This case illustrates a large right ventricular myxoma causing severe right ventricular outflow tract obstruction. Multimodality imaging, including echocardiography and CT, guided the diagnosis. The patient underwent successful surgical resection, with histopathology confirming the benign tumor, leading to hemodynamic relief.

This study reports a congenital heart disease, characterized by ventricular wall thinning and septal defects, caused by a heterozygous missense mutation (R755 W) in the glycolytic gene PFKP (platelet isoform of phosphofructokinase-1). The pathogenic mechanism involves the PFKP mutation impairing enzyme activity, which inhibits cardiomyocyte proliferation and leads to the thinning of the compact myocardium. In the mouse model, we found that administering the downstream metabolite, fructose-1,6-bisphosphate, reversed the myocardial hypoplasia in fetal mice, providing proof-of-concept for in utero intervention. Clinically, we successfully prevented the transmission of the disease using preimplantation genetic testing, resulting in the birth of a healthy infant.

Background: Cardiac amyloidosis (CA) is a significant and increasingly treatable cause of heart failure. Although echocardiography is the first-line imaging modality for CA screening, conventional parameters alone have limited ability to predict the presence of CA. This study aimed to develop a simple echocardiographic scoring tool to predict CA. Methods: We retrospectively identified 71 patients with CA at Beijing Anzhen Hospital, Capital Medical University, between January 2018 and December 2023. A contemporaneous control group comprised 126 non-CA patients. Candidate predictors were screened out using univariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression; a multivariable logistic regression model was then used to construct a nomogram. Internal validation employed bootstrap resampling to assess discrimination [receiver operating characteristic (ROC) curve/area under the curve (AUC)] and calibration (calibration plot and Hosmer-Lemeshow goodness-of-fit test). Clinical utility was evaluated using decision curve analysis (DCA) and clinical impact curve (CIC). Results: The final nomogram included five variables-biatrial enlargement, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), left-ventricular hypertrophy, and a CA index-and showed excellent discrimination [AUC =0.95; 95% confidence interval (CI): 0.94-0.96]. Calibration curves and the Hosmer-Lemeshow test (P>0.05) indicated good agreement between predicted and observed risk. DCA and CIC demonstrated favorable net clinical benefit across plausible decision thresholds. Conclusions: Echocardiography-based screening for CA is feasible. A concise score derived from routine structural and functional measurements captures pathophysiologic hallmarks of CA and can help clinicians identify high-risk patients simply and effectively, thereby informing referral and treatment decisions.

FRMD5 is a protein-coding gene on human chromosome 15q15.3 encoding a FERM domain-containing protein. Its mutations are linked to NEDEMA, a rare autosomal dominant neurodevelopmental disorder characterized by developmental delay, intellectual disability, ataxia, epilepsy, and eye movement abnormalities (Keller Sarmiento et al., 2024).We established a FRMD5 knockout (FRMD5(-/-)) human embryonic stem cell line via CRISPR/Cas9. This line shows normal karyotype, expresses pluripotency markers, and differentiates into three germ layers, serving as a valuable tool for studying FRMD5 in neural development.

To investigate the ascending aorta (AAO)–descending aorta (DAO) outer/internal distance index (AAO–DAO ODI/IDI) prediction value for fetal complete transposition of the great arteries (D-TGA). Selected D-TGA fetuses between January 2019 and June 2024 as the D-TGA group and an equal number of normal fetuses (gestational age (GA) matched ± 1 week) as the control group. The AAO–DAO outer/internal distance (AAO–DAO OD/ID) and DAO diameter were measured in the aortic arch long-axis view, and the AAO–DAO ODI/IDI were calculated, which are the ratios of AAO–DAO OD/ID to DAO. The relationship between AAO–DAO OD/ID and AAO–DAO ODI/IDI and GA of the normal group was analyzed. The differences in AAO–DAO ODI/IDI between the D-TGA and the normal fetuses were compared, and the difference between the D-TGA with intact ventricular septum (D-TGA-IVS) and the D-TGA with ventricular septal defects (D-TGA-VSD) was compared. The sensitivity and specificity of the receiver operating characteristic (ROC) curve were applied to analyze the discrimination ability of AAO–DAO ODI/IDI for D-TGA and normal fetuses and D-TGA-IVS and D-TGA-VSD. In the normal control group, the DOA ICC was 0.972 (95

Objectives This study endeavors to establish comprehensive normal reference ranges and Z score formulas for ductus venosus (DV) flow velocity parameters and calculated waveform indices across different gestational ages in low-risk fetuses. Furthermore, we aim to validate the predictive capabilities of these Z score calculation formulas in fetuses with diverse right heart diseases.Methods 8,953 singleton low-risk fetuses and 70 fetuses diagnosed with different types of right heart diseases were retrospectively enrolled. The DV blood flow velocities during the cardiac cycle (ventricular systolic wave velocity [S], ventricular diastolic wave velocity [D], atrial contraction wave velocity [A], and time-averaged maximum velocity [Tamx]) and calculated waveform indices (preload index [PLI], peak velocity index [PVI], pulsatility index [PI], S/A, and S/D) were obtained. Ninety low-risk fetuses were randomly selected as the control group to verify the predictive value of the Z score model for fetuses with different types of right heart diseases.Results As gestational age increased (16-39 weeks), the mean values of S, D, A, and Tamx progressively increased; conversely, the mean values of PLI, PVI, PI, and S/A decreased, respectively, and the median value of S/D remained stable. The Z score-transformed A, PLI, PVI, PI, and S/A could serve as predictors of overall right heart diseases. Different DV Doppler parameter Z scores exhibited varying predictive values for different subtypes of right heart diseases.Conclusions Normal reference ranges and corresponding Z score calculation formulas for DV hemodynamic parameters were established, which have demonstrated significant diagnostic values in identifying right heart diseases.

Objective: We present the first case of THOC6 variant with a prenatal clinical phenotype of double-outlet right ventricle. Case report: The fetus in this case presented with double-outlet right ventricle.Two compound heterozygous variations for the THOC6 gene (NM_024339.5), neither of which has been reported, (exon12: c.826C>T:p. Q276* and exon3:c.178G>T:p.E60*), were identified by exome sequencing in the pre-documented individuals. Conclusion: This case extends the variant spectrum and clinical characteristics of the THOC6 gene. It suggests that the double-outlet right ventricle may be a prenatal clinical feature caused by this gene variant. Fetal cardiac ultrasound can be used as an early screening method for these diseases, and it highlights the importance of prenatal whole-exome sequencing technology in elucidating prenatal diagnosis and prognosis.

Background: This study aimed to assess the pathogenicity of newly identified tuberous sclerosis Complex 1 (TSC1) and TSC2 variants, contributing definitive evidence for the diagnosis of TSC. Methods: A total of 103 TSC patients underwent TSC genetic testing using standardized protocols, and genetic testing was extended to their respective families. Analysis of genetic testing results considered clinical phenotype and gene pathogenicity based on the 2012 revision of the International Society of TSC. Results: Among participants, 12 exhibited previously unreported variants of TSC1 or TSC2 gene absent in relevant databases. All 12 clinically diagnosed TSC patients presented typical phenotypes, such as brain lesions and skin changes. Notably, there were 2 variants of TSC1 gene and 10 variants of TSC2 gene, encompassing 8 frameshift variants, 2 nonsense variants, and 2 missense variants. Conclusions: This study broadens the spectrum of variants of TSC1 and TSC2 genes, reaffirming the clinical diagnosis of patients through genetic testing.

OBJECTIVE:This seven-year study investigates risk factors for long-term mortality in AMI patients with ventricular septal rupture (VSR) to enhance clinical management and outcomes. METHODS:We conducted a retrospective cohort study of 180 AMI patients with VSR from January 2016 to October 2023. We collected data on demographics, clinical features, treatments, and outcomes. Patients were divided into survival and death groups and further classified by treatment (surgical repair vs. medical management). Cox proportional hazards regression identified predictors of long-term mortality. RESULTS:Median follow-up was 1028 days, with an overall mortality rate of 65.6%. The death group had a higher rate of medical management (83.1% vs. 35.5% in survivors). Long-term mortality rates were 33.3% for surgical repair and 81.7% for medical management. Independent predictors of poor outcomes included Killip Class 3-4, female gender, and advanced age. Surgical repair was a protective factor against mortality (HR 0.232). Killip Class 3-4 (HR 5.154) was a significant independent risk factor for long-term mortality among surgical patients. Killip Class 3-4 (HR, 3.268) and female gender (HR 2.548) were significant independent risk factors for long-term mortality among medical management patients. CONCLUSION:Surgical repair significantly reduces long-term mortality compared to medical management in AMI patients with VSR. Killip Class 3-4 affects prognosis, emphasizing the need for tailored management strategies.

Objectives: This study sought to echocardiographic manifestations and the related risk factors affecting the prognosis of isolated congenitally corrected transposition of the great arteries (CCTGA). Methods: A total of 143 patients (≥18 years of age) were diagnosed with isolated CCTGA at Anzhen Hospital. The patients were classified as the operation group and the non-operation group depending on whether they had undergone tricuspid valve surgery. The echocardiographic data and follow-up were compared, and the primary outcomes examined were defined as death or heart transplantation. Results: The average age of 143 patients with isolated CCTGA was 39.93 ± 13.50 years. Tricuspid valve surgery was performed in 31 patients with isolated CCTGA, and 112 patients did not undergo tricuspid valve surgery. The incidence of tricuspid valve structural changes in the operation group was 39.1%, and this group had higher numbers of patients with right ventricular diastolic diameter, right ventricular systolic diameter, left atrial dimensions, and regurgitation before surgery compared with the non-operation group (p < 0.05). Follow-up results showed no significant difference in the number of death/heart transplantations, and the incidence of systemic ventricular ejection fraction (SVEF) < 40% between the two groups. The survival rate of the surgery group was higher than that of the non-surgery group, although not statistically significant (p = 0.123). Age, right ventricular end-diastolic diameter, and decreased SVEF at the first diagnosis are independent predictive risk factors for major adverse outcomes. Conclusions: Adult patients with isolated CCTGA may have structural abnormalities in their tricuspid valves. There were no significant differences in the incidence of adverse outcomes, morphological right ventricular systolic dysfunction, and survival between the surgery group and the non-surgery group. However, this study is a retrospective study, and the sample size of the surgical group is relatively small, which may limit the generalizability of the research conclusions. In the future, a prospective, large-scale study will be conducted to evaluate the therapeutic effect of tricuspid valve surgery on such patients.

OBJECTIVES:To establish gestational-age-specific reference ranges and Z-score models for fetal echocardiographic measurements using a large multicenter dataset from China. METHODS:We retrospectively analyzed 22,357 fetal echocardiographic examinations conducted between 18 and 35 weeks of gestation across 3 tertiary medical centers in China. All fetuses had structurally and functionally normal hearts, confirmed by standardized echocardiographic protocols. A total of 43 cardiovascular parameters were assessed, including 13 structural and 30 pulsed-wave Doppler (PWD) measurements. Fractional polynomial regression was used to model the relationship between each parameter and gestational age (GA). Z-score models were developed using predicted means and GA-dependent standard deviations. Model performance was evaluated using residual analysis, quantile-quantile (QQ) plots, and goodness-of-fit statistics. RESULTS:Thirty-eight parameters (13 structural and 25 PWD) demonstrated satisfactory model fit. Five PWD parameters were excluded due to poor normality or inadequate regression fit. The final models showed strong statistical agreement with GA, and no mathematical transformations were necessary. Gestational-age-specific reference ranges and Z-scores were generated for each parameter, with full percentile tables provided. An online Z-score calculator (http://www.anzscore.com) was developed to facilitate clinical application. CONCLUSIONS:This study provides comprehensive reference ranges and Z-score models for fetal echocardiographic parameters based on a large Han Chinese population. These results offer a reliable foundation for prenatal cardiac assessment in Asian populations and support the development of population-specific diagnostic tools.

OBJECTIVE:This study investigates differences in frontal lobe development and fetal biometries in second-trimester fetuses with different phenotypes of congenital heart disease (CHD) and analyzes correlations between parameters. METHODS:A total of 137 fetuses of gestational age between 20 and 28 weeks diagnosed with CHD by ultrasound between 2017 and 2023 were retrospectively selected as the CHD group and divided into left-sided obstructive lesion (LSOL) and right-sided obstructive lesion (RSOL) groups according to the blood and/or oxygen supply to the brain. Normal fetuses matched for gestational age were selected as a control group. The frontal lobe anteroposterior diameter (FAPD) and occipitofrontal diameter (OFD) were measured and several fetal biometries were retrieved. After 1:1:1 propensity score matching across each group, each parameter was evaluated for between-group differences. RESULTS:Compared with the normal control group, the CHD group had significantly smaller FAPD, with the LSOL group having the smallest FAPD. Compared with the RSOL and normal control groups, the LSOL group had significantly lower FAPD/OFD ratio, MCA-PI, and CPR but higher UA-PI and average UtA-PI. In the CHD group, FAPD was positively correlated with MCA-PI and CPR and negatively correlated with UA-PI and average UtA-PI. CONCLUSION:Fetal frontal lobe development was impaired in second-trimester fetuses with CHD, with this impairment being more obvious in the LSOL group than in the RSOL group. Changes in cerebral perfusion and placental insufficiency in second-trimester fetuses with CHD might be related to impaired frontal lobe development.

The factors associated with the development of cardiac manifestations of neonatal lupus (cardiac-NL) in fetuses with positive anti-SSA/Ro and/or SSB/La (anti-SSA/SSB) antibodies are unclear. This study aimed to investigate the predictive factors of fetal cardiac-NL in anti-SSA/SSB antibody-positive pregnant women.A total of 669 pregnant women with positive anti-SSA/SSB antibodies were retrospectively included. We determined whether the fetus had cardiac-NL and collected relevant clinical data. Univariate and multivariate analyses were performed to analyze the correlation between fetal cardiac-NL and clinical characteristics.Among 669 pregnant women with positive anti-SSA/SSB antibody tests, 26 cases of fetal cardiac-NL occurred. Univariate analysis showed that fetal cardiac-NL was positively correlated with the assisted reproduction (odds ratio [OR]: 2.824; p = 0.045), strong positive anti-SSA/SSB antibody (OR: 6.437; p < 0.001), and clinical diagnosis of connective tissue disease (CTD; OR: 4.701; p = 0.037); it was negatively correlated with the use of hydroxychloroquine (HCQ; OR: 0.187; p < 0.001) and aspirin (OR: 0.369; p = 0.048). Multivariate analysis showed that the assisted reproduction (OR: 4.110; p = 0.029), strong positive anti-SSA/SSB antibody (OR: 8.691; p < 0.001), and clinical diagnosis of CTD (OR: 8.614; p = 0.010) were risk factors for fetal cardiac-NL; while HCQ (OR: 0.091; p < 0.001) and aspirin (OR: 0.318; p = 0.035) were protective factors for fetal cardiac-NL.This study determined that assisted reproduction, strong positive anti-SSA/SSB antibody, and clinical diagnosis of CTD are independent risk factors for fetal cardiac-NL. The use of HCQ and aspirin are independent protective factor for fetal cardiac-NL. · Anti-SSA/SSB antibodies can lead to fetal cardiac-NL.. · Assisted reproduction, strong positive anti-SSA/SSB antibodies, and CTD are risk factors.. · HCQ and aspirin use may lower the risk of fetal cardiac-NL..

BACKGROUND:Congenital heart disease (CHD) exhibits a marked male predominance in birth prevalence, yet the genetic mechanisms underlying this sex disparity remain poorly understood. This study investigates the contribution of rare damaging variants on autosomes and the X chromosome to sex differences in foetal CHD. METHODS:Parents of foetuses with CHD were recruited for the study. Rare damaging variants were identified by analysing whole-exome sequencing data from foetus-parental trios, and their contributions to sex differences were estimated through case-control studies. Functional enrichment analysis was conducted to assess functional differences in genetic variants between sexes. FINDINGS:820 foetal probands with CHD were recruited, including 487 males and 333 females. We identified a significant enrichment of X-linked rare damaging variants, primarily driven by maternally inherited hemizygous variants (MIHVs) in male probands (OR = 1·84, P < 0·05), which accounted for 7·2% of male cases in our cohort. These variants were not found to be enriched in female probands. Additionally, X-linked rare damaging de novo variants (DNVs) were not enriched in either male or female probands (female probands: 1·8% versus female controls: 0·7%, P = 0·6789; no DNVs observed in males). Gene-level variant burden analysis revealed three X-linked CHD candidate genes: DCX, CACNA1F, and MAP3K15. Autosomal rare variants did not show significant differences in variant burdens between sexes. Notably, male probands showed specific functional enrichments in cilia-related pathways for autosomal recessive variants, as well as in chromatin remodelling and nervous system development pathways for autosomal DNVs. INTERPRETATION:Male and female foetal CHD have significantly different genetic landscapes. The enrichment of X-linked rare damaging MIHVs in males provides a genetic explanation for the higher prevalence of CHD in males. This finding highlights the importance of incorporating sex-stratified approaches in clinical diagnostics and research. FUNDING:Natural Science Foundation of China and Key research and development project of Hebei Province.

Objectives Normal fetal echocardiography ratios reflect blood flow balance and developmental patterns, providing a basis for more accurate diagnosis and prediction of congenital heart disease in fetuses. Despite its significance, standardized studies with ample samples are lacking. We aim to establish reference ranges for fetal cardiac structural parameters and hemodynamics using extensive multicenter data, including 11 ratios, and to clarify how these ratios change with gestational age. Methods This is a multicenter cross-sectional retrospective study. 23,313 normal fetal echocardiographic examinations were enrolled from three medical centers. Analysis included 11 fetal cardiac-related ratios, such as right/left heart diameter ratio, mitral and tricuspid valve E/A-wave velocity ratio. To determine the reference ranges for various ratios across different gestational ages, a nonparametric quantile regression model, which does not presuppose normality, was utilized. The study investigated how the ratios change with gestational age by examining nonparametric regression plots and their first and second derivatives. Results We established normal percentile reference ranges for 11 ratios at each gestational day. Analysis of ratio changes across gestation reveals several key patterns: The right heart system consistently dominates, with the right heart/left heart internal diameter ratio accelerating from 21.7 weeks of gestation; throughout fetal development, the E/A ratio of the mitral and tricuspid valves initially remains below one but increases progressively with gestational age, both reaching their maximum growth rates at week 25.7. Conclusions This study provides new references for routine obstetric screening, may enhance the understanding of the growth and developmental patterns of normal fetal hearts.

In prenatal screening for fetal congenital heart disease (CHD), ultrasonic diagnosis and other methods are prone to being affected by regional resource differences and insufficient experience in diagnosing doctors, thus resulting in misdiagnosis of cases. This research puts forward a combined discriminative system, which integrates the iTransformer method and XGBoost to aid in the prenatal diagnosis of fetal CHD. This system, named INFO-iTransformer-XGBoost, merges a combined discriminative system, INFO (Weighted mean of vectors optimization algorithm), and SHAP (SHapley Additive exPlanations) explainable analysis prediction model. By comparing the model results with those from INFO-iTransformer and INFO-XGBoost alone, the study confirms the advantage of the combined discriminative system in prenatal CHD screening for fetuses. The study used the fetal CHD detection dataset provided by the Maternal and Fetal Medicine Center of Beijing Anzhen Hospital, Capital Medical University, from February 2018 to August 2024. The research shows that the INFO-iTransformer-XGBoost combined discriminative system and SHAP model explainability analysis can provide a quantitative diagnosis and clinically interpretable diagnostic solution for prenatal CHD screening.

PURPOSE:Study aimed to assess fetal heart morphology and function in pregnancies with systemic lupus erythematosus (SLE) utilizing speckle tracking echocardiography (STE) and to evaluate indicators for predicting fetal subclinical cardiac damage in this population. METHODS:The study involved 99 SLE-affected fetuses and 99 gestational age-matched controls. The fetal cardiac morphology and function parameters were calculated using STE (FetalHQ). RESULTS:The absolute values of left ventricular (LV) global longitudinal strain (GLS), right ventricular (RV) GLS, LV fractional area change (FAC), and RV FAC in the SLE group were lower than those in the control group (p < 0.001). The 24-segment fractional shortening (FS) analysis revealed significantly lower FS in the SLE group than the controls for LV segments 11-12 and RV segments 4-24. The 24-segment sphericity index (SI) analysis indicated significantly lower SI in the SLE group than the controls for LV segments 1-24 and RV segments 1-8. The LV GLS (AUC = 0.859) and RV GLS (AUC = 0.841) could be considered good predictors of subclinical myocardial damage in SLE-affected fetuses. CONCLUSIONS:STE indicated that fetuses in pregnant women with SLE present cardiac morphology and function that have changed compared to the controls. Further investigations are needed to evaluate STE indices such as the GLS, FAC, and 24-segment FS and SI to predict fetal prognosis in pregnant women with SLE.

Placental vascular development is critical for maternal‐fetal exchange, and altered fetal cardiovascular physiology in congenital heart disease (CHD) may impact placental circulation. This study aimed to assess whether Slow flow HD imaging technology could qualitatively evaluate alterations in placental vascular structure in CHD. A cross‐sectional study was conducted using Slow flow HD to image placental vasculature in 215 fetuses, normal ( n = 106) and CHD ( n = 109) including critical CHD (CCHD) ( n = 66) and other fetal heart disease (FHD) ( n = 43). Slow flow HD provided two‐dimensional (2D) and three‐dimensional (3D) imaging of placental villous tree structures. Differences in display rates and distribution characteristics of placental villous trees were analyzed between the normal, CCHD, and FHD groups. Slow flow HD imaging technology demonstrated high sensitivity in visualizing placental vascular structures, with overall display rates of 95.5%–100%. Primary, secondary, and tertiary villi were visualized with rates of 95.5%–100%, 69.7%–97.7%, and 34.8%–88.7%, respectively. Four distinct placental villous tree types (types 0–3) were identified, exhibiting different distribution characteristics. The composition ratios of these types differed significantly between normal and CCHD fetuses, as well as between CCHD and FHD groups ( P < 0.05). Slow flow HD imaging technology effectively identifies and characterizes placental villous tree structures. Placental villous trees in CCHD fetuses display sparser distribution patterns compared with normal fetuses, highlighting potential implications for maternal‐fetal exchange in CHD.

OBJECTIVE:Placental vascular development is critical for maternal-fetal exchange, and altered fetal cardiovascular physiology in congenital heart disease (CHD) may impact placental circulation. This study aimed to assess whether SlowflowHD imaging technology could qualitatively evaluate alterations in placental vascular structure in CHD. METHODS:A cross-sectional study was conducted using SlowflowHD to image placental vasculature in 215 fetuses, normal (n = 106) and CHD (n = 109) including critical CHD (CCHD) (n = 66) and other fetal heart disease (FHD) (n = 43). SlowflowHD provided two-dimensional (2D) and three-dimensional (3D) imaging of placental villous tree structures. Differences in display rates and distribution characteristics of placental villous trees were analyzed between the normal, CCHD, and FHD groups. RESULTS:SlowflowHD imaging technology demonstrated high sensitivity in visualizing placental vascular structures, with overall display rates of 95.5%-100%. Primary, secondary, and tertiary villi were visualized with rates of 95.5%-100%, 69.7%-97.7%, and 34.8%-88.7%, respectively. Four distinct placental villous tree types (types 0-3) were identified, exhibiting different distribution characteristics. The composition ratios of these types differed significantly between normal and CCHD fetuses, as well as between CCHD and FHD groups (P < 0.05). CONCLUSION:SlowflowHD imaging technology effectively identifies and characterizes placental villous tree structures. Placental villous trees in CCHD fetuses display sparser distribution patterns compared with normal fetuses, highlighting potential implications for maternal-fetal exchange in CHD.