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Reverse flow Retrograde flow (RF) of blood in the aortic isthmus can be observed in different types of fetal heart disease (FHD), including abnormalities in heart structure and function. This study sought to investigate the relationship between RF and blood flow parameters, and develop a computational fluid dynamics (CFD) model to understand the mechanisms underlying this observation.A total of 281 fetuses (gestational age [GA] 26.6±.3 weeks) with FHD and 2803 normal fetuses (GA: 26.1±.1 weeks) by fetal echocardiography collected from May 2016 to December 2018. Principal component analysis (PCA) was performed to find the relationship and the CFD model reconstructed from 3D/4D spatio-temporal image correlation (STIC) images to simulate hemodynamics.There was a significant difference in the percentages of RF between the study (80/201 (39%)) and control (29/2803 (1%)) groups (p 0.05). The RF occur when the aorta flow rate (left heart) is reduced to 60% by CFD stimulation. Pearson correlation analysis showed significant correlations between flow rate and wall shear stress(WSS) (r = .883, p = 0.047) variables at the AI.Volumetric flow rate of AO or left heart was the main component of the cause of RF. The hemodynamics of the cardiovascular system have highly complex behavior hinge on the turbulent nature of circulating blood flow.

We sought to investigate the effect of maternal hypothyroidism during pregnancy on fetal cardiac structural and functional remodeling using fetal echocardiography. A total of 59 pregnant women with history of hypothyroidism were prospectively enrolled as the study group, and 74 normal fetuses as the control group. Fetal echocardiography was performed on each subject. Demographic, clinical, and fetal echocardiographic variables were measured, including left ventricular (LV) and right ventricular (RV) free wall and ventricular septal thickness, fractional shortening (FS), stroke volume (SV), cardiac output (CO), combined cardiac output (CCO), cardiac index (CI), combined cardiac index (CCI), aortic and pulmonary artery velocity, ductus venosus (DV) and pulmonary vein (PV) spectral Doppler, and Tei index. The incidence of echogenic intracardiac foci (EIF) was higher in the study group than that in the control group (18.6% vs. 6.8%, p = .036). The thickness of LV free wall and interventricular septum was reduced, the pulmonary velocities and CCI, RV FS, CO, and CI were lower, the S, D, S/A, and pulsatility index (PI) of DV were higher, and LV Tei index was higher in the study group compared with the control group. There was no significant difference in other variables between the two groups. There is cardiac remodeling, and systolic, diastolic functional alterations in fetuses with maternal hypothyroidism. Further investigation is warranted to develop strategies to optimize the outcome of these fetuses.

Stanford type A aortic dissection (AAD) may affect the supra-aortic arteries, which are associated with acute ischemic stroke (AIS) or transient ischemic attack (TIA). This study aimed to investigate cerebral perfusion, the infarction incidence and risk factors in AAD patients.A total of 156 consecutive AAD patients were enrolled and divided into two groups according to whether the aortic arch branches were involved: the affected group (n = 90) and the unaffected group (n = 66). Clinical, echocardiographic/carotid Doppler data and cerebral infarction morbidity were compared between the groups. Independent predictors of 30-day AAD mortality were identified through multivariable Cox regression, and perioperative risk factors were analyzed.In total, 57.7% of AAD patients had aortic arch branch involvement. Abnormal Doppler waveforms were more common in the affected group (p 0.05). Regarding intracranial perfusion, the blood flow volumes (BFVs) of the bilateral internal carotid arteries (ICAs) and right vertebral artery (RVA) in the affected group were significantly reduced (p 0.05). The incidence of cerebral infarction in the affected group was significantly higher than that in the unaffected group (35.6% vs. 19.7%, p = 0.031). Multivariable analysis revealed that age45 years old, right internal carotid artery (RICA) involvement and reduced left ventricular ejection fraction (LVEF) were significant predictors of perioperative death.Aortic arch branch involvement is common in patients with AAD and is associated with reduced cerebral blood flow (especially on the right side) and a higher incidence of cerebral infarction. Age, extension of the RICA dissection and LVEF impairment are independent risk factors for AAD-related death.

Background: To investigate deep vein thrombosis (DVT) in hospitalized patients with coronavirus disease 2019 (COVID-19), we performed a single institutional study to evaluate its prevalence, risk factors, prognosis, and potential thromboprophylaxis strategies in a large referral and treatment center. Methods: We studied a total of 143 patients with COVID-19 from January 29, 2020 to February 29, 2020. Demographic and clinical data, laboratory data, including ultrasound scans of the lower extremities, and outcome variables were obtained, and comparisons were made between groups with and without DVT. Results: Of the 143 patients hospitalized with COVID-19 (age 63±14 years, 74 [51.7%] men), 66 patients developed lower extremity DVT (46.1%: 23 [34.8%] with proximal DVT and 43 [65.2%] with distal DVT). Compared with patients who did not have DVT, patients with DVT were older and had a lower oxygenation index, a higher rate of cardiac injury, and worse prognosis, including an increased proportion of deaths (23 [34.8%] versus 9 [11.7%]; P =0.001) and a decreased proportion of patients discharged (32 [48.5%] versus 60 [77.9%]; P P =0.031), Padua prediction score ≥4 (odds ratio, 4.016; P =0.04), D-dimer >1.0 μg/mL (odds ratio, 5.818; P 1.0 μg/mL has a sensitivity of 88.52% and a specificity of 61.43% for screening for DVT. In the subgroup of patients with a Padua prediction score ≥4 and whose ultrasound scans were performed >72 hours after admission, DVT was present in 18 (34.0%) patients in the subgroup receiving venous thromboembolism prophylaxis versus 35 (66.0%) patients in the nonprophylaxis group ( P =0.010). Conclusions: The prevalence of DVT is high and is associated with adverse outcomes in hospitalized patients with COVID-19. Prophylaxis for venous thromboembolism may be protective in patients with a Padua protection score ≥4 after admission. Our data seem to suggest that COVID-19 is probably an additional risk factor for DVT in hospitalized patients.

The Collaborative Approach to Reach Everyone with Familial Hypercholesterolemia (CARE-FH) study aims to improve diagnostic evaluation rates for FH at Geisinger, an integrated health delivery system. This clinical trial relies upon implementation science to transition the initial evaluation for FH into primary care, attempting to identify individuals prior to the onset of atherosclerotic cardiovascular disease events. The protocol for the CARE-FH study of this paper is available online. The first phase of the project focuses on trial design, including the development of implementation strategies to deploy evidence-based guidelines. The second phase will study the intervention, rolled out regionally to internal medicine, community medicine, and pediatric care clinicians using a stepped-wedge design, and analyzing data on diagnostic evaluation rates, and implementation, service, and health outcomes.

Background and Objective: The hemodynamics of fetal circulation and its alterations, as in cases of congenital heart defects (CHD), have been investigated in instrumented animal models or in human fetuses by noninvasive fetal echocardiography and Doppler (FED). There is little data in computational modeling of fetal circulation due to challenges in fetal cardiac imaging and the availability of validation methodologies. This study aims to develop and validate a computational model for assessing hemodynamics in aortic and ductal arches in human fetuses. Methods: Figure 1 shows our computational workflow. The process started by preparing a reconstructed 3D aortic and ductal arch anatomy derived from 3D FED. Then, the computational model was built and validated using clinical data from five human fetuses. The primary output was the velocity waveform at the aortic isthmus (AoI), validated using tracings from spectral Doppler. Results: Upon superimposing the reconstructed fetal aortic arch anatomies onto the original 3D FED stack, our results demonstrated a precise rendering of each subject’s unique vessel structure. Simulations were run for ten cardiac cycles, with each velocity waveform at the AoI showing a discrepancy of less than 15% when compared with the Doppler echocardiography tracings. These findings indicate a good agreement between our computational model and the FED data. Conclusion: This study presents the development and validation of a computational model for assessing patient-specific hemodynamics in the aortic arches of human fetuses. Continued investigation is warranted to further validate and apply this approach to improve the diagnosis, prognosis, and treatment of CHD in human fetuses.

Biological stimuli that are present during the pathogenesis of disease have gained considerable interest as a critical element for the design of smart drug delivery systems. Recently, the utilization of biological stimuli-responsive (bioresponsive) nanotheranostic agents to treat atherosclerosis and ischemic-related diseases has demonstrated significant outcomes in preclinical studies. Those diseases share similar hallmarks, including high levels of endogenous reactive oxygen species (ROS), low pH, and high enzyme activity. Interestingly, other relevant biological stimuli such as shear stress, cholesterol, and glutathione have recently been explored as internal stimuli to trigger drug release and some particular actions. In addition, a number of strategies can be proposed to enhance their targeting efficiency, diagnostic properties, and efficacy rate. This review discusses recent advancements in the preclinical studies of bioresponsive nanotherapeutics as diagnostic and therapeutic agents against atherosclerosis and ischemic-related diseases as well as some potential strategies to overcome the current limitations.

Magnesium and its alloys are not normally used as bio-resorbable temporary implants due to their high and uncontrolled degradation rate in physiological liquid environment. The improvement of corrosion resistance to simulated body fluids (SBF) of a Magnesium alloy (AZ31) coated with poly-β-hydroxybutyrate (PHB) was investigated. Scanning electron microscopy, Fourier transform infrared spectrometer, and contact angle measurements were used to characterize surface morphology, material composition and wettability, respectively. pH modification of the SBF corroding medium, mass of Mg2+ ions released, and weight loss of the samples exposed to the SBF solution, and electrochemical experiment were used to describe the corrosion process and its kinetics. Materials biocompatibility was described by evaluating the effect of corrosion by products collected in the SBF equilibrating solution on hemolysis ratio, cytotoxicity, Nitric Oxide (NO), and total antioxidant capacity (T-AOC). The results showed that the PHB coating can diffusively control the degradation rate of Magnesium alloy improving its biocompatibility: hemolysis rate of materials was lower than 5%, while in vitro Human Umbilical Vein Endothelial Cells（HUVECs) compatibility experiments showed that PHB coated Mg alloy promoted cell proliferation and had no effect on the NO content, the T-AOC was enhanced compared with the normal group and bare AZ31 alloy. PHB coated AZ31 Magnesium alloy extraction fluids have a less toxic behavior due to the lower concentration of corrosion by-products deriving from the diffusion control exerted by the PHB coating films both from metal surface to the solution and vice versa. These findings provide more reference value for the selection of such system as tunable bioresorbable prosthetic materials

Magnesium and its alloys are not normally used as bioresorbable temporary implants due to their high and uncontrolled degradation rate in a physiological liquid environment. The improvement of corrosion resistance to simulated body fluids (SBF) of a magnesium alloy (AZ31) coated with poly-β-hydroxybutyrate (PHB) was investigated. Scanning electron microscopy, Fourier transform infrared spectrometer, and contact angle measurements were used to characterize surface morphology, material composition, and wettability, respectively. pH modification of the SBF corroding medium, mass of Mg2+ ions released, weight loss of the samples exposed to the SBF solution, and electrochemical experiments were used to describe the corrosion process and its kinetics. The material’s biocompatibility was described by evaluating the effect of corrosion by products collected in the SBF equilibrating solution on hemolysis ratio, cytotoxicity, nitric oxide (NO), and total antioxidant capacity (T-AOC). The results showed that the PHB coating can diffusively control the degradation rate of magnesium alloy, improving its biocompatibility: the hemolysis rate of materials was lower than 5%, while in vitro human umbilical vein endothelial cell (HUVEC) compatibility experiments showed that PHB-coated Mg alloy promoted cell proliferation and had no effect on the NO content and that the T-AOC was enhanced compared with the normal group and bare AZ31 alloy. PHB-coated AZ31 magnesium alloy extraction fluids have a less toxic behavior due to the lower concentration of corrosion byproducts deriving from the diffusion control exerted by the PHB coating films both from the metal surface to the solution and vice versa. These findings provide more reference value for the selection of such systems as tunable bioresorbable prosthetic materials.

Background. The immune mechanisms underlying low-intensity ultrasound- (LIUS-) mediated suppression of inflammation and tumorigenesis remain poorly determined. Methods. We used microarray datasets from the NCBI GEO DataSet repository and conducted comprehensive data-mining analyses, where we examined the gene expression of 1376 innate immune regulators (innatome genes (IGs) in cells treated with LIUS. Results. We made the following findings: (1) LIUS upregulates proinflammatory IGs and downregulates metastasis genes in cancer cells, and LIUS upregulates adaptive immunity pathways but inhibits danger-sensing and inflammation pathways and promote tolerogenic differentiation in bone marrow (BM) cells. (2) LIUS upregulates IGs encoded for proteins localized in the cytoplasm, extracellular space, and others, but downregulates IG proteins localized in nuclear and plasma membranes, and LIUS downregulates phosphatases. (3) LIUS-modulated IGs act partially via several important pathways of reactive oxygen species (ROS), reverse signaling of immune checkpoint receptors B7-H4 and BTNL2, inflammatory cytokines, and static or oscillatory shear stress and heat generation, among which ROS is a dominant mechanism. (4) LIUS upregulates trained immunity enzymes in lymphoma cells and downregulates trained immunity enzymes and presumably establishes trained tolerance in BM cells. (5) LIUS modulates chromatin long-range interactions to differentially regulate IGs expression in cancer cells and noncancer cells. Conclusions. Our analysis suggests novel molecular mechanisms that are utilized by LIUS to induce tumor suppression and inflammation inhibition. Our findings may lead to development of new treatment protocols for cancers and chronic inflammation.

Caudal regression syndrome (CRS) is a rare congenital malformation with varying degrees of early gestational developmental failure. It is characterized by agenesis of the sacrum and lumbar spine, with lower limb neurological deficit and accompanying deformities of the pelvis, lower extremities, genitourinary, and gastrointestinal systems. We report a case of CRS associated with rare complex congenital heart defect, that is, heterotaxy syndrome, diagnosed prenatally.

In patients with disabling symptoms caused by hypertrophic obstructive cardiomyopathy (HOCM), echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) could be a less invasive treatment option.This study aimed to investigate the safety and efficacy of the PIMSRA for left ventricular outflow tract (LVOT) gradient reduction in HOCM.The study enrolled 15 patients with HOCM. These patients underwent electrocardiography, imaging, and blood biochemistry examination over 6 months of follow-up.At 6 months of follow-up, patients showed significant reductions in peak LVOT gradients (resting gradient: from 88.00 [66.00] mm Hg to 11.00 [6.00] mm Hg; p = 0.001; stress-induced gradient: from 117.00 [81.00] mm Hg to 25.00 [20.00] mm Hg; p = 0.005) and interventricular septum (IVS) thickness (anterior IVS: from 25.00 [21.00] mm to 14.00 [12.00] mm; p = 0.001; posterior IVS: from 24.00 [21.00] mm to 14.00 [11.50] mm; p = 0.001). The reductions in IVS thickness and LVOT gradients were associated with improvement in New York Heart Association functional classification (from 3.00 [2.00] to 1.00 [1.00]; p 0.001), total exercise time (from 6.00 [5.50] min to 9.00 [8.00] min; p = 0.007), and pro B-type natriuretic peptide levels (from 924.00 [370.45] pg/ml to 137.45 [75.73] pg/ml; p = 0.028). No patient had bundle branch block or complete heart block.PIMSRA is a safe and effective treatment approach for severe, symptomatic HOCM and results in sustained improvement in exercise capacity, persistent reduction in LVOT gradient, and sustained improvement in cardiac function.

Objectives We sought to investigate pulmonary hypoplasia (PH) and associated risk factors in fetuses with congenital conotruncal defect (CTD). Methods A total of 75 fetuses with CTD (gestational age (GA): 22-32 weeks) and 150 normal GA-matched fetuses as the control group were studied. We measured diameters of aorta (Ao); main, left, and right pulmonary artery (PA); and their Z-scores by fetal echocardiography (FE). We also measured the lung area, lung area/chest area ratio (LCR), lung-to-head circumference ratio (LHR), right lung area/head circumference2 (quantitative lung index, QLI), and Z-scores. Results The PA, left pulmonary artery (LPA), RPA, and their Z-scores and the lung area measurements (except for QLI) were significantly smaller in the CTD group, compared with the normal control group. Subgroup analysis showed the following: (1) CTD with right ventricular outflow tract obstruction (RVOTO) had smaller main and branch PA dimensions and small lung areas in contrast to CTD without RVOTO. (2) CTD with pulmonary atresia had smaller LPA and RPA dimensions but no difference in lung areas. (3) In the common types of CTD, lung area variables were mostly smaller in double outlet right ventricle (DORV) and tetralogy of Fallot (TOF), but there was no difference in transposition of the great arteries (TGA). Conclusions CTD is associated with hypoplastic main and branch pulmonary arteries as well as PH. Risk factors for PH included defect types (DORV and TOF but not TGA) and RVOTO. It is plausible that pulmonary blood flow, rather than the type of CTD, RVOTO, or pulmonary artery dimensions, plays a key role in PH.

BACKGROUND AND OBJECTIVE It is hypothesized that diminished cerebral vascular resistance or the "brain sparing effect" is associated with fetuses with complex congenital heart defects (CHD) and may affect their neurodevelopmental outcome. An alternative explanation is that it is related to the location, cardiac output, pressure, and resistance in left heart obstructive CHDs. We sought to determine the effects of various left and right heart obstructive defects on the cerebral and placental hemodynamics and to evaluate the utility of these variables for the assessment and prognosis of CHDs. METHODS A total of 290 fetal echocardiograms were reviewed, including 91 fetuses with CHD and 199 normal ones. The CHD fetuses were divided into four groups, that is, left-sided obstructive lesions (LSOL), hypoplastic left heart syndrome (HLHS), right-sided obstructive lesions (RSOL), and hypoplastic right heart syndrome (HRHS). The pulsatility index of middle cerebral artery (MCA-PI) and umbilical artery (UA-PI) were measured by pulse-wave Doppler, and their Z scores were also derived. Cerebroplacental ratio (CPR) was calculated as: CPR=MCA-PI/UA-PI. RESULTS There was no significant difference in MCA-PI between the 4 CHD and normal control groups (P>.05). However, MCA-PI and Z score decreased in aortic stenosis but not in interrupted aortic arch or coarctation subgroups, whereas they increased in pulmonary atresia but not pulmonary stenosis or tetralogy of Fallot subgroups compared with normal group (P

Background and objectives Retrograde flow (RF) in the aortic isthmus is frequently observed in fetuses in various hemodynamic states including congenital heart defects (CHD). This study sought to: 1) establish the association between this observation and variables of CHD by fetal echocardiography (FE); and 2) to computer flow dynamic (CFD) model to probe the causes and mechanisms underlying this observation. Methods A total of 256 (gestational age (GA) 26.3±9.8 weeks) fetuses with CHD and 168 (GA: 25.8±10.3weeks) with normal FE were examined from January, 2011 to May, 2016. The study group was divided into: 1) no RF, 2) end systolic RF, end diastolic RF, systolic RF, diastolic RF, and systolic and diastolic RF sub-groups (Figure upper). GA, cerebroplacental ratio (CPR) of pulsatility index (PI) in middle cerebral and umbilical arteries, cardiothoracic area ratio (CTR), left and right atrial dimensions (LA/RA), left and right ventricular dimensions (LV/RV), aortic and pulmonary artery dimensions (AO/PA), and aortic isthmus and ductal arch dimensions (AI/DA), velocity ratio of aorta and pulmonary artery (AO/PAv), aortic isthmus and ductal arch in systolic (AI/DAvs) and diastolic (AI/DAvd). Using principal component analysis (PCA), the component score coefficient matrix and optional variance percent (OVP) was calculated by PCA and the RF pattern was simulated by CFD (Figure lower). Results RF modeling by CFD was feasible (Figure B). Component analysis by PCA showed that four types of variables were associated with RF: 1) Structural variables contribute 23.7% OVP, including LV/RV, LA/ RA, AO/PA, and IS/DA; 2) Resistance variables 16.8% OVP, i.e. CPR; 3) Growth variables 12.2% OVP, i,e, GA and CTR; and 4) Velocity variables 10.9% OVP, i.e. AO/PAv, AI/DAvd. Retrograde flow by fetal echo and CFD Conclusions Retrograde flow in the aortic isthmus is associated with structural, resistance, growth, and velocity variables in fetal circulation in various CHD and normal 3rd trimester pregnancies. Simulation and modeling by CFD is feasible and may be useful to understand the causes and mechanisms of retrograde flow and its utility in diagnosis and prognosis in CHD. Acknowledgement/Funding Research on prevention and control of reproductive health and major birth defects

The ozonation of acid red 18 (AR18) wastewater was investigated in an integrated process consisting of O3/Ca(OH)2 system and a newly-developed micro bubble gas-liquid reactor. The effects of operating parameters such as Ca(OH)2 dosage, reactor pressure, liquid phase temperature, initial dye concentration and inlet ozone concentration on decolorization and mineralization (TOC removal) were studied in order to know the ozonation performance of this new integrated process. The decolorization and TOC removal efficiency increased with increasing inlet ozone concentration and increasing Ca(OH)2 dosage before 2 g/L, as well as decreasing initial dye concentration. The optimum Ca(OH)2 dosage should exceed Ca(OH)2 solubility in liquid phase. The reactor pressure and liquid phase temperature have little effects on the decolorization and TOC removal efficiency. When Ca(OH)2 dosage exceeded 3 g/L, the decolorization and TOC removal of AR 18 almost reached 100% at 6 and 25 min, respectively. The intensification mechanism of Ca(OH)2 assisted ozonation was explored through the determination of CO32− and SO42− ions formed in the liquid phase and analysis of the precipitated substances. The mechanism for Ca(OH)2 intensified mineralization of dye solution is the simultaneous removal of CO32− ions, as hydroxyl radical scavengers, due to the presence of Ca2+ ions. Results indicated that the proposed new integrated process is a high efficient ozonation process for persistent organic wastewater treatment.

This study was designed to determine the long-term safety and efficacy of using modified double-disk occluders for perimembranous ventricular septal defect (pmVSD) closure in adults. From January 2004 to December 2014, 337 adults with pmVSDs were treated through transcatheter intervention using 2 types of double-disk occluders; 302 patients received a symmetrical concentric pmVSD occluder, and 35 patients received an asymmetrical concentric pmVSD occluder. All patients were followed up through electrocardiography and transthoracic echocardiography until June 2015. The success rate was 100% for both procedures. During the median 71-month follow-up period, no cases of infective endocarditis, cerebrovascular accidents, heart failure, or death occurred. Two major adverse events (0.6%) were recorded: complete atrioventricular block requiring surgical treatment in one patient and severe tricuspid valvular regurgitation requiring surgical repair in another patient. Cardiac conduction block was the most common minor adverse event. The mean left ventricular (LV) end-diastolic volume decreased from 96.6 ± 23.2 ml before intervention to 86.0 ± 22.0 ml (p

In this Special Issue of the Journal, 8 review articles that represent the new developments and applications of fetal echocardiography and fetal cardiology for diagnosis, prognosis, and treatment of fetal cardiovascular disease are included. The goal was to provide an updated review of the evidence for the current and emerging use of fetal echocardiography and cardiac magnetic resonance, improved diagnosis of challenging congenital heart disease, new tools for evaluation of fetal systolic and diastolic function, better prognosis and risk stratification of newborns with congenital heart diseases, and new and promising therapies for fetuses with cardiovascular disease.

BACKGROUND The previous literature on common pulmonary vein atresia (CPVA) mainly consists of neonatal case reports. There is a lack of research on the prenatal diagnosis of CPVA. METHODS We conducted a retrospective study of all fetuses with CPVA confirmed by autopsy between August 2010 and May 2018. Prenatal echocardiographic features, autopsy findings, and genetic test results were analyzed. We compared fetal CPVA with total anomalous pulmonary venous return (TAPVR) and neonatal CPVA. RESULTS During the study period, fetal echocardiography was performed on 31 617 fetuses. Six cases of CPVA were identified by autopsies, including 1 case performed with a cardiovascular cast. All 6 cases (100%) had asplenia syndrome (AS) and bilateral superior vena cava (BSVC). In 1 case (16.7%), the prenatal ultrasound results were in complete agreement with the postmortem findings. Four cases (66.7%) were misdiagnosed as TAPVR by prenatal echocardiography. For the remaining case (16.7%), no pulmonary venous anomalies were detected on prenatal echocardiography. No aneuploidy was identified in any of the cases. There were no statistically significant differences among the proportions of associated complex anomalies and AS between the fetal CPVA and TAPVR groups. The proportion of associated complex anomalies and AS in the fetal CPVA group was higher than that in the neonatal group (P

Background Premature restriction or closure of foramen ovale (FO) in otherwise structurally normal hearts may be associated with right ventricular dilation, tricuspid regurgitation, pericardial effusion, heart failure, even poor perinatal outcomes. Data about these rare conditions are lacking. Methods We retrospectively reviewed the echocardiographic records of 9704 fetuses seen from 2010 to 2014 in Beijing Anzhen Hospital, a regional and national referral center, to ascertain the presence of restriction or closure of FO. We collected the fetal echocardiography and perinatal outcome data for this group of fetuses with restriction or closure of FO. Results In this large, single-institution cohort (n = 9704), 6707 fetuses seen between 23 and 37 weeks of gestation had normal heart structures; of these, 60 (0.89%) had restrictive FO (rFO) and 5 (0.07%) had closure of FO (cFO). Fetal echocardiographic images showed right atrial dilation in 48 (73.84%), right ventricular dilation in 38 (58.46%), tricuspid regurgitation in 19 (29.23%), and pericardial effusion in 10 (15.38%). Also in this group, 50 (83.3%) with rFO and 4 (80.0%) with cFO had follow-up data. No prenatal deaths occurred in either the rFO or the cFO group, but the neonatal mortality included 1 in the rFO group and 2 in the cFO group. Conclusion Premature rFO/cFO are rare in fetuses with otherwise structurally normal hearts. The fetal echocardiographic characteristics include right atrial and ventricular dilated, tricuspid regurgitation, and pericardial effusion. Most fetuses had a good outcome, although there was an association between rFO, especially cFO, with neonatal morality and complications (prematurity, maternal preeclampsia and placental abruption, hydrops fetalis, and necrotizing enterocolitis with perforation).

Although fetal cardiac rhabdomyoma can be the initial finding in patients with tuberous sclerosis complex (TSC), the challenges of precise genetic diagnosis of TSC can now be potentially overcome by new whole or targeted genomic sequencing. The goals of this study were to investigate the correlation between suspected cardiac rhabdomyoma and TSC to provide the information for a prenatal diagnosis of TSC and to validate the TSC genotype in this cohort of fetuses with suspected prenatal cardiac rhabdomyoma. We retrospectively analyzed 10,728 fetal echocardiograms from January 2013 to March 2016 in our institution. A total of 32 fetuses were suspected of having cardiac rhabdomyomas. Among them, 15 subjects met the inclusion criteria and provided written consent. Samples from fetuses (n = 13 after terminations) and newborns (n = 2) were available for targeted genomic sequencing of the exons and introns of the TSC1 and TSC2 genes and the adjacent 10 base pairs and for validated studies using Sanger sequencing. Among the 15 subjects with suspected cardiac rhabdomyoma and TSC genomic sequencing data, 7 subjects were familial and 8 subjects were sporadic cases. Fetal echocardiography showed a single tumor in 2 fetuses and multiple tumors in 13 fetuses. Gene sequencing analysis showed no mutation of the TSC1 or TSC2 gene in 2 subjects with a single tumor but positive mutations in all 13 subjects with multiple tumors. Among the latter, 5 mutations were “pathogenic” and have been previously reported (4 familial and 1 sporadic). Six new mutations were “likely pathogenic” and had not been previously reported (3 familial and 3 sporadic); 1 was of “uncertain significance” (sporadic), and 1 was suspected of being “likely benign” (sporadic). Prenatal suspected cardiac rhabdomyoma detected by fetal echocardiography should raise the suspicion of TSC. In fetuses with multiple tumors, especially the familial cases, genomic sequencing has a high yield of detecting TSC-causing genes. Patient history, prenatal fetal echocardiography, and targeted genomic sequencing may facilitate screening for, diagnosis of, and counseling for TSC.

Normative ranges of fetal echocardiographic measurements are important for quantitative diagnosis of fetal cardiovascular disease. The current normative ranges were derived from small samples and were based on the hypothesis of a normal distribution of these measurements during fetal cardiovascular growth. The aims of this study were to test the hypothesis of a normal distribution of fetal echocardiographic measurements in a large multicenter cohort and to propose a reference system without the normal distribution hypothesis to improve accuracy of fetal echocardiographic measurements.Fifty-two variables from 6,343 normal fetal echocardiographic examinations were acquired from seven Chinese centers. The hypothesis of a normal distribution used in ordinary least squares regression was tested with the Jarque-Bera test. The quantile score (q score) derived from quantile regression without normal distribution hypothesis was compared with the Z score derived from ordinary least squares regression. A total of 288 fetuses with outflow tract and great artery abnormalities and 300 normal fetuses were used to compare the diagnostic accuracy of q and Z scores.All fetal echocardiographic measurements showed non-normal distributions (P .001). The normal range was underestimated by ordinary least squares regression compared with quantile regression by 30 ± 11%. The partial normalized areas under the receiver operating characteristic curve within the 20% false-positive rate were 0.62 and 0.50 for the q and Z scores, respectively.The q score provides a more robust system for determining normative ranges of fetal echocardiographic measurements. The improved sensitivity of matched false-positive rates makes the q score a more accurate reference for prenatal diagnosis, assessment, and prognosis of fetal cardiovascular disease.

Magnesium alloys are being actively studied for intravascular stent applications because of their good mechanical strength and biocompatibility. To rule out the high allergenicity of nickel and neurotoxicity of aluminum element, four kinds of WE magnesium alloys (where "W" represents the metallic element Y and "E" represents mixed rare earth (RE) elements; Y: 2.5, 5.0, 6.5, and 7.5 wt %; Nd: 1.0, 2.6, 2.5, and 4.2 wt %; Zr: 0.8 wt %) were chosen for in vitro investigation of their biocompatibility using cell culture. The results showed that, with the increase of rare earth elements in WE magnesium alloys, fibrinogen adsorption decreased and coagulation function was improved. It was also found that WE magnesium alloys promoted the adhesion of endothelial cells. With the increase of adhesion time, adhered cell numbers increased gradually. With 25% extracts, all the WE alloys promoted cell migration, while 100% extracts were not conducive to cell migration. Based on the above results, WE magnesium alloys 5.0WE (5.0Y-2.6Nd-0.8Zr) and 6.5WE (6.5Y-2.5Nd-0.8Zr) have better biocompatibility as compared with that with 2.5WE (2.5Y-1.0Nd-0.8Zr) and 7.5WE (7.5Y-4.2Nd-0.8Zr), and could be as the promising candidate materials for medical stent applications.

Objective Prenatal diagnosis of total anomalous pulmonary venous connection (TAPVC) by fetal echocardiography (FE) remains a challenge. We sought to ascertain the diagnostic accuracy of 2D and 3D spatiotemporal image correlation (STIC) FE and the potential incremental value of 3D STIC FE for prenatal diagnosis and assessment of TAPVC. Methods This study was conducted retrospectively in a single tertiary referral center. The study population consisted of 74 TAPVC from 17 063 fetuses by FE from August 2010 to April 2016. The 3D volume acquisition was also performed by STIC. Results A total of 17 063 fetal echocardiograms in our institution were queried and 74 (0.4%) were identified with TAPVC. In the TAPVC group, 11 had postnatal echocardiographic study, 25 had autopsies, 36 declined autopsy and 2 lost for follow-up. The sensitivity of FE for diagnosis of TAPVC was 97.14%, specificity 99.98%, respectively. In our cohort, 31 fetuses were evaluated by both 2D and 3D STIC and were confirmed by postnatal echocardiography or autopsies. TAPVC was diagnosed in all 31 patients (100%) by both 2D FE and 3D STIC. Furthermore, the classification of subtypes of TAPVC and accurate diagnosis of the drainage pathway was correct in 26 (83.9%) and 24 (77.4%) cases by 2D FE, respectively; but in 31 (100%) and 31 (100%) cases by 3D STIC. Conclusion 2D and 3D STIC FE provide accurate diagnosis of TAPVC with excellent sensitivity and specificity. 3D STIC FE has incremental value in further evaluation of classification of TAPVC types and drainage pathways.

Objectives We sought to develop a hemodynamic model of aortic and ductal arches using computational fluid dynamics (CFD) and 3D/4D spatio-temporal image correlation (STIC) fetal echocardiography and to investigate the hemodynamics of coarctation of aorta (CoA) in human fetuses using this approach. Methods We obtained 3D/4D STIC fetal echocardiographic images of the aortic and ductal arches (DA) in five normal fetuses. Based on these images, we simulated the hemodynamics in the two arches using CFD. Subsequently, we reduced the dimensions of aortic isthmus from 100% to 85%, 70%, 55%, 40%, and 25% of the original dimension digitally. Numerical simulation was repeated in each condition, and flow profile, velocity, pressure, and wall shear stress (WSS) were compared with those of the baseline normal aortic and ductal arches. Results With the progressive narrowing in the aortic isthmus, there were alterations in the flow profile, velocity, pressure, and WSS. The downstream vortexes disappeared, and the double helix profile became single helix. When the aortic isthmus reduced by 55% in dimension, there was an exponential increase in velocity and WSS and decrease in pressure. Conclusions The aortic and ductal arch geometry and flow lead to the alterations in flow profile, velocity, pressure, and WSS in the aortic isthmus in normal and CoA models, which are conductive of ductal issue migration into these areas. A 55% reduction in the dimension of aortic isthmus is associated with exponential change in velocity, pressure, and WSS, a probable threshold for hemodynamically significant CoA.

Diabetic cardiomyopathy (DCM) is the leading cause of morbidity and mortality among the diabetic patients and currently there is no effective means to reverse its pathological progress. Basic fibroblast growth factor (bFGF) has shown promise as a molecular therapy for DCM, but its delivery is inefficient and non-specific. In the present study, a therapy combining nanoparticle (NP) carrier and ultrasound-targeted microbubble destruction (UTMD) was reported the first time for bFGF delivery to the heart of diabetic rats. bFGF-loaded NP (bFGF-NP) were prepared with Poloxamer 188-grafted heparin copolymer using water-in-water technique, and the morphology, encapsulation efficiency, and bioactivity of bFGF-NP were studied. The cellular uptake and cytotoxicity of bFGF-NP were evaluated with primary cultures of the left ventricular (LV) cardiomyocytes in vitro. Therapeutic effects of bFGF-NP/UTMD on the heart of DCM rats were studied by measuring LV systolic and diastolic functions, hemodynamic characteristics and indicators of cardiac remodeling including myocardial collagen volume fraction and capillary density. Results demonstrated that bFGF-NP showed good round morphology, efficient bFGF encapsulation and stable bioactivity of bFGF in vitro. bFGF-NP/UTMD combined treatment significantly enhanced the efficiency of bFGF cellular uptake (P

Objectives The objective of this study was to evaluate the safety and efficacy of the surgical versus transcatheter approach to correct perimembranous ventricular septal defects (pmVSDs) in a prospective, randomized, controlled clinical trial. Background pmVSD is a common congenital heart disease in children. Surgical closure of pmVSD is a well-established therapy but requires open-heart surgery with cardiopulmonary bypass. Although the transcatheter approach is associated with significant incidence of complete atrioventricular block, it may provide a less invasive alternative. Critical comparison of the safety and efficacy of the 2 interventions necessitates a prospective, randomized, controlled trial. Methods Between January 2009 and July 2010, 229 children with pmVSD were randomly assigned to surgical or transcatheter intervention. Clinical, laboratory, procedural, and follow-up data over a 2-year period were compared. Results Neither group had mortality or major complications. However, statistical analysis of the 2 groups demonstrated significant differences (p Conclusions Transcatheter device closure and surgical repair are effective interventions with excellent midterm results for treating pmVSD in children. Transcatheter device closure has a lower incidence of myocardial injury, less blood transfused, faster recovery, shorter hospital stay, and lower medical expenses. (Transcatheter Closure Versus Surgery of Perimembranous Ventricular Septal Defects; NCT00890799 )

In this study, Co3O4 microspheres, with diameters of 1.0–2.5[Formula: see text][Formula: see text]m were prepared by a facile additive-free solvothermal method in combination with a post-annealing treatment. The catalytic properties of the as-prepared microspherical Co3O4 on the pyrolysis of ammonium perchlorate (AP) were explored using the differential scanning calorimetry (DSC) method. The experimental results showed that Co3O4 microspheres played an important role in accelerating the AP pyrolysis. The pyrolysis temperature decreased by 111∘C and the activation energy of AP pyrolysis reduced from [Formula: see text][Formula: see text]kJ[Formula: see text]mol[Formula: see text] to [Formula: see text][Formula: see text]kJ[Formula: see text]mol[Formula: see text], when 2[Formula: see text]wt.% of Co3O4 microspheres were added. Moreover, the introduction of Co3O4 microspheres led to a 2.76-fold increase in the exothermic heat during AP pyrolysis. This study reveals that Co3O4 microspheres can be served as a potential catalyst for the AP pyrolysis.

Quantitative measurement of left ventricular (LV) volumes, mass, and function is one of the most common and important indications for echocardiography. These measurements are among the most powerful tools for diagnosis and prognosis of congenital and acquired heart diseases and for assessment of medical, percutaneous, and surgical interventions. Awareness is also growing of the importance of right ventricular (RV) volume, mass, and function in many cardiopulmonary diseases. Furthermore, there are challenges and opportunities to measure the volume, mass, and function of complex chambers such as the left atrium, right atrium, and the univentricular heart. As echocardiography continues to be the imaging modality of choice for these measurements, the strengths and limitations of M-mode, two-dimensional (2D), and recently three-dimensional (3D) echocardiographic (3DE) methodologies for accurate and reproducible measurement of these indices have been extensively investigated for congenital and acquired heart diseases. Evidence suggests that 3DE provides improved accuracy and reproducibility over 2D methods for measurement of LV volume and function calculation in adults and in children. Data have accumulated on the utility of 3DE for measuring chamber volumes and function for the RV and for the single ventricle, which may become more widely used in clinical and research arenas in the future. Finally, new advanced modes of analysis such as 3D strain and synchrony analysis by 3DE are promising methodologies that warrant further investigation.

Objective To evaluate the value and improve the diagnostic accuracy of echocardiography in the diagnosis of a sinus of Valsalva aneurysm (SVA) with rare pathological patterns. Methods Echocardiographic features and surgical findings from 270 Chinese patients with SVA treated in the last 18 years (1995–2013) at the Union Hospital were compared retrospectively; 22 of 270 cases had rare patterns. Results The patients with SVA, a rare origin, a rare extending position, or a rare course accounted for 3.4%, 7.4%, and 0.4% of the 270 cases, respectively. The three most common aneurysmal complications of the patients with rare patterns were severe aortic regurgitation (16), obstruction of the ventricular outflow tract or valvular orifice (3), and conduction disturbance (3). The origin, course, extending position and rupture status of the SVAs determined by echocardiography were entirely consistent with surgical findings in 81.8% of the 22 cases. With the exception of one failed diagnosis of an aneurysmal wall dissection and one misdiagnosis of a descending aortic dissection, the echocardiographic results of SVA complications and associated cardiovascular lesions were also confirmed. Conclusion We could accurately diagnose SVAs with rare pathological patterns by echocardiographic identification of distinguishing features. However, for several conditions, we could not accurately identify the origin or course of the aneurysm or define its relationship to adjacent structures using conventional echocardiography alone. Therefore, we recommend combining conventional echocardiography with different imaging techniques, such as transesophageal echocardiography, three-dimensional echocardiography, computed tomography angiography, and aortic angiography.