Prenatal detection of congenital heart disease: Recent experience across the state of Arizona.

OBJECTIVE: To determine the prenatal detection rate (PDR) of congenital heart disease (CHD) in Arizona as well as describe various factors that may influence detection rates. METHODS: This was a retrospective chart review using the Society of Thoracic Surgeons and Phoenix Children's Fetal Cardiology databases. We included all cases of CHD requiring surgery <1 year of age between 2013 and 2018. A total of 1137 patients met the criteria, and various demographic, socioeconomic, and patient outcome data were collected. RESULTS: The overall PDR was 58% with an improving detection rate over the course of our study, with the final year having a PDR of 67%. Over time, PDR improved in urban communities, but this was not seen in rural communities. Rural address, public insurance, and Native American ethnicity were associated with lower PDR. Postnatal outcomes, including Apgars, initial pH, and lactate, did not differ with the presence of a prenatal diagnosis. Diagnoses typically identified with the outflow tract and 3-vessel views on the fetal echocardiogram were less likely to be detected prenatally. CONCLUSIONS: The PDR of CHD continues to improve with evolving technologies and guidelines. We highlight a discrepancy between urban, rural, and Native American populations. Additionally, by supplying descriptors of missed diagnosis and associated echocardiography views, we hope to provide data for future interventions.

Four-dimensional fetal cardiac imaging in a cohort of fetuses with suspected congenital heart disease.

BACKGROUND: Fetal cardiac magnetic resonance imaging (MRI) requires high spatial and temporal resolution and robustness to random fetal motion to capture the dynamics of the beating fetal heart. Slice-to-volume reconstruction techniques can produce high-resolution isotropic images while compensating for random fetal motion. OBJECTIVE: The objective of this study was to evaluate image quality for slice-to-volume reconstruction of four-dimensional balanced steady-state free precession (bSSFP) imaging of the fetal heart. MATERIALS AND METHODS: A cohort of 13 women carrying fetuses with congenital heart disease were imaged with real-time bSSFP sequences. Real-time bSSFP sequences were post-processed using a slice-to-volume reconstruction algorithm to produce retrospectively gated 4-D sequences with isotropic spatial resolution. Two radiologists evaluated slice-to-volume reconstruction image quality on a scale from 0 to 4 using 11 categories based on a segmental approach to defining cardiac anatomy and pathology. A score of 0 corresponded to cardiac structures not visualized at all and four corresponded to high quality and distinct appearance of structures. RESULTS: In 11 out of 13 cases, the average radiologist score of image quality across all categories was 3.0 or greater. In the remaining two cases, slice-to-volume reconstruction was not possible due to insufficient image quality in the acquisition. CONCLUSION: Slice-to-volume reconstruction has the potential to produce isotropic images with high spatial and temporal resolution that can display the anatomy of the fetal heart in arbitrary imaging planes retrospectively. More rapid, motion-robust acquisitions may be necessary to successfully reconstruct the fetal heart in all patients.

Reducing the burden of surveillance in pregnant women with no history of fetal atrioventricular block using the negative predictive value of anti-Ro/SSA antibody titers.

BACKGROUND: The risk of fetal atrioventricular block in anti-Ro/SSA antibody-exposed pregnancies with no previous affected offspring is approximately 2%. A high antibody titer is necessary but not sufficient for atrioventricular block, and specific antibody titers do not predict risk. However, there are no data on the negative predictive value of antibody titer to identify pregnancies at low risk of fetal atrioventricular block, and may not require surveillance. OBJECTIVE: This study aimed to define anti-Ro52 and anti-Ro60 antibody thresholds for the identification of fetuses unlikely to develop atrioventricular block using clinically validated and research laboratory tests. STUDY DESIGN: This study performed a multicenter review of pregnant subjects who tested positive in their local commercial laboratories for anti-Ro/SSA antibodies at the University of Colorado Children's Hospital (2014-2021) and Phoenix Children's Hospital (2014-2021) and enrolled in the Research Registry for Neonatal Lupus (RRNL) at New York University Langone Medical Center (2002-2021). The subjects were referred on the basis of rheumatologic symptoms or history of atrioventricular block in a previous pregnancy and were retrospectively grouped on the basis of pregnancy outcome. Group 1 indicated no fetal atrioventricular block in current or past pregnancies; group 2 indicated fetal atrioventricular block in the current pregnancy; and group 3 indicated normal current pregnancy but with fetal atrioventricular block in a previous pregnancy. Maternal sera were analyzed for anti-Ro52 and anti-Ro60 antibodies using a clinically validated multiplex bead assay (Associated Regional and University Pathologists Laboratories, Salt Lake City, UT) and a research enzyme-linked immunosorbent immunoassay (New York University). This study calculated the negative predictive value separately for anti-Ro52 and anti-Ro60 antibodies and for the 2 combined using a logistic regression model and a parallel testing strategy. RESULTS: This study recruited 270 subjects (141 in group 1, 66 in group 2, and 63 in group 3). Of note, 89 subjects in group 1 had data on hydroxychloroquine treatment: anti-Ro/SSA antibody titers were no different between those treated (n=46) and untreated (n=43). Mean anti-Ro52 and anti-Ro60 titers were the lowest in group 1 and not different between groups 2 and 3. No case of fetal atrioventricular block developed among subjects with anti-Ro52 and anti-Ro60 titers of <110 arbitrary units per milliliter using the multiplex bead assay of the Associated Regional and University Pathologists Laboratories (n=141). No case of fetal atrioventricular block developed among subjects with research laboratory anti-Ro52 titers of <650 and anti-Ro60 of <4060 enzyme-linked immunosorbent immunoassay units (n=94). Using these 100% negative predictive value thresholds, more than 50% of the anti-Ro/SSA antibody pregnancies that ultimately had no fetal atrioventricular block could be excluded from surveillance based on clinical and research titers, respectively. CONCLUSION: Study data suggested that there is a clinical immunoassay level of maternal anti-Ro/SSA antibodies below which the pregnancy is at low risk of fetal atrioventricular block. This study speculated that prospectively applying these data may avert the costly serial echocardiograms currently recommended for all anti-Ro/SSA-antibody positive pregnancies and guide future management.

Contribution of fetal magnetic resonance imaging in fetuses with congenital heart disease.

BACKGROUND: Increasing evidence supports an association among congenital heart disease (CHD), structural brain lesions on neuroimaging, and increased risk of neurodevelopmental delay and other structural anomalies. Fetal MRI has been found to be effective in demonstrating fetal structural and developmental abnormalities. OBJECTIVE: To determine the contribution of fetal MRI to identifying cardiovascular and non-cardiovascular anomalies in fetuses with CHD compared to prenatal US and fetal echocardiography. MATERIALS AND METHODS: We performed a retrospective study of fetuses with CHD identified by fetal echocardiography. Exams were performed on 1.5-tesla (T) or 3-T magnets using a balanced turbo field echo sequence triggered by an external electrocardiogram simulator with a fixed heart rate of 140 beats per minute (bpm). Fetal echocardiography was performed by pediatric cardiologists and detailed obstetrical US by maternal-fetal medicine specialists prior to referral to MRI. We compared the sensitivity of fetal MRI and fetal echocardiography for the diagnosis of cardiovascular anomalies, as well as the sensitivity of fetal MRI and referral US for the diagnosis of non-cardiac anomalies. We performed statistical analysis using the McNemar test. RESULTS: We identified 121 anomalies in 31 fetuses. Of these, 73 (60.3%) were cardiovascular and 48 (39.7%) involved other organ systems. Fetal echocardiography was more sensitive for diagnosing cardiovascular anomalies compared to fetal MRI, but the difference was not statistically significant (85.9%, 95% confidence interval [CI] 77.8-94.0% vs. 77.5%, 95% CI 67.7-87.2%, respectively; McNemar test 2.29; P=0.13). The sensitivity of fetal MRI was higher for diagnosing extracardiac anomalies when compared to referral US (84.1%, 95% CI 73.3-94.9% vs. 31.8%, 95% CI 18.1-45.6%, respectively; McNemar test 12.9; P<0.001). The additional information provided by fetal MRI changed prognosis, counseling or management for 10/31 fetuses (32.2%), all in the group of 19 fetuses with anomalies in other organs and systems besides CHD. CONCLUSION: Fetal MRI performed in a population of fetuses with CHD provided additional information that altered prognosis, counseling or management in approximately one-third of the fetuses, mainly by identifying previously unknown anomalies in other organs and systems.

Prospective Evaluation of High Titer Autoantibodies and Fetal Home Monitoring in the Detection of Atrioventricular Block Among Anti-SSA/Ro Pregnancies.

OBJECTIVE: This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti-SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second-degree atrioventricular block (AVB). METHODS: Women with anti-SSA/Ro autoantibodies by commercial testing were stratified into high and low anti-52-kD and/or 60-kD SSA/Ro titers applying at-risk thresholds defined by previous evaluation of AVB pregnancies. The high-titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17-26 weeks. Abnormal FHRM prompted urgent echocardiography to identify AVB. RESULTS: Anti-52-kD and/or 60-kD SSA/Ro met thresholds for monitoring in 261 of 413 participants (63%); for those, AVB frequency was 3.8%. No cases occurred with low titers. The incidence of AVB increased with higher levels, reaching 7.7% for those in the top quartile for anti-60-kD SSA/Ro, which increased to 27.3% in those with a previous child who had AVB. Based on levels from 15 participants with paired samples from both an AVB and a non-AVB pregnancy, healthy pregnancies were not explained by decreased titers. FHRM was considered abnormal in 45 of 30,920 recordings, 10 confirmed AVB by urgent echocardiogram, 7 being second-degree AVB, all <12 hours from normal FHRM and within another 0.75 to 4 hours to echocardiogram. The one participant with second/third-degree and two participants with third-degree AVB were diagnosed by urgent echocardiogram >17 to 72 hours from an FHRM. Surveillance echocardiograms detected no AVB when the preceding interval FHRM recordings were normal. CONCLUSION: High-titer antibodies are associated with an increased incidence of AVB. Anti-SSA/Ro titers remain stable over time and do not explain the discordant recurrence rates, suggesting that other factors are required. Fetal heart rate and rhythm (FHRM) with results confirmed by a pediatric cardiologist reliably detects conduction abnormalities, which may reduce the need for serial echocardiograms.

Congenitally Corrected Transposition of the Great Arteries: Fetal Diagnosis, Associations, and Postnatal Outcome: A Fetal Heart Society Research Collaborative Study.

Background Fetal diagnosis of congenitally corrected transposition of the great arteries (ccTGA) has been increasingly reported; however, predictors of clinical outcomes remain underexplored. We undertook a multicenter, retrospective study to investigate natural history, associated anomalies, and outcomes of fetal ccTGA. Methods and Results Fetuses with ccTGA diagnosed from January 2004 to July 2020 within 20 North American programs were included. Fetuses with severe ventricular hypoplasia thought to definitively preclude biventricular repair were excluded. We included 205 fetuses diagnosed with ccTGA at a median gestational age of 23 (interquartile range, 21-27) weeks. Genetic abnormalities were found in 5.9% tested, with extracardiac anomalies in 6.3%. Associated cardiac defects were diagnosed in 161 (78.5%), with atrioventricular block in 23 (11.3%). On serial fetal echocardiogram, 39% demonstrated a functional or anatomic change, most commonly increased tricuspid regurgitation (6.7%) or pulmonary outflow obstruction (11.1%). Of 194 fetuses with follow-up, 26 were terminated, 3 experienced fetal death (2 with atrioventricular block), and 165 were live-born. Of 158 with postnatal data (median follow-up 3.7 years), 10 (6.6%) had death/transplant before 1 year. On univariable analysis, fetal factors associated with fetal death or death/transplant by 1 year included ≥ mild tricuspid regurgitation, pulmonary atresia, aortic obstruction, fetal arrhythmia, and worsening hemodynamics on serial fetal echocardiogram (defined as worse right ventricular function, tricuspid regurgitation, or effusion). Conclusions Associated cardiac lesions and arrhythmias are common in fetal ccTGA, and functional changes commonly occur through gestation. Worse outcomes are associated with fetal tricuspid regurgitation (≥mild), any arrhythmia, pulmonary atresia, aortic obstruction, and worsening hemodynamics on serial echocardiograms. These findings can inform prenatal counseling and perinatal management planning.

Telehealth multidisciplinary prenatal consultation during the COVID-19 pandemic: enhancing patient care coordination while maintaining high provider satisfaction.

OBJECTIVE: Comprehensive fetal care centers address congenital anomalies by developing pre- and post-natal care plans in a multidisciplinary format. To reduce exposure during the Coronavirus Infectious Disease-2019 (COVID-19) pandemic, the Centers for Medicare & Medicaid Services (CMS) broadened access to telehealth services. We assessed provider satisfaction with the rapid transition from in-person prenatal visits to multidisciplinary consultations via telehealth as an adaptive response to the pandemic. METHODS: Patients referred to an urban academic fetal care center during the first 6 weeks of the COVID-19 pandemic underwent advanced imaging including fetal MRI, focused ultrasound, and fetal echocardiography. Subsequently, multidisciplinary telehealth consultations occurred with all providers attending virtually. Patients were given the option of attending the multidisciplinary telehealth consultation in a conference room in the hospital or from home. During these meetings, relevant images were reviewed with all participants via screen sharing through a secure video platform. Provider satisfaction with the telehealth paradigm was assessed using an electronic survey. RESULTS: Twenty-two surveys were administered with a response rate of 82%. 89% of providers were highly satisfied with the telehealth format. 72% of providers would prefer the multidisciplinary telehealth format to an in-person visit for future visits after COVID-19 restrictions are lifted. 22% of providers would leave the choice to the patient's family. One provider preferred in-person visits. Some providers noted that virtual conferences limited the ability to draw pictures, show educational materials, and provide emotional support. CONCLUSION: Providers were overwhelmingly supportive of continuing multidisciplinary telehealth conferences for complex prenatal consultations, even after restrictions are lifted, which has led to the continuation of this model for the duration of the pandemic. Providers highlighted the convenience and improved care coordination across specialties. Further studies to examine the patient experience with virtual consultations are warranted.

Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants.

BACKGROUND: The FUEL trial (Fontan Udenafil Exercise Longitudinal) demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle function in this cohort has not been studied. METHODS: The 400 enrolled participants were randomized 1:1 to udenafil or placebo. Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil/placebo. Linear regression compared change from baseline indices of single ventricle systolic, diastolic and global function, atrioventricular valve regurgitation, and mean Fontan fenestration gradient in the udenafil cohort versus placebo, controlling for ventricular morphology (left ventricle versus right ventricle/other) and baseline value. RESULTS: The udenafil participants (n=191) had significantly improved between baseline and 26 weeks visits compared to placebo participants (n=195) in myocardial performance index (P=0.03, adjusted mean difference [SE] of changes between groups -0.03[0.01]), atrioventricular valve inflow peak E (P=0.009, 3.95 [1.50]), and A velocities (P=0.034, 3.46 [1.62]), and annular Doppler tissue imaging-derived peak e' velocity (P=0.008, 0.60[0.23]). There were no significant differences in change in single ventricle size, systolic function, atrioventricular valve regurgitation severity, or mean fenestration gradient. Participants with a dominant left ventricle had significantly more favorable baseline values of indices of single ventricle size and function (lower volumes and areas, E/e' ratio, systolic:diastolic time and atrioventricular valve regurgitation, and higher annular s' and e' velocity). CONCLUSIONS: FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort. REGISTRATION: URL: https://clinicaltrials.gov; Unique Identifier: NCT02741115.

Contemporary Outcomes in Tetralogy of Fallot With Absent Pulmonary Valve After Fetal Diagnosis.

Background Tetralogy of Fallot with absent pulmonary valve is associated with high mortality, but it remains difficult to predict outcomes prenatally. We aimed to identify risk factors for mortality in a large multicenter cohort. Methods and Results Fetal echocardiograms and clinical data from 19 centers over a 10-year period were collected. Primary outcome measures included fetal demise and overall mortality. Of 100 fetuses, pregnancy termination/postnatal nonintervention was elected in 22. Of 78 with intention to treat, 7 (9%) died in utero and 21 (27%) died postnatally. With median follow-up of 32.9 months, no deaths occurred after 13 months. Of 80 fetuses with genetic testing, 46% had chromosomal abnormalities, with 22q11.2 deletion in 35%. On last fetal echocardiogram, at a median of 34.6 weeks, left ventricular dysfunction independently predicted fetal demise (odds ratio [OR], 7.4; 95% CI 1.3, 43.0; P=0.026). Right ventricular dysfunction independently predicted overall mortality in multivariate analysis (OR, 7.9; 95% CI 2.1-30.0; P=0.002). Earlier gestational age at delivery, mediastinal shift, left ventricular/right ventricular dilation, left ventricular dysfunction, tricuspid regurgitation, and Doppler abnormalities were associated with fetal and postnatal mortality, although few tended to progress throughout gestation on serial evaluation. Pulmonary artery diameters did not correlate with outcomes. Conclusions Perinatal mortality in tetralogy of Fallot with absent pulmonary valve remains high, with overall survival of 64% in fetuses with intention to treat. Right ventricular dysfunction independently predicts overall mortality. Left ventricular dysfunction predicts fetal mortality and may influence prenatal management and delivery planning. Mediastinal shift may reflect secondary effects of airway obstruction and abnormal lung development and is associated with increased mortality.

Value of plasma B-type natriuretic peptide as a marker for rejection in pediatric heart transplant recipients.

We analyzed 211 consecutive plasma B-type natriuretic peptide (BNP) measurements in 59 pediatric heart transplant patients along with echocardiographic and right ventricular endomyocardial biopsy samples. Patients with a biopsy specimen negative for rejection had significantly lower BNP levels than those patients with a biopsy positive (p

Hybrid procedure as treatment for large obstructive left ventricular rhabdomyoma.

We present one of the first reported cases of a neonate with a prenatal diagnosis of large left ventricular rhabdomyoma obstructing the outflow tract that underwent a hybrid procedure with stenting of the patent duct arteriosus and bilateral pulmonary artery banding.

B-type natriuretic peptide monitoring in the Pediatric ICU population.

The natriuretic peptide system plays an active role in the regulation of fluid balance and systemic vascular resistance. Assays of these peptides are now available and may be used for both diagnostic and prognostic purposes. Despite its primary use in adults, it may have a diagnostic role in the Pediatric ICU as well. The basic physiology of the natriuretic system is discussed and the potential applications of B-type natriuretic peptide (BNP) monitoring as a diagnostic tool in various clinical scenarios in infants and children in the Pediatric ICU setting is reviewed.

Delayed magnetic resonance imaging contrast enhancement of synthetic ventricular septum.

This is a report of a magnetic resonance imaging with delayed contrast enhancement on an adult patient with double-inlet left ventricle and L-transposition of the great arteries who has undergone staged ventricular septation in childhood. This report is unique demonstration of delayed contrast enhancement of the synthetic Teflon septum.