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Evaluation of the fetal heart involves two approaches. The first describes a screening protocol in which the heart is imaged in transverse planes that includes the four-chamber view (4CV), left and right outflow tracts, and the 3-vessel-tracheal view. The second approach is a fetal echocardiogram that requires additional cardiac images as well as evaluating ventricular function using diagnostic tools such as M-mode and pulsed Doppler ultrasound. Speckle tracking analysis of the ventricular and atrial endocardium of the fetal heart has focused primarily on computing longitudinal global strain. However, the technology enabling this measurement to occur has recently been adapted to enable the clinician to obtain numerous additional measurements of the size, shape, and contractility of the ventricles and atrial chambers. By using the increased number of measurements derived from speckle tracking analysis, we have reported the ability to screen for tetralogy of Fallot, D-transposition of the great arteries (D-TGA), and coarctation of the aorta by only imaging the 4CV. In addition, we have found that measurements derived from speckle tracking analysis of the ventricular and atrial chambers can be used to compute the risk for emergent neonatal balloon atrial septostomy in fetuses with D-TGA. The purpose of this review is to consolidate our experience in one source to provide perspective on the benefits of speckle tracking analysis to measure the size, shape, and contractility of the ventricles and atria imaged in the 4CV in fetuses with congenital heart defects.
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Coração Fetal , Cardiopatias Congênitas , Contração Miocárdica , Ultrassonografia Pré-Natal , Humanos , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/embriologia , Ultrassonografia Pré-Natal/métodos , Coração Fetal/diagnóstico por imagem , Coração Fetal/fisiopatologia , Contração Miocárdica/fisiologia , Ecocardiografia/métodos , Técnicas de Imagem por Elasticidade/métodos , Interpretação de Imagem Assistida por Computador/métodos , FemininoRESUMO
Fibrillin-1 and fibrillin-2, encoded by FBN1 and FBN2, respectively, play significant roles in elastic fiber assembly, with pathogenic variants causing a diverse group of connective tissue disorders such as Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCD). Different genomic variations may lead to heterogeneous phenotypic features and functional consequences. Recent high-throughput sequencing modalities have allowed detection of novel variants that may guide the care for patients and inform the genetic counseling for their families. We performed clinical phenotyping for two newborn infants with complex congenital heart defects. For genetic investigations, we employed next-generation sequencing strategies including whole-genome Single-Nucleotide Polymorphism (SNP) microarray for infant A with valvular insufficiency, aortic sinus dilatation, hydronephrosis, and dysmorphic features, and Trio whole-exome sequencing (WES) for infant B with dextro-transposition of the great arteries (D-TGA) and both parents. Infant A is a term male with neonatal marfanoid features, left-sided hydronephrosis, and complex congenital heart defects including tricuspid regurgitation, aortic sinus dilatation, patent foramen ovale, patent ductus arteriosus, mitral regurgitation, tricuspid regurgitation, aortic regurgitation, and pulmonary sinus dilatation. He developed severe persistent pulmonary hypertension and worsening acute hypercapnic hypoxemic respiratory failure, and subsequently expired on day of life (DOL) 10 after compassionate extubation. Cytogenomic whole-genome SNP microarray analysis revealed a deletion within the FBN1 gene spanning exons 7-30, which overlapped with the exon deletion hotspot region associated with neonatal Marfan syndrome. Infant B is a term male prenatally diagnosed with isolated D-TGA. He required balloon atrial septostomy on DOL 0 and subsequent atrial switch operation, atrial septal defect repair, and patent ductus arteriosus ligation on DOL 5. Trio-WES revealed compound heterozygous c.518C>T and c.8230T>G variants in the FBN2 gene. Zygosity analysis confirmed each of the variants was inherited from one of the parents who were healthy heterozygous carriers. Since his cardiac repair at birth, he has been growing and developing well without any further hospitalization. Our study highlights novel FBN1/FBN2 variants and signifies the phenotype-genotype association in two infants affected with complex congenital heart defects with and without dysmorphic features. These findings speak to the importance of next-generation high-throughput genomics for novel variant detection and the phenotypic variability associated with FBN1/FBN2 variants, particularly in the neonatal period, which may significantly impact clinical care and family counseling.
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Fibrilina-1 , Fibrilina-2 , Cardiopatias Congênitas , Síndrome de Marfan , Humanos , Fibrilina-1/genética , Síndrome de Marfan/genética , Fibrilina-2/genética , Masculino , Recém-Nascido , Cardiopatias Congênitas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Feminino , Polimorfismo de Nucleotídeo Único , Mutação , Genômica/métodos , Fenótipo , Sequenciamento do Exoma , AdipocinasRESUMO
A very large fetal pericardial teratoma was diagnosed at 28 weeks' gestation, prompting urgent multidisciplinary expert consultations to weigh the risks and benefits of various prenatal invasive procedures and preterm delivery for postnatal surgical management. Ultimately, the infant was born by planned cesarean section and underwent immediate cardiopulmonary bypass and surgical resection.
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Fetal congenital heart block is a widely recognized complication of pregnancies with anti Ro/La antibodies. Less common presentations, including dilated cardiomyopathy, myocarditis, valvular insufficiency, and endocardial fibroelastosis, have also been described in these fetuses. We present two cases where recognition of isolated basal echogenicity of the fetal heart, an unconventional manifestation of anti-SSA antibodies during pregnancy, led to a suspicion and ultimately diagnosis of antibody positivity in the mother. These cases highlight the importance of being aware of this rare manifestation of anti-SSA antibodies during pregnancy, as early recognition of antibody positivity may lead to improve fetal and maternal outcomes.
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Anticorpos Antinucleares , Bloqueio Cardíaco , Gravidez , Feminino , Humanos , Bloqueio Cardíaco/congênito , Coração Fetal/diagnóstico por imagem , Mães , UltrassonografiaRESUMO
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.
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Bloqueio Atrioventricular , Complicações na Gravidez , Criança , Gravidez , Humanos , Feminino , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/epidemiologia , Autoanticorpos , Estudos Prospectivos , Anticorpos Antinucleares , Ecocardiografia/métodosRESUMO
Standard of care echocardiography can have limited diagnostic accuracy in certain cases of fetal congenital heart disease. Prenatal cardiovascular magnetic resonance (CMR) imaging has potential to provide additional anatomic imaging information, including excellent soft tissue images in multiple planes, improving prenatal diagnostics and in utero hemodynamic assessment. We conducted a literature review of fetal CMR, including its development and implementation into clinical practice, and compiled and analyzed the results. Our findings included the fact that technological and innovative approaches are required to overcome some of the challenges in fetal CMR, in part due to the dynamic nature of the fetal heart. A number of reconstruction algorithms and cardiac gating strategies have been developed over time to improve fetal CMR image quality, allowing unique investigations into fetal hemodynamics, oxygenation, and growth. Studies demonstrate that incorporating CMR in the prenatal arena influences postnatal clinical management. With further refinement and experience, fetal CMR in congenital heart disease continues to evolve and demonstrate ongoing potential as a complementary imaging modality to fetal echocardiography in the care of these patients.
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As an essential component of the sarcomere, actin thin filament stems from the Z-disk extend toward the middle of the sarcomere and overlaps with myosin thick filaments. Elongation of the cardiac thin filament is essential for normal sarcomere maturation and heart function. This process is regulated by the actin-binding proteins Leiomodins (LMODs), among which LMOD2 has recently been identified as a key regulator of thin filament elongation to reach a mature length. Few reports have implicated homozygous loss of function variants of LMOD2 in neonatal dilated cardiomyopathy (DCM) associated with thin filament shortening. We present the fifth case of DCM due to biallelic variants in the LMOD2 gene and the second case with the c.1193G>A (p.W398*) nonsense variant identified by whole-exome sequencing. The proband is a 4-month male infant of Hispanic descent with advanced heart failure. Consistent with previous reports, a myocardial biopsy exhibited remarkably short thin filaments. However, compared to other cases of identical or similar biallelic variants, the patient presented here has an unusually late onset of cardiomyopathy during infancy. Herein, we present the phenotypic and histological features of this variant, confirm the pathogenic impact on protein expression and sarcomere structure, and discuss the current knowledge of LMOD2-related cardiomyopathy.
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Cardiomiopatias , Cardiomiopatia Dilatada , Recém-Nascido , Lactente , Masculino , Humanos , Cardiomiopatia Dilatada/genética , Sequenciamento do Exoma , Homozigoto , CoraçãoRESUMO
INTRODUCTION: Speckle tracking analysis was used to evaluate right (RA) and left (LA) atria size, shape and contractility to create a probability calculator to identify fetuses at risk for urgent neonatal balloon atrial septostomy (BAS). METHODS: The study group consisted of 39 fetuses with D-TGA, of which 55% (N = 22) required neonatal BAS and 45% (N = 17) did not. The RA and LA end-diastolic areas, lengths, widths, and sphericity indices as well as global, longitudinal, and transverse contractility were measured with speckle tracking analysis. The z-scores of the measurements were compared to 200 controls. Logistic regression analysis of the computed z-score measurements was performed to separate fetuses requiring urgent neonatal atrial BAS from those who did not. RESULTS: The following z-score values for all fetuses with D-TGA, irrespective of whether they required neonatal BAS, that were significantly less than controls: RA base sphericity index, basal-apical length fractional shortening, fractional area change, lateral wall annular plane systolic excursion (APSE), and longitudinal reservoir strain; LA mid-chamber width, fractional shortening, ejection fraction, basal-apical length fractional shortening, atrial ejection volume, septal wall APSE, and reservoir strain. The following z-score values were significantly larger than control values: RA/LA mid-chamber width, RA/LA base width, and RA mid-chamber length. Logistic regression analysis identified the following five measurements that correctly identified 19 of 22 fetuses requiring urgent neonatal atrial BAS with a sensitivity of 86.4%, a false-positive rate of 11.8% and a positive predictive value of 90.4%: (1) LA mid-chamber transverse fractional shortening, (2) RA mid-chamber end-diastolic width, (3) RA basal-apical length fractional shortening, (4) RA mid-chamber fractional shortening, and (5) RA fractional area change. CONCLUSION: Using the measurements described in this study identified significant differences between all fetuses with D-TGA and controls, as well as identified measurements that predicted the probability of D-TGA fetuses requiring neonatal septostomy.
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Fibrilação Atrial , Transposição dos Grandes Vasos , Recém-Nascido , Feminino , Gravidez , Humanos , Ecocardiografia , Ultrassonografia Pré-Natal , Coração Fetal/diagnóstico por imagem , ArtériasRESUMO
INTRODUCTION: Speckle tracking analysis of the endocardium of the right (RV) and left (LV) ventricles was used to evaluate the size, shape, and contractility of these chambers in fetuses with D-Transposition of the great arteries (D-TGA) to identify fetuses that would require emergent balloon atrial septostomy (BAS) after birth. METHODS: This was a retrospective analysis of fetuses with D-TGA and intact ventricular septum that were divided into 2 groups. Group 1 underwent urgent BAS after birth because of a restrictive atrial septum and group 2 did not. Using speckle tracking analysis, the end-diastolic and end-systolic RV and LV areas, lengths, widths, sphericity indices, and contractility were computed. Logistic regression analysis was performed to identify fetuses who would require urgent neonatal BAS. RESULTS: Of the 39 fetuses with D-TGA, 55% (n = 22) required urgent neonatal BAS (group 1) and 45% (n = 17) (group 2) did not. When comparing D-TGA groups 1 and 2, differences were seen in RV and LV area, sphericity index for segment 1 of the LV, LV fractional area of change and free wall annular plane systolic excursion, fractional shortening for LV segment 12, and RV free wall strain. Regression analysis of these measurements identified 91% of neonates who underwent BAS, with a false-positive rate of 12%. CONCLUSION: Using speckle tracking analysis to evaluate the RV and LV, measurable differences were identified for the RV and LV size, shape, and contractility between fetuses who underwent neonatal urgent BAS vs. those who did not require this procedure.
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Fibrilação Atrial , Transposição dos Grandes Vasos , Recém-Nascido , Humanos , Transposição dos Grandes Vasos/diagnóstico por imagem , Transposição dos Grandes Vasos/cirurgia , Ecocardiografia/métodos , Estudos Retrospectivos , Ventrículos do Coração/diagnóstico por imagem , Coração Fetal/diagnóstico por imagem , Coração Fetal/cirurgiaRESUMO
OBJECTIVES: The prenatal detection of D-Transposition of the great arteries (D-TGA) and tetralogy of Fallot (TOF) has been reported to be less than 50% to as high as 77% when adding the outflow tracts to the four-chamber screening protocol. Because many examiners still struggle with the outflow tract examination, this study evaluated whether changes in the size and shape of the heart in the 4CV as well as the ventricles occurred in fetuses with D-TGA and TOF could be used to screen for these malformations. METHODS: Forty-four fetuses with the pre-and post-natal diagnosis of D-TGA and 44 with TOF were evaluated between 19 and 36 weeks of gestation in which the 4CV was imaged. Measurements of the end-diastolic width, length, area, and global sphericity index were measured for the four-chamber view and the right and left ventricles. Using z-score computed values, logistic regression was performed between the 88 study and 200 control fetuses using the hierarchical forward selection protocol. RESULTS: Logistic regression identified 10 variables that correctly classified 83/88 of fetuses with TOF and TGA, for a sensitivity of 94%. Six of 200 normal controls were incorrectly classified for a false-positive rate of 3%. The area under the receiver operator classification curve was 98.1%. The true positive rate for D-TGA was 93.2%, with a false-negative rate to 6.8%. The true positive rate for TOF was 95.5%, with a false negative rate of 4.5%. CONCLUSIONS: Measurements of the 4CV and of the RV and LV may help identify fetuses at risk for D-TGA or TOF.
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Tetralogia de Fallot , Transposição dos Grandes Vasos , Gravidez , Feminino , Humanos , Transposição dos Grandes Vasos/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Tetralogia de Fallot/diagnóstico por imagem , Ecocardiografia/métodos , Artérias , Feto , Ultrassonografia Pré-Natal/métodosRESUMO
Background: Congenital heart disease (CHD) affects 8 in 1,000 live births with significant postnatal implications including growth failure, neurodevelopmental delay, and mortality. The placenta develops concomitantly with the fetal heart. High rates of placental pathology and discordant growth in pregnancies affected by CHD highlight the significance of the fetal-placental-cardiac axis. Objectives: This study aimed to characterize the relationship between neonatal birthweight (BW), head circumference, placental weight (PW), and placental pathology in pregnancies affected by CHD. PW:BW provides a surrogate to assess placental efficiency, or nutrient exchange and delivery by the placenta, across CHD phenotypes. Methods: Retrospective cohort of 139 live-born singletons with postnatally confirmed CHD with placental pathology. Placental examination, infant BW, head circumference, and CHD categories (septal defects, right-sided defects, left-sided defects, conotruncal anomalies, and others) were included. Chi-square, Fisher's exact, or Kruskall-Wallis tests and multinomial logistic regressions, as appropriate. Results: Median birthweight and head circumference percentile was 33 and 35, respectively. Placental pathology was documented in 37% of cases. PW to BW ratios were <10th percentile for 78% and <3rd percentile for 54% of the cohort, with no difference between CHD categories (P = 0.39 and P = 0.56, respectively). Conclusions: Infants with CHD have preserved BW and head circumferences in the setting of small placentas and increased prevalence of placental pathology, suggesting placental efficiency. Detection of abnormal placental growth could add prenatal diagnostic value. Placental and neonatal discordant growth may allude to a vascular anomaly predisposing fetuses to developing CHD. Further studies are needed to explore fetal nutrient delivery and utilization efficiency.
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Purpose of Review: Established telehealth practices in pediatrics and pediatric cardiology are evolving rapidly. This review examines several concepts in contemporary telemedicine in our field: recent changes in direct-to-consumer (DTC) pediatric telehealth (TH) and practice based on lessons learned from the pandemic, scientific data from newer technological innovations in pediatric cardiology, and how TH is shaping global pediatric cardiology practice. Recent Findings: In 2020, the global pandemic of COVID-19 led to significant changes in healthcare delivery. The lockdown and social distancing guidelines accelerated smart adaptations and pivots to ensure continued pediatric care albeit in a virtual manner. Remote cardiac monitoring technology is continuing to advance at a rapid pace secondary to advances in the areas of Internet access, portable hand-held devices, and artificial intelligence. Summary: TH should be approached programmatically by pediatric cardiac healthcare providers with careful selection of patients, technology platforms, infrastructure setup, documentation, and compliance. Payment parity with in-person visits should be advocated and legislated. Newer remote cardiac monitoring technology should be expanded for objective assessment and optimal outcomes. TH continues to be working beyond geographical boundaries in pediatric cardiology and should continue to expand and develop.
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Fetal echocardiography may be performed because of noncardiac indications (the pregnancy is identified as high risk for fetal cardiac disease), or because of fetal cardiac indications (abnormal fetal heart at the time of a screening ultrasound). Considering recent improvements in fetal cardiac screening over the past decade, the goal of this single institution study was to reconsider the importance of performing fetal echocardiography purely for screening (noncardiac) indications. We performed a retrospective analysis to review screening and fetal cardiac indications and fetal cardiac findings for fetal echocardiograms performed at UCLA between 2015 and 2019. Fetal heart disease was identified in 391 (15%) of 2592 pregnancies in this study. Among these 391 cases, 227 (58%) occurred in low-risk pregnancies (without screening indications). While 79% of the cases of fetal cardiac disease were referred with fetal cardiac indications, 21% of the cases were referred with exclusively screening indications. Fetal cardiac disease was discovered on fetal echocardiograms in 4% of pregnancies referred for exclusively screening indications, but the frequency of fetal cardiac disease following normal fetal cardiac screening has decreased from 6% in 2015 to 3% in 2019. In our population, we recommend continued referral for fetal echocardiography for pregnancies identified as high risk for CHD. However, as fetal cardiac screening continues to improve, referral for fetal echocardiography following normal fetal cardiac screening will have diminishing value and yield.
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BACKGROUND: Racial disparities in outcomes have been shown to persist in many operative specialties, including the management of congenital heart disease. Using a demographic-adjusted methodology, we examined whether patient race influenced access to high-performing centers for the operative management of hypoplastic left heart syndrome. METHODS: The 2005-2017 National Inpatient Sample was queried to identify all pediatric (≤5 years) hospitalizations with an operation for hypoplastic left heart syndrome. A racial disparity index was generated for each hospital and defined as the proportion of White patients receiving operative management for hypoplastic left heart syndrome divided by the proportion of White patients admitted for respiratory failure. This methodology quantified hospital-level racial variation while adjusting for the local racial makeup of each center. RESULTS: Of the 17,275 patients who met inclusion criteria, 64.1% were managed at high-volume centers. Patients at high-volume centers had a similar distribution of operative type, age, and burden of comorbidities. The mean racial disparity index steadily grew from 1.06 at the lowest volume decile of operative volume to 1.51 at the highest, indicating an increasing proportion of White patients as volume increased. Using risk-adjusted analysis, each decile increase in hospital volume was associated with a 14% relative reduction in odds of mortality and a 0.06 increase in predicted racial disparity index. Increasing volume was further associated with reduced odds of non-home discharge but did not alter resource utilization. CONCLUSION: We demonstrate that high-volume centers disproportionally serve White patients and have superior clinical outcomes compared to low-volume centers. This study highlights the critical importance of equitable access to expert care for high-risk conditions such as hypoplastic left heart syndrome.
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Síndrome do Coração Esquerdo Hipoplásico , Criança , Mortalidade Hospitalar , Humanos , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Cuidados Paliativos/métodos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVES: This study examines fetuses with tetralogy of Fallot (TOF) and evaluates the right (RV) and left (LV) ventricular contractility and LV function using speckle-tracking analysis of the endocardium. METHODS: The study group consisted of 44 fetuses with TOF, of which 34% had pulmonary valve atresia (N = 15) and 59% (N = 26) had pulmonary valve stenosis. The RV and LV global fractional area change, longitudinal contractility (longitudinal strain, free wall strain, septal strain, free wall and septal annular fractional shortening, and free wall and septal wall annular plane systolic excursion), and transverse contractility (24-segment fractional shortening) as well as LV functional assessment (stroke volume, cardiac output, and ejection fraction) were measured using speckle-tracking analysis. The z-scores of the measurements were compared to 200 controls. RESULTS: Compared to controls, measurements of LV contractility in fetuses with TOF demonstrated significantly abnormal values for global contractility, longitudinal contractility, and transverse contractility of the mid and apical segments. LV function was abnormal for stroke volume (SV), cardiac output (CO), and ejection fraction (EF). In comparison, RV contractility demonstrated no significant difference between TOF and control z-score values for RV global contractility. Only two RV measurements were found to be abnormal: longitudinal contractility and transverse contractility of the apical segments. CONCLUSION: Using multiple measurement tools to evaluate global, longitudinal, and transverse contractility, this study identified significant differences between fetuses with TOF and healthy controls, with greater contractility abnormalities seen in the LV than in the RV.
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Tetralogia de Fallot , Disfunção Ventricular Direita , Humanos , Tetralogia de Fallot/diagnóstico por imagem , Função Ventricular Esquerda , Ventrículos do Coração/diagnóstico por imagem , Volume Sistólico , Feto , Função Ventricular DireitaRESUMO
OBJECTIVES: One of the problems for the clinician who desires to measure the interventricular septum (IVS) in a high-risk fetus is to know where to make the measurement. The purpose of this study was to use speckle-tracking analysis to measure the IVS area, 24-segment widths, and length at end-diastole (ED) and end-systole (ES) in normal fetuses. METHODS: From the 4-chamber view, speckle-tracking analysis was performed at ED and ES on the IVS in 200 normal fetuses. The following were computed and regressed against gestational age (GA) and fetal biometric (FB) measurements: area, length, and the 24-segment transverse widths from the apex to the crux. The 24-segment width/length ratio was also measured. The speckle-tracking measurements of the ED area and length were compared using a point-to-point measurement tool available on all ultrasound machines. RESULTS: The ED and ES areas, lengths, and 24-segment widths increased with GA and FB. The ED and ES areas were virtually identical. The 24-segment width/length ratio decreased from the apex to the crux of the septum. There was no significant difference in the measurement of the ED area and the length between speckle-tracking and the point-to-point measurements. CONCLUSIONS: Measurement of the area and length of the IVS are simple to obtain and provide a new diagnostic tool to evaluate the fetus at risk for IVS hypertrophy which may be observed in fetuses of mothers with pregestational and gestational diabetes.
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Coração Fetal , Septo Interventricular , Feminino , Gravidez , Humanos , Coração Fetal/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Septo Interventricular/diagnóstico por imagem , Idade Gestacional , Hipertrofia , Ventrículos do Coração/diagnóstico por imagemRESUMO
OBJECTIVES: The purpose of this study was to use speckle tracking analysis to evaluate the size, shape, and function of the atrial chambers in normal fetuses and develop a z-score calculator that can be used in future studies in fetuses at risk for cardiovascular disease. METHODS: The control group consisted of 200 normal fetuses examined between 20 and 40 weeks of gestation in which speckle tracking analysis of right (RA) and left (LA) atrial chambers was performed. The atrial end-diastolic and end-systolic endocardial borders for each chamber were identified from which measurements of atrial length, width, area, and volume were computed. Equations were derived using fractional polynomial regression analysis to compute z-score equations. RESULTS: The LA end-diastolic volume, RA and LA end-diastolic area, length, base width, and mid-chamber widths increased with gestational age and fetal size. Left atrial emptying and ejection volumes increased with gestational age and fetal size. The fractional area change was significantly less for the RA than the LA. The LA base and mid-chamber fractional shortening were significantly greater than the RA. There was a significant difference between the RA and LA global contractile strain. CONCLUSION: Mean and standard deviation equations for each of the measurements described in this study were computed to create a z-score calculator that can be utilized in the clinical environment when evaluating fetuses with suspected atrial pathology that could alter the size, shape, and function of the atrial chambers.
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Átrios do Coração , Ultrassonografia Pré-Natal , Diástole , Feminino , Feto , Idade Gestacional , Átrios do Coração/diagnóstico por imagem , Humanos , GravidezRESUMO
Among neonatal cardiomyopathies, primary endocardial fibroelastosis (pEFE) remains a mysterious disease of the endomyocardium that is poorly genetically characterized, affecting 1/5000 live births and accounting for 25% of the entire pediatric dilated cardiomyopathy (DCM) with a devastating course and grave prognosis. To investigate the potential genetic contribution to pEFE, we performed integrative genomic analysis, using whole exome sequencing (WES) and RNA-seq in a female infant with confirmed pathological diagnosis of pEFE. Within regions of homozygosity in the proband genome, WES analysis revealed novel parent-transmitted homozygous mutations affecting three genes with known roles in cilia assembly or function. Among them, a novel homozygous variant [c.1943delA] of uncertain significance in ALMS1 was prioritized for functional genomic and mechanistic analysis. Loss of function mutations of ALMS1 have been implicated in Alstrom syndrome (AS) [OMIM 203800], a rare recessive ciliopathy that has been associated with cardiomyopathy. The variant of interest results in a frameshift introducing a premature stop codon. RNA-seq of the proband's dermal fibroblasts confirmed the impact of the novel ALMS1 variant on RNA-seq reads and revealed dysregulated cellular signaling and function, including the induction of epithelial mesenchymal transition (EMT) and activation of TGFß signaling. ALMS1 loss enhanced cellular migration in patient fibroblasts as well as neonatal cardiac fibroblasts, while ALMS1-depleted cardiomyocytes exhibited enhanced proliferation activity. Herein, we present the unique pathological features of pEFE compared to DCM and utilize integrated genomic analysis to elucidate the molecular impact of a novel mutation in ALMS1 gene in an AS case. Our report provides insights into pEFE etiology and suggests, for the first time to our knowledge, ciliopathy as a potential underlying mechanism for this poorly understood and incurable form of neonatal cardiomyopathy. KEY MESSAGE: Primary endocardial fibroelastosis (pEFE) is a rare form of neonatal cardiomyopathy that occurs in 1/5000 live births with significant consequences but unknown etiology. Integrated genomics analysis (whole exome sequencing and RNA sequencing) elucidates novel genetic contribution to pEFE etiology. In this case, the cardiac manifestation in Alstrom syndrome is pEFE. To our knowledge, this report provides the first evidence linking ciliopathy to pEFE etiology. Infants with pEFE should be examined for syndromic features of Alstrom syndrome. Our findings lead to a better understanding of the molecular mechanisms of pEFE, paving the way to potential diagnostic and therapeutic applications.
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Síndrome de Alstrom , Cardiomiopatias , Ciliopatias , Fibroelastose Endocárdica , Síndrome de Alstrom/genética , Síndrome de Alstrom/metabolismo , Síndrome de Alstrom/patologia , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Ciliopatias/genética , Ciliopatias/metabolismo , Ciliopatias/patologia , Fibroelastose Endocárdica/genética , Fibroelastose Endocárdica/metabolismo , Fibroelastose Endocárdica/patologia , Transição Epitelial-Mesenquimal , Feminino , Fibroblastos , Humanos , Lactente , Mutação , Miocárdio/metabolismo , Miocárdio/patologia , Fenótipo , RNA-Seq , TranscriptomaRESUMO
Background Prenatal diagnosis of congenital heart disease has been associated with early-term delivery and cesarean delivery (CD). We implemented a multi-institutional standardized clinical assessment and management plan (SCAMP) through the University of California Fetal-Maternal Consortium. Our objective was to decrease early-term (37-39 weeks) delivery and CD in pregnancies complicated by fetal congenital heart disease using a SCAMP methodology to improve practice in a high-risk and clinically complex setting. Methods and Results University of California Fetal-Maternal Consortium site-specific management decisions were queried following SCAMP implementation. This contemporary intervention group was compared with a University of California Fetal-Maternal Consortium historical cohort. Primary outcomes were early-term delivery and CD. A total of 496 maternal-fetal dyads with prenatally diagnosed congenital heart disease were identified, 185 and 311 in the historical and intervention cohorts, respectively. Recommendation for later delivery resulted in a later gestational age at delivery (38.9 versus 38.1 weeks, P=0.01). After adjusting for maternal age and site, historical controls were more likely to have a CD (odds ratio [OR],1.8; 95% CI, 2.1-2.8; P=0.004) and more likely (OR, 2.1; 95% CI, 1.4-3.3) to have an early-term delivery than the intervention group. Vaginal delivery was recommended in 77% of the cohort, resulting in 61% vaginal deliveries versus 50% in the control cohort (P=0.03). Among pregnancies with major cardiac lesions (n=373), vaginal birth increased from 51% to 64% (P=0.008) and deliveries ≥39 weeks increased from 33% to 48% (P=0.004). Conclusions Implementation of a SCAMP decreased the rate of early-term deliveries and CD for prenatal congenital heart disease. Development of clinical pathways may help standardize care, decrease maternal risk secondary to CD, improve neonatal outcomes, and reduce healthcare costs.