James E. O'Brien

A Novel Bioresorbable Film Reduces Postoperative Adhesions After Infant Cardiac Surgery

BACKGROUND Adhesions encountered in reoperative cardiac surgery can prolong operating time and increase risk. This study was designed to evaluate the ability of a novel bioresorbable barrier film to reduce adhesions in infants. METHODS A comparative, evaluator-masked, randomized, multicenter study design was used. Before chest closure, infants undergoing initial sternotomy for eventual staged palliative cardiac operations were randomized to barrier film placement (n = 54) or control (no treatment, n = 49) at 15 centers. At repeat sternotomy 2 to 13 months later, the extent and severity of adhesions at the investigational surgical site (ISS) were assessed. A four-grade adhesion severity scoring system was standardized as follows: none, mild (filmy, noncohesive, requiring blunt dissection), moderate (filmy, noncohesive, requiring sharp and blunt dissection), and severe (dense, cohesive, requiring extensive sharp dissection). RESULTS There were significantly fewer patients with any severe adhesions (29.6% vs 71.4%, p < 0.0001), and a significantly lower percentage of the ISS had severe adhesion involvement (21.1 +/- 36.9% vs 49.5 +/- 42.7%, p = 0.0005) in the barrier group compared with the control group at the second sternotomy. Delayed chest closure (p = 0.0101), Norwood procedure (p = 0.0449), and cardiopulmonary bypass (p = 0.0001) were univariate risk factors for more severe adhesions. Multivariate analysis revealed only control group to be a significant risk factor for more severe adhesions (p = 0.003). There were no statistically significant differences in adverse events between the groups. No adverse events were definitely attributed to the study device. CONCLUSIONS Use of a novel bioresorbable film was safe and effective in reducing the extent and severity of postoperative adhesions in infants undergoing repeat median sternotomy.

Repair of “Simple” Total Anomalous Pulmonary Venous Connection: A Review From the Pediatric Cardiac Care Consortium

BACKGROUND Outcomes for repair of total anomalous pulmonary venous connection (TAPVC) from individual institutions suggest a significant improvement in mortality over the past several decades. The purpose of this study is to review the outcomes after repair of TAPVC from a large multiinstitutional registry. METHODS A retrospective review of the multiinstitutional database, the Pediatric Cardiac Care Consortium (PCCC), was used to identify patients with the diagnosis of TAPVC who underwent complete correction between 1982 and 2007. Data reviewed included age, decade of primary operation, anatomic type, presentation, and in-hospital mortality. RESULTS Of the 118,084 surgical procedures submitted to the PCCC, 2,191 (1.9%) consisted of primary surgical correction of TAPVC. Sixty-one percent of the cohort was male, with 6.8% reported as premature. Overall in-hospital surgical mortality for simple TAPVC was 13%. Mortality was 20% from 1982 to 1989, 16% from 1990 to 1999, and 8% from 2000 to 2007. Obstruction to the anomalous pulmonary venous connection occurred in 29%, with a mortality of 26%. CONCLUSIONS Surgical outcomes from repair of congenital cardiac anomalies have significantly improved over the past several decades. Multiinstitutional large databases are needed to confirm results published from single-institution experiences. Although improvements in surgical repair of TAPVC have occurred over the past three decades, specific subtypes still experience significant mortality.

The Nonfenestrated Extracardiac Fontan Procedure: A Cohort of 145 Patients

BACKGROUND There are limited data available on the outcomes of single-ventricle patients who have undergone a nonfenestrated extracardiac Fontan procedure. This study examined the clinical experience of a large cohort of patients from a single institution who received this procedure. METHODS A retrospective data set of 145 patients who underwent a nonfenestrated extracardiac Fontan procedure from July 1997 to September 2008 was reviewed. RESULTS The hospital survival was 94.5%. Takedown of the Fontan conduit was necessary in 4 patients (2.8%), and 3 of these 4 patients were also operative deaths. Although female sex (p = 0.048), cardiopulmonary bypass time (p = 0.002), and aortic cross-clamp time (p = 0.007) were found to be significant in the univariate analysis, only sex (p = 0.035; odds ratio, 3.869; 95% confidence limits, 1.097 to 13.644) and cardiopulmonary bypass time in minutes (p = 0.001; odds ratio, 1.023; 95% confidence limits, 1.009 to 1.037) were found to be significant in the multivariate analysis for hospital survival. The late survival was 95.6% (131 of 137 patients) with a mean follow-up of 3.3 years (range, 0.0 to 10.8 years). The freedom from Fontan failure was 92% at 1 year, 89% at 5 years, and 82% at 10 years. Stepwise logistic regression found cardiopulmonary bypass time (p = 0.003; odds ratio, 1.023; 95% confidence limits, 1.008 to 1.039) to be a significant risk factor for late survival. CONCLUSIONS The nonfenestrated extracardiac Fontan procedure can be successfully used in the palliation of single-ventricle patients.

Intraoperative Hyperglycemia and Postoperative Bacteremia in the Pediatric Cardiac Surgery Patient

BACKGROUND Intraoperative hyperglycemia has been found to be associated with a higher incidence of postoperative infections in the adult cardiac surgery population. The goal of this study was to determine the association of intraoperative hyperglycemia and postoperative bacteremia in the pediatric population. METHODS A retrospective chart review of all cardiac surgical cases for patients 18 years of age or younger requiring cardiopulmonary bypass support between June 2002 and July 2007 yielded 1,132 total cases representing 992 unique patients. Patient demographic and clinical data of interest were collected. Descriptive statistics and regression analyses were performed to investigate the hypothesized relationship between glucose levels and infection rates. RESULTS From the 992 patient records examined, 15 patients exhibited a bacteremia within 14 days of surgery (1.5%). The association between the highest glucose during cardiopulmonary bypass and bacteremia reached statistical significance when the glucose level reached 175 mg/dL (chi(2) = 4.59, 1 degree of freedom; p = 0.032). A patient was more than three times as likely to have a postoperative bacteremia when the glucose level reached this amount or exceeded it (odds ratio, 3.3, 95% confidence interval, 1.04 to 10.39). Ten of the 15 (66.7%) postoperative infections occurred in patients with peak bypass glucose levels of at least 175 mg/dL. CONCLUSIONS Intraoperative hyperglycemia was found to be associated with a higher risk of postoperative bacteremia in the pediatric cardiac surgery population.

MicroRNA-421 Dysregulation is Associated with Tetralogy of Fallot

The importance of microRNAs for maintaining stability in the developing vertebrate heart has recently become apparent. In addition, there is a growing appreciation for the significance of microRNAs in developmental pathology, including the formation of congenital heart defects. We examined the expression of microRNAs in right ventricular (RV) myocardium from infants with idiopathic tetralogy of Fallot (TOF, without a 22q11.2 deletion), and found 61 microRNAs to be significantly changed in expression in myocardium from children with TOF compared to normally developing comparison subjects (O’Brien et al. 2012). Predicted targets of microRNAs with altered expression were enriched for gene networks that regulate cardiac development. We previously derived a list of 229 genes known to be critical to heart development, and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlations with 33 microRNAs, each of which also had significantly changed expression. Here, we focus on miR-421, as it is significantly upregulated in RV tissue from infants with TOF; is predicted to interact with multiple members of cardiovascular regulatory pathways; and has been shown to regulate cell proliferation. We knocked down, and over expressed miR-421 in primary cells derived from the RV of infants with TOF, and infants with normally developing hearts, respectively. We found a significant inverse correlation between the expression of miR-421 and SOX4, a key regulator of the Notch pathway, which has been shown to be important for the cardiac outflow track. These findings suggest that the dysregulation of miR-421 warrants further investigation as a potential contributor to tetralogy of Fallot.

Outcomes in children with hypoplastic left heart syndrome undergoing open fundoplication

BACKGROUND/PURPOSE Some institutions recommend early fundoplication in patients with hypoplastic left heart syndrome (HLHS) with signs of gastroesophageal reflux disease because of the risk of reflux-related cardiac events. However, their cardiac physiology may impose high perioperative morbidity and mortality. Therefore, we reviewed our experience with fundoplication in this population to allow for assessment of the risk-benefit ratio. METHODS A retrospective review of patients with a diagnosis of HLHS who underwent a fundoplication from January 1990 to July 7, 2009, was performed. All patients underwent open fundoplication between first and second stages of cardiac repair. RESULTS Thirty-nine patients were identified. There were 3 intraoperative complications: hemodynamic instability (n = 2) and a pulmonary hypertensive crisis requiring extracorporeal membrane oxygenation and termination of the procedure (n = 1). There were 27 postoperative complications in 16 patients. There were 2 deaths (4%) within 30 days, and there were 9 deaths (23%) in patients between their first and second stage of cardiac repair during the study period. CONCLUSIONS Noncardiac surgical procedures in patients palliated for HLHS have a high morbidity and mortality. We recommend that routine fundoplication in this population should only be performed under prospective protocols until the relative risk of operation vs risk of reflux is delineated.

Initial Pediatric Cardiac Experience With Decellularized Allograft Patches

PURPOSE This study examines use patterns, early outcomes, and technical surgical adaptability of a newly approved decellularized allograft pulmonary artery patch for right ventricular outflow tract reconstructions in neonates and infants, including primary operations and reoperations. DESCRIPTION The study includes the 44 consecutive initial patients in which 46 patches were used for cardiovascular reconstruction between September 2009 and September 2010. Recorded variables include sex, age at operation, adverse outcome end points (eg, death, stenosis, aneurysm), congenital diagnoses, postoperative complications, and number, type, and location of patches. EVALUATION Patients were a mean age of 290±343 days at operation, and 54.5% were boys. Three types of patch were used: 58.7% thin, 21.7% thick, and 19.6% hemipulmonary. No device-related deaths or adverse events occurred. A biopsy specimen of one patch at elective reoperation demonstrated active recellularization, with no inflammation. CONCLUSIONS These patches have a wide range of applicability. Handling and technical flexibility is excellent and superior to standard options. There appears to be potential for autologous revitalization of the tissue.

Pulmonary Arterioplasty With Decellularized Allogeneic Patches

BACKGROUND Decellularized allogeneic nonvalved pulmonary artery patches for arterioplasty are a relatively new option compared with cryopreserved allogeneic, crosslinked xenogeneic bioprosthetic or synthetic materials. This study examines the midterm experience with a new decellularized allogeneic patch for congenital cardiac reconstructions. METHODS For this prospective postmarket approval, nonrandomized, inclusive observational study, we collected data on a consecutive cohort of 108 patients with cardiovascular reconstructions using 120 decellularized allogeneic pulmonary artery patches (MatrACELL; LifeNet Health, Inc, Virginia Beach, VA) between September 2009 and December 2012. One hundred of the patches were used for pulmonary arterioplasties. Two patients were lost early to follow-up and excluded from subsequent survival and durability analyses. Data included demographics, surgical outcomes, subsequent reoperations, and catheter reinterventions. These variables were also collected for an immediately preceding retrospective consecutive cohort of 100 patients with 101 pulmonary arterioplasty patches who received classical cryopreserved pulmonary artery allografts (n=59 patches and patients) or synthetic materials (n=41 patients with 42 patches) for pulmonary arterioplasties between 2006 and 2009. RESULTS In 106 patients with 118 decellularized patches, there were no device-related serious adverse events, no device failures, and no evidence of calcifications on chest roentgenograms. In contrast, the prior comparative pulmonary arterioplasty cohort of 100 patients experienced an overall 14.0% patch failure rate requiring device-related reoperations (p<0.0001) at mean duration of 194±104 days (range, 25 to 477 days). CONCLUSIONS The intermediate-term data obtained in this study suggest favorable performance by decellularized pulmonary artery patches, with no material failures or reoperations provoked by device failure.

OUTCOMES FOLLOWING PROLONGED EXTRA CORPOREAL MEMBRANE OXYGENATION SUPPORT IN CHILDREN WITH CARDIAC DISEASE: EXTRACORPOREAL LIFE SUPPORT ORGANIZATION REGISTRY STUDY

Optimal timing for discontinuation of Extra Corporeal Membrane Oxygenation (ECMO) in children with cardiac insufficiency unable to wean from ECMO is ill defined. Outcomes following prolonged ECMO support (≥14 days) for cardiac insufficiency in children <18 years of age were examined. We reviewed