Health Systems Strengthening to Tackle the Global Burden of Pediatric and Congenital Heart Disease: A Diagonal Approach

1 Background Congenital heart disease(CHD)is the most common major congenital anomaly,affecting approximately one in every 100 live births[1].Among congenital anomalies,66%of preventable deaths are due to CHD,and 58%of the avertable morbidity and mortality due to congenital anomalies would result from scaling congenital heart surgery services[2].Every year,nearly 300,000 children and adults die from CHD,the majority of whom live in low-and middle-income countries(LMICs)[3].Approximately 49%of all individuals with CHD will require surgical or interventional care at some point in their lifetime[4];as a result of advances in access to and the delivery of such services,over 95%of children born with CHD in high-income countries now live into adulthood[3].Here,adults have surpassed children in the number of CHD cases at a ratio of 2:1[5].

Machine Learning-Based Intelligent Auscultation Techniques in Congenital Heart Disease:Application and Development

Congenital heart disease(CHD),the most prevalent congenital ailment,has seen advancements in the“dual indi-cator”screening program.This facilitates the early-stage diagnosis and treatment of children with CHD,subse-quently enhancing their survival rates.While cardiac auscultation offers an objective reflection of cardiac abnormalities and function,its evaluation is significantly influenced by personal experience and external factors,rendering it susceptible to misdiagnosis and omission.In recent years,continuous progress in artificial intelli-gence(AI)has enabled the digital acquisition,storage,and analysis of heart sound signals,paving the way for intelligent CHD auscultation-assisted diagnostic technology.Although there has been a surge in studies based on machine learning(ML)within CHD auscultation and diagnostic technology,most remain in the algorithmic research phase,relying on the implementation of specific datasets that still await verification in the clinical envir-onment.This paper provides an overview of the current stage of AI-assisted cardiac sounds(CS)auscultation technology,outlining the applications and limitations of AI auscultation technology in the CHD domain.The aim is to foster further development and refinement of AI auscultation technology for enhanced applications in CHD.

Femoral Access with Ultrasound-Guided Puncture and Z-Stitch Hemostasis for Adults with Congenital Heart Diseases Undergoing Electrophysiological Procedures

Aims:Although the application of ultrasound-guided vascular puncture and Z-stitch hemostasis to manage femoral access has been widely utilized,there is limited data on this combined application in adult congenital heart disease(ACHD)patients undergoing electrophysiological(EP)procedures.We sought to evaluate the safety and efficacy of ultrasound-guided puncture and postprocedural Z-stitch hemostasis for ACHD patients under-going EP procedures.Methods and Results:The population of ACHD patients undergoing transfemoral EP pro-cedures at the University of Zurich Heart Center between January 2019 and December 2022 was observed and analyzed.During the study period,femoral access(left/right,arterial/venous)was performed under real-time ultrasound guidance.At the end of the procedure,a single Z-stitch was performed at the puncture site.We eval-uated the incidence of in-hospital complications associated with femoral access puncture in this population.Among 101 patients who had a total of 147 previous ipsilateral vascular punctures(mean 1.5 per person),100 patients underwent successful femoral vascular access for EP procedures.The median age of the patients was 47±15 years and 34(34%)were male.Z-stitches were performed after the procedure in 100 patients with 303 femoral vascular accesses(mean 3 punctures per person).No patient developed vascular puncture relevant inguinal hematoma,pseudo aneurysm,arteriovenousfistula,venous or arterial thrombosis.Conclusion:In ACHD patients undergoing EP procedures,optimal femoral access management can be achieved with ultra-sound-guided puncture and postprocedural Z-stitch hemostasis.

DNA Methylation Variation Is Identified in Monozygotic Twins Discordant for Congenital Heart Diseases

Aims:Multiple genes and environmental factors are known to be involved in congenital heart disease(CHD),but epigenetic variation has received little attention.Monozygotic(MZ)twins with CHD provide a unique model for exploring this phenomenon.In order to investigate the potential role of Deoxyribonucleic Acid(DNA)methyla-tion in CHD pathogenesis,the present study examined DNA methylation variation in MZ twins discordant for CHD,especially ventricular septal defect(VSD).Methods and Results:Using genome-wide DNA methylation profiles,we identified 4004 differentially methylated regions(DMRs)in 18 MZ twin pairs discordant for CHD,and 2826 genes were identified.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed a list of CHD-associated pathways.To further investigate the role of DNA methylation in VSD,data from 7 pairs of MZ twins with VSD were analyzed.We identified 1614 DMRs corresponding to 1443 genes associated with arrhythmogenic right ventricular cardiomyopathy,cyclic guanosine monopho-sphate-protein kinase G(cGMP-PKG)signaling pathway by KEGG analysis,and cell-cell adhesion,calcium ion transmembrane transport by GO analysis.A proportion of DMR-associated genes were involved in calcium signaling pathways.The methylation changes of calcium signaling genes might be related to VSD pathogenesis.Conclusion:CHD is associated with differential DNA methylation in MZ twins.CHD may be etiologically linked to DNA methylation,and methylation of calcium signaling genes may be involved in the development of VSD.

Transcatheter Closure of Postoperative Residual Atrial or Ventricular Septal Shunts in Patients with Congenital Heart Disease

Background:Transcatheter closure(TCC)has emerged as the preferred treatment for selected congenital heart disease(CHD).While TCC offers benefits for patients with postoperative residual shunts,understanding its mid-and long-term efficacy and safety remains crucial.Objective:This study aims to assess the mid-and long-term safety and efficacy of TCC for patients with residual atrial or ventricular septal shunts following CHD correction.Methods:In this consecutive retrospective study,we enrolled 35 patients with residual shunt who underwent TCC or surgical repair of CHD between June 2011 to October 2022.TCC candidacy was determined based on established criteria.Echocardiography and electrocardiogram were conducted during the perioperative period and continued as part of long-term follow-up.Results:Among the patients,5(14.3%)exhibited interatrial shunt-ing,while 30(85.7%)had interventricular shunting.TCC was successfully implemented in 33 of 35 patients,with exceptions in two cases of post-ventricular septal defect repair due to anatomical challenges involving the shape and aortic angulation.This resulted in a TCC success rate of 94.3%.Trace residual shunt was detected in two interventricular shunting cases and a mild residual shunt in one interventricular shunting case;all resolved by the three-month follow-up after TCC.Minor complications included one hematoma at the puncture site and one transient junctional rhythm during the perioperative period.During a median follow-up of 73 months,there were no instances of residual shunt,device embolization,occluder displacement,valve insufficiency,malignant arrhythmia,infective endocarditis,death,or other serious complications.Conclusion:TCC is an effective and safe therapy for patients with residual atrial or ventricular septal shunts following CHD correction.Thesefindings support the consideration of TCC as the preferred treatment option for appropriate patient populations.

Use of Patient-Specific “4D” Tele-Education to Enhance Actual and Perceived Knowledge in Congenital Heart Disease (CHD) Patients

Background:Patients with congenital heart disease(CHD)will transition to lifelong adult congenital cardiac care.However,their structural heart disease is challenging to convey via two-dimensional drawings.This study utilized a tele-educational environment,with personalized three-dimensional(3D)modeling and health Details(3D+Details=“4D”),to improve actual and perceived knowledge,both important components of transition readiness in CHD patients.Methods:Participants aged≥13 years with a history of CHD and cardiac magnetic resonance imaging(MRI)studies were eligible.Cardiac MRI datasets were then used to segment and create 3D heart models(using Mimics,Materialize Inc.).Participantsfirst completed the MyHeart Questionnaire,a validated survey of actual knowledge.A tele-educational session was then scheduled,during which participants were shown a 3D model of a normal heart,followed by their personal 3D heart model and specific health details.Participants then repeated the actual knowledge survey,in addition to questionnaires assessing perceived knowledge pre-and post-session,as well as a satisfaction survey.Results:Twenty-two patients were included.Actual knowledge increased from 75%±15%to 89%±20%(p=0.00043)and perceived knowledge increased infive of seven questions.Actual knowledge correlated with perceived knowledge(r=0.608,p<0.0001).Ninety-one percent of participants ranked the 3D model as“very satisfactory”and ninety-five percent ranked the educational session as“very help-ful”or“extremely helpful.”Conclusions:The use of“4D”tele-education increased both actual and perceived knowledge and may help improve transition readiness in CHD patients.

Risk Stratification and Prognosis of Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Background:Current guidelines for managing pulmonary arterial hypertension(PAH)recommend a risk strati-fication approach.However,the applicability and accuracy of these strategies for PAH associated with congenital heart disease(PAH-CHD)require further validation.This study aims to validate the reliability and predictive accuracy of a simplified stratification strategy for PAH-CHD patients over a three-year follow-up.Additionally,new prognostic variables are identified and novel risk stratification methods are developed for assessing and managing PAH-CHD patients.Methods:This retrospective study included 126 PAH-CHD patients.Clinical and biochemical variables across risk groups were assessed using Kruskal-Wallis and Fisher’s exact tests.Indepen-dent risk factors were identified using ordered logistic regression,while Kaplan-Meier and Cox proportional hazards regression analyses evaluated their impact on all-cause mortality.A new stratification model for the PAH-CHD population was constructed based on these analyses.Results:Significant survival differences across stratified risk groups were observed(p<0.001),validating the effectiveness of the simplified risk stratification method in PAH-CHD patients.Prothrombin activity was a strong independent predictor of adverse outcomes of PAH-CHD patients(Hazard ratio 0.95,p<0.001,C-index 0.70).A model combining N-terminal pro-brain natriuretic peptide,prothrombin activity,albumin,and right atrial area achieved an area under the curve of 0.89 and a C-index of 0.85.Conclusions:The simplified risk stratification method is applicable to PAH-CHD patients.Prothrombin activity is a strong independent predictor of adverse outcomes.A comprehensive risk stratification approach,incorporating both established and novel biomarkers,enhances accessibility and offers predictive efficacy during follow-up for PAH-CHD patients,comparable to established models.

Long-Term Mortality of Children with Congenital Heart Disease Admitted to the Departmental University Hospital of Borgou/Alibori from 2011 to 2022

Background: Congenital heart disease is a public health issue due to its incidence and mortality rate. The aim of this study was to investigate the long-term mortality of children with congenital heart disease admitted to the Departmental University Hospital of Borgou/Alibori (CHUD-B/A) from 2011 to 2022. Methods: This descriptive longitudinal study with analytical aims covered 11 years (April 1, 2011 to December 31, 2022). It consisted of a review of the records of children under 15 years of age with echocardiographically confirmed congenital heart disease. This was followed by an interview with the parents to assess the children’s current condition. Data were entered using Kobocollect software and analyzed using R Studio 4.2.2. software. Results: A total of 143 complete files were retained. The median age at diagnosis was 14 months (IIQ: Q1 = 4;Q3 = 60) with a range of 2 days and 175 months, and the sex-ratio (M/F) was 0.96. Left-to-right shunts were the most frequent cardiopathy group (62.9%). Only 35 children (24.5%) benefited from restorative treatment. The mortality rate was 31.5%. Median survival under the maximum bias assumption was 114 months and 216 months under the assumption of minimum bias. Survival was significantly better in children with right-to-left shunts (p = 0.0049) under the assumption of minimum bias. The death risk factors were: age at diagnosis less than 12 months (aHR = 7.58;95% CI = 3.36 - 17.24;p Conclusion: The long-term mortality of congenital heart disease is high and favoured by the absence of restorative treatment. Local correction of congenital heart disease and medical follow-up will help to reduce this mortality.

Impact of Social Determinants of Health on Self-Perceived Resilience: An Exploratory Study of Two Cohorts of Adults with Congenital Heart Disease

Social determinants of health(SDOH)affect quality of life.We investigated SDOH impacts on self-perceived resilience among people with adult congenital heart disease(ACHD).Secondary analysis of data from two com-plementary studies:a survey study conducted May 2021–June 2022 and a qualitative study conducted June 2020–August 2021.Resilience was assessed through CD-RISC10 score(range 0–40,higher scores reflect greater self-perceived resilience)and interview responses.Sociodemographic and SDOH(education,employment,living situa-tion,monetary stability,financial dependency,area deprivation index)data were collected by healthcare record review and self-report.We used linear regression with robust standard errors to analyze survey data and performed a thematic analysis of interview data.Survey participants(N=127)mean age was 42±14 years;51%were female,87%white.ACHD was moderate(75%)or complex(25%);41%functional class C or D.Resilience(mean 30±7)varied by monetary stability:compared to people with difficulty paying bills,resilience was 15.0 points higher(95%CI:6.9–23.1,p<0.001)for people reporting having enough money and 14.2 points higher(95%CI:5.9–22.4,p=0.001)for those reporting just enough money.Interview participants’(N=25)mean age was 32 years(range 22–44);52%were female,72%white.ACHD was moderate(56%)or complex(44%);76%functional class C or D.Participants discussed factors affecting resilience aligned with each of the major SDOH,prominently,economic stability and healthcare access and quality.Financial stability may be important for supporting self-perceived resi-lience in ACHD.This knowledge can inform the development of resilience interventions for this population.

Congenital Heart Disease Referred for Surgery: Analysis and Epidemiological Description in the Cardiology Department of CHU Ignace Deen

Introduction: Congenital heart disease includes all cardiac and vascular malformations. It accounts for approximately one third of all congenital malformations and is a public health problem, particularly in developing countries. The aim of this study was to analyze the epidemiological, clinical and paraclinical aspects of congenital heart disease. Methods: This was a retrospective descriptive and analytical study based on the records of 135 patients referred for surgery and followed up in the cardiology department of the Ignace Deen University Hospital, collected in November 2022. Results: Hospital prevalence was 5%. The mean age was 71 months, ranging from 1 month to 19 years. The age group over 24 months was the most represented (62%). The M/F sex ratio was 1.36. Urban origin was predominant (58%). The rate of children not attending school or dropping out was high (16%). Siblings with fewer than 4 children were the most common (88%). A heart murmur was the most frequent sign (78%), followed by cyanosis (36%) and heart failure (29%). The association between heart murmurs and CHD was proven with a p-value Conclusion: CHDs represent the main indication for paediatric cardiac surgery and follow-up (95%). We stress the importance of implementing a screening and management strategy for congenital heart disease.

Loss to Specialized Cardiology Follow-Up in Adults Living with Congenital Heart Disease

Background:Much has been written about the loss to follow-up in the transition between pediatric and adult Congenital Heart Disease(CHD)care centers.Much less is understood about the loss to follow-up(LTF)after a successful transition.This is critical too,as patients lost to specialised care are more likely to experience mor-bidity and premature mortality.Aims:To understand the prevalence and reasons for loss to follow-up(LTF)at a large Australian Adult Congenital Heart Disease(ACHD)centre.Methods:Patients with moderate or highly complex CHD and gaps in care of>3 years(defined as LTF)were identified from a comprehensive ACHD data-base.Structured telephone interviews examined current care and barriers to clinic attendance.Results:Overall,407(22%)of ACHD patients(n=1842)were LTF.The mean age at LTF was 31(SD 11.5)years and 54%were male;311(76%)were uncontactable.Compared to adults seen regularly,lost patients were younger,with a greater socio-economic disadvantage,and had less complex CHD(p<0.05 for all).We interviewed 59 patients(14%).The top 3 responses for care absences were“feeling well”(61%),losing track of time(36%),and not needing fol-low-up care(25%).Conclusions:A large proportion of the ACHD population becomes lost to specialised cardiac care,even after a successful transition.This Australian study reports younger age,moderate complexity defects,and socio-economic disadvantage as predictive of loss to follow-up.This study highlights the need for novel approaches to patient-centered service delivery even beyond the age of transition and resources to maintain patient engagement within the ACHD service.

Exploring kidney biopsy findings in congenital heart diseases:Insights beyond cyanotic nephropathy

BACKGROUND The association between congenital heart disease and chronic kidney disease is well known.Various mechanisms of kidney damage associated with congenital heart disease have been established.The etiology of kidneydisease has commonly been considered to be secondary to focal segmental glomerulosclerosis(FSGS),however,this has only been demonstrated in case reports and not in observational or clinical trials.AIM To identify baseline and clinical characteristics,as well as the findings in kidney biopsies of patients with congenital heart disease in our hospital.METHODS This is a retrospective observational study conducted at the Nephrology Depart-ment of the National Institute of Cardiology“Ignacio Chávez”.All patients over 16 years old who underwent percutaneous kidney biopsy from January 2000 to January 2023 with congenital heart disease were included in the study.RESULTS Ten patients with congenital heart disease and kidney biopsy were found.The average age was 29.00 years±15.87 years with pre-biopsy proteinuria of 6193 mg/24 h±6165 mg/24 h.The most common congenital heart disease was Fallot’s tetralogy with 2 cases(20%)and ventricular septal defect with 2(20%)cases.Among the 10 cases,one case of IgA nephropathy and one case of membranoproliferative glomerulonephritis associated with immune complexes were found,receiving specific treatment after histopathological diagnosis,delaying the initiation of kidney replacement therapy.Among remaining 8 cases(80%),one case of FSGS with perihilar variety was found,while the other 7 cases were non-specific FSGS.CONCLUSION Determining the cause of chronic kidney disease can help in delaying the need for kidney replacement therapy.In 2 out of 10 patients in our study,interventions were performed,and initiation of kidney replacement therapy was delayed.Prospective studies are needed to determine the usefulness of kidney biopsy in patients with congenital heart disease.

Epidemiological, Clinical Progress Aspects of Congenital Heart Disease with Neonatal Revelation at the Mother-Child Hospital of Bingerville (HME) Concerning 98 Cases from January 2021 to December 2022 (Côte d’Ivoire)

Introduction The distribution of congenital heart disease (CHD) in sub-Saharan Africa is highly imprecise and varies from one region to another due to the inequality of diagnostic facilities. The aim of this study was to determine the in-hospital prevalence of congenital heart disease in children at the Mother-Child hospital of Bingerville (HME) by specifying the diagnostic, therapeutic and evolutionary aspects. Materials and methods We conducted a retrospective, descriptive, cross-sectional study at HME of Bingerville from January 2021 to December 2022. All newborns with congenital heart disease confirmed by echocardiography were included in the study. Results Of 656 admissions to the neonatology department over the study period, congenital heart disease accounted for 14.9% (98/656) of cases. In our series, 76.7% were diagnosed before the 1st week of life, with a mean chronological age of 5.18 days and extremes of 0 and 46 days. There were as many male patients (50%) as female (50%), i.e. a sex ratio of 1. These newborns were premature in 60.2% of cases, with a mean and median gestational age of 34 weeks’ amenorrhea. Most were left-right shunts (90.8%). Persistent ductus arteriosus (PDA) (48.9%) predominated, followed by atrial septal defect (38.7%), ventricular septal defect (13.3%), common trunk artery (CTA) (3.1%) and open septal pulmonary atresia (OSPA) (1%) as the primary cyanogenic heart disease. Pulmonary arterial hypertension (PAH) (50%) was primary in 38.8% and secondary (61.2%). The mortality rate was 30.6%, and all CTA patients died (100%), with a significant statistical relationship (p = 0.027). Progression under treatment was marked by clinical stabilization (68/98) in 69.4% of cases. Conclusion: Congenital heart disease is relatively common at the Bingerville HME. Access to echocardiography should be facilitated in neonatology departments for rapid diagnosis and optimal management of congenital heart disease in newborns.

Prediction of cyanotic and acyanotic congenital heart disease using machine learning models

BACKGROUND Congenital heart disease is most commonly seen in neonates and it is a major cause of pediatric illness and childhood morbidity and mortality.AIM To identify and build the best predictive model for predicting cyanotic and acyanotic congenital heart disease in children during pregnancy and identify their potential risk factors.METHODS The data were collected from the Pediatric Cardiology Department at Chaudhry Pervaiz Elahi Institute of Cardiology Multan,Pakistan from December 2017 to October 2019.A sample of 3900 mothers whose children were diagnosed with identify the potential outliers.Different machine learning models were compared,and the best-fitted model was selected using the area under the curve,sensitivity,and specificity of the models.RESULTS Out of 3900 patients included,about 69.5%had acyanotic and 30.5%had cyanotic congenital heart disease.Males had more cases of acyanotic(53.6%)and cyanotic(54.5%)congenital heart disease as compared to females.The odds of having cyanotic was 1.28 times higher for children whose mothers used more fast food frequently during pregnancy.The artificial neural network model was selected as the best predictive model with an area under the curve of 0.9012,sensitivity of 65.76%,and specificity of 97.23%.CONCLUSION Children having a positive family history are at very high risk of having cyanotic and acyanotic congenital heart disease.Males are more at risk and their mothers need more care,good food,and physical activity during pregnancy.The best-fitted model for predicting cyanotic and acyanotic congenital heart disease is the artificial neural network.The results obtained and the best model identified will be useful for medical practitioners and public health scientists for an informed decision-making process about the earlier diagnosis and improve the health condition of children in Pakistan.

Analysis of Perioperative Respiratory Care Methods and their Application Value in Children with Congenital Heart Disease

Objective:To analyze the perioperative respiratory care methods and application value in children with congenital heart disease.Methods:60 children with congenital heart disease(treated from January 2021 to October 2023)were screened and divided into two groups randomly.Each group consisted of 30 cases.The perioperative routine was used in the control group.The observation group underwent the perioperative routine along with better respiratory care.Oxygenation indicators,surgical complications,and family satisfaction levels of the groups were compared.Results:There was no significant difference in the oxygenation index between the two groups of children at admission(P>0.05).At discharge,the oxygenation indicators in the observation group were better than those of the control group,and the incidence of surgical complications was lower than that of the control group.The total satisfaction of family members in the observation group was higher than that of the control group(P<0.05).Conclusion:During the perioperative period for children with congenital heart disease,the implementation of respiratory care,which mainly involves symptomatic care,catheter care,sputum suction care,etc.,can actively improve the oxygenation indicators,reduce surgical complications,and promote faster and better recovery,of children with congenital heart disease.

Effect of continuous nursing on treatment compliance and side effect management of coronary heart disease

BACKGROUND There are relatively few studies on continuing care of coronary heart disease(CHD),and its research value needs to be further clarified.AIM To investigate the effect of continuous nursing on treatment compliance and side effect management in patients with CHD.METHODS This is a retrospective study with patients from January 2021 to 2023.The study was divided into two groups with 30 participants in each group.Self-rating anxiety scale(SAS)and Self-rating depression scale(SDS)were used to assess patients'anxiety and depression,and medical coping questionnaire was used to assess patients'coping styles.The pelvic floor dysfunction questionnaire(PFDI-20)was used to assess the status of pelvic floor function,including bladder symptoms,intestinal symptoms,and pelvic symptoms.RESULTS SAS score decreased from 57.33±3.01before treatment to 41.33±3.42 after treatment,SDS score decreased from 50.40±1.45 to 39.47±1.57.The decrease of these two indexes was statistically significant(P<0.05).PFDI-20 scores decreased from the mean 16.83±1.72 before treatment to 10.47±1.3the mean after treatment,which was statistically significant(P<0.05).CONCLUSION The results of this study indicate that pioneering research in continuous care of CHD has a positive impact on improving patients'treatment compliance,reducing anxiety and depression levels,and improving coping styles and pelvic floor functional status.

Treatment of Coronary Heart Disease from the Perspective of Liver Controlling Dispersion

The liver is in charge of distributing and regulating the movement of qi throughout the whole body,coordinating the transportation and transformation of the internal organs in the middle part of the body,promoting the biochemical circulation of qi,blood,and body fluids,and regulating emotions.Liver dysfunction can disrupt the transportation and transformation of qi,blood,and body fluids,causing phlegm turbidity,blood stasis,and other unwanted symptoms.Poor regulation of emotion further aggravates the accumulation of pathological substances,resulting in the obstruction of heart vessels,and ultimately coronary heart disease(CHD).Through regulating lipid metabolism,inflammatory reaction,vasoactive substances,platelet function,neuroendocrine,and other factors,liver controlling dispersing qi plays a comprehensive role in the prognosis of atherosclerosis,the primary cause of CHD.Therefore,it is recommended to treat CHD from the perspective of liver-controlling dispersion.

Expert Consensus on Nutritional Support for Children with Congenital Heart Disease(2023 Edition)

The second edition of the expert consensus on pediatric nutrition was formed based on a global update of pedia-tric nutrition guidelines or consensus worldwide,the management of congenital heart disease,and the results of multi-center clinical nutrition research for congenital heart disease following thefirst Chinese consensus edition of 2016.The consensus was also shaped by the results of three discussion sessions and two questionnaires con-ducted by the 13-member collaboration group.This process was informed by both clinical guidelines and expert consensus.The quality of literature,both in English and Chinese,and the level of recommendations were evaluated using the Grading of Recommendations Assessment,Development,and Evaluations(GRADE)system.

Insights into the genetic architecture of congenital heart disease from animal modeling

Congenital heart disease(CHD)is observed in up to 1%of live births and is one of the leading causes of mortality from birth defects.While hundreds of genes have been implicated in the genetic etiology of CHD,their role in CHD pathogenesis is still poorly understood.This is largely a reflection of the sporadic nature of CHD,as well as its variable expressivity and incomplete penetrance.We reviewed the monogenic causes and evidence for oligogenic etiology of CHD,as well as the role of de novo mutations,common variants,and genetic modifiers.For further mechanistic insight,we leveraged single-cell data across species to investigate the cellular expression characteristics of genes implicated in CHD in developing human and mouse embryonic hearts.Understanding the genetic etiology of CHD may enable the application of precision medicine and prenatal diagnosis,thereby facilitating early intervention to improve outcomes for patients with CHD.

CHDTEPDB:Transcriptome Expression Profile Database and Interactive Analysis Platform for Congenital Heart Disease

CHDTEPDB(URL:http://chdtepdb.com/)is a manually integrated database for congenital heart disease(CHD)that stores the expression profiling data of CHD derived from published papers,aiming to provide rich resources for investigating a deeper correlation between human CHD and aberrant transcriptome expression.The develop-ment of human diseases involves important regulatory roles of RNAs,and expression profiling data can reflect the underlying etiology of inherited diseases.Hence,collecting and compiling expression profiling data is of critical significance for a comprehensive understanding of the mechanisms and functions that underpin genetic diseases.CHDTEPDB stores the expression profiles of over 200 sets of 7 types of CHD and provides users with more convenient basic analytical functions.Due to the differences in clinical indicators such as disease type and unavoidable detection errors among various datasets,users are able to customize their selection of corresponding data for personalized analysis.Moreover,we provide a submission page for researchers to submit their own data so that increasing expression profiles as well as some other histological data could be supplemented to the database.CHDTEPDB is a user-friendly interface that allows users to quickly browse,retrieve,download,and analyze their target samples.CHDTEPDB will significantly improve the current knowledge of expression profiling data in CHD and has the potential to be exploited as an important tool for future research on the disease.