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.

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.

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.

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.

Pediatric Appropriate Use Criteria for Outpatient Echocardiography: Practice Variations among Pediatric Cardiologists, Noncardiologist Subspecialists, and Primary Care Providers.

BACKGROUND: The first pediatric appropriate use criteria (AUC) address the use of initial transthoracic echocardiography in outpatients by all ordering providers. The aim of this study was to appraise the performance of the AUC across pediatric cardiologists, noncardiologist subspecialists, and primary care providers (PCPs). A further aim was to describe the variations in ordering patterns of different groups of practitioners, which could serve as the basis for targeted quality improvement activities. METHODS: Electronic health records for Seattle Children's Hospital and its four regional sites were retrospectively reviewed for initial transthoracic echocardiographic studies performed on patients aged ≤18 years. A sample of 1,000 consecutive studies and a sample of 1,514 studies in which studies ordered by noncardiologists were enriched were reviewed. The ordering provider type, study indication, and findings (normal, incidental, or abnormal) were classified. Indications mapped to three categories: appropriate (A), may be appropriate (M), and rarely appropriate (R). If multiple indications were documented, the highest level of appropriateness was used. RESULTS: In the consecutive sample, pediatric cardiologists ordered 81%, noncardiologist subspecialists 13%, and PCPs 5% of the total studies. In the enriched sample, only 4% were unclassifiable by the AUC. Abnormal findings were identified in 23% of A, 13% of M, and 9% of R studies (P = .03). Appropriateness varied among the three groups of providers (P < .001). For pediatric cardiologists, 67% of studies were indication category A, 13% M, and 14% R. Noncardiologist subspecialists ordered the highest percentage of A studies (88%) and the lowest percentage of R studies (1%). PCPs had the highest percentage of R indications (18%), and 23% could not be fully classified, because of insufficient order information. Yield of abnormal findings was highest for subspecialists (23%), intermediate for cardiologists (19%), and lowest for PCPs (15%; P = .03). CONCLUSIONS: The AUC performed well across all provider types, as measured by the low percentage of unclassifiable indications and the observed relationship between greater appropriateness and higher yield of abnormal findings. The three provider types differed in appropriateness rates and had distinct ordering patterns, which could form the basis for future targeted quality improvement efforts.

Fatal spontaneous dissection of a Contegra conduit in a child.

The Contegra bovine jugular vein conduit (Medtronic, Minneapolis, MN) is one of the most widely used grafts for surgical reconstruction of the right ventricular outflow tract in both pediatric and adult patients with congenital heart disease. In this report, we describe a case of acute dissection of a neointimal peel in a Contegra conduit resulting in conduit stenosis and death of a child.

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.

Echocardiographic methods, quality review, and measurement accuracy in a randomized multicenter clinical trial of Marfan syndrome.

BACKGROUND: The Pediatric Heart Network is conducting a large international randomized trial to compare aortic root growth and other cardiovascular outcomes in 608 subjects with Marfan syndrome randomized to receive atenolol or losartan for 3 years. The authors report here the echocardiographic methods and baseline echocardiographic characteristics of the randomized subjects, describe the interobserver agreement of aortic measurements, and identify factors influencing agreement. METHODS: Individuals aged 6 months to 25 years who met the original Ghent criteria and had body surface area-adjusted maximum aortic root diameter (ROOTmax) Z scores > 3 were eligible for inclusion. The primary outcome measure for the trial is the change over time in ROOTmaxZ score. A detailed echocardiographic protocol was established and implemented across 22 centers, with an extensive training and quality review process. RESULTS: Interobserver agreement for the aortic measurements was excellent, with intraclass correlation coefficients ranging from 0.921 to 0.989. Lower interobserver percentage error in ROOTmax measurements was independently associated (model R(2) = 0.15) with better image quality (P = .002) and later study reading date (P < .001). Echocardiographic characteristics of the randomized subjects did not differ by treatment arm. Subjects with ROOTmaxZ scores ≥ 4.5 (36%) were more likely to have mitral valve prolapse and dilation of the main pulmonary artery and left ventricle, but there were no differences in aortic regurgitation, aortic stiffness indices, mitral regurgitation, or left ventricular function compared with subjects with ROOTmaxZ scores < 4.5. CONCLUSIONS: The echocardiographic methodology, training, and quality review process resulted in a robust evaluation of aortic root dimensions, with excellent reproducibility.

Prepregnancy body mass index and congenital heart defects among offspring: a population-based study.

OBJECTIVE: The purpose of this study was to evaluate the association between fetal development of congenital heart defects (CHD) and maternal prepregnancy body mass index (BMI, kg/m(2)) in the largest population-based case-control study to date. BACKGROUND: Mounting evidence implicates maternal obesity as a risk factor for birth defects. However, the association between maternal obesity and CHD in offspring has been less completely described. METHODS: We conducted a study of CHD using linked birth-hospital discharge records for Washington State between 1992-2007. All infants with CHD (n = 14,142) were identified based on ICD9-CM discharge diagnosis codes. 141,420 controls, frequency matched on year of delivery, were selected at random from among infants without CHD. Maternal BMI was calculated from maternal prepregnancy data. Odds ratios (OR) and 95% confidence intervals (CI) for the association of CHD relative to maternal BMI were calculated, adjusted for gestational diabetes. RESULTS: Infants with CHD were more likely to have an obese mother (OR 1.22, 95% CI 1.15-1.30). The strength of association increased with increasing BMI (BMI 30-34.9: OR 1.16, 95% CI 1.07-1.25; BMI 35-39.9: OR 1.25, 95% CI 1.13-1.39; BMI > = 40: OR 1.49, 95% CI 1.32-1.69). The association was greatest for left and right ventricular outflow tract defects (OR 1.27, 95% CI 1.02-1.59 and OR 1.43, 95% CI 1.20-1.69, respectively). Hypoplastic left heart syndrome was markedly associated (OR 1.86, 95% CI 1.13-3.05). There was no association with conotruncal defects (OR 1.04, 95% CI: 0.82-1.33). CONCLUSIONS: We confirmed the association between CHD and maternal obesity and observed increasing risk with increasing obesity. Outflow tract defects appear uniquely associated. A greater risk of CHD among offspring is an important outcome of maternal obesity, and suggests a need for targeted medical management strategies.

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.

Aortic root dilatation is a rare complication of Noonan syndrome.

Molecular analysis of the gene encoding the protein tyrosine phospatase, nonreceptor type 11 (PTPN11), identified a single base change at nucleotide 228 in an individual manifesting Noonan syndrome with aortic root widening and dysplastic aortic and mitral valves. This missense mutation changes glutamate to aspartate at position 76 of the protein (E76D or Glu76Asp), which likely disrupts intramolecular hydrogen bonding of this protein. There are few reports of aortic root dilatation in Noonan syndrome, and to our knowledge this is the first case with a confirmed PTPN11 mutation.

Echocardiographic evaluation of asymptomatic parental and sibling cardiovascular anomalies associated with congenital left ventricular outflow tract lesions.

OBJECTIVE: Left ventricular outflow tract obstructive (LVOTO) malformations are a leading cause of infant mortality from birth defects. Genetic mechanisms are likely, and there may be a higher rate of asymptomatic LVOTO anomalies in relatives of affected children. This study sought to define the incidence of cardiac anomalies in first-degree relatives of children with congenital aortic valve stenosis (AVS), coarctation of the aorta (CoA), and hypoplastic left heart syndrome (HLHS). METHODS: A total of 113 probands with a nonsyndromic LVOTO malformation of AVS (n = 25), BAV (n = 3), CoA (n = 52), HLHS (n = 30), and aortic hypoplasia with mitral valve atresia (n = 2) were ascertained through chart review or enrolled at the time of diagnosis. Echocardiography was performed on 282 asymptomatic first-degree relatives. RESULTS: Four studies had poor acoustic windows, leaving 278 studies for analysis. BAV were found in 13 (4.68%) first-degree relatives. The relative risk of BAV in the relatives was 5.05 (95% confidence interval: 2.2-11.7), and the broad sense heritability was 0.49, based on a general population frequency of 0.9%. BAV was more common in multiplex families compared with sporadic cases. An additional 32 relatives had anomalies of the aorta, aortic valve, left ventricle, or mitral valve. CONCLUSIONS: The presence of an LVOTO lesion greatly increases the risk of identifying BAV in a parent or sibling, providing additional support for a complex genetic cause. The parents and siblings of affected patients should be screened by echocardiography as the presence of an asymptomatic BAV may carry a significant long-term health risk.

Genotype-phenotype correlation in congenital heart disease.

PURPOSE OF REVIEW: The understanding of the etiology of congenital cardiac lesions is rapidly progressing from the recognition of embryologic origins to insight into the genetic basis for these disorders. Concurrently, in this era, great effort is being expended to gather data that will generate clinically useful genotype-phenotype correlation. This rapidly evolving area of inquiry, in which the clinical implications of mutation status are fully explored, makes available information applicable to those involved in all aspects of congenital cardiac disease. RECENT FINDINGS: Three syndromes with cardiovascular phenotypes were selected for review. Each has received a great deal of attention in the recent past based on improved understanding of the range of mutations expressed and the relation of these mutations to clinical findings. These three syndromes--Noonan, Marfan, and long QT syndrome--span the range of congenital heart disease and provide examples of genotype-phenotype correlation. SUMMARY: Better understanding of the clinical implications of specific mutations should allow not only for more sensitive and specific diagnoses to be made but also for improvements in therapeutic options and efficacy.

Pulmonary-to-systemic blood flow ratio effects of sevoflurane, isoflurane, halothane, and fentanyl/midazolam with 100% oxygen in children with congenital heart disease.

UNLABELLED: The cardiovascular effects of volatile anesthetics in children with congenital heart disease have been studied, but there are limited data on the effects of anesthetics on pulmonary-to-systemic blood flow ratio (Qp:Qs) in patients with intracardiac shunting. In this study, we compared the effects of halothane, isoflurane, sevoflurane, and fentanyl/midazolam on Qp:Qs and myocardial contractility in patients with atrial (ASD) or ventricular (VSD) septal defects. Forty patients younger than 14 yr old scheduled to undergo repair of ASD or VSD were randomized to receive halothane, sevoflurane, isoflurane, or fentanyl/midazolam. Cardiovascular and echocardiographic data were recorded at baseline, randomly ordered 1 and 1.5 mean alveolar anesthetic concentration (MAC) levels, or predicted equivalent fentanyl/midazolam plasma levels. Ejection fraction (using the modified Simpson's rule) was calculated. Systemic (Qs) and pulmonary (Qp) blood flow was echocardiographically assessed by the velocity-time integral method. Qp:Qs was not significantly affected by any of the four regimens at either anesthetic level. Left ventricular systolic function was mildly depressed by isoflurane and sevoflurane at 1.5 MAC and depressed by halothane at 1 and 1.5 MAC. Sevoflurane, halothane, isoflurane, or fentanyl/midazolam in 1 or 1.5 MAC concentrations or their equivalent do not change Qp:Qs in patients with isolated ASD or VSD. IMPLICATIONS: Sevoflurane, halothane, isoflurane, and fentanyl/midazolam do not change pulmonary-to-systemic blood flow ratio in children with atrial and ventricular septal defects when administered at standard anesthetic doses with 100% oxygen.