Options for mechanical circulatory support as a bridge to heart transplantation in children with severe heart failure are limited.
We conducted a prospective, single-group trial of a ventricular ...assist device designed specifically for children as a bridge to heart transplantation. Patients 16 years of age or younger were divided into two cohorts according to body-surface area (cohort 1, <0.7 m(2); cohort 2, 0.7 to <1.5 m(2)), with 24 patients in each group. Survival in the two cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) was compared with survival in two propensity-score-matched historical control groups (one for each cohort) undergoing extracorporeal membrane oxygenation (ECMO).
For participants in cohort 1, the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days (P<0.001 by the log-rank test). For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively (P<0.001 by the log-rank test). Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42% and 50% of patients, respectively), infection (in 63% and 50%), and stroke (in 29% and 29%).
Our trial showed that survival rates were significantly higher with the ventricular assist device than with ECMO. Serious adverse events, including infection, stroke, and bleeding, occurred in a majority of study participants. (Funded by Berlin Heart and the Food and Drug Administration Office of Orphan Product Development; ClinicalTrials.gov number, NCT00583661.).
Objective We sought to examine the relationship between extracorporeal membrane oxygenation center case volume and survival in pediatric patients requiring extracorporeal membrane oxygenation ...support. Methods Pediatric patients (≤20 years) undergoing extracorporeal membrane oxygenation cannulation were identified using the Healthcare Cost and Utilization Project Kids’ Inpatient Database for 2000 to 2009. Annual hospital extracorporeal membrane oxygenation volume tertiles were <15 patients/year (low volume), 15 to 30 patients/year (medium volume), and >30 patients/year (high volume). Cases of extracorporeal membrane oxygenation were segregated by indication into cardiac and noncardiac groups. Cases of cardiac extracorporeal membrane oxygenation were mapped to Risk Adjustment for Congenital Heart Surgery categories to adjust for case complexity. Weighted multivariable logistic and linear regression models identified determinants of in-hospital mortality. Results Overall, 3867 cases of extracorporeal membrane oxygenation were identified, yielding a national estimate of 6333 ± 495 cases. Extracorporeal membrane oxygenation was used with nearly equivalent prevalence across volume tertiles for all Risk Adjustment for Congenital Heart Surgery categories, suggesting that patient selection for extracorporeal membrane oxygenation was fairly uniform. A higher annual extracorporeal membrane oxygenation volume tertile was associated with reduced in-hospital mortality ( P = .01) within nearly all Risk Adjustment for Congenital Heart Surgery categories. After adjustment for Risk Adjustment for Congenital Heart Surgery category and other patient variables, lower extracorporeal membrane oxygenation volume remained an important determinant of in-hospital death (odds ratio, 1.75; 95% confidence interval, 1.03-2.94; P = .03). Conclusions Higher extracorporeal membrane oxygenation case volume is associated with improved hospital survival in pediatric cardiac extracorporeal membrane oxygenation patients. The results of this study may support the paradigm of regionalized centers of excellence for managing pediatric cardiac extracorporeal membrane oxygenation patients.
Objective Criteria for simultaneous heart-kidney transplant (HKTx) recipients are unclear. We characterized the evolution of combined HKTx in the United States over time compared with isolated heart ...transplantation (HTx) and determined factors maximizing post-transplant survival. We focused on whether a threshold estimated glomerular filtration rate (eGFR) could be identified that justified combined transplantation. Methods A supplemented United Network Organ Sharing Dataset identified HTx and HKTx recipients from 2000 to 2010. eGFR was calculated for HTx and recipients were grouped into eGFR quintiles. Time-related mortality was compared among recipients, with multivariable factors sought using Cox proportional hazard regression models. Results We identified 26,183 HTx recipients, of whom 593 were HKTx recipients. HTx increased modestly over time (3.6%), whereas prevalence of HKTx increased dramatically (147%). Risk-unadjusted survival was similar among HTx recipients (8.4 ± 0.04 years) and HKTx recipients (7.7 ± 0.2 years) ( P = .76). Isolated HTx recipients in the lowest eGFR quintile had decreased survival ( P < .001), but those in the third eGFR quintile had superior survival, suggesting a benefit in this subgroup. HTx recipients in the lowest eGFR quintile (eGFR less than mean 37 mL/minute) had worse survival than combined HKTx recipients (7.1 ± 0.07 vs 7.7 ± 0.2; P < .001). Multivariable factors for increased mortality among HTx recipients included lower eGFR, higher recent panel reactive antibody score, older age, African American race, diabetes, longer ischemic time, and certain diagnoses. Conclusions Performance of combined HKTx is increasing out of proportion to isolated HTx. eGFR is an important determinant of improved HTx survival. Combined HKTx recovers post-transplant survival in patients with eGFR <37 mL/minute and can be recommended in this subgroup.
Recent data suggest that the Berlin Heart EXCOR Pediatric ventricular assist device is superior to extracorporeal membrane oxygenation for bridge to heart transplantation. Published data are limited ...to 1 in 4 children who received the device as part of the US clinical trial. We analyzed outcomes for all US children who received the EXCOR to characterize device outcomes in an unselected cohort and to identify risk factors for mortality to facilitate patient selection.
This multicenter, prospective cohort study involved all children implanted with the Berlin Heart EXCOR Pediatric ventricular assist device at 47 centers from May 2007 through December 2010. Multiphase nonproportional hazards modeling was used to identify risk factors for early (<2 months) and late mortality. Of 204 children supported with the EXCOR, the median duration of support was 40 days (range, 1-435 days). Survival at 12 months was 75%, including 64% who reached transplantation, 6% who recovered, and 5% who were alive on the device. Multivariable analysis identified lower weight, biventricular assist device support, and elevated bilirubin as risk factors for early mortality and bilirubin extremes and renal dysfunction as risk factors for late mortality. Neurological dysfunction occurred in 29% and was the leading cause of death.
Use of the Berlin Heart EXCOR has risen dramatically over the past decade. The EXCOR has emerged as a new treatment standard in the United States for pediatric bridge to transplantation. Three-quarters of children survived to transplantation or recovery; an important fraction experienced neurological dysfunction. Smaller patient size, renal dysfunction, hepatic dysfunction, and biventricular assist device use were associated with mortality, whereas extracorporeal membrane oxygenation before implantation and congenital heart disease were not.
In this study, we analyzed our clinical experience performing the arterial switch operation in the first hours of life using autologous umbilical cord blood transfusion (AUCBT). The safety and ...efficiency of AUCBT was assessed and compared with surgery with the use of homologous blood transfusion.
Between September 2009 and February 2011, 61 neonates underwent ASO at our institution. Patients were enrolled and allocated to two groups with different modalities of management strategies for neonates with dextrotransposition of the great arteries.
The groups were similar in diagnoses, birth weight, cardiopulmonary bypass protocol, and surgical technique, excepting timing of surgery and blood management strategy. Preoperative mean hematocrit did not differ significantly between the groups (45% versus 45%). Mean hematocrit was significantly lower in the study group than in the control group during cardiopulmonary bypass (24% versus 31%). The hematocrit progressively increased in the study group to 38% on the first postoperative day. Serum lactate levels were higher in the study group till the second day after surgery. There were no significant differences in postoperative clinical profiles. There were no hospital deaths and no AUCBT-related side effects in our study.
The arterial switch operation can be performed in the first hours of life with AUCBT. Therefore, AUCBT is a safe and an efficient alternative to homologous blood in neonatal open heart surgery. During the study, we also identified positive economic effects associated with this approach.
OBJECTIVES/SPECIFIC AIMS: This study aims to assess the safety, feasibility, clinical benefits and pharmacodynamics of adding allopurinol to standard maintenance therapy that includes 6-mecaptopurine ...(6-MP) in pediatric patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. Our goal is to investigate if allopurinol improves hepatotoxicity and GI toxicity, if it safely decreases acute neutrophil count (ANC), if it reduces the 6-MP dose required during chemotherapy, and if it works through our hypothesized mechanism by lowering the levels of the toxic metabolite, 6-methylmecaptopurine (6-MMP) and by raising the levels of the active metabolite, 6-thioguanine (6-TGN). METHODS/STUDY POPULATION: This is a single arm, nonblinded pilot study of patients under age 30 years who were being treated in the maintenance phase of therapy for ALL or lymphoblastic lymphoma, and had adverse effects such as high 6-MMP:6-TGN ratio, high ANC, and high liver enzymes. Patients enrolled were started with allopurinol in addition to ongoing oral chemotherapy. Data from beginning maintenance to end of chemotherapy was collected in the electronic medical record, EPIC for the 13 patients enrolled at Johns Hopkins, and data analysis was conducted using STATA and Excel. RESULTS/ANTICIPATED RESULTS: Initial data analysis reveals that the required dose of 6-MP after addition of allopurinol to the chemotherapy regimen was significantly lower compared with that before the addition of allopurinol in 11 out of the 12 patients assessed (
p
<0.05). Among the 10 patients that were assessed for 6MMP:6TG ratio, all had lower average 6MMP:6TGN ratios after allopurinol compared to before allopurinol; the percentage of weeks that goal 6MMP:6TGN ratio (<40) were maintained were statistically significant in 6 patients (
p
<0.05) and close to significance in 2 other patients (
p
=0.057). The percentage of weeks that patients maintained alanine aminotransferase levels below 120 was significantly greater after addition of allopurinol compared to before the addition of allopurinol in 9 out of 13 patients assessed, suggesting that allopurinol may be associated with reduced hepatotoxicity. Further data analysis is ongoing to assess the percentage of weeks that patients maintained goal total bilirubin, direct bilirubin, and ANC, as well as average number of admissions for infections and average number of therapy holds after allopurinol addition compared to before allopurinol addition. DISCUSSION/SIGNIFICANCE OF IMPACT: Allopurinol is associated with reduction in required 6-MP dose, decrease in the percentage of weeks that patients have hepatotoxicity, and reduction in the ratio of toxic metabolite to active anti-leukemic metabolite in several patients. We hope that the results of this study can be used for further research and for guiding clinical practice since there are no established guidelines in pediatric oncology regarding addressing side effects of oral chemotherapy using 6-MP. If allopurinol indeed is safe and effective, adding it to the standard chemotherapy regimen can lead to better tolerance and compliance to oral maintenance chemotherapy, and hopefully improved outcomes for children with ALL and lymphoblastic leukemia.
We report the case of 4-year-old male with sinus venous thrombosis leading to bilateral thalamic and basal ganglia strokes presenting as generalized choreiform movements. Acute-onset chorea in the ...pediatric population is most commonly associated with Sydenham chorea, which is a manifestation of acute rheumatic fever. Chorea is a much less commonly noted sign of stroke, and when it occurs, it typically presents as hemichorea. Given the unlikely presentation, rapid and appropriate imaging was the key to diagnosis.
Pyruvate produces inotropic responses in the adult reperfused heart. Pyruvate oxidation and anaplerotic entry into the tricarboxylic acid (TCA) cycle via carboxylation are linked to the stimulation ...of contractile function. The goals of this study were to determine if these metabolic pathways operate and are maintained in the developing myocardium after reperfusion. Immature male swine (age: 10-18 days) were subjected to cardiopulmonary bypass (CPB). Intracoronary infusion of 2-(13)Cpyruvate (to achieve an estimated final concentration of 8 mM) was given for 35 min, starting either during weaning (group I) and after its discontinuation (group II) or without (control) CPB. Hemodynamic data were collected. 13C NMR spectroscopy was used to determine the fraction of pyruvate entering the TCA cycle via pyruvate carboxylation (PC) to total TCA cycle entry (PC plus decarboxlyation via pyruvate dehydrogenase). Liquid chromatography-mass spectrometry was used to determine total glutamate enrichment. Pyruvate infusion starting during the weaning of mechanical circulatory support improved maximum dP/dt (P<0.05) but waiting to start the infusion until after the discontinuation of CPB did not. Glutamate fractional enrichment was confirmed by liquid chromatography-mass spectroscopy as adequate (>5%) to provide signal to noise in the NMR experiment in all groups. The ratio of pyruvate carboxylase to total pyruvate entry into the TCA cycle did not differ between groups (group I: 20+/-4%, group II: 23+/-7%, and control: 27+/-7%). These data show that robust PC operates in the neonatal pig heart and is maintained during reperfusion under conditions that emulate CPB and reperfusion in human infants.
Abstract
Objective: The use of extracorporeal membrane oxygenation (ECMO) to support patients with early postcardiotomy heart failure may be associated with catastrophic bleeding, making its use ...undesirable. However, postcardiotomy mechanical circulatory assistance is necessary in some patients to allow for myocardial recovery. We have assembled a centrifugal pump system (CPS) that does not require early systemic anticoagulation. This study compares postoperative bleeding in pediatric patients placed on standard ECMO versus CPS within 24 h of cardiotomy. Methods: Between November 2002 and February 2007, 25 patients (age 0 days-1.72 years) received postcardiotomy mechanical support. Fourteen patients were placed on ECMO and 11 patients were placed on CPS within 24 h of surgical repair. Retrospective analysis was performed of chest-tube drainage at multiple time points following initiation of mechanical support. Additional variables, including Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) score, total time on mechanical support, 30-day mortality, activated clotting time, blood-product administration, circuit-related complications, and circuit changes were also analyzed. Results: Patients on ECMO (0.30 ± 0.39 years) and CPS (0.40 ± 0.56 years) were of similar age (p = 0.64). Patients on ECMO (0.3 ± 0.1 m2) and CPS (0.3 ± 0.1 m2) had similar body surface areas (p = 0.46). Patients placed on CPS had significantly less chest-tube drainage during the first 4 h of support. Activated clotting times appeared to be higher during the first 12 h of ECMO versus CPS. There was no statistical difference between ECMO and CPS with respect to the following variables: RACHS-1 score, time on support, 30-day mortality, circuit-related complications, and circuit changes. Blood-product administration at 24 h of support was significantly less (p = 0.04) for patients on CPS versus ECMO. Conclusions: Mechanical circulatory support can be provided without the complication of clinically significant bleeding if a specialized circuit is used. This has important implications for the decision to use mechanical support in the immediate postoperative period in the face of ventricular failure. In addition, early mechanical support can be used with a low incidence of circuit-related complications.