Pediatric extracorporeal life support for refractory status asthmaticus: ELSO Registry trends from the past decade.

BACKGROUND: Extracorporeal life support (ECLS) for status asthmaticus (SA) is rare. Increased safety and experience may increase utilization of ECLS for SA. METHODS: We reviewed pediatric (<18 years old) patients requiring ECLS for SA between 1998 and 2019 within the Extracorporeal Life Support Organization (ELSO) Registry and Nemours Children's Health (NCH) system. We compared patient characteristics, pre-ECLS medications, clinical data, complications, and survival to discharge between Early (1988-2008) and Late (2009-2019) eras. RESULTS: From the ELSO Registry, we identified 173 children, 53 in Early and 120 in Late eras, with primary diagnosis of SA. Pre-ECLS hypercarbic respiratory failure was similar between eras (median pH 7.0 and pCO2 111 mm Hg). Venovenous mode (79% vs. 82%), median ECLS time (116 vs. 99 h), time to extubation (53 vs. 62 h), and hospital survival (89% vs. 88%) also remained similar. Intubation to cannulation time significantly decreased (20 vs. 10 h, p = 0.01). ECLS without complication occurred more in the Late era (19% vs. 39%, p < 0.01), with decreased hemorrhagic (24% vs. 12%, p = 0.05) and noncannula-related mechanical (19% vs. 6%, p = 0.008) complications. Within NCH, we identified six Late era patients. Pre-ECLS medication favored intravenous beta agonists, bronchodilators, magnesium sulfate, and steroids. One patient died from neurological complications following pre-ECLS cardiac arrest. CONCLUSIONS: Collective experience supports ECLS as a rescue therapy for pediatric SA. Survival to discharge remains good, and complication rates have improved. Pre-ECLS cardiac arrest may potentiate neurologic injury and impact survival. Further study is needed to evaluate causal relationships between complications and outcomes.

Idiopathic Pericardial Effusions in Children: Workup and Final Diagnoses.

Pediatric idiopathic pericardial effusions are common and often have a prolonged clinical course. We hypothesized that these effusions have no standardized diagnostic workup, and ultimately have a final etiology not initially appreciated. To test these hypotheses, a hospital system-wide retrospective (1/1/1990-10/1/2019) cohort study of pericardial effusions in children (< 18 years) was conducted. Effusions were grouped by etiology and patients receiving an initial idiopathic diagnosis were further analyzed. Effusion size, diagnostic workup, final diagnosis, and time to resolution were abstracted. In total, 42/366 effusions were initially diagnosed as idiopathic. Workup was not standardized and included up to six laboratory tests including pericardial fluid analysis and infectious, metabolic, rheumatologic and thyroid workups. Treatment course involved 1 readmission in 24%, and > 1 readmission in 12%. Resolution of effusion occurred in 83% of patients within a median of 1 admission (range 1-4). Of those effusions initially deemed idiopathic, 12/42 (29%) were later found to have an underlying etiologic diagnosis including: autoimmune (7, 58%), neoplastic (2, 16%), infectious (2, 16%), and renal (1, 8%). Children initially diagnosed with idiopathic pericardial effusions have an underlying etiologic diagnosis 29% of the time, and a standardized workup may prevent delays in definitive diagnosis and treatment.

A shifting landscape: Practice patterns and outcomes of cystic fibrosis and non-cystic fibrosis pediatric lung transplantation.

BACKGROUND: New drugs may further decrease the need for lung transplant (LTx) in pediatric patients with cystic fibrosis (CF), but few studies highlight pediatric non-CF LTx characteristics and outcomes. METHODS: The ISHLT registry was used to report morbidity, graft failure, and survival for primary pediatric (<18 years) LTx performed 1990-2017. Recipient/donor characteristics and long-term outcomes were analyzed for CF and non-CF recipients. Survival was assessed using Kaplan-Meier curves. RESULTS: Of 2232 primary LTx, (43% in males), 918 (41%) were performed for non-CF indications; most commonly pulmonary hypertension (43%). Non-CF patients were younger (median age 11 vs. 15, p < .001), and more frequently on inotropes and/or extracorporeal membrane oxygenation (15% vs. 2.4%, p < .001) at transplant, compared to CF recipients. In-hospital major complications more commonly affected CF LTx recipients (57% vs. 48%, p = .003), but 30-day mortality was higher in the non-CF group (9% non-CF vs. 5% CF, p < .001). One-, five-, and ten-year mortality was 18%, 50%, and 65% for CF recipients, respectively, and 21%, 45%, and 58% for non-CF recipients (p = .01 at 10 years). Five-year survival was significantly better for non-CF females versus CF females (56% vs. 48%, p = .013), but was similar between groups for males (55% vs. 54%, p = .305). While age was a late outcomes risk factor, pulmonary hypertension and later transplants eras were protective. CONCLUSIONS: Early mortality is higher and late mortality is lower in non-CF LTx. Current non-CF LTx outcomes leave room for improvement. Further study is needed to evaluate the effects of center volume and pediatric-specific experience on outcomes.

Does age estimated from teeth forming in different early life periods show differential discrepancy with known age?

OBJECTIVES: The aim of this study is to explore growth discrepancies in the dentition of impoverished children and examine how dental development is impacted by environmental influences throughout childhood, thereby identifying which teeth are more sensitive to the effects of biocultural factors and are consequently less useful to predict age. METHODS: Length measurements of developing teeth (deciduous and permanent) were taken from individuals of known age and sex (n = 61) from the Certosa collection, a 19th century skeletal assemblage representing Italian children of low socioeconomic status. Discrepancies between age estimates based on tooth length and chronological age were calculated, and the accuracy and precision of age prediction between earlier forming teeth and later forming teeth were compared. RESULTS: Deciduous teeth produced more precise dental age estimates (mean age discrepancy -0.092 years), while discrepancies between chronological age and age based on developing permanent dentition were larger (-0.628 years). The difference between these discrepancies in age estimates for deciduous and permanent teeth was significant (p < 0.001), indicating that age prediction from deciduous tooth length is more accurate than age predicted using permanent tooth length. CONCLUSION: An increasing variation and delay in tooth length for age reflects increasing susceptibility to biocultural factors, which impacts tooth growth during the course of childhood. Teeth whose development occurs earlier in life are less variable in their growth and provide more accurate estimations of age as a result.

Cardiac venous malformation in a teenager.

We present the case of a 17-year-old boy with a cardiac venous malformation. This case highlights the diagnostic challenges of such tumours and demonstrates the potential efficacy of a watch-and-wait management approach.

Regional Differences in Cost and Length of Stay in Neonates with Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) is a highly resource-intensive diagnosis. Geographic variation in cost and length of stay (LOS) in HLHS is not well described. Neonates diagnosed with HLHS between 2000 and 2012 were identified using the Kids' Inpatient Database. Hospitalizations were stratified into two groups: (1) birth and (2) secondary. United States regional differences in hospital charges and LOS were compared using adjusted linear regression. Of 2431 birth hospitalizations, 449 neonates (18.5%) died while inpatient and mortality rates differed by region (p = 0.02). After birth, 40.5% (n = 985) of neonates were transferred; transfers were most common in the Midwest (p < 0.0001). Adjusted average LOS was shortest in the West and longest in the South (26.1 days; 95% CI 24.0, 35.1 vs. 34.9 days; 95% CI 31.8, 38.1). Average adjusted charges were lowest in the Northeast ($324,600; 95% CI $271,400, $377,900) and highest in the West ($400,500; 95% CI $346,700, $454,300, p = 0.05). Among 1895 secondary hospitalizations, 24.9% of neonates died as inpatients, and the average adjusted LOS was shortest in the West (26.8 days; 95% CI 23.9, 29.7) and longest in the South (38.5 days; 95% CI 34.4, 42.4). Average adjusted charges were lowest in the Northeast ($326,900; 95% CI $270,700, $383,100) and highest in the South ($505,900; 95% CI $450,200, $561,500, p < 0.0001). Significant geographic variations in mortality, LOS, and hospital charges exist in care of US HLHS neonates. Reducing variation in care should remain a priority in national quality efforts in congenital heart disease.

Feasibility of a healthcare system-based tetralogy of Fallot patient registry.

BACKGROUND: Patient-reported outcomes and epidemiological studies in adults with tetralogy of Fallot are lacking. Recruitment and longitudinal follow-up investigation across institutions is particularly challenging. Objectives of this study were to assess the feasibility of recruiting adult patients with tetralogy of Fallot for a patient-reported outcomes study, describe challenges for recruitment, and create an interactive, online tetralogy of Fallot registry. METHODS: Adult patients living with tetralogy of Fallot, aged 18-58 years, at the University of North Carolina were identified using diagnosis code query. A survey was designed to collect demographics, symptoms, history, and birth mother information. Recruitment was attempted by phone (Part I, n=20) or by email (Part II, n=20). Data analysis included thematic grouping of recruitment challenges and descriptive statistics. Feasibility threshold was 75% for recruitment and for data fields completed per patient. RESULTS: In Part I, 60% (12/20) were successfully contacted and eight (40%) were enrolled. Demographics and birth mother information were obtained for all enrolled patients. In Part II, 70% (14/20) were successfully contacted; 30% (6/20) enrolled and completed all data fields linked to REDCap database; the median time for survey completion was 8 minutes. Half of the patients had cardiac operations/procedures performed at more than one hospital. Automatic electronic data entry from the online survey was uncomplicated. CONCLUSIONS: Although recruitment (54%) fell below our feasibility threshold, enrolled individuals were willing to complete phone or online surveys. Incorrect contact information, privacy concerns, and patient-reported time constraints were challenges for recruitment. Creating an online survey and linked database is technically feasible and efficient for patient-reported outcomes research.

Geographic distribution of live births with tetralogy of Fallot in North Carolina 2003 to 2012.

BACKGROUND: Geographic variation in congenital heart disease is not well-described. This study uses geographic information systems (GIS) to describe the spatial epidemiology of tetralogy of Fallot (TOF), in North Carolina (NC) and to compare travel time for cases to congenital heart centers in NC. METHODS: Using the NC Birth Defects Monitoring Program database, live births with TOF born between 2003 and 2012 were identified. Birth certificates provided demographic variables. A denominator of live births/zip code was obtained from the NC live births database. ArcGIS® software was used to illustrate TOF prevalence by zip code, and SatScanTM was used to identify spatial clusters of TOF cases and to identify changes in cluster location over time. Driving time to each of five NC congenital heart centers was predicted based on road systems information. RESULTS: A total of 496 infants were born with TOF between 2003 and 2012. The prevalence was 4.2/10,000 live births. A large cluster (330 zip codes, 306 cases) was identified in northeastern NC. Average driving time for each case to closest congenital heart center was: University of North Carolina 37 min, Vident Medical Center 64 min, Duke University 58 min, Carolina's Medical Center 89 min, and Wake Forest Baptist Health 57 min. Overall, average predicted driving time to the nearest congenital heart center was 61 min. CONCLUSION: Approximately 50 infants/year were born with TOF in NC. One cluster was identified. Further study is necessary to explore potential explanations for the observed case cluster. As interest in regionalization of congenital heart surgery grows, GIS and spatial analysis can become increasingly useful tools for health care planning. Birth Defects Research (Part A) 106:881-887, 2016. © 2016 Wiley Periodicals, Inc.

Meta-analysis reveals differential gene expression in tetralogy of Fallot versus controls.

OBJECTIVES: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect in the United States. We aimed to identify genetic variations associated with TOF using meta-analysis of publicly available digital samples to spotlight targets for prevention, screening, and treatment strategies. METHODS: We used the Search Tag Analyze Resource for Gene Expression Omnibus (STARGEO) platform to identify 39 TOF and 19 non-TOF right ventricle tissue samples from microarray data and identified upregulated and downregulated genes. Associated gene expression data were analyzed using ingenuity pathway analysis and restricted to genes with a statistically significant (p < .05) difference and an absolute experimental log ratio >0.1 between disease and control samples. RESULTS: Our analysis identified 220 genes whose expression profiles were significantly altered in TOF vs. non-TOF samples. The most striking differences identified in gene expression included genes FBXO32, PTGES, MYL12a, and NR2F2. Some top associated canonical pathways included adrenergic signaling, estrogen receptor signaling, and the role of NFAT in cardiac hypertrophy. In general, genes involved in adaptive, defensive, and reparative cardiovascular responses showed altered expression in TOF vs. non-TOF samples. CONCLUSIONS: We introduced the interpretation of open "big data" using the STARGEO platform to define robust genomic signatures of congenital heart disease pathology of TOF. Overall, our meta-analysis results indicated increased metabolism, inflammation, and altered gene expression in TOF patients. Estrogen receptor signaling and the role of NFAT in cardiac hypertrophy represent unique pathways upregulated in TOF patients and are potential targets for future pharmacologic treatments.

A 1-Day-Old Girl With Infantile Hemangioma and Sternal Cleft.

CASE PRESENTATION: A newborn girl presented to the hospital on the first day of life because of respiratory failure. She was born at home at 37 weeks' gestation with minimal prenatal care and was found to be small for gestational age. The patient was found to have partial sternal agenesis and sternal cleft, cutis aplasia, left facial hemangioma, micrognathia, wide-spaced nipples, and low-set ears. The mother's and baby's urine toxicology screening were positive for amphetamines. Chest radiographs on admission showed bilateral hazy opacities. CT scan of the chest showed an absent sternum with midline chest wall concavity. The patient was monitored preoperatively in the cardiac ICU for risks of arrythmia, respiratory failure, altered cardiac output, and acute cardiopulmonary decompensation.

Lifetime Management of Adolescents and Young Adults with Congenital Aortic Valve Disease.

In this invited expert review, we focus on evolving lifetime management strategies for adolescents and young adults with congenital aortic valve disease, acknowledging that these patients often require multiple interventions during their lifetime. Our goal is to preserve the native aortic valve when feasible. Leveraging advanced multimodality imaging, a detailed assessment of the aortic valve and root complex can be obtained, and a surgical approach tailored to an individual patient's anatomy and pathology can be employed. In turn, aortic valve repair and reconstruction can be offered to a greater number of patients, either as a definitive strategy or as a component of a staged strategy to delay the need for aortic valve replacement until later in life when more options are available. In adolescents and young adults with unrepairable aortic valve disease, our preferred strategies are aortic valve replacement with pulmonary autograft (Ross procedure) or autologous pericardium (Ozaki procedure). Aortic valve replacement with a bioprosthetic or mechanical valve is a safe and reproducible option reserved as a "last resort" in adolescents and young adults due to the cumulative lifetime risk of valve-related complications and ongoing attrition of these patients during follow-up.

The Society of Thoracic Surgeons Clinical Practice Guidelines on the Management of Neonates and Infants with Coarctation.

BACKGROUND: Although coarctation of the aorta without concomitant intracardiac pathology is relatively common, there is lack of guidance regarding aspects of its management in neonates and infants. METHODS: A panel of experienced congenital cardiac surgeons, cardiologists, and intensivists was created, and key questions related to the management of isolated coarctation in neonates and infants were formed using the PICO (Patients/Population, Intervention, Comparison/Control, Outcome) Framework. A literature search was then performed for each question. Practice guidelines were developed with classification of recommendation and level of evidence using a modified Delphi method. RESULTS: For neonates and infants with isolated coarctation, surgery is indicated in the absence of obvious surgical contraindications. For patients with risk factors for surgery, medical management before intervention is reasonable. For those stable off prostaglandin E1, the threshold for intervention remains unclear. Thoracotomy is indicated when arch hypoplasia is not present. Sternotomy is preferable when arch hypoplasia is present that cannot be adequately addressed through a thoracotomy. Sternotomy may also be considered in the presence of a bovine aortic arch. Antegrade cerebral perfusion may be reasonable when the repair is performed through a sternotomy. Extended end-to-end, arch advancement, and patch augmentation are all reasonable techniques. CONCLUSIONS: Surgery remains the standard of care for the management of isolated coarctation in neonates and infants. Depending on degree and location, arch hypoplasia may require a sternotomy approach as opposed to a thoracotomy approach. Significant opportunities remain to better delineate management in these patients.

Educating Surgeons to Construct Valved Conduits: What Does It Take to Achieve Reproducible Results?

BACKGROUND: Despite the demonstrated utility of surgeon-fashioned polytetrafluoroethylene (PTFE) valved conduits, methods for educating surgeons to reproducibly construct these conduits are lacking. We present a surgeon education process and early outcomes for children receiving surgeon-fashioned PTFE valved conduits during the initial learning curve. METHODS: The educational curriculum included 4 hours of proctored instruction/supervised valve construction, followed by 2 hours of individual practice. A surgeon with prior mastery of the technique provided templated designs, videos, and follow-up consultation. A retrospective medical record review (2017-2022) described early outcomes and valve function for patients receiving surgeon-fashioned PTFE right ventricle-to-pulmonary artery conduits. RESULTS: Two surgeons were educated using the method described. Fifteen valved conduits were implanted in 14 patients (median patient age, 38 months; conduit size range, 10-24 mm). At discharge, no patient had more than mild stenosis or regurgitation, and 12 of 15 valves (80%) had none or trivial regurgitation. Median follow-up was 14 months (range, 1-52 months). At the last follow-up, median peak conduit gradient of the 15 valves was low (18 mm Hg), 1 (7%) had moderate stenosis, and 1 (7%) had mild-moderate regurgitation. Two conduits were replaced concomitantly during repair of associated lesions at 14 and 38 months (sizes 10 and 12 mm, respectively). There were no deaths and no infectious complications. CONCLUSIONS: Four hours of proctored surgeon education plus deliberate practice is an effective method for teaching valved PTFE conduit construction and is associated with excellent early valve function. This study provides educational methods and initial evidence of safety for congenital surgeons wishing to learn and adopt this technique.

Tetralogy of Fallot Associated With Right Aortic Arch and Isolated Left Brachiocephalic Artery.

A newborn presented with tetralogy of Fallot (TOF), right aortic arch (RAA), and isolated left brachiocephalic artery. The RAA supplied the right common carotid artery, right vertebral artery, and right subclavian artery, in that order. The left common carotid and left subclavian arteries were in continuity with no aortic origin. Ultrasound demonstrated retrograde flow in the left vertebral artery supplying antegrade flow to the diminutive left subclavian artery (ie, "steal phenomenon"). The patient underwent repair of TOF without intervention on the left common carotid or left subclavian arteries and is being followed conservatively.

Commentary: Gender differences in payments to cardiothoracic surgeons are unacceptable.

Every effort must be made by the leaders in our field, as well as by every individual cardiothoracic surgeon, to assure equal opportunity for all cardiothoracic surgeons, regardless of race, gender or any other sociodemographic source of bias. Every effort must be made by every surgeon, not just those in particular leadership roles. Opportunities for advancement must be equal in multiple domains, including clinical practice, patient referral, clinical leadership, academic leadership, institutional leadership and leadership in professional medical and surgical societies. Such actions to minimize bias and promote inclusivity will also ensure that cardiothoracic surgical care is provided by a workforce that represents the diversity of patients whom we serve. In the final analysis, it is an absolute fact that gender differences in payments to cardiothoracic surgeons are absolutely unacceptable and cannot be tolerated.

The Society of Thoracic Surgeons Congenital Heart Surgery Database: 2022 Update on Outcomes and Research.

The Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database continues to be one of the most comprehensive clinical outcomes registries capturing almost all pediatric cardiothoracic surgical operations undertaken in the United States. The latest analysis of aggregate outcomes was performed after the 33rd data harvest and included congenital and pediatric cardiac operations performed between July 1, 2017 and June 30, 2021. This article summarizes these contemporary outcomes and provides a context for the interpretation of these outcomes. In addition this article describes ongoing efforts to improve data collection and augment analytical approaches. Finally, research activities undertaken in the last year using data from the database are also summarized.

Development of a Novel Society of Thoracic Surgeons Adult Congenital Mortality Risk Model.

BACKGROUND: Operative mortality risk models for adults with congenital heart disease (ACHD) undergoing cardiac operations are essential, given the growing population of these patients, yet they are currently unavailable. Existing adult Society of Thoracic Surgeons (STS) models exclude congenital procedures, whereas existing congenital models exclude operations for acquired disease. We aimed to develop an STS mortality risk model for ACHD patients undergoing cardiac operations. METHODS: Leveraging a comprehensive list of diagnostic and procedure codes, ACHD patients who underwent cardiac operations were identified from the STS Adult Cardiac Surgery Database (versions: v2.73, v2.81, and v2.9) between 2011 and 2019. The model was developed and validated in the ACHD population using a 60/40 development/validation split. Univariate analyses and clinical expertise informed the addition of ACHD-relevant procedure and diagnosis variables to existing STS adult risk model variables. Model performance was assessed overall and in 38 subgroups based on patient demographics, procedures, and diagnoses. RESULTS: Forty-seven procedure and diagnosis variables relevant to ACHD were added to existing STS adult risk model variables. The derived ACHD model for operative mortality was well calibrated within demographic, procedural, and diagnosis subgroups and the overall ACHD population, and discrimination in the validation cohort was excellent (C statistic, 0.815) compared with the model using only existing STS adult risk model variables (C statistic, 0.79; P < .0001). CONCLUSIONS: A novel, high-performing STS ACHD mortality risk model has been developed on the basis of contemporary patient data. The ACHD risk model represents an important expansion of the STS portfolio. Implementation with an online risk calculator is planned.

Concurrent double aortic arch and circumflex aorta repair in a symptomatic child: a case report.

Double aortic arch with circumflex aorta is a rare type of vascular ring. Symptoms result from external compression of the trachea and esophagus. The best surgical approach for patients with double arch and circumflex aorta is debated, and options include the highly complex aortic uncrossing procedure. Herein we describe the surgical treatment of a patient with concurrent double aortic arch and circumflex aorta by division of the non-dominant arch and ligamentum arteriosum, plication and posterior tacking of the diverticulum of Kommerell. This left thoracotomy approach provided complete symptom resolution.

Extracorporeal Life Support for Status Asthmaticus: Early Outcomes in Teens and Young Adults.

Extracorporeal life support (ECLS) may be life saving for patients with status asthmaticus (SA), a difficult-to-treat, severe subset of asthma. Contemporary ECLS outcomes for SA in teens and young adults are not well described. The Extracorporeal Life Support Organization (ELSO) Registry was reviewed (2009-2019) for patients (15-35 years) with a primary diagnosis of SA. In-hospital mortality and complications were described. Multivariable logistic regression was used to identify independent risk factors for hospital mortality. Overall, 137 patients, (26 teens and 111 young adults; median age 25 years) were included. Extracorporeal life support utilization for SA sharply increased in 2010, coinciding with increased ECLS utilization overall. Median ECLS duration and length of stay were 97 hours and 11 days, respectively. In-hospital mortality and major complication rates were 10% and 11%, respectively. Nonsurvivors were more likely to have experienced ECLS complications, compared to survivors (86% vs. 42%, p = 0.003). Independent risk factors for in-hospital mortality included pre-ECLS arrest and any renal and/or neurologic complication. Prospective studies designed to evaluate complications and subsequent failure to rescue may help optimize quality improvement efforts.

A Minimal Opioid Postoperative Management Protocol in Congenital Cardiac Surgery: Safe and Effective.

There is evidence that reducing opioid exposure in children undergoing cardiac surgery may enhance postoperative recovery. We aimed to describe a minimal opioid postoperative management protocol in children undergoing cardiac surgery and our early outcomes with this strategy. We reviewed the medical records of children (6 months-18 years) who underwent elective cardiac surgery through a median sternotomy with cardiopulmonary bypass at our institution between 2016 and 2018. All patients were managed postoperatively using a standardized protocol. 101 children (median age 5 years) were included and 85% were extubated in the operating room. Although most patients (96%) received opioids postoperatively, opioid requirements decreased steadily over time, with 88%, 58%, and 18% of children receiving opioids on postoperative day 1, 2, and 3, respectively; 41% received no opioids after postoperative day 1. The median cumulative opioid exposure was 0.25 morphine milligram equivalents per kg (interquartile range, 0.10-0.75). Greater than mild pain was rare (<10%) at each time point. The rates of operative mortality and major complication were 0% and 3%, respectively. The median postoperative length of stay was 3 days, and 13% required readmission within 30 days. Age, cardiopulmonary bypass time, and number of benzodiazepine doses were independently associated with cumulative opioid exposure. Any complication, chest tube time, and higher STAT Category were independently associated with prolonged postoperative length of stay. A minimal opioid postoperative management protocol can be safe and effective in children undergoing cardiac surgery. Future prospective studies are needed to determine optimal practice and patient selection.