have an uncomplicated postoperative course, and within 24 h after cardiopulmonary bypass, the cardiac function returns back to baseline. Some patients have severe forms of LCOS not responsive to medical management alone, requiring temporary mechanical circulatory support to prevent end-organ injury and to decrease myocardial stress and oxygen demand. Occasionally, cardiac function does not recover and heart transplantation is necessary. Long-term mechanical circulatory support devices are used as a bridge to transplantation because of limited availability of donor hearts. Experience in usage of continuous flow ventricular assist devices in the pediatric population is increasing.

Development and Preliminary Testing of the Coordination Process Error Reporting Tool (CPERT), a Prospective Clinical Surveillance Mechanism for Teamwork Errors in the Pediatric Cardiac ICU.

BACKGROUND: Patient safety reporting systems (PSRSs) may not detect teamwork or coordination process errors that affect all dimensions of quality defined by the Institute of Medicine. This study aimed to develop and observe the performance of a novel tool, the Coordination Process Error Reporting Tool (CPERT), as a prospective clinical surveillance mechanism for teamwork errors in the pediatric cardiac ICU. METHODS: Providers and parents used the qualitative nominal group technique to identify coordination process error examples. Using categories developed from these discussions, the CPERT was designed and observed to assess agreement among providers and with the PSRS. For each patient at the end of each observed shift, the nurse, frontline clinician, and attending physician were invited to complete the CPERT online. Responses among providers were compared to assess interobserver agreement. Patients with errors identified by the CPERT were matched 1:1 with patients without CPERT errors within the same shift. The PSRS and medical record were reviewed to judge whether a coordination process error occurred and whether patients with CPERT errors differed from controls. RESULTS: Eight categories of errors were identified and incorporated into the CPERT. During 10 shifts (218 patients), the CPERT completion rate was 74%. Fifty-one patient shifts had errors identified by the CPERT (23%); these patients did not differ significantly from those without CPERT- reported errors. Only 5 CPERT-reported errors (10%) were identified by two or more providers. Of the 51 CPERT- reported errors, 43 (84%) were not documented in the PSRS. CONCLUSION: The CPERT detects coordination process errors not identified through PSRS, making it or similar tools potentially useful for improvement efforts.

Heart Retransplant Recipients Have Better Survival With Concurrent Kidney Transplant Than With Heart Retransplant Alone.

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

Renal function assessment in child and adolescent heart transplant recipients during routine cardiac catheterization.

CKD identification after pediatric heart transplantation (PHT) is limited by inaccuracies in estimates of GFR. We hypothesized that GFR can be measured by a modified iohexol clearance protocol in PHT recipients and that the CKiD formula provides a better estimate of GFR than other estimating equations. A cross-sectional study of PHT recipients, ages 2-18 yr, undergoing coronary angiography was undertaken. The angiography dose of iohexol was divided by the area under the curve from three iohexol levels post-infusion to calculate GFR. Agreement between iGFR and multiple estimating equations (eGFR) was assessed. In 31 subjects, median age was 15.0 yr (IQR 7.6, 16.6). Mean iGFR was 93.8 (s.d. 22.5) mL/min/1.73 m(2) ; 16 (52%) had an iGFR <90 mL/min/1.73 m(2) . The full CKiD formula (mean eGFR 88.9, s.d. 14.9) had low bias (-5.0), narrowest 95% limits of agreement (-42.0, 32.1), highest 30% (94%) and 10% (52%) accuracy, and highest correlation coefficient (0.576) relative to iGFR. We describe a novel modified iohexol clearance method to assess GFR after PHT. Over half of the cohort had an iGFR <90, suggesting CKD. The full CKiD formula performs best with respect to bias, accuracy, and correlation.

Retrospective analysis of beta-blocker instituted for treatment of hemangiomas (RABBIT study).

OBJECTIVE: To evaluate the safety and efficacy of our institutional beta-blocker protocol for treatment of complicated infantile hemangiomas (IH). STUDY DESIGN: A retrospective descriptive study of 76 infants/children with IH treated with oral propranolol at the Children's Hospital of Philadelphia between June 2008 and August 2010 was performed, assessing both the safety and efficacy of propranolol. Based on preliminary data showing hemangioma recrudescence off-treatment, we reviewed 9 additional patients with recrudescence between August 2010 and December 2011. RESULTS: Mild adverse events included asymptomatic bradycardia, gastrointestinal symptoms, asymptomatic hypotension, cool hands/feet, asymptomatic hypoglycemia, and sleep disturbance. Sixteen patients had recrudescence of IH off-treatment, with propranolol discontinued at a median age of 14 months (interquartile range 10-15 months). CONCLUSIONS: Propranolol appears to be associated with minor, not severe symptomatic adverse events. Propranolol appears to be effective in treating complicated IH. Recrudescence can occur off-treatment, even with discontinuing propranolol as late as 15 months of age.

Ethics and clinical trials in congenital heart disease.

There is a strong need for well-designed clinical trials in congenital heart disease. Research in children, including children with congenital heart disease, must adhere to the highest ethical standards at all times.

Persistence of anti-human leukocyte antibodies in congenital heart disease late after surgery using allografts and whole blood.

BACKGROUND: Allografts are used for vascular reconstruction in many forms of congenital heart disease. Although allografts induce anti-human leukocyte antibody (HLA) formation, much about this response is unknown. METHODS: Three groups of patients aged 8 to 18 years old underwent analysis for class I and II anti-HLA antibodies using Luminex. Groups were defined by timing of allograft exposure and diagnosis at Norwood for hypoplastic left heart syndrome (neonatal group), at Glenn for single-ventricle lesions not requiring arch reconstruction (infant group), and cardiac defects repaired during infancy without allografts (controls). Patients had significant anti-HLA (sensitization) if mean fluorescence intensity was ≥ 1500. RESULTS: The study enrolled 29 patients (median age, 10.1 years). Significant class I anti-HLA antibodies were seen in 44% (8 of 18) of the neonatal group, 25% (1 of 4) of the infant group, and 14% (1 of 7) of controls; class II anti-HLA antibodies were seen in 44% (8 of 18) of the neonatal group, 25% (1 of 4) of the infant group, and 29% (2 of 7) of controls. All patients received fresh whole blood, but the neonatal group had greater exposure (p = 0.001). There was less sensitization with increasing time from last receipt of allograft(s) or blood transfusion (p = 0.05). CONCLUSIONS: Exposure to allograft at the Norwood procedure is associated with long-term sensitization to anti-HLA antibodies in 56% of patients. Sensitization also occurs in those without prior exposure to allografts, may decrease over time, and appears related to whole blood. These findings have implications for those in whom heart transplant is considered late in the clinical course.

Ventricular remodeling and survival are more favorable for myocarditis than for idiopathic dilated cardiomyopathy in childhood: an outcomes study from the Pediatric Cardiomyopathy Registry.

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.

Clinical performance of decellularized cryopreserved valved allografts compared with standard allografts in the right ventricular outflow tract.

BACKGROUND: Although decellularized cryopreserved valved allografts (DCAs) have reduced immunogenicity, proof of clinical superiority over standard cryopreserved allografts (SCAs) is lacking. To assess functional results and durability, we studied a group of patients with DCAs implanted between 2000 and 2005 and compared them with a similar group with SCAs. METHODS: From July 2000 until January 2005, 47 patients underwent insertion of a DCA between the right ventricle and pulmonary arteries. The DCA patients were compared with 47 age-matched and diagnosis-matched controls receiving SCAs. All patients received pulmonary allografts and were matched for valve position (orthotopic versus heterotopic). We analyzed each group for survival, reoperation, reintervention (surgical or catheter-based), stenosis, and regurgitation. RESULTS: There were no differences between groups with respect to weight, age, valve size, or survival. Actuarial freedom from reintervention at 8 years was 79% for DCAs as compared with 63% for SCAs (p = 0.31, log-rank). Echocardiogram in the DCA group (median 66 months) showed a slightly lower median peak gradient of 16 mm Hg (range, 0 to 82 mm Hg) as compared with 22 mm Hg (range, 0 to 63) in the SCA group (median 61 months, p = 0.051, Wilcoxon). However, when conduits 18 mm or less in diameter were compared, DCA patients had a median peak gradient of 10 mm Hg (range, 0 to 43) compared with 25 mm Hg in SCAs (range, 0 to 55 mm Hg, p = 0.03). There were no differences in the degree of allograft insufficiency in either group. CONCLUSIONS: Decellularized cryopreserved valved allografts have a nonsignificant trend toward lower peak valve gradient and reintervention in comparison with SCAs. Small valve sizes (18 mm or less) show a slight but significant improvement in peak gradient, but no advantage in valve insufficiency. These findings and a significantly higher cost (>$3,000) make further direct comparisons necessary before widespread use of DCAs can be justified.

Indications for heart transplantation in pediatric heart disease: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young; the Councils on Clinical Cardiology, Cardiovascular Nursing, and Cardiovascular Surgery and Anesthesia; and the Quality of Care and Outcomes Research Interdisciplinary Working Group.

BACKGROUND: Since the initial utilization of heart transplantation as therapy for end-stage pediatric heart disease, improvements have occurred in outcomes with heart transplantation and surgical therapies for congenital heart disease along with the application of medical therapies to pediatric heart failure that have improved outcomes in adults. These events justify a reevaluation of the indications for heart transplantation in congenital heart disease and other causes of pediatric heart failure. METHODS AND RESULTS: A working group was commissioned to review accumulated experience with pediatric heart transplantation and its use in patients with unrepaired and/or previously repaired or palliated congenital heart disease (children and adults), in patients with pediatric cardiomyopathies, and in pediatric patients with prior heart transplantation. Evidence-based guidelines for the indications for heart transplantation or retransplantation for these conditions were developed. CONCLUSIONS: This evaluation has led to the development and refinement of indications for heart transplantation for patients with congenital heart disease and pediatric cardiomyopathies in addition to indications for pediatric heart retransplantation.

Two-year reduction of panel reactive human leukocyte antigen antibodies in children receiving mycophenolate mofetil after valved allograft placement.

Allografts used in the repair of congenital heart defects in children induce a persistent broad HLA antibody response. We have previously shown that a 3-month course of mycophenolic mofetil (MMF) significantly reduces the HLA class I antibody response to valved allograft implantation in children. The purpose of this study was to determine if this reduction in HLA antibody persists after discontinuation of MMF. We conducted follow-up (mean 2 +/- 0.5 years) of seven patients who had received allograft placement for repair of congenital heart defects. These patients received 3 months of immunosuppression with MMF following allograft implantation. When compared to historical controls, patients who received MMF following surgery showed a significantly decreased HLA class I antibody response at 2 years postimplantation. This study demonstrates the ability to persistently alter the HLA class I antibody response using 3 months of MMF following allograft implantation in children.

Long-term, randomized comparison of balloon angioplasty and surgery for native coarctation of the aorta in childhood.

BACKGROUND: The purpose of this study was to compare the long-term outcomes of children randomized to surgery or balloon angioplasty (BA) for native coarctation (CoA). A prior randomized, short-term comparison of BA and surgery for native CoA in 36 children demonstrated equivalent relief of obstruction. The risk of aneurysm formation and possibly restenosis was higher among patients treated with BA. METHODS AND RESULTS: Blood pressure, residual aortic obstruction, and exercise performance were evaluated. Need for repeat intervention was reviewed. Aortic arch anatomy was assessed with magnetic resonance angiography. For subjects who were not available to return for evaluation, the most recent clinical record was utilized. Among the 36 subjects initially randomized, 21 returned for evaluation (11 BA, 10 surgery). The average time since initial intervention to evaluation for all subjects was 10.6+/-4.7 years for BA subjects and 11.3+/-3.7 years for surgical subjects. Resting blood pressure, CoA gradient, exercise performance, MRI analysis of the aortic arch, and need for repeat interventions were not different for the 2 treatment strategies. There was a higher incidence of aneurysm formation (35% versus 0%) and a greater difference in blood pressure between the right and left legs with exercise among BA subjects. Some aneurysms developed late, first being detected more than 5 years after the initial intervention. Only 50% of BA subjects remained free of both aneurysm formation and repeat intervention compared with 87.5% of surgical subjects (P=0.03). CONCLUSIONS: BA for the treatment of childhood CoA is associated with a higher incidence of aneurysm formation and iliofemoral artery injury than surgery. These differences should be considered when undertaking treatment for native CoA during childhood.

The sensitized pediatric heart transplant candidate: causes, consequences, and treatment options.

Sensitization to HLA antigens and the subsequent development of HLA antibodies in children under consideration for heart transplantation is a significant impediment to survival after listing. This is related both to the frequent need for prospective donor-specific crossmatching (thus limiting donor availability and increasing pretransplant morbidity and mortality), and to the increased risk of adverse outcomes after transplantation. This article will review the scope of this problem in children under consideration for heart transplantation, the different methods available for diagnosing HLA sensitization, the known causes of HLA sensitization, the consequences of these preformed antibodies on outcomes before and after heart transplantation, and the different methods of preventing and treating this sensitization that are currently available. Improved methods of diagnosing, preventing, and treating this problem can only lead to better outcomes for children who require heart transplantation.

Panel-reactive antibodies late after allograft implantation in children.

BACKGROUND: Circulating human leukocyte antigen (HLA) panel-reactive antibodies (PRA > 10%) have been independently associated with increased risk of rejection and mortality in patients who undergo cardiac transplantation. Cryopreserved allografts used to repair heart defects induce broadly reactive HLA antibodies in children that persist for an undetermined duration of time. The purpose of this study was to prospectively determine the level of HLA sensitization several years after implantation of cryopreserved allografts in children. METHODS: We conducted late follow-up of 13 children previously screened for PRA before and after implantation of valved and nonvalved allografts who are alive and free from allograft replacement. Panel-reactive antibodies against HLA class I and II antigens were determined using flow cytometry and classified as high reactive (>50% PRA), low reactive (11% to 50%), or absent (0% to 10%). Follow-up PRA was compared with PRA obtained 3 months after initial allograft implantation. RESULTS: Elevated HLA class I PRA persisted at late follow-up in 12 of 13 children, although it decreased significantly from high to low or from low to absent in 12 of 13 patients (p < 0.001). Elevated HLA class II PRA persisted at late follow-up in 6 of 13 children (46%) and had decreased significantly from prior levels (p = 0.011). CONCLUSIONS: Circulating HLA antibodies induced by cryopreserved allograft tissue persist up to 8 years after implantation although they decrease with time. Therefore, children who have received cryopreserved allografts before cardiac transplantation may be at greater risk for transplant rejection.

Mycophenolic mofetil reduces the HLA antibody response of children to valved allograft implantation.

BACKGROUND: Valved allografts induce a brisk, broadly reactive human leukocyte antigen (HLA) antibody response in children after implantation. Mycophenolic mofetil (MMF) is a powerful immunosuppressant that inhibits the proliferation of both T cells and B cells and has been reported to possibly reduce HLA panel reactive antibody (PRA) in sensitized transplant recipients. METHODS: The purpose of this study was to determine whether MMF can blunt the HLA antibody response to valved allografts in children. Eight patients completed (of 28 approached) a pilot study to determine the effects of 3 months of twice daily MMF (600 mg/m(2)/dose) on the HLA antibody response measured before surgery, at 1 month, and at 3 months after implantation. Patients were 7.5 +/- 4 yrs old (mean +/- standard deviation [SD]), with 5 patients undergoing repair of tetralogy of Fallot, 2 Ross procedures, and 1 aortic valve replacement. RESULTS: In contrast to historical controls with a virtual 100% HLA class I PRA response to valved allograft implantation, MMF markedly decreased the HLA class I antibody response at 1 and 3 months postimplantation. In 6 cases where the HLA type of the donor was defined, PRA specificity correlated with incompatible antigens on the allograft. One patient withdrew after 2 weeks due to a sinus infection that was successfully treated with oral antibiotics, and 3 patients had a transient adverse effect of postoperative vomiting. CONCLUSIONS: This study demonstrates the ability to pharmacologically abrogate the HLA class I antibody response to valved allograft implantation in children using MMF.

Safety of endomyocardial biopsy in children.

Endomyocardial biopsy in children remains important in the evaluation of cardiomyopathy, myocarditis, and rejection following cardiac transplantation. We sought to evaluate the morbidity associated with endomyocardial biopsy on the basis of a large experience from a single institution. We reviewed records of all endomyocardial biopsies performed at our institution. Complications were defined as adverse events resulting from the biopsy requiring intervention or additional observation. We also reviewed the most recent echocardiogram from all the patients for the presence and severity of tricuspid valvar regurgitation. Between November 1986 and April 2002, we performed 1051 endomyocardial biopsies in 135 patients ranging in age from 9 days to 18 years. The internal jugular vein was the site of vascular access in 68% of the procedures. There were 10 acute procedural complications requiring intervention or additional observation. Severe tricuspid regurgitation developed in two patients who had undergone multiple biopsies after cardiac transplantation, one of whom underwent subsequent replacement of the tricuspid valve. There were no deaths or cardiac perforations. The total incidence of morbidity was 1.1%. No demographic or procedural factors were identified to be predictive of complications. In experienced hands, therefore, endomyocardial biopsy can be safely performed in children with very low morbidity.

Immunogenicity of decellularized cryopreserved allografts in pediatric cardiac surgery: comparison with standard cryopreserved allografts.

BACKGROUND: Recognition of the immunogenicity of standard cryopreserved allografts has led to the development of new decellularized allografts (CryoValve SG; CryoLife, Inc, Kennesaw, Ga). This preliminary study examined the HLA antibody response to these decellularized allografts and compared it with the response to standard allograft material. METHODS: We prospectively measured the frequency of panel-reactive HLA class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DR/DQ) alloantibodies in 14 children (age 8.5 +/- 7.9 years) receiving decellularized, cryopreserved allografts, including 6 undergoing allograft patch insertion and 8 with a valved pulmonary allograft. We compared them with 20 historical control subjects (age 1.7 +/- 2.4 years) undergoing implantation of standard cryopreserved allografts, 8 with valves and 12 with allograft patch. All patients had panel-reactive antibody levels measured before and at 1, 3, and 12 months after the operation. HLA class I and class II panel-reactive antibody levels were determined with a sensitive flow cytometry technique. RESULTS: We found panel-reactive antibody levels in decellularized allografts to be elevated slightly from preoperative levels for both class I and class II antibodies at 1, 3, and 12 months (P >.05). The panel-reactive antibody level for both class I and class II antibodies were significantly lower for decellularized allografts as compared to standard allografts. Functionally, the allografts were similar with decellularized valved grafts showing a peak echo-determined systolic gradient of 13 +/- 15 mm Hg at 8 +/- 2.6 months postoperatively as compared to a gradient of 24 +/- 18 mm Hg measured 12 +/- 6 months postoperatively in standard allografts (P =.11). CONCLUSIONS: Decellularized grafts elicited significantly lower levels of class I and class II HLA antibody formation at 1, 3, and 12 months after implantation than did standard cryopreserved allografts. Early hemodynamic function of decellularized grafts was similar to that of standard cryopreserved allograft valves. Further experience is necessary to determine whether the reduced immunogenicity of decellularized allografts will truly allow tissue ingrowth and improved long-term durability in patients.