To investigate the expression of HOX transcript antisense RNA (HOTAIR) in cardiac tissues and plasma of patients with congenital heart diseases (CHDs).

Heart diseases (HDs) represent a common group of diseases that involve the heart, a number of which are characterized by high morbidity and lethality. Recently, increasing evidence demonstrates diverse non-coding RNAs (ncRNAs) play critical roles in HDs. However, currently there lacks a systematic investigation of the association between HDs and ncRNAs. Here, we developed a Heart Disease-related Non-coding RNAs Database (HDncRNA), to curate the HDs-ncRNA associations from 3 different sources including 1904 published articles, 3 existing databases [the Human microRNA Disease Database (HMDD), miR2disease and lncRNAdisease] and 5 RNA-seq datasets. The HDs-ncRNA associations with experimental validations curated from these articles, HMDD, miR2disease and part of data from lncRNAdisease were 'direct evidence'. Relationships got from high-through data in lncRNAdisease and annotated differential expressed lncRNAs from RNA-seq data were defined as 'high-throughput associations'. Novel lncRNAs identified from RNA-seq data in HDs had least credibility and were defined as 'predicted associations'. Currently, the database contains 2304 HDs-ncRNA associations for 133 HDs in 6 species including human, mouse, rat, pig, calf and dog. The database also has the following features: (i) A user-friendly web interface for browsing and searching the data; (ii) a visualization tool to plot miRNA and lncRNA locations in the human and mouse genomes; (iii) information about neighboring genes of lncRNAs and (iv) links to some mainstream databases including miRbase, Ensemble and Fantom Cat for the annotated lncRNAs and miRNAs. In summary, HDncRNA provides an excellent platform for exploring HDs related ncRNAs.Database URL: http://hdncrna.cardiacdev.com.

A high inflammatory state, such as atherosclerosis, is a major underlying cause of coronary heart diseases (CHDs). Inflammatory mediators are known to lead to endothelial dysfunction and play a key role in initiation, progression, and rupture of atherothrombotic plaque. Chronic inflammatory dental infections such as periodontitis and lesions of endodontic origin or chronic apical periodontitis (CAP) may provide an environment conducive for such events. Atherosclerosis has shown to share a common spectrum of inflammatory markers with apical periodontitis. The possible correlation between CHD and CAP is emerging at microbiological, clinical, inflammatory, and molecular levels. This less recognized fact should be discussed more among the dental and medical fraternity so that more awareness and positive approach toward oral health can be created among patients and health-care providers.

To compare the fetal brain structures assessed in routine sonographic scans during the second and third trimesters in fetuses with and without congenital heart disease (CHD).

Transpulmonary thermodilution is recommended in the treatment of critically ill patients presenting with complex shock. However, so far it has not been validated in hemodynamically stable patients with heart disease.

Pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) has serious consequence and plasma protein profiles in CHD-PAH are unknown. We aimed to reveal the differential plasma proteins in 272 CHD patients with or without PAH. Various types of CHD-PAH were studied. Differential plasma proteins were first detected by iTRAQ proteomic technology and those with significant clinical relevance were selected for further ELISA validation in new cohort of patients. Among the 190 differential plasma proteins detected by iTRAQ, carbamoyl-phosphate synthetase I (CPSI, related to urea cycle and endogenous nitric oxide production) and complement factor H-related protein 2 (CFHR2, related to complement system and coagulant mechanism) were selected for further ELISA validation in new cohort of 152 patients. Both CPSI and CFHR2 were down-regulated with decreased plasma levels (p < 0.01). Thus, we for the first time in CHD-PAH patients identified a large number of differential plasma proteins. The decreased CPSI expression in CHD-PAH patients may reveal a mechanism related to endogenous nitric oxide and the decrease of CFHR2 protein may demonstrate the deficiency of the immune system and coagulation mechanism. The findings may open a new direction for translational medicine in CHD-PAH with regard to the diagnosis and progress of the disease.

Comorbidities of coronavirus disease 2019 (COVID-19)/coronary heart disease (CHD) pose great threats to disease outcomes, yet little is known about their shared pathology. The study aimed to examine whether comorbidities of COVID-19/CHD involved shared genetic pathology, as well as to clarify the shared genetic variants predisposing risks common to COVID-19 severity and CHD risks.

In the domain of healthcare, most importantly pediatric healthcare, the role of artificial intelligence (AI) has significantly impacted the medical field. Congenital heart diseases represent a group of heart diseases that are known to be some of the most critical cardiac conditions present at birth. These heart diseases need a swift diagnosis as well as an intervention to ensure the wellbeing of newborns. Fortunately, with the help of AI, including the highly advanced algorithms, analytics and imaging involved, it provides us with a promising era for neonatal care. This article reviewed published data in PubMed, Science Direct, UpToDate, and Google Scholar between the years 2015-2023. To conclude The use of artificial intelligence in detecting congenital heart diseases has shown great promise in improving the accuracy and efficiency of diagnosis. Several studies have demonstrated the efficacy of AI-based approaches for diagnosing congenital heart diseases, with results indicating that the systems can achieve high levels of sensitivity and specificity. In addition, AI can help reduce the workload of healthcare professionals allowing them to focus on other critical aspects of patient care. Despite the potential benefits of using AI, in addition to detecting congenital heart disease, there are still some challenges to overcome, such as the need for large amounts of high-quality data and the requirement for careful validation of the algorithms. Nevertheless, with ongoing research and development, AI is likely to become an increasingly valuable tool for improving the diagnosis and treatment of congenital heart diseases.

Despite a strong genetic component, only a few genes have been identified in congenital heart diseases (CHDs). We introduced systems analyses to uncover the hidden organization on biological networks of mutations in CHDs and leveraged network analysis to integrate the protein interactome, patient exomes, and single-cell transcriptomes of the developing heart. We identified a CHD network regulating heart development and observed that a sub-network also regulates fetal brain development, thereby providing mechanistic insights into the clinical comorbidities between CHDs and neurodevelopmental conditions. At a small scale, we experimentally verified uncharacterized cardiac functions of several proteins. At a global scale, our study revealed developmental dynamics of the network and observed its association with the hypoplastic left heart syndrome (HLHS), which was further supported by the dysregulation of the network in HLHS endothelial cells. Overall, our work identified previously uncharacterized CHD factors and provided a generalizable framework applicable to studying many other complex diseases. A record of this paper's Transparent Peer Review process is included in the supplemental information.

We previously demonstrated that endothelial microparticles (EMPs) are increased in mitral valve diseases and impair valvular endothelial cell function. Perioperative systemic inflammation is an important risk factor and complication of cardiac surgery. In this study, we investigate whether EMPs increase in congenital heart diseases to promote inflammation and endothelial dysfunction.

It remains a great challenge for targeted therapy of heart diseases. To achieve desirable heart targeting, we developed a polyphenol-assisted nanoprecipitation/self-assembly approach for facile engineering of functional nanoparticles. Three different materials were employed as representative carriers, while gallic acid, catechin, epigallocatechin gallate, and tannic acid (TA) served as typical polyphenols with varied numbers of phenolic hydroxyl groups. By optimizing different parameters, such as polyphenol types and the weight ratio of carrier materials and polyphenols, well-defined nanoparticles with excellent physicochemical properties can be easily prepared. Regardless of various carrier materials, TA-derived nanoparticles showed potent reactive oxygen species-scavenging activity, especially nanoparticles produced from a cyclodextrin-derived bioactive material (TPCD). By internalization into cardiomyocytes, TPCD/TA nanoparticles (defined as TPTN) effectively protected cells from hypoxic-ischemic injury. After intravenous injection, TPTN considerably accumulated in the injured heart in two murine models of ventricular fibrillation cardiac arrest in rats and myocardial hypertrophy in mice. Correspondingly, intravenously delivered TPTN afforded excellent therapeutic effects in both heart diseases. Preliminary experiments also revealed good safety of TPTN. These results substantiated that TPTN is a promising nanotherapy for targeted treatment of heart diseases, while polyphenol-assisted self-assembly is a facile but robust strategy to develop heart-targeting delivery systems.

Predictive genetic testing (PGT) is offered to asymptomatic relatives at risk of hereditary heart disease, but the impact of result disclosure has been little studied. We evaluated the psychosocial impacts of PGT in hereditary heart disease, using self-report questionnaires (including the State-Trait Anxiety Inventory) in 517 adults, administered three times to the prospective cohort (PCo: n = 264) and once to the retrospective cohort (RCo: n = 253). The main motivations for undergoing PGT were "to remove doubt" and "for their children". The level of anxiety increased between pre-test and result appointments (p <0.0001), returned to baseline after the result (PCo), and was moderately elevated at 4.4 years (RCo). Subjects with a history of depression or with high baseline anxiety were more likely to develop anxiety after PGT result (p = 0.004 and p <0.0001, respectively), whatever it was. Unfavourable changes in professional and/or family life were observed in 12.4% (PCo) and 18.7% (RCo) of subjects. Few regrets about PGT were expressed (0.8% RCo, 2.3% PCo). Medical benefit was not the main motivation, which emphasises the role of pre/post-test counselling. When PGT was performed by expert teams, the negative impact was modest, but careful management is required in specific categories of subjects, whatever the genetic test result.

Congenital heart disease (CHD) survivors are at risk for neurodevelopmental disability (NDD), and recent studies identify genes associated with both disorders, suggesting that NDD in CHD survivors may be of genetic origin. Genes contributing to neurogenesis, dendritic development and synaptogenesis organize neural elements into networks known as the connectome. We hypothesized that NDD in CHD may be attributable to genes altering both neural connectivity and cardiac patterning. To assess the contribution of de novo variants (DNVs) in connectome genes, we annotated 229 published NDD genes for connectome status and analyzed data from 3,684 CHD subjects and 1,789 controls for connectome gene mutations. CHD cases had more protein truncating and deleterious missense DNVs among connectome genes compared to controls (OR = 5.08, 95%CI:2.81-9.20, Fisher's exact test P = 6.30E-11). When removing three known syndromic CHD genes, the findings remained significant (OR = 3.69, 95%CI:2.02-6.73, Fisher's exact test P = 1.06E-06). In CHD subjects, the top 12 NDD genes with damaging DNVs that met statistical significance after Bonferroni correction (PTPN11, CHD7, CHD4, KMT2A, NOTCH1, ADNP, SMAD2, KDM5B, NSD2, FOXP1, MED13L, DYRK1A; one-tailed binomial test P ≤ 4.08E-05) contributed to the connectome. These data suggest that NDD in CHD patients may be attributable to genes that alter both cardiac patterning and the connectome.

Congenital heart diseases (CHD) are a large group of prevalent and complex anatomic malformations of the heart, with the genetic basis remaining largely unknown. Since genes or factors associated with the differentiation of human embryonic stem (HES) cells would affect the development of all embryonic tissues, including cardiac progenitor cells, we postulated their potential roles in CHD. In this study, we focused on ZW10, a kinetochore protein involved in the process of proper chromosome segregation, and conducted comparative studies between CHD patients and normal controls matched in gender and age in Chinese Han populations. We identified three variations in the ZW10 gene, including rs2885987, rs2271261 and rs2459976, which all had high genetic heterozygosity. Association analysis of these genetic variations with CHD showed correlation between rs2459976 and the risk of CHD. We conclude that rs2459976 in the ZW10 gene is associated with CHD in Chinese Han populations.

Circular RNAs (circRNA) are involved in a variety of human heart diseases, however, circRNA expression profiles and circRNA-miRNA-mRNA regulatory network in human atrial fibrillation (AF) especially with valvular heart diseases (VHD) remain poorly understood. A high-throughput RNA sequencing was used to investigate the differentially expressed circRNAs in left atrial appendage from VHD patients with or without persistent AF. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the potential functions of the host genes of differentially expressed circRNA and their downstream targets. CircRNA-miRNA-mRNA regulatory network was constructed to identify mechanisms underlying circRNAs. qRT-PCR and sanger sequencing were further performed to validate the results. Compared with sinus rhythm (SR) patients, there were 3094 upregulated and 4472 downregulated circRNAs in AF patients respectively. The expression of 10 most differentially expressed circRNAs (circ 255-ITGA7, circ 418-KCNN2, circ 13913-MIB1, circ 44670-BARD1, circ 44782-LAMA2, circ 81906-RYR2, circ 35880-ANO5, circ 22249-TNNI3K, circ 3136-TNNI3K, circ 56186-TNNI3K) between SR and persistent AF patients were verified by qRT-PCR. In addition, specific back-splicing sites of these circRNAs was confirmed by sanger sequencing. GO and KEGG pathway analysis indicated that cAMP signal pathway and Wnt signal pathway might play important role in the development of AF in VHD patients, which might be affected by circRNAs. This study provided a preliminary landscape of circRNAs expression profiles which are involved in persistent AF due to VHD, and established the possibility for future related researches in this field.

Cardiac myosin binding protein C (cMyBP-C) is a cardiac structural and regulatory protein; mutations of cMyBP-C are frequently associated with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Cardiac special transcription factors may regulate the expression of cMyBP-C. However, the role of cMyBP-C in congenital heart diseases (CHD) remains poorly understood. In the current study, western blotting and the MRM approach showed that cMyBP-C expression was significantly reduced in fetuses with CHD compared to those without. Furthermore, we found that cMyBP-C interacted with KLHL3 by immunoprecipitation and immunofluorescence, and the degradation of cMyBP-C was caused by KLHL3-mediated ubiquitination. In addition, homocysteine (Hcy, a risk factor of CHD) treatment caused a decrease in cMyBP-C and an increase in KLHL3 expression, and the proteasome inhibitor MG132 reversed the Hcy-induced reduction of cMyBP-C expression. Finally, we verified that reduced cMyBP-C by Hcy promoted apoptosis in cardiomyocytes. These results demonstrate that Hcy decreases the expression of cMyBP-C through a KLHL3-mediated ubiquitin-proteasome pathway, and thereby influences heart development.

Background: 3D technology support is an emerging technology in the field of congenital heart diseases (CHD). The goals of 3D printings or models is mainly a better analysis of complex anatomies to optimize the surgical repair or intervention planning. Method: We performed a systematic review to evaluate the accuracy and reliability of CHD modelization and 3D printing, as well as the proof of concept of the benefit of 3D printing in planning interventions. Results: Correlation studies showed good results with anatomical measurements. This technique can therefore be considered reliable with the limit of the operator's subjectivity in modelizing the defect. In cases series, the benefits of the 3D technology have been shown for describing the vessels anatomy and guiding the surgical approach. For intra-cardiac complex anatomy, 3D models have been shown helpful for the planification of intracardiac repair. However, there is still lack of evidence based approach for the usefulness of 3D models in CHD in changing outcomes after surgery or interventional procedures due to the difficulty to design a prospective study with comprehensive and clinically meaningful end-points. Conclusion: 3D technology can be used to improve the understanding of anatomy of complex CHD and to guide surgical strategy. However, there is a need to design clinical studies to identify the place of this approach in the current clinical practice.

The aim of this study was to explore the trend of ischemic heart disease (IHD) admission and the prescriptions of IHD medications in England and Wales.

Cerebral ischemia and ischemic heart diseases, common entities nowadays, are the main manifestation of circulatory diseases. Cardiovascular diseases, followed by stroke, represent the leading cause of mortality worldwide. Both entities share risk factors, pathophisiology and etiologic aspects by means of a main common mechanism, atherosclerosis. However, each entity has its own particularities. Ischemic stroke shows a variety of pathogenic mechanisms not present in ischemic heart disease. An ischemic stroke increases the risk of suffering a coronary heart disease, and viceversa. The aim of this chapter is to review data on epidemiology, pathophisiology and risk factors for both entities, considering the differences and similarities that could be found in between them. We discuss traditional risk factors, obtained from epidemiological data, and also some novel ones, such as hyperhomocisteinemia or sleep apnea. We separate risk factors, as clasically, in two groups: nonmodifiables, which includes age, sex, or ethnicity, and modifiables, including hypertension, dyslipidemia or diabetis, in order to discuss the role of each factor in both ischemic events, ischemic stroke and coronary heart disease.

The goal of this study was to summarize anesthesia management for pediatrics with congenital heart diseases who undergo cardiac catheterization procedure in China.