Nucleated Red Blood Cell Counts Differentiate Cardiac from Respiratory Causes of Cyanosis at Birth.

Tissue hypoxia increases erythropoietin production and release of immature erythrocytes that can be measured using nucleated red blood cell counts (nRBC). We hypothesized that hypoxia due to congenital heart disease (CHD) is chronic and is better tolerated than hypoxia due to respiratory disease (RD), which is an acute stress in newborns leading to higher nRBC. This study assesses the utility of nRBC as a marker to differentiate hypoxia due to CHD vs RD in term neonates. This was a single-center, retrospective study of term neonates with cyanosis from 2015 to 2022. Neonates < 37 weeks of gestation, with hypoxic-ischemic encephalopathy, and those with other causes of cyanosis were excluded. The patients were divided into 2 groups: cyanotic CHD and cyanotic RD. Clinical and laboratory data done within 12 h and 24-36 h after birth were collected. Data are represented as median and Interquartile range. Of 189 patients with cyanosis, 80 had CHD and 109 had RD. The absolute nRBC count at ≤ 12 h of age was lower in the CHD (360 cells/mm3) compared to RD group (2340 cells/mm3) despite the CHD group having significantly lower baseline saturations. A value of 1070 cells/mm3 was highly sensitive and specific for differentiating CHD from RD. The positive predictive value for this cut-off value of 1070 cells/mm3 was 0.94 and the negative predictive value was 0.89. The absolute nRBC is a simple screening test and is available worldwide. A nRBC < 1070 cells/mm3 in cyanotic newborns should hasten the search for CHD etiology with the possible need for prostaglandin therapy.

Blood Pressure Response to Treadmill Cardiopulmonary Exercise Test in Children with Normal Cardiac Anatomy and Function.

OBJECTIVES: To describe blood pressure (BP) responses during cardiopulmonary exercise testing (CPET) and propose criteria for abnormal BP responses in children with normal hearts. STUDY DESIGN: Treadmill CPET data of children <18 years with normal hearts were retrospectively analyzed to evaluate BP responses to exercise at the Children's Hospital of Michigan over an 8-year period (2011-2018). RESULTS: Our cohort included 1085 children (boys, 59%) aged 7-17 years. Analysis of variance for systolic BP at peak exercise (peak SBP) and SBP change (Δ) showed significant age and sex effects and age-sex interaction effects (P < .01). In the multiple linear regression model (P < .001, R square 0.298, standard error of the estimate 17.15), peak SBP (mm Hg) was predicted as 132.27 + 1.37 × age (years) + (3.31 × age (years) - 31.88) × sex [boys 1, girls 0]. The following criteria for abnormal BP responses in children were proposed: hypertensive BP response was defined by peak SBP with a 90% CI upper limit of reference values based on age and sex, and blunted BP response as ΔSBP <10 mm Hg for aged 7-11 years, <20 mm Hg for boys aged 12-17 years, and ΔSBP <10 mm Hg in girls. CONCLUSIONS: BP responses to treadmill CPET depend on age and sex in children with normal hearts. The proposed criteria for abnormal BP responses in children during CPET will need to be verified in a large pediatric cohort.

Optimal criteria for transcatheter closure of Fontan fenestration: a single-center experience with a review of literature.

Fenestration closure is considered to remove the persistent right-to-left shunt after the Fontan operation. However, the criteria for effective transcatheter closure of fenestration to avoid both acute and chronic Fontan failure have not been clarified. The objective of this study was to describe the hemodynamic data with test occlusion of the Fontan fenestration for patients who underwent a closure and those who did not, along with subsequent development of Fontan-associated diseases (FAD) at follow-up. This was a retrospective study conducted to assess the outcome of Fontan fenestration closure at Children's Hospital of Michigan over 27 years (1993-2019). The inclusion criteria were patients undergoing cardiac catheterization indicated for Fontan fenestration closure. Data were compared between the two groups: closure and non-closure patients. Baseline characteristics and hemodynamic variables with the fenestration occlusion test were analyzed. The primary outcome was the development of composite events of death/transplant, deteriorated New York Heart Association class symptoms, or FAD. Among the 38 patients who were brought to the catheterization laboratory, 33 received fenestration closure and 5 did not. On a median follow-up of 3.4 years (range, 1 month-12.6 years), the incidence of primary adverse outcomes was 13% (5/38). The incidence of primary outcome was significantly higher in the non-closure group (60% vs. 6%, p < 0.01). The non-closure group had a higher incidence of moderate or severe atrioventricular valve regurgitation, New York Heart Association class III symptoms, use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, furosemide use, and sildenafil use. The multivariable logistic regression model showed that the hemodynamic variables associated with the non-closure group were mean left atrial pressure (odds ratio 1.74, p < 0.05) and change of mean Fontan pressure at the balloon occlusion (odds ratio 2.2, p < 0.05). The judgment of fenestration closure appeared appropriate in our cohort. Fontan fenestration closure may not be advisable in cases with a high baseline left atrial pressure or a significant increase in Fontan pressure on balloon occlusion testing.

Treatment of Refractory Infantile Hemangiomas and Pulmonary Hypertension With Sirolimus in a Pediatric Patient.

Infantile hemangioma is a benign vascular neoplasm that spontaneously involutes over time. Management, when needed, consists of medications, laser treatment and surgical excision. We describe a 3-year-old girl who presented shortly after birth with diffuse cutaneous hemangiomas, hepatosplenomegaly with liver lesions, anemia, and acute heart failure. She was diagnosed with hepatic and cutaneous infantile hemangioma based on skin biopsy. She developed progressive pulmonary hypertension with numerous pulmonary nodules suspicious for pulmonary arteriovenous malformations. She was started on sirolimus and had significant improvement in her pulmonary hypertension and liver lesions. This report supports prior studies that sirolimus is effective for vascular anomalies including IH refractory to conventional therapy.

Reversal of severe mitral regurgitation by device closure of a large patent ductus arteriosus in a premature infant.

We report a critically ill premature infant with severe mitral valve regurgitation associated with pulmonary hypertension and a severely dilated left atrium from a large patent ductus arteriosus. The mitral valve regurgitation improved significantly with normalisation of left atrial size 4 weeks after percutaneous closure of the patent ductus arteriosus. This case highlights the potential reversibility of severe mitral valve regurgitation with treatment of an underlying cardiac shunt.

Severity of mitral regurgitation predicts risk of death or cardiac transplantation in children with idiopathic dilated cardiomyopathy.

Clinical outcomes among children with idiopathic dilated cardiomyopathy (IDC) are diverse, which makes the decision as to when a patient should be listed for a cardiac transplantation challenging. This study aimed to determine echocardiographic and clinical variables that can help clinicians identify those at highest risk for death or cardiac transplantation. The study was a single-center, retrospective chart review of children with IDC. Patients younger than 18 years with a diagnosis of IDC, as defined by a left ventricular end-diastolic dimension (LVEDD) z-score higher than 2, and fractional shortening of less than 28 % on the initial echocardiogram, were included in the study. Echocardiographic parameters including mitral regurgitation (MR) grade and certain clinical parameters at the time of presentation were assessed. A follow-up echocardiogram was similarly studied. The study included 49 children with IDC. Those who died or underwent cardiac transplantation were grouped as "nonsurvivors" (n = 26). The remaining children who either completely recovered or experienced chronic dilated cardiomyopathy were grouped as "survivors" (n = 23). The median age overall was 1.25 years (range 0.1-17 years). The follow-up echocardiograms of the survivors showed significant improvement in left ventricle size, systolic function, left atrial volume, and MR grade, whereas these parameters did not change in the nonsurvivor group. The use of inotropic medications at initial presentation was an independent predictor of death or cardiac transplantation (p < 0.05). The presence of moderate to severe MR at diagnosis also was predictive of a worse outcome.

Child Health Needs and the Pediatric Cardiology Workforce: 2020-2040.

This article evaluates the pediatric cardiology (PC) workforce and forecasts its future supply. Produced as part of a supplement in Pediatrics, this effort represents a collaboration among the American Board of Pediatrics Foundation, the University of North Carolina at Chapel Hill's Carolina Health Workforce Research Center, the Strategic Modeling and Analysis Ltd., and members of the pediatric subspecialty community. PC is a complex subspecialty including care from fetal life through adulthood and in practice settings that range from the outpatient clinic to procedural settings to the cardiac ICU. Complex subdisciplines include imaging, electrophysiology, heart failure, and interventional and critical care. Using American Board of Pediatrics data, US Census Bureau data, and data from the modeling project, projections were created to model the subspecialty workforce through 2040. Across all modeling scenarios considered, there is considerable projected growth in the supply of pediatric cardiologists by 2040. However, there is significant regional variation in the projected supply of trainees relative to demand in terms of local population growth, with evidence of a likely mismatch between areas surrounding training centers versus areas of greatest workforce need. In addition, this article highlights areas for future focus, including efforts to attract more residents to the subspecialty in general, particularly underrepresented minority members; increased support, more part-time career options, and improved academic career advancement for women in PC; and the development of better "real-time" workforce data to guide trainees and training programs in decisions regarding sub-subspecialty job availability.

The Ross classification for heart failure in children after 25 years: a review and an age-stratified revision.

Accurate grading of the presence and severity of heart failure (HF) signs and symptoms in infants and children remains challenging. It has been 25 years since the Ross classification was first used for this purpose. Since then, several modifications of the system have been used and others proposed. New evidence has shown that in addition to signs and symptoms, data from echocardiography, exercise testing, and biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP) all are useful in stratifying outcomes for children with HF. It also is apparent that grading of signs and symptoms in children is dependent on age because infants manifest HF differently than toddlers and older children. This review culminates in a proposed new age-based Ross classification for HF in children that incorporates the most useful data from the last two decades. Testing of this new system will be important to determine whether an age-stratified scoring system can unify the way communication of HF severity and research on HF in children is performed in the future.

Cardiac catheterization for hemoptysis in a Children's Hospital Cardiac Catheterization Laboratory: A 15 year experience.

OBJECTIVES: The aim of this study was to evaluate the diagnostic utility of cardiac catheterization and the efficacy of transcatheter intervention in patients with hemoptysis. BACKGROUND: Cardiac catheterization may play a role in identifying the etiologies of hemoptysis with the potential for transcatheter intervention. METHODS: This was a retrospective study of all the patients who were brought to the pediatric cardiac catheterization laboratory for the indication of hemoptysis over a 15-year period (2006-2020). RESULTS: Twenty-one patients underwent 28 cardiac catheterizations. The median age was 17.4 years (range 0.3-60.0 years), and the underlying cardiac diagnoses were normal heart n = 3, pulmonary hypertension 1, heart transplant 1, pulmonary arteriovenous malformation 1, pulmonary vein disease 3, biventricular congenital heart diseases 5, and single ventricles 7. The diagnostic utility of catheterization was 81% (17/21). At two-thirds (18/28) of catheterizations, transcatheter interventions were performed in 14/21 (67%) patients: aortopulmonary collateral embolization 14, aortopulmonary and veno-venous collateral embolization 1, and pulmonary arteriovenous malformation embolization 3. Although recurrent hemoptysis was frequent (50%) post-intervention, the final effectiveness of transcatheter interventions was 79% (11/14 patients). Overall mortality was 19% (4/21), all in those presenting with massive hemoptysis. CONCLUSIONS: Cardiac catheterization was shown to have good diagnostic utility for hemoptysis especially in patients with underlying congenital heart disease. Despite the high mortality and recurrent hemoptysis rate, transcatheter interventions were effective in our cohort.

Noninvasive Echocardiographic Measures of Pulmonary Vascular Resistance in Children and Young Adults with Cardiomyopathy.

BACKGROUND: Patients with cardiomyopathy (CM) are at increased risk for pulmonary hypertension (PH). Data are lacking on the use of noninvasive PH measures by echocardiography in patients with CM. The aim of this study was to evaluate the correlation between Doppler-derived echocardiographic indices and catheterization-based measurement of pulmonary vascular resistance (PVR) in children and young adults with CM. METHODS: Imaging studies were retrospectively reviewed from pediatric patients with CM who underwent both echocardiography and cardiac catheterization within a 72-hour period. The ratio of peak tricuspid regurgitation velocity to right ventricular outflow tract velocity-time integral, the S/D ratio, and right ventricular myocardial performance index were correlated with invasive PVR. Receiver operating characteristic curves were developed to determine cutoffs for detecting PVR ≥ 6 indexed Wood units, a value associated with higher heart transplantation risk. RESULTS: Twenty-three patients with CM (median age, 11.7 years; range, 0.5-21 years) met the criteria for analysis, the majority (n = 17 [74%]) of whom had dilated CM. Linear regression showed significant correlations between echocardiography-based ratio of peak tricuspid regurgitation velocity to right ventricular outflow tract velocity-time integral, S/D ratio, and right ventricular myocardial performance index versus invasive PVR (r = 0.84, r = 0.72, and r = 0.72, respectively, P < .001). All echocardiographic measures showed high sensitivity, specificity, and predictive values to detect PVR ≥ 6 indexed Wood units, with ratio of peak tricuspid regurgitation velocity to right ventricular outflow tract velocity-time integral demonstrating the highest area under the curve (0.958; 95% CI, 0.866-1). CONCLUSIONS: Right-sided Doppler-derived echocardiographic indices correlate with PVR measured by cardiac catheterization in children and young adults with CM. These parameters may serve as useful adjuncts in serial assessment of right ventricular hemodynamics in this population.

Large pseudoaneurysm following right ventricle to pulmonary artery homograft placement in an infant.

Pseudoaneurysm (PSA) is a known but rare complication of the right ventricle to pulmonary artery (RV-PA) conduits. The patient's clinical presentation can be variable ranging from asymptomatic to potential rupture. We describe an unusual case of a massive PSA in an infant who underwent RV-PA pulmonary homograft placement after relief of right ventricular outflow tract obstruction.

NT-pro BNP-A marker for worsening respiratory status and mortality in infants and young children with pulmonary hypertension.

AIM: To evaluate predictors of morbidity and mortality in pediatric patients with pulmonary hypertension (PH), laboratory and echocardiographic measures of PH were analyzed. METHODS: A retrospective review of all infants and children < 2 years of age with PH from January 2011 to August 2016 was conducted. Correlations were determined using Spearman's rank correlation coefficients. Differences in characteristics between survivors and nonsurvivors were analyzed and Kaplan-Meier survival curves were generated. RESULTS: Of 56 patients, the majority were extremely premature; of African American ethnicity; and had bronchopulmonary dysplasia. Patients who died were more likely to have underlying congenital heart disease; have a higher increase in the concentration of carbon dioxide in the blood (pCO2 ) with a corresponding greater mean percentage decrease in pH and percentage rise in NT-pro BNP during PH exacerbations; more likely to have been on medications for pulmonary hypertension; and have a higher RVSP/SBP (%) ratio and S/D ratio. There were positive correlations between percentage rise in NT-pro BNP and pCO2 ; NT-pro BNP and RVSP/SBP (%) ratio; and RVSP/SBP (%) ratio and S/D ratio. CONCLUSIONS: Infants and young children with pulmonary hypertension have increased morbidity and mortality. NT-pro BNP is a useful biomarker for both respiratory exacerbations and mortality, and RVSP/SBP (%) ratio and S/D ratio are echocardiographic identifiers for increased mortality.

Reducing radiation exposure by lowering frame rate in children undergoing cardiac catheterization: A quality improvement study.

INTRODUCTION: Reduction of radiation dosage in the pediatric cardiac catheterization laboratory (PCL) is important to reduce the risk of its stochastic effect in children with congenital heart disease. Lowering the frame rate would reduce radiation dosage possibly at the expense of image quality, potentially resulting in higher fluoroscopic time and procedural complication rate. METHODS: The data were retrospectively analyzed in three eras: era 1 (n = 234), cineangiography 30 frames/sec (f/s) and fluoroscopy 15 pulse/sec (p/s); era 2 (n = 381), cineangiography 30 f/s and fluoroscopy 6 p/s; and era 3 (n = 328), cineangiography 15 f/s and fluoroscopy 6 p/s. Also, three operators blinded to the frame rate setting evaluated cineangiography image quality. In this study, the impact of lowering the default frame rates on radiation dosage, fluoroscopic time, contrast volume, diagnostic image quality, and complication rates in the PCL was assessed. RESULTS: Overall radiation dosage progressively declined during these eras (70.0 vs 64.1 vs 36.6 µGym2 /kg, P < .001) without a difference in significant adverse event rates. There was no significant increase in either fluoroscopy time or contrast volume. There was no difference in the diagnostic image quality between cineangiography 30 and 15 f/s. Lowering the default frame/pulse rates of both fluoroscopy and cineangiography significantly decreased the overall radiation dosage in the PCL. Importantly, fluoroscopy time, contrast volume, and complication rates did not increase while maintaining diagnostic image quality. CONCLUSION: This quality improvement project proved successful in lowering radiation dosage without compromising the efficacy and safety of catheterizations.

Carvedilol for children and adolescents with heart failure: a randomized controlled trial.

CONTEXT: Although beta-blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents. OBJECTIVE: To prospectively evaluate the effects of carvedilol in children and adolescents with symptomatic systemic ventricular systolic dysfunction. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, double-blind, placebo-controlled study of 161 children and adolescents with symptomatic systolic heart failure from 26 US centers. In addition to treatment with conventional heart failure medications, patients were assigned to receive placebo or carvedilol. Enrollment began in June 2000 and the last dose was given in May 2005 (each patient received medication for 8 months). INTERVENTIONS: Patients were randomized in a 1:1:1 ratio to twice-daily dosing with placebo, low-dose carvedilol (0.2 mg/kg per dose if weight <62.5 kg or 12.5 mg per dose if weight > or =62.5 kg), or high-dose carvedilol (0.4 mg/kg per dose if weight <62.5 kg or 25 mg per dose if weight > or =62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not. MAIN OUTCOME MEASURES: The primary outcome was a composite measure of heart failure outcomes in patients receiving carvedilol (low- and high-dose combined) vs placebo. Secondary efficacy variables included individual components of this composite, echocardiographic measures, and plasma b-type natriuretic peptide levels. RESULTS: There was no statistically significant difference between groups for the composite end point based on the percentage of patients who improved, worsened, or were unchanged. Among 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%); among 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group vs the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A prespecified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and those whose systemic ventricle was not a left ventricle (nonbeneficial trend). CONCLUSIONS: These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, given the lower than expected event rates, the trial may have been underpowered. There may be a differential effect of carvedilol in children and adolescents based on ventricular morphology. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00052026.