Annexin A2 Loss After Cardiopulmonary Bypass and Development of Acute Postoperative Respiratory Dysfunction in Children.

The primary objective of this study was to determine whether expression of the multifunctional and adherens junction-regulating protein, annexin A2 (A2), is altered following cardiopulmonary bypass (CPB). A secondary objective was to determine whether depletion of A2 is associated with post-CPB organ dysfunction in children. DESIGN: In a prospective, observational study conducted over a 1-year period in children undergoing cardiac surgery requiring CPB, we analyzed A2 expression in peripheral blood mononuclear cells at different time points. We then assessed the relationship of A2 expression with organ function at each time point in the early postoperative period. SETTING: Twenty-three-bed mixed PICU in a tertiary academic center. PARTICIPANTS: Patients 1 month to 18 years old undergoing cardiac surgery requiring CPB. MEAN OUTCOME MEASUREMENTS AND RESULTS: We analyzed A2 expression in 22 enrolled subjects (n = 9, 1-23 mo old; n = 13, 2-18 yr old) and found a proteolysis-mediated decline in intact A2 immediately after bypass (p = 0.0009), reaching a median of 4% of baseline at 6 hours after bypass (p < 0.0001), and recovery by postoperative day 1. The degree of A2 depletion immediately after bypass in 1-23-month-olds correlated strongly with the extent of organ dysfunction, as measured by PICU admission Vasoactive-Ventilation-Renal (p = 0.004) and PEdiatric Logistic Organ Dysfunction-2 (p = 0.039) scores on postoperative day 1. A2 depletion immediately after bypass also correlated with more protracted requirement for both respiratory support (p = 0.007) and invasive ventilation (p = 0.013) in the 1-23-month-olds. CONCLUSIONS AND RELEVANCE: The degree of depletion of A2 following CPB correlates with more severe organ dysfunction, especially acute respiratory compromise in children under 2 years. These findings suggest that loss of A2 may contribute to pulmonary microvascular leak in young children following CPB.

Chylous pericardial effusion with cardiac tamponade in a child treated with imatinib.

Chylous pericardial effusions are extremely rare outside of thoracic and cardiac surgery patients. We report the case of an 8-year-old girl with history of recurrent benign giant cell granulomas who developed a large chylous pericardial effusion with cardiac tamponade soon after beginning therapy with imatinib. In this article, we discuss the presentation, diagnosis, and management and review the published literature of this rarely reported side effect of this medication.

Contemporary Outcomes in Tetralogy of Fallot With Absent Pulmonary Valve After Fetal Diagnosis.

Background Tetralogy of Fallot with absent pulmonary valve is associated with high mortality, but it remains difficult to predict outcomes prenatally. We aimed to identify risk factors for mortality in a large multicenter cohort. Methods and Results Fetal echocardiograms and clinical data from 19 centers over a 10-year period were collected. Primary outcome measures included fetal demise and overall mortality. Of 100 fetuses, pregnancy termination/postnatal nonintervention was elected in 22. Of 78 with intention to treat, 7 (9%) died in utero and 21 (27%) died postnatally. With median follow-up of 32.9 months, no deaths occurred after 13 months. Of 80 fetuses with genetic testing, 46% had chromosomal abnormalities, with 22q11.2 deletion in 35%. On last fetal echocardiogram, at a median of 34.6 weeks, left ventricular dysfunction independently predicted fetal demise (odds ratio [OR], 7.4; 95% CI 1.3, 43.0; P=0.026). Right ventricular dysfunction independently predicted overall mortality in multivariate analysis (OR, 7.9; 95% CI 2.1-30.0; P=0.002). Earlier gestational age at delivery, mediastinal shift, left ventricular/right ventricular dilation, left ventricular dysfunction, tricuspid regurgitation, and Doppler abnormalities were associated with fetal and postnatal mortality, although few tended to progress throughout gestation on serial evaluation. Pulmonary artery diameters did not correlate with outcomes. Conclusions Perinatal mortality in tetralogy of Fallot with absent pulmonary valve remains high, with overall survival of 64% in fetuses with intention to treat. Right ventricular dysfunction independently predicts overall mortality. Left ventricular dysfunction predicts fetal mortality and may influence prenatal management and delivery planning. Mediastinal shift may reflect secondary effects of airway obstruction and abnormal lung development and is associated with increased mortality.

The Deconditioning Effect of the COVID-19 Pandemic on Unaffected Healthy Children.

The COVID-19 pandemic has had devastating direct consequences on the health of affected patients. It has also had a significant impact on the ability of unaffected children to be physically active. We evaluated the effect of deconditioning from social distancing and school shutdowns implemented during the COVID-19 pandemic on the cardiovascular fitness of healthy unaffected children. This is a single-center, retrospective case-control study performed in an urban tertiary referral center. A cohort of 10 healthy children that underwent cardiopulmonary exercise testing after COVID-19 hospital restrictions were lifted was compared to a matched cohort before COVID-19-related shutdowns on school and after-school activities. Comparisons of oxygen uptake (VO2) max and VO2 at anaerobic threshold between the pre- and post-COVID-19 cohorts were done. The VO2 max in the post-COVID cohort was significantly lower than in the pre-COVID cohort (39.1 vs. 44.7, p = 0.031). Only one out of ten patients had a higher VO2 max when compared to their matched pre-COVID control and was also the only patient with a documented history of participation in varsity-type athletics. The percentile of predicted VO2 was significantly lower in the post-COVID cohort (95% vs. 105%, p = 0.042). This study for the first time documented a significant measurable decline in physical fitness of healthy children as a result of the COVID-19 pandemic and its associated restrictions. Measures need to be identified that encourage and facilitate regular exercise in children in a way that are not solely dependent on school and organized after-school activities.

Comparison of Echocardiographic Diagnostic Criteria of Left Ventricular Noncompaction in a Pediatric Population.

BACKGROUND: There is controversy regarding the best echocardiographic diagnostic criteria for left ventricular noncompaction (LVNC). We assessed the diagnostic utility and reproducibility of the previously proposed echocardiographic diagnostic criteria in a pediatric population using a segmental approach. METHODS: Echocardiograms were matched for patients with and without a clinical diagnosis of LVNC. Blinded reviews of echocardiograms measured (1) depths of intertrabecular recesses (X/Y), (2) noncompaction-to-compaction ratio (NC/C), and (3) number of trabeculations, using a segmental approach. Measurements were analyzed for area under the receiver operating characteristic curves (AUC), sensitivity, and specificity. RESULTS: There were 30 echocardiograms in the initial cohort (15 LVNC cases, 15 controls). Median age was 1.7 years (IQR 0.2-6.9 years) and systolic function was decreased in 40%. Comparison of diagnostic criteria demonstrated the best interrater agreement and AUC with an X/Y ratio measured in end-diastole in the parasternal short axis in the apical anterolateral segment (κ 0.72, CI 0.43-1.00, p value <0.001), yielding 100% sensitivity and 70-86% specificity, among readers. The least predictive and reproducible method was the NC/C ratio. A validation cohort confirmed the superiority of the X/Y ratio, although the interrater agreement and AUC decreased. CONCLUSION: Measurements according to existing LVNC diagnostic criteria vary by echocardiographic view and segment. Modification of the Chin et al. criteria (Circulation 82:507-513, 1990) using an X/Y ratio <0.5 had the greatest interrater reliability and predictive validity when measured in end-diastole in the parasternal short axis in the apical anterolateral segment. The NC/C ratio had the lowest reliability and predictive validity.

Triple outlet right ventricle: a previously unknown cardiac malformation.

We present the case of an infant with three distinct outflow tracts from the right ventricle. Three outlets from the heart have been previously named the "Tritruncal Heart". We review the two previously reported cases of tritruncal hearts and describe the anatomy, diagnosis, surgical management, and outcome of our case. Embryologic implications are also discussed.

The impact of gestational age on resource utilization after open heart surgery for congenital cardiac disease from birth to 1 year of age.

The impact of gestational age on perioperative morbidity was examined using a novel construct, the resource utilization index (RUI). The medical records of subjects from birth to 1 year of age entered into a pediatric cardiothoracic surgery database from a major academic medical center between 2007 and 2011 were reviewed. The hypothesis tested was that infants born at 37-38 weeks (early-term infants) experience greater resource utilization after open heart surgery than those born at 39 completed weeks and that this association can be observed until 1 year of age. The results support the premise that resource utilization increases linearly with declining gestational age among infants at 0-12 months who undergo cardiac surgery. Five of the six variables comprising the RUI showed statistically significant linear associations with gestational age in the predicted direction. Multivariate linear regression analysis showed that gestational age was a significant predictor of an increased RUI composite. Further investigation is needed to test the concept and to expand on these findings.

Age less than two years is not a risk factor for mortality after mitral valve replacement in children.

BACKGROUND: Outcomes for mitral valve replacement (MVR) in the pediatric population are generally reported as poor, particularly in patients less than 2 years old. We compared long-term morbidity and mortality associated with MVR between patients less than 2 years old and patients 2 to 18 years old. METHODS: We evaluated pediatric patients undergoing MVR from March 1990 to November 2007 at our institution. Morbidity and mortality was compared between patients less than 2 years and patients 2 to 18 years old. Primary endpoints measured were postoperative survival, long-term survival, reoperation, cerebrovascular accident or transient ischemic attack, and significant bleeding events. RESULTS: Forty-five patients underwent 54 MVRs. Median age was 3.1 years; 18 patients were under 2 years. Median follow-up time was 5.4 years. There was no statistically significant difference between long-term or short-term survival between the two age groups, with 30-day survival of 89% (younger patients) versus 100% (older patients), and 10-year survival of 82% (younger patients) versus 85% (older patients). Freedom from reoperation for the younger age group was 40% at 10 years versus 96% for the older patients, p = 0.003. CONCLUSIONS: In our population, there was no statistically significant difference in survival between patients less than 2 years and patients 2 to 18 years. In children undergoing MVR, age less than 2 years remains a risk factor for reoperation but not for mortality.

Parvovirus-mediated fetal cardiomyopathy with atrioventricular nodal disease.

Acute parvovirus B19 infection (API) in pregnancy has been associated with fetal anemia and hydrops fetalis. Direct myocardial damage from API in a fetus and an infant has been described. This report presents a case of fetal second-degree heart block and cardiomyopathy secondary to API. A 19-year-old G4P1112 (gravida 4 para 2 with 1 term delivery, 1 preterm delivery, 1 termination, and 2 living children) was referred at 20 weeks gestation for fetal bradycardia. A 2:1 atrioventricular block was identified by fetal echocardiography at 23 weeks. Hydrops developed at 25 weeks. Amniocentesis and percutaneous umbilical blood sampling demonstrated API. At 31 weeks, the patient presented with preterm labor and delivered a viable female infant, who died of poor cardiac function and arrhythmia on the first day of life. In addition to fetal anemia and hydrops fetalis, API in pregnancy may cause direct fetal myocardial damage and conduction system disease.

Left-ventricular noncompaction in a pediatric population: predictors of survival.

Left-ventricular noncompaction (LVNC) is an echocardiographic finding of increasing frequency in pediatrics; however, predictors of outcomes have been difficult to identify. We conducted a retrospective review of pediatric patients at the Morgan Stanley Children's Hospital of New York from January of 1993 to September of 2009 to identify predictors of the primary outcome of death or heart transplantation. LVNC was identified in 50 patients, 34 of them < 1 year of age. Death or transplantation occurred in 26 patients, with a median survival of 1.17 years after presentation. Patients surviving 1 year after presentation had 75% conditional survival, and patients surviving 2 years after presentation had 92% conditional survival. Hemodynamic instability, poor ventricular function, and LV dilatation were each independent predictors of poor outcome. Of the 21 patients who presented with hemodynamic instability, 17 died or underwent transplantation at a median of 0.08 years after presentation. In conclusion, LVNC is recognized more in younger patients; however, age is not a predictor of outcome. Patients who present with hemodynamic instability and poor ventricular function have decreased transplant-free survival, and most poor outcomes occur within the first year after presentation. Therefore, early listing for transplant may lead to better outcomes in this population.

Novel pore mutation in SCN5A manifests as a spectrum of phenotypes ranging from atrial flutter, conduction disease, and Brugada syndrome to sudden cardiac death.

OBJECTIVES: The purpose of this study was to determine the clinical and biophysical characteristics of a novel SCN5A mutation. BACKGROUND: Brugada syndrome and isolated cardiac conduction defect have been linked to SCN5A mutations. METHODS: Eleven members of a western European family underwent electrophysiologic investigations and mutation analysis of the SCN5A gene. Wild-type and mutant SCN5A channels were expressed in HEK293 cells, and whole cell currents were studied using patch clamp procedures. RESULTS: A novel mutation, R376H, in the first pore segment of SCN5A variably causes Brugada syndrome and/or conduction disease in a single family. Biophysical analysis demonstrated a significant current reduction for the mutant, a pathophysiologic profile consistent with Brugada syndrome and isolated cardiac conduction defect. Among 11 family members, 9 were carriers of the mutation. The proband's initial presentation was a saddleback Brugada ECG, atrial flutter, and diffuse conduction disturbances. He had no inducible ventricular arrhythmias but experienced sudden cardiac death. His brother was affected by atrial flutter and had a clear conduction disorder, but he did not display baseline or evocable ECG signs of Brugada syndrome. He received an implantable cardioverter-defibrillator that delivered one appropriate shock after 1 year of follow-up. The phenotype in the family members was highly variable and ranged from noninducible and inducible asymptomatic carriers of the mutations to isolated conduction disease and to symptomatic Brugada syndrome. CONCLUSIONS: We describe the functional characterization of a novel SCN5A pore mutation, R376H, with variable clinical expression in the same family. Differentiating between electrophysiologic entities (Brugada syndrome-isolated cardiac conduction defect) is more challenging. Recognition of factors modifying the clinical presentation may be important for clinical decision making.

Preoperative diagnosis of co-existing divided left atrium and tetralogy of Fallot.

We present the eighth published case of divided left atrium co-existing with tetralogy of Fallot. This is the first report of preoperative echocardiographic diagnosis of this unusual combination of defects. Demonstration of a partition within the left atrium is imperative for successful repair of the combined lesions. We draw attention to the need for careful echocardiography in patients where an obstruction to pulmonary venous drainage would dramatically affect the outcome subsequent to surgical correction.