Ubiquitin C-Terminal Hydrolase 1 and Phosphorylated Axonal Neurofilament Heavy Chain in Infants Undergoing Cardiac Surgery: Preliminary Assessment as Potential Biomarkers of Brain Injury.

BACKGROUND: There are no reliable markers to assess brain injury in neonates following cardiac surgery. We examine ubiquitin C-terminal hydrolase 1 (UCHL1) and phosphorylated axonal neurofilament heavy chain (pNF-H), neuronal-specific biomarkers released following axonal and cortical injury, in neonates undergoing cardiac surgery involving cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). METHODS: Twenty-six patients younger than three months were prospectively enrolled (CPB only, n = 12 and DHCA, n = 14). Healthy newborns (n = 22) served as the control. Blood samples were collected preoperatively and postoperatively upon intensive care unit admission (hour 0) and subsequently at 12, 24, 36, and 48 hours. Serum was tested for UCHL1 and pNF-H using enzyme-linked immunosorbent assay. Concomitant arterial blood gas, lactate, and cerebral near-infrared spectroscopy (NIRS) monitoring were performed. RESULTS: Ubiquitin C-terminal hydrolase 1 showed a significant rise at 0 hours in the DHCA group compared to baseline (74.9 ± 13.7 pg/mL vs 33.9 ± 37.3 pg/mL, P < .0001). Levels returned to baseline at 12 hours. There was an early rise in UCHL1 at 0 hours in the CPB group, P = .09. Phosphorylated axonal neurofilament heavy chain was decreased at 0 hours in both the CPB and DHCA groups compared to baseline, P = .06. There was no difference between control and baseline levels of UCHL1 ( P = .9) or pNF-H ( P = .77). Decreased NIRS was observed in the DHCA group at 0 hours (57.3 ± 10.5) versus baseline (64.2 ± 12.3), but not significant ( P = .21). There was no correlation between biomarkers and NIRS at 0 hours. CONCLUSION: A rapid rise in UCHL1 levels was observed in the DHCA group, suggesting that it may be a marker for acute brain injury. Follow-up with neurodevelopmental studies is ongoing.

The use of mechanical circulatory support as a bridge to transplantation in pediatric patients: an analysis of the United Network for Organ Sharing database.

OBJECTIVES: The use of mechanical circulatory support to bridge pediatric patients to cardiac transplantation presents unique challenges because of the difficult anatomy and physiology in these patients. METHODS: The United Network for Organ Sharing provided deidentifed patient-level data. The study population included 2532 transplantations performed on patients less than 19 years old in status 1/1A/1B between 1995 and 2005. Mechanical circulatory support was used in 431 patients: 241 (9.5%) received ventricular assist devices, 171 (6.8%) underwent extracorporeal membrane oxygenation, and 19 (0.8%) received intra-aortic balloon pumps. RESULTS: Patients supported on ventricular assist devices had similar levels of hospitalization and intensive care use and less need for inotropic support (P < .0002) than had those not needing support. Five- and 10-year posttransplantation survival was better in patients receiving ventricular assist devices and patients not receiving mechanical circulatory support than in patients receiving extracorporeal membrane oxygenation or intra-aortic balloon pumping (P < .0001). Among mechanically supported patients, patients with a body surface area of less than 0.30 (odds ratio, 1.70; 95% confidence interval, 1.18-2.43) and those requiring extracorporeal membrane oxygenation (odds ratio, 1.65; 95% confidence interval, 1.15-2.35) or intra-aortic balloon pumping (odds ratio, 1.91; 95% confidence interval, 1.02-3.56) had higher long-term mortality. The use of a ventricular assist device at transplantation did not predict higher long-term, posttransplantation mortality. CONCLUSIONS: Pediatric patients requiring a pretransplantation ventricular assist device have long-term survival similar to that of patients not receiving mechanical circulatory support. Early survival among patients undergoing extracorporeal membrane oxygenation and infants is poor, reinforcing the need for improvements in device design and physiologic management of infants and neonates.

Predicting survival among high-risk pediatric cardiac transplant recipients: an analysis of the United Network for Organ Sharing database.

OBJECTIVE: Studies of high-risk pediatric cardiac transplant recipients are lacking. The purpose of this study is to evaluate early posttransplant survival in high-risk pediatric patients. METHODS: The United Network for Organ Sharing (UNOS) provided de-identified patient-level data. The study population included 3502 recipients aged less than 21 years who underwent transplantation from January 1, 1995, through December 31, 2005. Recipients were stratified on the basis of the presence or absence of high-risk criteria: pulmonary vascular resistance index greater than 6 Wood units/m2 (n = 285, 8.1%), creatinine clearance less than 40 mL/min (308, 8.8%), hepatitis C positivity (33, 0.9%), donor/recipient weight ratio less than 0.7 (80, 2.3%), panel reactive antibody greater than 40% (235, 6.7%), retransplantation (235, 6.7%), and age less than 1 year old (840, 24.0%). RESULTS: Overall, 1575 (45.0%) patients met at least one high-risk criterion. Higher numbers of high-risk criteria in a patient were correlated with increased 30-day mortality (0 high-risk criteria: 5.2%; 1 criterion: 7.9%; 2 criteria: 12.9%; and 3 or more criteria: 25.0%; P < .0001) and poor long-term survival (P < .0001). Among patients with high-risk criteria, a simplified scoring scale accurately predicts both 30-day and contingent 1-year mortality (P < .0001). CONCLUSIONS: Individually, the effect of high-risk criteria on posttransplant survival varied; however, increasing numbers of criteria in a patient resulted in a cumulative increase in mortality. A scoring scale allows for the prediction of approximate mortality rates after transplantation. These findings suggest that recipient criteria for transplantation should focus on the number of high-risk criteria as well as clinical status, rather than the presence or absence of a single risk factor.