Prenatal Diagnosis Rate of Critical Congenital Heart Disease Remains Inadequate with Significant Racial/Ethnic and Socioeconomic Disparities and Technical Barriers.

Prenatal diagnosis (preDx) of critical congenital heart disease (CCHD) decreases neonatal morbidity and mortality. Obstetrical fetal cardiac imaging guidelines in 2013 aimed to increase preDx. The objectives of this study were to determine the contemporary preDx rate of CCHD and identify maternal-fetal factors and variations in prenatal care that may be potential barriers. This retrospective single center study evaluated maternal demographics and characteristics of infants with CCHD (requiring cardiac catheterization or surgical intervention before 6 months-old) between 2016 and 2019. 58% of the 339 infants with CCHD had preDx. Infants with preDx were more likely to have mothers ≥ 35 years-old (p = 0.028), family history of CHD (p = 0.017), health insurance (p = 0.002), or anatomic scan with perinatology (p < 0.001). Hispanic infants were less likely to have preDx (45.6%, p = 0.005). PreDx rates were higher in infants with extracardiac/genetic anomalies (p < 0.001) and significantly different between CCHD subtypes (76% for single ventricle, 51% for biventricular/four-chamber view, 59% for proximal outflow tract anomalies, and 48% for distal great artery anomalies; p = 0.024). In infants without preDx, 25% of their mothers had indication for, but did not undergo, fetal echocardiography. PreDx rates of CCHD remains inadequate across subtypes detectable by standard fetal cardiac screening views, particularly in uninsured and Hispanic communities.

Minute Stroke Distance Is a More Reproducible Measurement Than Cardiac Output in the Assessment of Fetal Ventricular Systolic Function.

BACKGROUND: Echocardiographic quantification of fetal cardiac output (CO) aids clinical decision-making in the management of various cardiac and extracardiac diseases. Small variability in measuring semilunar valve dimension significantly reduces the reproducibility of the calculated CO. The authors propose minute stroke distance or velocity-time integral (VTI) as a more reproducible measure reflecting fetal ventricular systolic function. The aim of this study was to test the hypothesis that right and left ventricular minute VTI increase predictably with estimated fetal weight and are more reproducible than CO. METHODS: Five hundred seventy-one singleton fetuses without cardiovascular pathology between 16 and 36 weeks' gestation were reviewed retrospectively. Twenty-two fetuses with pathology resulting in low- or high-CO states were also assessed for comparison. VTI was measured in both ventricular outflow tracts at the level of the semilunar valve, excluding a Doppler insonation angle of >30°. Heart rate, semilunar valve dimension, and VTI determined minute VTI and CO. Inter- and intrarater variability were evaluated in a random 10% subset. RESULTS: Minute VTI and CO measurements were feasible in 67% to 89% of fetuses in this retrospective study. Minute VTI and CO increased with estimated fetal weight nonlinearly (R = 0.61-0.94). The mean inter- and intrarater variability for VTI, 6% and 5.7%, were significantly less than for CO, 25% and 23.7% (P < .001 for all). CONCLUSIONS: Minute VTI is an easily measured, highly reproducible method of quantifying fetal ventricular systolic function. Variability in calculated CO from valve measurement differences is minimized by solely using VTI. Nomograms of minute VTI provide an efficient and precise assessment of fetal systolic function and may be used to track fetuses in disease states with low or high CO.

Prenatal diagnosis of congenital heart defects: echocardiography.

Congenital heart defects (CHD) are the most common congenital anomaly, and the majority can be diagnosed during prenatal life. Prenatal detection rates remain highly variable, as most CHD occur in low risk pregnancies and therefore depend on the maternal obstetric provider to recognize fetal cardiac abnormality on obstetric screening anatomic ultrasound. Fetuses with abnormal findings on obstetric screening anatomic ultrasound and/or risk factors for cardiac disease should be referred for evaluation with fetal echocardiography. Fetal echocardiography should be performed by specialized sonographers and interpreted by physicians with knowledge of evolving fetal cardiac anatomy and physiology throughout gestation. A fetal echocardiography examination, which can be done from the late first trimester onward, utilizes a standardized and systemic approach to diagnose fetuses with CHD or other forms of primary or secondary cardiac disease. The field of fetal cardiology has advanced past the accurate prenatal diagnosis of simple and complex CHD, as fetal echocardiography enables understanding of dynamic fetal cardiac physiology and consideration of potential fetal/neonatal treatment. The greatest impact of fetal echocardiography remains identification of critical CHD before birth to allow immediate cardiac management after delivery to decrease neonatal morbidity and mortality. Analyzing the severity of abnormal cardiac physiology in various forms of CHD before birth allows the fetal cardiologist to prognosticate effects on the developing fetus, predict risk of postnatal hemodynamic instability, guide delivery planning through multidisciplinary collaboration, and anticipate how the disease will impact the neonate after delivery.

Effect of In Utero Non-Steroidal Anti-Inflammatory Drug Therapy for Severe Ebstein Anomaly or Tricuspid Valve Dysplasia (NSAID Therapy for Fetal Ebstein anomaly).

Ebstein anomaly (EA) and tricuspid valve dysplasia (TVD) are rare congenital malformations associated with nearly 50% mortality when diagnosed in utero. The diseases often produce severe tricuspid regurgitation (TR) in the fetus and in some cases, pulmonary regurgitation (PR) and circular shunting ensue. Since the ductus arteriosus (DA) plays a critical role in the circular shunt and may be constricted by transplacental nonsteroidal anti-inflammatory drugs (NSAIDs), we sought to assess the effect of NSAIDs on fetuses with EA/TVD. We reviewed mothers of singleton fetuses with EA/TVD and PR, indicative of circular shunting, who were offered NSAIDs at multiple centers from 2010 to 2018. Initial dosing consisted of indomethacin, followed by ibuprofen in most cases. Twenty-one patients at 10 centers were offered therapy at a median gestational age (GA) of 30.0 weeks (range: 20.9 to 34.9). Most (15/21 = 71%) mothers received NSAIDs, and 12 of 15 (80%) achieved DA constriction after a median of 2.0 days (1.0 to 6.0). All fetuses with DA constriction had improved PR; 92% had improved Doppler patterns. Median GA at pregnancy outcome (live-birth or fetal demise) was 36.1 weeks (30.7 to 39.0) in fetuses with DA constriction versus 33 weeks (23.3 to 37.3) in fetuses who did not receive NSAIDs or achieve DA constriction (p = 0.040). Eleven of 12 patients (92%) with DA constriction survived to live-birth, whereas 4 of 9 patients (44%) who did not receive NSAIDs or achieve DA constriction survived (p = 0.046). In conclusion, our findings demonstrate the proof of concept that NSAIDs mitigate circular shunt physiology by DA constriction and improve PR among fetuses with severe EA/TVD. Although the early results are encouraging, further investigation is necessary to determine safety and efficacy.

Detailed Fetal Anatomic Ultrasound Examination: Effect of the 2014 Consensus Report on a Tertiary Referral Center.

This study evaluates the impact of extended cardiac views on examination time, repeat imaging, and anomaly detection before and after implementation of 76811 guidelines (American Institute of Ultrasound in Medicine Consensus 2014). It is a retrospective study of singleton pregnancies undergoing detailed ultrasound imaging at 18 weeks' gestation or greater before and after the protocol change in an academic, tertiary care fetal center. Views required prior to 2014: 4-chamber, left outflow tract, right outflow tract. Additional views required after 2014: bicaval, aortic arch, 3-vessel, and 3-vessel trachea. Fetuses with known anomalies were excluded. Rates of detection of congenital heart disease (CHD), examination completion, repeat examination recommendation, fetal echocardiogram recommendation, completion by body mass index, and cardiac examination time were determined. Six hundred twenty-four subjects were included, 217 before and 407 after protocol change. Views obtained were as stated in the American Institute of Ultrasound in Medicine/Society for Maternal-Fetal Medicine consensus. Detection of CHD was not improved. Examination times increased by 20% (6.4 vs 7.7 minutes, P < 0.05). Number of incomplete studies increased by 130% (11% to 26%, P < 0.05). Twice as many patients were referred for repeat examination (6% vs 13%, P < 0.05). Completion rates were negatively correlated with body mass index. Recommendations for fetal echocardiogram were unchanged (5% vs 6%, P = 0.6). Additional imaging did not increase detection rate of CHD (3% vs 2%, P = 0.3). Extended cardiac views resulted in increased examination time, more incomplete examinations, and more repeat examinations without changing detection rates of CHD.

Prenatal detection of critical cardiac outflow tract anomalies remains suboptimal despite revised obstetrical imaging guidelines.

BACKGROUND: Fetal echocardiography can accurately diagnose critical congenital heart disease prenatally, but relies on referrals from abnormalities identified on routine obstetrical ultrasounds. Critical congenital heart disease that is frequently missed due to inadequate outflow tract imaging includes anomalies such as truncus arteriosus, double outlet right ventricle, transposition of the great arteries, tetralogy of Fallot, pulmonary stenosis, and aortic stenosis. OBJECTIVE: This study evaluated the prenatal detection rate of critical outflow tract anomalies in a single urban pediatric hospital before and after "AIUM Practice Guideline for the Performance of Obstetric Ultrasound Examinations," which incorporated outflow tract imaging. DESIGN: Infants with outflow tract anomalies who required cardiac catheterization and/or surgical procedure(s) in the first 3 months of life were retrospectively identified. This study evaluated two time periods; pre-guidelines from June 2010 to May 2013 and post-guidelines from January 2015 to June 2016. June 2013-December 2014 was excluded as a theoretical period necessary for obstetrical practices to implement the revised guidelines. RESULTS: Overall, prenatal diagnosis occurred in 55% of infants with critical outflow tract anomalies; of the three most common defects, prenatal diagnosis occurred in 53% of D-transposition of the great arteries, 63% of tetralogy of Fallot, and 80% of double outlet right ventricle patients. Pre-guidelines, prenatal diagnosis occurred in 52% (52 of 102) infants with critical outflow tract anomalies requiring early cardiac intervention. Post-guidelines, prenatal diagnosis occurred in 61% (33 of 54) infants, not significantly different than the prenatal detection rate pre-guidelines (P = .31). CONCLUSIONS: Despite revised obstetrical guidelines highlighting the importance of outflow tract imaging, referrals and prenatal diagnosis of these types of critical congenital heart disease remain low. Education of obstetrical sonographers and practitioners who perform fetal anatomic screening is vital to increase referrals and prenatal detection of critical outflow tract anomalies.

Utility of Echocardiography as Screening for Late-onset Anthracycline-induced Cardiotoxicity in Pediatric Cancer Survivors: Observations from the First Decade After End of Therapy.

Current screening guidelines are available for anthracycline-induced cardiotoxicity. However, the utility of echocardiogram screening for late-onset anthracycline cardiotoxicity especially in the decade immediately after end of therapy is debatable. A retrospective chart review of patients seen in the Thriving after Cancer Clinic at Rady Children's Hospital January 2006 to December 2013 was performed. Treatment data, echocardiogram results, cardiology referral notes and cardiac medication data were abstracted from anthracycline-exposed survivors. Descriptive and univariate comparative statistics were performed. Of 368 patients (45% female, median 5.3 y old at diagnosis [range 0 to 18.3], median 5.0 y from end of therapy [EOT] [range 0 to 18.2]), a total of 4 patients (10-year cumulative incidence after EOT 1.3%; 95% confidence interval, 0.1%-19.7%) required cardiac medication for late-onset cardiotoxicity (>1 y after EOT). Those requiring medication for late-onset cardiotoxicity were exposed to more anthracyclines than survivors without cardiotoxicity (median, 360 mg/m [range, 300 to 375 mg/m] vs. 182 mg/m [range, 26 to 515 mg/m], P=0.009). None had neck or chest radiation. In this population, medication initiation for late-onset anthracycline cardiotoxicity was limited predominantly to the first 3 years after EOT, with the next >13 years after EOT. These findings add to the growing body of literature assessing current guidelines to inform improvements in screening practices of survivorship providers.

Peripheral Endothelial Function After Arterial Switch Operation for D-looped Transposition of the Great Arteries.

Coronary artery re-implantation during arterial switch operation in patients with D-looped transposition of the great arteries (D-TGA) can alter coronary arterial flow and increase shear stress, leading to local endothelial dysfunction, although prior studies have conflicting results. Endothelial pulse amplitude testing can predict coronary endothelial dysfunction by peripheral arterial testing. This study tested if, compared to healthy controls, patients with D-TGA after arterial switch operation had peripheral endothelial dysfunction. Patient inclusion criteria were (1) D-TGA after neonatal arterial switch operation; (2) age 9-29 years; (3) absence of known cardiovascular risk factors such as hypertension, diabetes, hypercholesterolemia, vascular disease, recurrent vasovagal syncope, and coronary artery disease; and (4) ability to comply with overnight fasting. Exclusion criteria included (1) body mass index ≥85th percentile, (2) use of medications affecting vascular tone, or (3) acute illness. We assessed endothelial function by endothelial pulse amplitude testing and compared the results to our previously published data in healthy controls (n = 57). We tested 20 D-TGA patients (16.4 ± 4.8 years old) who have undergone arterial switch operation at a median age of 5 days (0-61 days). Endothelial pulse amplitude testing indices were similar between patients with D-TGA and controls (1.78 ± 0.61 vs. 1.73 ± 0.54, p = 0.73).In our study population of children and young adults, there was no evidence of peripheral endothelial dysfunction in patients with D-TGA who have undergone arterial switch operation. Our results support the theory that coronary arterial wall thickening and abnormal vasodilation reported in these patients is a localized phenomenon and not reflective of overall atherosclerotic burden.

Double trouble: fetal diagnosis of a pulmonary artery sling and vascular ring.

Left pulmonary artery slings and vascular rings are rare congenital anomalies definable by fetal echocardiography. Left pulmonary artery slings are associated with high respiratory morbidity and mortality. Prenatal diagnosis of a left pulmonary artery sling should prompt delivery planning for postnatal management at a pediatric tertiary care center.

Unusual consequence of a fetal atrial septal aneurysm.

We describe the case of a significant fetal atrial septal aneurysm causing left ventricular inflow obstruction. Serial fetal echocardiograms demonstrated potential left heart hypoplasia. The fetal cardiologist guided the perinatal team to electively deliver the infant early and modify the course of developing hypoplastic left heart.

Transcatheter device closure of a congenital aortic-left atrial tunnel.

Rare cases of aortic-left atrial tunnel exist in the literature. This case report highlights the echocardiographic characterization of this vascular anomaly and provides the first description of an aortic-left atrial tunnel closed by interventional cardiac catheterization in a pediatric patient.

Fetal MRI correlates with postnatal CT angiogram assessment of pulmonary anatomy in tetralogy of Fallot with absent pulmonary valve.

In tetralogy of Fallot with absent pulmonary valve, pulmonary stenosis and regurgitation results in significant pulmonary artery dilatation. Branch pulmonary artery dilatation often compresses the tracheobronchial tree, causing fluid trapping in fetal life and air trapping and/or atelectasis after birth. Prenatal diagnosis predicts poor prognosis, which depends on the degree of respiratory insufficiency from airway compromise and lung parenchymal disease after birth. Fetal magnetic resonance imaging (MRI) has been useful in evaluating the effects of congenital lung lesions on lung development and indicating severity of pulmonary hypoplasia. This report is the first demonstrating the utility of fetal MRI in tetralogy of Fallot/absent pulmonary valve patients, which predicted postnatal pulmonary artery size and visualized airway compression and lung parenchymal lesions. The distribution of lobar fluid trapping on fetal MRI correlated with air trapping on postnatal computed tomography angiogram.

Coronary sinus obstruction after atrioventricular canal defect repair.

The coronary sinus can become obstructed with any instrumentation at or near the ostium such as in atrioventricular canal defect repairs. This complication may lead to a wide range of consequences including dyspnea, angina, myocardial infarction, and sudden death. The following report illustrates the importance of careful perioperative echocardiographic evaluation of the coronary sinus in procedures that may affect the sinus and its ostium.

Pediatric plastic bronchitis: case report and retrospective comparative analysis of epidemiology and pathology.

Plastic bronchitis (PB) is a pathologic condition in which airway casts develop in the tracheobronchial tree causing airway obstruction. There is no standard treatment strategy for this uncommon condition. We report an index patient treated using an emerging multimodal strategy of directly instilled and inhaled tissue plasminogen activator (t-PA) as well as 13 other cases of PB at our institution between 2000 and 2012. The majority of cases (n = 8) occurred in patients with congenital heart disease. Clinical presentations, treatments used, histopathology of the casts, and patient outcomes are reviewed. Further discussion is focused on the epidemiology of plastic bronchitis and a systematic approach to the histologic classification of casts. Comorbid conditions identified in this study included congenital heart disease (8), pneumonia (3), and asthma (2). Our institutional prevalence rate was 6.8 per 100,000 patients, and our case fatality rate was 7%.

Decremental left ventricular deformation after pulmonary artery band training and subsequent repair in ventriculoarterial discordance.

BACKGROUND: Patients with ventriculoarterial discordance, such as congenitally corrected and d-transposition of the great arteries, may undergo a morphologic left ventricular (LV) training strategy consisting of surgical pulmonary artery band (PAB) placement and subsequent anatomic repair to establish ventriculoarterial concordance. The purpose of this study was to characterize morphologic LV function and deformation longitudinally using speckle-tracking strain analysis in patients with ventriculoarterial discordance who underwent LV training. METHODS: Twenty-nine patients (12 with d-transposition of the great arteries and 17 with congenitally corrected transposition of the great arteries) who underwent LV training with PAB placement were evaluated retrospectively. LV ejection fraction and global and regional longitudinal strain and strain rate were measured before and 7 ± 5 days after PAB placement and subsequent anatomic repair. RESULTS: PAB placement caused reductions in the mean LV ejection fraction from 76.1 ± 10.2% to 66.7 ± 7.8% (P < .001), in mean global strain from -17.7 ± 9% to -13.3 ± 7.5% (P = .01), and in mean lateral wall strain from -23.3 ± 12.8% to -17.5 ± 10.3% (P = .01). After anatomic repair (a median of 21 months after PAB placement; range, 0.5-104 months), mean LV ejection fraction decreased further from 63.3 ± 8.6% to 52.4 ± 14.9% (P < .05). Mean global strain declined from -17.6% ± 4.4 to -12.6 ± 4% (P = .01), and mean lateral wall strain decreased from -18.2 ± 11.4% to -12.6 ± 5.3% (P = .04). CONCLUSIONS: In patients with ventriculoarterial discordance undergoing PAB placement for LV training and anatomic repair, the morphologic left ventricle demonstrated decremental systolic function and global longitudinal deformation acutely. Frequent functional assessment is warranted to understand long-term myocardial mechanics in these patients.

Myocardial deformation in the fetal single ventricle.

BACKGROUND: In postnatal life, patients with single ventricle (SV) with morphologic right ventricles have a worse prognosis than those with morphologic left ventricles. The aim of this study was to test the hypotheses that (1) the SV in fetuses with SV has decreased longitudinal strain compared with fetuses with normal cardiac anatomy, and (2) fetuses with SV right ventricular (RV) morphology have decreased strain compared with those with SV left ventricular (LV) morphology. METHODS: Fetal echocardiograms with SV RV and SV LV morphology were retrospectively compiled. Postprocessing analysis of the dominant ventricle was done using syngo Velocity Vector Imaging version 2.0. Peak global longitudinal strain (GLS) and global longitudinal strain rate (GL SR) were generated. Both the right and left ventricles were analyzed in fetuses with normal cardiac anatomy for comparison. RESULTS: Fifty-four fetuses with SV (18 with LV morphology and 36 with RV morphology) were included in the study and compared with 54 controls matched for gestational age. Global longitudinal strain and GL SR were compared between fetuses with SV and normal fetuses and among SV subsets. When all four categories were compared (normal left ventricle, normal right ventricle, SV left ventricle, and SV right ventricle), there was no difference in GLS (P = .49) or in GL SR (P = .32) between any of the categories. CONCLUSIONS: Comparable GLS and GL SR values between fetal SV of LV or RV morphology, as well as normal fetal left and right ventricles, reflect in utero preservation of systolic function of the SV heart.

Outcomes of children following a first hospitalization for dilated cardiomyopathy.

BACKGROUND: We hypothesized that children with dilated cardiomyopathy who require hospital admission are at increased risk for death or transplantation during their first hospitalization and in the first year that follows. We also assessed the value of routine data collected during that time to predict death or the need for transplantation prior to discharge and within 1 year of admission. METHODS AND RESULTS: We conducted a retrospective review of 83 pediatric patients with dilated cardiomyopathy whose initial hospitalization fell between 2004 and 2009. The mean age at hospitalization was 7 years. The majority of patients demonstrated moderate or severe left ventricular dysfunction on initial echocardiogram (80%) and/or the need for intravenous inotropes within 7 days of hospital admission (69%). Five patients (6%) died, and 15 (18%) were transplanted in the initial hospitalization. At 1 year, 11/71 (15%) had died, and 27/71 (38%) were transplanted. The overall freedom from death, transplantation, or rehospitalization at 1 year following admission was 21%. Fractional shortening, left ventricular ejection fraction, serum cholesterol, uric acid, mixed venous saturation, and atrial filling pressures were all predictive of death or transplantation during the initial hospitalization. Left ventricular ejection fraction was predictive of death or transplantation at 1 year. CONCLUSIONS: The first hospitalization for dilated cardiomyopathy marks a period of high risk for clinical decline, end stage heart failure, and the need for cardiac transplantation. Echocardiographic function and hemodynamic and serum measurements may aid in predicting outcomes. Despite medical management, most patients will be rehospitalized and/or require cardiac transplantation within 1 year of admission.