Fetal Echocardiographic Evaluation of Tricuspid Valve and Right Ventricular Function Including Global Longitudinal Strain in Hypoplastic Left Heart Syndrome and Association with Postnatal Outcomes.

Despite significant advancements in the care of patients with hypoplastic left heart syndrome (HLHS) morbidity and mortality remain high. Postnatal right ventricular dysfunction and tricuspid regurgitation (TR) are associated with worse outcomes in HLHS. We aim to determine if right ventricle functional parameters and TR on fetal echocardiogram are associated with postnatal outcomes in HLHS patients. Retrospective review was performed on all fetuses with HLHS from 2014 to 2022 at our institution. Initial and follow up fetal echocardiogram measurements of right ventricular myocardial performance index (MPI), fractional area change (FAC) and global longitudinal strain (GLS) were retrospectively measured. The presence and severity of TR was recorded from the fetal echocardiogram reports. Postnatal outcomes including transplant-free survival, hospital length of stay > 30 days after initial palliation and need for bidirectional Glenn at < 4 months were reviewed. Forty-three subjects met inclusion criteria. Mean gestational age at presentation was 26.1 ± 5.9 weeks. Nine subjects died and 3 required heart transplantation. Initial fetal echocardiogram MPI was significantly lower (better) (0.36 ± 0.06 vs 0.44 ± 0.11; p = < 0.001) and FAC was significantly higher (better) (45 ± 6% vs 40 ± 8%; p = 0.035) in transplant-free survivors. Fetal right ventricular GLS and presence of mild TR were not associated with postnatal outcome. In fetuses with HLHS, abnormal MPI and right ventricular FAC are associated with decreased transplant-free survival. There was no observed association between GLS and postnatal outcomes. To our knowledge this is the first study examining fetal right ventricular function and GLS in HLHS patients and its link to postnatal outcomes.

Suboptimal Imaging on Obstetric Ultrasound Should Prompt Early Referral for Fetal Echocardiography.

Recent studies suggest that suboptimal cardiac imaging on routine obstetric anatomy ultrasound (OB-scan) is not associated with a higher risk for congenital heart disease (CHD) and, therefore, should not be an indication for fetal echocardiography (F-echo). We aim to determine the incidence of CHD in patients referred for suboptimal imaging in a large catchment area, including regions that are geographically distant from a tertiary care center. We conducted a retrospective chart review of patients referred to Seattle Children's Hospital (SCH) and SCH Regional Cardiology sites (SCH-RC) from 2011 to 2021 for F-echo with the indication of suboptimal cardiac imaging by OB-scan. Of 454 patients referred for suboptimal imaging, 21 (5%) of patients were diagnosed with CHD confirmed on postnatal echo. 10 patients (2%) required intervention by age one. Mean GA at F-echo was significantly later for suboptimal imaging compared to all other referral indications (27.5 ± 3.9 vs 25.2 ± 5.2 weeks, p < 0.01). Mean GA at F-echo was also significantly later at SCH-RC compared to SCH (29.2 ± 4.6 vs 24.2 ± 2.9 weeks; p < 0.01). In our experience, CHD in patients referred for suboptimal imaging is higher (5%) than previously described, suggesting that routine referral for is warranted. Furthermore, while suboptimal imaging was associated with a delayed F-echo compared to other indications, this delay was most striking for those seen at regional sites. This demonstrates a potential disparity for these patients and highlights opportunities for targeted education in cardiac assessment for primary providers in these regions.

Bias estimation in the certification of steroid reference materials for carbon isotope delta measurements via elemental analyser and gas chromatography-combustion-isotope ratio mass spectrometry.

RATIONALE: Two new certified reference materials (CRMs) have been prepared providing three steroids certified for stable carbon isotope delta values, δ(13 C) ‰. These materials have been designed to assist anti-doping laboratories in validating their calibration method or to be employed as calibrant for stable carbon isotope measurements of Boldenone, Boldenone Metabolite 1 and Formestane. These CRMs will allow for accurate and traceable analysis in compliance with World Anti-Doping Agency (WADA) Technical Document TD2021IRMS. METHODS: Certification was performed using an elemental analyser-isotope ratio mass spectrometry (EA-IRMS) primary reference method on the bulk carbon isotope ratios of nominally pure steroid starting materials. EA-IRMS analyses were carried out on a Flash EA Isolink CN coupled via a Conflo IV to a Delta V plus mass spectrometer. Confirmation analysis was performed by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) using a Trace 1310 GC coupled to a Delta V plus mass spectrometer via GC Isolink II. RESULTS: Based on the EA-IRMS analysis, the materials were certified with δ(13 C) values of -30.38‰ (Boldenone), -29.71‰ (Boldenone Metabolite 1) and 30.71‰ (Formestane). Noting that the assumption of 100% purity in the starting materials has the potential to introduce bias, this was investigated using GC-C-IRMS analysis and theoretical modelling based on purity assessment data. CONCLUSIONS: Careful application of this theoretical model was shown to provide reasonable estimates of uncertainty while avoiding the introduction of errors associated with analyte-specific fractionation during GC-C-IRMS analysis.

Utility of Screening Fetal Echocardiogram Following Normal Anatomy Ultrasound for In Vitro Fertilization Pregnancies.

In vitro fertilization (IVF) is associated with a higher incidence of congenital heart disease, resulting in universal screening fetal echocardiograms (F-echo) even when cardiac structures on obstetric scan (OB-scan) are normal. Recent studies suggest that when OB-scan is normal, F-echo may add little benefit and increases cost and anxiety. We aim to determine the utility of screening F-echo in IVF pregnancies with normal cardiac anatomy on prior OB-scan. We conducted a retrospective chart review of IVF pregnancies referred for F-echo at the Seattle Children's Hospital between 2014 and 2020. OB-scan results and subspecialty of interpreting physician (Obstetrics = OB; Maternal Fetal Medicine = MFM; Radiology = Rads), F-echoes, and postnatal outcomes were reviewed. Cardiac anatomy on OB-scans was classified as complete if 4-chamber and outflow-tract views were obtained. Supplemental views (three-vessel and sagittal aortic arch views) on OB-scan were also documented. Of 525 IVF referrals, OB-scan reports were available for review in 411. Normal anatomy was demonstrated in 304 (74%) interpreted by OB (128; 42%), MFM (80; 26%), and Rads (96; 32%). F-echo was normal in 278 (91%). Of the 26 abnormal F-echo, none required intervention (17 muscular and 5 perimembranous ventricular septal defects, and 4 minor valve abnormalities). There was no difference in OB-scan accuracy for identifying normal cardiac anatomy when comparing 4-chamber and outflow-tract views vs. addition of supplemental views (91% vs 92% normal F-echo; p > 0.1). Evaluation of OB-scan accuracy by interpreting physician subspecialty demonstrated normal F-echo in 95%, 85%, and 92% (p = 0.95) as read by OB, MFM, and Rads, respectively. A majority of IVF referrals with normal cardiac anatomy visualized on OB-scan using 4-chamber and outflow-tract views resulted in normal F-echo, regardless of interpreting physician subspecialty or addition of supplemental views. Of the minority with abnormal F-echo, none required intervention. Consideration should be given to the cost/benefit of screening F-echo for the indication of IVF if normal cardiac anatomy is demonstrated on OB-scan.

Accuracy of Fetal Echocardiography in Defining Pulmonary Artery Anatomy and Source of Pulmonary Blood flow in Pulmonary Atresia with Ventricular Septal Defect (PA/VSD).

Precise delineation of central and branch pulmonary artery anatomy, patent ductus arteriosus, and major aorto-pulmonary collateral artery anatomy in the fetal diagnosis of pulmonary atresia with ventricular septal defect is challenging but important to prenatal counseling and postnatal management. We aimed to evaluate the accuracy of fetal echocardiography to determine these anatomical nuances in pulmonary atresia with ventricular septal defect. This was a retrospective, single-institution, 10-year chart review of consecutive prenatal diagnosis of pulmonary atresia with ventricular septal defect for assessment of pulmonary artery, patent ductus arteriosus, and major aorto-pulmonary collateral artery anatomy and comparison with postnatal imaging including echocardiography, cardiac catheterization, and computerized tomography angiography. Twenty-six fetuses were diagnosed with pulmonary atresia with ventricular septal defect during the review period and complete postnatal follow-up was available in 18, all confirming the basic prenatal diagnosis. Fetal echocardiography accurately predicted central and branch pulmonary artery anatomy in 16 (89%) [confluent in 14, discontinuous in 2], patent ductus arteriosus status in 15 (83%) [present in 10, absent in 5], and major aorto-pulmonary collateral arteries in 17 (94%) [present in 9, absent in 8]. Accuracy increased to 100% for pulmonary artery anatomy (16/16) and major aorto-pulmonary collateral artery (17/17) when excluding patients whose anatomy was reported as uncertain on fetal echocardiography. Fetal echocardiography can provide accurate anatomical details in the vast majority of fetuses with pulmonary atresia with ventricular septal defect. This allows for more anatomy-specific counseling, prognostication, and improved selection of postnatally available management options.

Validation of Prenatal Aortic Arch Angle Measurements in the Diagnosis of Neonatal Coarctation of the Aorta.

Prenatal prediction of coarctation of the aorta (CoA) is challenging. Methods identifying prenatal CoA have high sensitivity with significant false positives. We previously derived prenatal aortic arch angles for identifying CoA with high sensitivity and specificity and aim to validate these angles and compare them with a model utilizing ascending aorta (AAo) and isthmus (Aoi) measures. Retrospective case/cohort study of fetuses with prenatal suspicion for CoA. 35 fetuses were included. Measurements included: ascending-descending aortic angle (AAo.DAo), transverse-descending aortic angle (TAo.DAo); diameters and z-scores of Aoi from sagittal (Aoi-sag), three-vessel (Aoi-3VV) view and AAo. Discriminant functions for the 5 variables were compared using histograms and positive/negative predictive values (PPV/NPV). CoA was confirmed in 28/35 neonates. The PPV and NPV for angle measures were 100% and 77%. The AAo + Aoi-3VV model PPV and NPV were 92% and 80% and Aoi-sag + Aoi-3VV model were 82% and 71%. A linear discriminant model utilizing the 3 most predictive variables improved NPV to 90% and PPV to 100%. In conclusion, we validate that angle measures are superior to standard models of predicting CoA. An optimized 3 variable model maintains accuracy of identifying CoA while eliminating false positives.

Is biventricular vascular coupling a better indicator of ventriculo-ventricular interaction in congenital heart disease?

BACKGROUND: Ventriculo-ventricular interactions are known to exist, though not well quantified. We hypothesised that the ventricular-vascular coupling ratio assessed by cardiovascular MRI would provide insight into this relationship. We also sought to compare MRI-derived ventricular-vascular coupling ratio to echocardiography and patient outcomes. METHODS: Children with cardiac disease and biventricular physiology were included. Sanz's and Bullet methods were used to calculate ventricular-vascular coupling ratio by MRI and echocardiography, respectively. Subgroup analysis was performed for right and left heart diseases. Univariate and multivariate regressions were performed to determine associations with outcomes. RESULTS: A total of 55 patients (age 14.3 ± 2.5 years) were included. Biventricular ventricular-vascular coupling ratio by MRI correlated with each other (r = 0.41; p = 0.003), with respect to ventricle's ejection fraction (r = -0.76 to -0.88; p < 0.001) and other ventricle's ejection fraction (r = -0.42 to -0.47; p < 0.01). However, biventricular ejection fraction had only weak correlation with each other (r = 0.31; p = 0.02). Echo underestimated ventricular-vascular coupling ratio for the left ventricle (p < 0.001) with modest correlation to MRI-derived ventricular-vascular coupling ratio (r = 0.43; p = 0.002). There seems to be a weak correlation between uncoupled right ventricular-vascular coupling ratio with the need for intervention and performance on exercise testing (r = 0.33; p = 0.02). CONCLUSION: MRI-derived biventricular ventricular-vascular coupling ratio provides a better estimate of ventriculo-ventricular interaction in children and adolescents with CHD. These associations are stronger than traditional parameters and applicable to right and left heart conditions.

A genome-wide association study of congenital cardiovascular left-sided lesions shows association with a locus on chromosome 20.

Congenital heart defects involving left-sided lesions (LSLs) are relatively common birth defects with substantial morbidity and mortality. Previous studies have suggested a high heritability with a complex genetic architecture, such that only a few LSL loci have been identified. We performed a genome-wide case-control association study to address the role of common variants using a discovery cohort of 778 cases and 2756 controls. We identified a genome-wide significant association mapping to a 200 kb region on chromosome 20q11 [P= 1.72 × 10-8 for rs3746446; imputed Single Nucleotide Polymorphism (SNP) rs6088703 P= 3.01 × 10-9, odds ratio (OR)= 1.6 for both]. This result was supported by transmission disequilibrium analyses using a subset of 541 case families (lowest P in region= 4.51 × 10-5, OR= 1.5). Replication in a cohort of 367 LSL cases and 5159 controls showed nominal association (P= 0.03 for rs3746446) resulting in P= 9.49 × 10-9 for rs3746446 upon meta-analysis of the combined cohorts. In addition, a group of seven SNPs on chromosome 1q21.3 met threshold for suggestive association (lowest P= 9.35 × 10-7 for rs12045807). Both regions include genes involved in cardiac development-MYH7B/miR499A on chromosome 20 and CTSK, CTSS and ARNT on chromosome 1. Genome-wide heritability analysis using case-control genotyped SNPs suggested that the mean heritability of LSLs attributable to common variants is moderately high ([Formula: see text] range= 0.26-0.34) and consistent with previous assertions. These results provide evidence for the role of common variation in LSLs, proffer new genes as potential biological candidates, and give further insight to the complex genetic architecture of congenital heart disease.

Utility of novel fetal echocardiographic morphometric measures of the aortic arch in the diagnosis of neonatal coarctation of the aorta.

OBJECTIVES: Prenatal diagnosis of neonatal coarctation of the aorta (CoA) is challenging; there is a high false-positive rate, yet 60-80% are not identified prenatally. We aimed to identify novel fetal echocardiographic measures to improve prenatal identification of CoA. METHODS: A retrospective review was conducted of subjects seen from 1/2007-1/2014 with prenatal suspicion for CoA and postnatal follow-up. The last fetal echocardiogram prior to delivery was evaluated for right/left ventricular dimensions, ascending (AAo), transverse (TAo), descending aorta (DAo), aortic isthmus (AoI), ductus arteriosus (DA), and main pulmonary artery diameters, and AoI and DA spectral Doppler. Three novel fetal measurements were performed: left common carotid-to-left subclavian artery distance (LCSA), AAo-DAo angle, and TAo-DAo angle. Postnatal data included diagnosis, surgical approach, and timing. RESULTS: Forty subjects were identified (mean gestational age at fetal echo 32.8 ± 4.2 weeks) with prenatal suspicion for CoA. Comparing subjects with (n = 20) and without CoA (n = 20), significant differences were detected for LCSA, AAo-DAo angle, and TAo-DAo angle (p < 0.0001). An LCSA >4.5 mm (sensitivity 80%,specificity 95%), AAo-DAo angle ≤20.31° (sensitivity 95%,specificity 100%) and TAo-DAo angle ≥96.15°(sensitivity 90%,specificity 100%) identified CoA. CONCLUSIONS: Fetal LCSA, AAo-DAo angle, and TAo-DAo angles are novel measures that can differentiate between subjects with and without CoA.

Comparison of left ventricular function assessment between echocardiography and MRI in Duchenne muscular dystrophy.

BACKGROUND: Cardiomyopathy in Duchenne muscular dystrophy (DMD) is associated with death in approximately 40% of patients. Echocardiography is routinely used to assess left ventricular (LV) function; however, it has limitations in these patients. OBJECTIVE: We compared echocardiographic measures of cardiac function assessment to cardiac MRI. MATERIALS AND METHODS: We included children and young adults with DMD who had MRI performed between January 2010 and July 2015. We measured echocardiographic and MRI parameters of function assessment, including strain. Presence of late gadolinium enhancement (LGE) was assessed by MRI. Subjects were divided into two groups based on MRI left ventricular ejection fraction (LVEF): group I, LVEF ≥55% and group II, LVEF <55%. RESULTS: We included 41 studies in 33 subjects, with 25 in group I and 16 in group II. Mean age of subjects was 13.6 ± 2.8 years and mean duration between echocardiogram and MRI was 7.6 ± 4.1 months. Only 8 of 16 (50%) patients in group II had diminished function on echocardiogram. Echocardiographic images were suboptimal in 16 subjects (39%). Overall, echocardiographic parameters had weak correlation with MRI-derived ejection fraction percentage. MRI-derived myocardial strain assessment has better correlation with MRI ejection fraction as compared to echocardiography-derived strain parameters. CONCLUSION: Echocardiography-based ventricular functional assessment has weak correlation with MRI parameters in children and young adults with Duchenne muscular dystrophy. While this correlation improves in the subset of subjects with adequate echocardiographic image quality, it remains modest and potentially suboptimal for clinical management. Accordingly, we conclude that MRI should be performed routinely and early in children with DMD, not only for LGE imaging but also for functional assessment.

What Makes an Effective Chief of Pediatric Cardiology: Insights From Chiefs of North American Pediatric Programs.

BACKGROUND: Although the position of a pediatric cardiology chief is often seen as the apex of one's academic career, its roles, responsibilities, and qualifications are not well defined in the literature. This study was done to gain further insight of the role and attributes of a pediatric cardiology chief by surveying those who are currently serving the position across North American centers. METHODS AND RESULTS: This was a mixed-methods study with a survey given to North American pediatric cardiology chiefs at programs with fellowship training programs. The survey was a semistructured questionnaire that was independently reviewed by 3 cardiologists. Smaller private practice groups and nonacademic programs were excluded. Survey inventory included items rated on a 5-point Likert scale, open-ended prompts, and targeted questions. A total of 40 of 65 (62%) pediatric cardiology chiefs responded to the survey. Respondents identified key chief attributes included communication skills, honesty/transparency, and conflict-resolution skills. Likert scale data demonstrated participants were satisfied with their position, although many reported growing concerns of increased demands from administration, faculty, and pressures of program performance in the current era. There is also a noted paucity of diversity among those serving in leadership positions within pediatric cardiology, which was acknowledged by survey respondents. CONCLUSIONS: We gathered information directly from current North American pediatric cardiology chiefs examining the current era of its role. There are resounding themes on the emphasis for communication, honesty, conflict resolution, and mentorship. Future studies should examine faculty perceptions and a global perspective of the role.

Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy.

BACKGROUND: The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome randomized to receive atenolol or losartan. We report here the characteristics of the screened population and enrolled subjects. METHODS AND RESULTS: Between 2007 and 2011, 21 clinical sites randomized 608 subjects, aged 6 months to 25 years who met the original Ghent criteria and had a body surface area-adjusted aortic root diameter z-score >3.0. The mean age at study entry was 11.2 years, 60% were male, and 25% were older teenagers and young adults. The median aortic root diameter z-score was 4.0. Aortic root diameter z-score did not vary with age. Mitral valve prolapse and mitral regurgitation were more common in females. Among those with a positive family history, 56% had a family member with aortic surgery, and 32% had a family member with a history of aortic dissection. CONCLUSIONS: Baseline demographic, clinical, and anthropometric characteristics of the randomized cohort are representative of patients in this population with moderate to severe aortic root dilation. The high percentage of young subjects with relatives who have had aortic dissection or surgery illustrates the need for more definitive therapy; we expect that the results of the study and the wealth of systematic data collected will make an important contribution to the management of individuals with Marfan syndrome.

Use of Everolimus to treat cardiac rhabdomyomas and incessant arrhythmias in a newborn: Benefits and complications.

We report treating a term neonate with tuberous sclerosis and giant rhabdomyomas who presented with incessant supraventricular tachycardia with Everolimus. The treatment was efficient in reducing tumor size and assisted as an adjunct therapy in controlling arrhythmia and limiting preexcitation. Treatment was challenged by difficulty to achieve stable drug level and limited by neutropenia as a serious side effect.

Association of common variants in ERBB4 with congenital left ventricular outflow tract obstruction defects.

BACKGROUND: The left ventricular outflow tract (LVOT) defects aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic left heart syndrome (HLHS) represent an embryologically related group of congenital cardiovascular malformations. They are common and cause substantial morbidity and mortality. Prior evidence suggests a strong genetic component in their causation. METHODS: We selected NRG1, ERBB3, and ERBB4 of the epidermal growth factor receptor (EGFR) signaling pathway as candidate genes for investigation of association with LVOT defects based on the importance of this pathway in cardiac development and the phenotypes in knockout mouse models. Single nucleotide polymorphism (SNP) genotyping was performed on 343 affected case-parent trios of European ancestry. RESULTS: We identified a specific haplotype in intron 3 of ERBB4 that was positively associated with the combined LVOT defects phenotype (p=0.0005) and in each anatomic defect AVS, COA, and HLHS separately. Mutation screening of individuals with an LVOT defect failed to identify a coding sequence or splice site change in ERBB4. RT-PCR on lymphoblastoid cells from LVOT subjects did not show altered splice variant ratios among those homozygous for the associated haplotype. CONCLUSION: These results suggest ERBB4 is associated with LVOT defects. Further replication will be required in separate cohorts to confirm the consistency of the observed association.

ASE Statement on Adapting Pediatric, Fetal, and Congenital Heart Disease Echocardiographic Services to the Evolving COVID-19 Pandemic.

Over the 12 months since the start of the coronavirus disease 2019 pandemic, an explosion of investigation and an increase in experience have led to vast improvement in our knowledge about this disease. However, coronavirus disease 2019 remains a huge public health threat.

Coronavirus Disease 2019 (COVID-19) Pandemic Implications in Pediatric and Adult Congenital Heart Disease.

The corona virus disease -2019 (COVID-19) is a recently described infectious disease caused by the severe acute respiratory syndrome corona virus 2 with significant cardiovascular implications. Given the increased risk for severe COVID-19 observed in adults with underlying cardiac involvement, there is concern that patients with pediatric and congenital heart disease (CHD) may likewise be at increased risk for severe infection. The cardiac manifestations of COVID-19 include myocarditis, arrhythmia and myocardial infarction. Importantly, the pandemic has stretched health care systems and many care team members are at risk for contracting and possibly transmitting the disease which may further impact the care of patients with cardiovascular disease. In this review, we describe the effects of COVID-19 in the pediatric and young adult population and review the cardiovascular involvement in COVID-19 focusing on implications for patients with congenital heart disease in particular.

Usefulness of bicuspid aortic valve phenotype to predict elastic properties of the ascending aorta.

Bicuspid aortic valve (BAV) affects about 0.5% to 2% of the population and predisposes patients to aortic dilation and dissection. We hypothesized that aortic size and elastic properties are related to BAV phenotype. In a retrospective study of 158 consecutive patients with BAV referred for echocardiography, the phenotype was defined as anterior-posterior (A-P) leaflet orientation or right-left (R-L) leaflet orientation. The 29 subjects with R-L BAV were matched 1:1 for age, gender, and grade of aortic valve dysfunction with 29 subjects with A-P BAV. Aortic dimensions were measured at the sinuses of Valsalva, ascending aorta, and aortic arch. Distensibility and stiffness index were calculated using cuff blood pressure. Mean age was 41.5 years (range 21 to 67), and 59% were men. Aortic diameter was larger with A-P BAV than R-L at the sinuses (mean +/- 1 SD 3.48 +/- 0.49 vs 3.06 +/- 0.59, p <0 .01) and smaller at the arch (2.34 +/- 0.40 vs 2.83 +/- 0.45, p <0.001). At the sinuses, A-P BAV had a higher stiffness index (median 12.98, range 2.78 to 42.07 vs 6.41, range 2.75 to 59.72, p <0.01) and lower distensibility. Stiffness index in the ascending aorta and arch (but not at the sinus) increased with age. In conclusion, A-P BAV is associated with a larger stiffer sinus of Valsalva and smaller arch diameter. The potential impact of BAV phenotype and aortic elasticity on clinical outcomes merits further study.

Diagnostic Approach in Fetal Coarctation of the Aorta: A Cost-Utility Analysis.

BACKGROUND: Coarctation of the aorta (CoA) is difficult to diagnose by fetal echocardiogram (F-Echo), often requiring multiple F-Echos during gestation and neonatal echocardiograms (N-Echos) after birth. Furthermore, CoA is the most common ductal-dependent lesion missed on routine physical exam. OBJECTIVES: We sought to determine the most cost-effective diagnostic approach in caring for infants in whom an initial F-Echo is concerning for CoA. METHODS: Four paradigms for management after initial F-Echo could not rule out CoA were compared, with a single paradigm involving additional F-Echos: (1) multiple F-Echos for diagnostic clarity and performance of N-Echo on neonates with remaining high suspicion for CoA on F-Echos (prenatal-multiple), (2) no further F-Echo and performance of N-Echo on neonates with high suspicion for CoA on initial F-Echo (postnatal-selective), (3) no further F-Echo and performance of N-Echo on all neonates (postnatal-all), and (4) no further F-Echo or N-Echo with reliance on routine physical exam to identify afflicted infants (postnatal-none). Decision analysis models were constructed. Probabilities dictating clinical course and costs were calculated using our institution's study population. The utility-state values were derived from existing literature. The measure of effectiveness was quality-adjusted life years. To represent societal perspectives, cost was defined as hospital reimbursement payments. RESULTS: From 2007 to 2014 at our institution, 92 patients were diagnosed with CoA and met the inclusion criteria for this study. These patients presented to care either through prenatal diagnosis (n = 31), postnatal examination findings while clinically well (n = 41), or after clinical deterioration in extremis (n = 20), with one patient subsequently dying. Presenting in extremis was associated with a 20% increase in the cost of their subsequent care and with a 51% increase in length of hospital stay. Postnatal-none was the least effective paradigm but also the least costly, thus forming the baseline model. Of the three other diagnostic approaches modeled, Postnatal-all was the cost-effective paradigm, maximizing utility due to avoidance of high-cost/low-utility disease states such as presentation in extremis and death. Prenatal-multiple was the next most effective but was also the most expensive. CONCLUSIONS: Echocardiography is the screening gold standard in avoiding the devastating clinical manifestations of a missed CoA. When a diagnosis of CoA cannot be ruled out on initial F-Echo, the most cost-effective approach is performance of N-Echo on all neonates with no further prenatal evaluation.