Association of Congenital Heart Defects (CHD) with Factors Related to Maternal Health and Pregnancy in Newborns in Puerto Rico

Background:Given the pervasive issues of obesity and diabetes both in Puerto Rico and the broader United States,there is a compelling need to investigate the intricate interplay among body mass index(BMI),pregesta-tional,and gestational maternal diabetes,and their potential impact on the occurrence of congenital heart defects(CHD)during neonatal development.Methods:Using the comprehensive System of Vigilance and Surveillance of Congenital Defects in Puerto Rico,we conducted a focused analysis on neonates diagnosed with CHD between 2016 and 2020.Our assessment encompassed a range of variables,including maternal age,gestational age,BMI,pregestational diabetes,gestational diabetes,hypertension,history of abortion,and presence of preeclampsia.Results:A cohort of 673 patients was included in our study.The average maternal age was 26 years,within a range of 22 to 32 years.The mean gestational age measured 39 weeks,with a median span of 38 to 39 weeks.Of the 673 patients,274(41%)mothers gave birth to neonates diagnosed with CHD.Within this group,22 cases were linked to pre-gestational diabetes,while 202 were not;20 instances were associated with gestational diabetes,compared to 200 without;and 148 cases exhibited an overweight or obese BMI,whereas 126 displayed a normal BMI.Conclusion:We identified a statistically significant correlation between pre-gestational diabetes mellitus and the occurrence of CHD.However,our analysis did not show a statistically significant association between maternal BMI and the likelihood of CHD.These results may aid in developing effective strategies to prevent and manage CHD in neonates.

Real-Time Remote-Mentored Echocardiography in Management of Newborns with Critical Congenital Heart Defects

Background:The management of suspected critical congenital heart defects(CCHD)relies on timely echocardiographic diagnosis.The availability of experienced echocardiographers is limited or even non-existent in many hospitals with obstetric units.This study evaluates remote-mentored echocardiography performed by physicians without experience in imaging of congenital heart defects(CHD).Methods:The setup included a pediatric cardiologist in a separate room,guiding a physician without experience in echocardiographic imaging of CHD in the examination of a symptomatic newborn.This remote-mentoring pair was blinded to the diagnosis of the newborn and presented with a simplified patient history.The echocardiographic images were streamed to the laptop of the mentor,along with a webcam feed showing the probe position.The task was to identify CCHD in need of immediate transfer to a pediatric cardiac surgical center.The result was compared to the previously completed echocardiographic report and the clinical decision of the patient-responsible pediatric cardiologist.Results:During 17 months,15 newborns were recruited.All six newborns with CCHD were correctly labeled by the remotementoring pair.One newborn with Tetralogy of Fallot was erroneously labeled as needing immediate transfer.Eight newborns without CCHD were correctly labeled.Conclusions:Remote-mentored echocardiography performed by examiners without experience in imaging CHD identified all newborns with CCHD in need of immediate transfer for specialist care.The setup shows promising results for improving the management of CCHD in hospitals without continuous pediatric cardiology service.

Congenital heart“Challenges”in Down syndrome

In this editorial,we comment on the article by Kong et al published in the recent issue of the World Journal of Cardiology.In this interesting case,the authors present the challenges faced in managing a 13-year-old patient with Down syndrome(DS)and congenital heart disease(CHD)associated with pulmonary arterial hypertension.In this distinct population,the Authors underscore the need for early diagnosis and management as well as the need of a multidisciplinary approach for decision making.It seems that the occurrence of CHD in patients with DS adds layers of complexity to their clinical management.This editorial aims to provide a comprehensive overview of the intricate interplay between DS and congenital heart disorders,offering insights into the nuanced diagnostic and therapeutic considerations for physicians.

Circulating microRNAs as potential biomarkers for diagnosis of congenital heart defects

BACKGROUND: Micro RNAs are small non-coding RNAs of approximately 22 nucleotides in length, and play important regulatory roles in normal heart development and the pathogenesis of heart diseases. Recently, a few prospective studies have implicated the diagnostic role of micro RNAs in congenital heart defects(CHD).DATA RESOURCES: This review retrieved the research articles in Pub Med focusing on the altered microR NAs in cardiac tissue or serum of patients with CHD versus healthy normal controls, as well as the studies exploring circulating microR NAs as potential biomarkers for(fetal) CHD.RESULTS: Most of the studies of interest were conducted in recent years, implicating that the topic in this review is a newly emerging field and is drawing much attention. Moreover, a number of differentially expressed microR NAs between CHD specimens and normal controls have been reported.CONCLUSION: Circulating micro RNAs may serve as potential biomarkers for diagnosis of CHD in the future, with more efforts paving the road to the aim.

Family lifestyle factors related to children's congenital heart defects in China:a case-control study

Objective To explore the multiple risk factors for family lifestyle of children with congenital heart defects(CHDs)in Shaanxi Province,China.Methods A 1∶1 case-control study was carried out to investigate 60 pairs of children and their parents.The univariate and multivariable logistic regression models were used to analyze the influence of risk factors related to parents’ lifestyle on CHDs.Results Several possible risk factors were found for CHDs,including fever(OR=4.465,P=0.017),pesticides contact(OR=2.234,P=0.083),passive smoking during pregnancy(OR=20.529,P=0.007)and father’s smoking(OR=3.342,P=0.005);fever(OR=2.428,P=0.012)and passive smoking during pregnancy(OR=1.201,P=0.037)were also correlated with ventricular sepal defect(VSD).Conclusion Fever,pesticides contact and passive smoking are associated with CHDs during pregnancy.We should focus our attention on health care during pregnancy to avoid the above-mentioned risk factors and call on parents to hold on to a good healthy lifestyle.

Association between Maternal Drug Use and Cytochrome P450 Genetic Polymorphisms and the Risk of Congenital Heart Defects in Offspring

Objective This study aimed to assess the associations between maternal drug use,cytochrome P450(CYP450)genetic polymorphisms,and their interactions with the risk of congenital heart defects(CHDs)in offspring.Methods A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.Results After adjusting for potential confounding factors,the results show that mothers who used ovulatory drugs(adjusted odds ratio[a OR]=2.12;95% confidence interval[CI]:1.08-4.16),antidepressants(a OR=2.56;95%CI:1.36-4.82),antiabortifacients(a OR=1.55;95%CI:1.00-2.40),or traditional Chinese drugs(a OR=1.97;95%CI:1.26-3.09)during pregnancy were at a significantly higher risk of CHDs in offspring.Maternal CYP450 genetic polymorphisms at rs1065852(A/T vs.A/A:OR=1.53,95%CI:1.10-2.14;T/T vs.A/A:OR=1.57,95%CI:1.07-2.31)and rs16947(G/G vs.C/C:OR=3.41,95%CI:1.82-6.39)were also significantly associated with the risk of CHDs in offspring.Additionally,significant interactions were observed between the CYP450 genetic variants and drug use on the development of CHDs.Conclusions In those of Chinese descent,ovulatory drugs,antidepressants,antiabortifacients,and traditional Chinese medicines may be associated with the risk of CHDs in offspring.Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.

Congenital Heart Diseases Diagnosed on Transthoracic Echocardiography: Perspectives from the University of Maiduguri Teaching Hospital, Nigeria

In a retrospective study of 1224 transthoracic echocardiograms performed between January 2011 and December 2013, we evaluated the spectrum of congenital heart disease (CHD) diagnosed at a tertiary referral centre in Maiduguri, north-eastern Nigeria. Diagnosis of CHD was made in 88 (8.3%) subjects, comprising 23 (26.1%) adults and 65 (73.9%) aged less than 18 years. Forty six (52.3%) of those with CHD were females, while 42 (47.7%) were males. The frequencies of the CHD in decreasing order were: ventricular septal defect 23 (26.1%), tetralogy of Fallot (TOF) 14 (15.9%) and atrial septal defect (ASD) and atrioventricular septal defect (AVSD) were 11 (12.5%) each. One of the patients with AVSD had Ellis Van Creveldt syndrome. Six (6.8%) cases of patent ductus arteriosus (PDA) were diagnosed in those younger than 18 years, while all the 5 (5.7%) cases of Ebstein’s anomaly were diagnosed in adults. There were 6 (6.8%) cases of Eisenmenger syndrome involving three cases of AVSD, one case of ASD and two cases of Ebstein’s anomaly. Timely definitive cares for these patients are still lacking in Nigeria and many areas of sub-Saharan Africa. We recommend sensitization of all relevant clinicians to actively look for congenital heart defects. Pulse oximetry and postnatal echocardiographic new-born screening which were previously validated should be implemented at secondary and tertiary levels, and efforts should be made towards providing the needed care for patients with CHD.

Prenatal congenital heart defects in southern China:detection rate and termination of preqnancy,2006-2016

Objective Congenital heart defect (CHD) is one of the most common birth anomalies with high morbidity and mortality. Previous studies of CHD mostly focus on the postnatal prevalence, mortality and successful rate of operation, etc. This study aimed to explore the detection rate of prenatal CHD and CHD factors that attribute to termination of pregnancy (TOP).

CORRELATION OF vWF： Ag LEVELS WITH PULMONARY HYPERTENSION IN CONGENITAL HEART DEFECTS

vWF: Ag is an important factor reflecting the injury of pulmonary vascular endothelium. We measured plasma concentrations of vWF: Ag in 89 patients with congenital heart defects (left to right shunting) by quantitative immunoelectrophoresis and assessed endothelial vWF: Ag directly by an immunoperoxidase stain applied io lung biopsy tissue in 10 patients. The patients with pulmonary hypertension had significanthigher vWF: Ag levels, the elevation was associated with the elevation of PVR (P<0.01). The vWF: Ag levels varied directly with PVR and PAR (r=0.89, 0.82, P<0.05).The regression equations of vWF: Ag-PVR. vWF: Ag-PAR we made cam help us to estimate PVR noninvasiverly. Our study will provide us a theoretical basis to choose an appropriate occasion for corrective suryery.

Maternal Vascular Dysfunction in Congenital Heart Defects

Background:Research on fetal congenital heart defect(CHD)mostly focuses on etiology and mechanisms.However,studies on maternal complications or pathophysiology are limited.Our objective was to determine whether vascular dysfunction exists in pregnant women carrying a fetus with congenital heart defects.Methods:We conducted a case-control study.27 cases of pregnant women carrying a fetus with major CHD admitted to our hospital for delivery between April 2021 and August 2022 were selected.Every case was matched with about 2 pregnant complication-free controls without fetal abnormalities.The proangiogenic and anti-angiogenic factors and pregnancy outcomes were compared.Results:The proangiogenic factors include vascular endothelial growth factor(VEGF)and placental growth factor(PlGF).The anti-angiogenic factors involve soluble fms-like tyrosine kinase 1(sFlt-1)and soluble endoglin(sEng).No differences were found in maternal plasma concentrations of PlGF,VEGF,and sFlt-1 between case-control groups when analyzed at 36 weeks≤gestational age(GA)<39 weeks and 39 weeks≤GA≤41 weeks.The concentrations of sEng in maternal plasma in the fetal CHD group were significantly higher than those in the control group:0.60(0.77)vs.0.32(0.26)ng/ml at 36 weeks≤GA<39 weeks,p=0.001 and 0.75(0.55)vs.0.28(0.27)ng/ml at 39 weeks≤GA≤41 weeks,p<0.001.Conclusion:Vascular dysfunction exists in pregnant women with fetal congenital heart defects,manifesting significantly elevated sEng concentration at delivery.

Current Advances in Transcatheter Intervention for Children Born with Congenital Heart Defects: A Review of Literature

This review aims to sum up the improvements witnessed in the field of interventional cardiology during recent times. The last decade has witnessed significant technical advances in the field of radiological imaging and also in interventional cardiology which has helped to offer more non-invasive solutions for the management of congenital heart defects. This has resulted from the use of advanced 3-dimensional fusion imaging instead of conventional 2-dimensional angiography, applying interactive real-time enhancement and using computed tomography and Magnetic Resonance Imaging for interventional procedures. Similarly the introduction of next generation devices, have not only improved the final outcome of the procedure but also has helped in reducing the challenges that were faced before and with the initial generation of devices. These advances have helped not only in reducing the radiation exposure, the use of contrast medium dose but also have resulted in improved early survival. The field of neonatal cardiology has advanced at an unprecedented pace. The transcatheter closure of patent ductus arteriosus has evolved over time and now it has been made possible at much lower body weight. Similarly, early use of stents for aortic coarctation has been found effective in some patients, especially when surgical intervention had been denied. The application of the hybrid approach for the management of complex congenital heart defects has also been effectively applied. More recently transcatheter placement of the pulmonary valve has been introduced for severely stenotic and/or regurgitant pulmonary valve in adolescents and adults. It is anticipated that in near future, this procedure would be available for relatively younger patients. In conclusion: last 2 decades have improvised pediatric interventional cardiology to incorporate less invasive solutions for CHD. The current advances in radio-diagnostic imaging, gadgetry and technical expertise have improved significantly and led to manage many of such defects by trans-catheter approach. This has led also, to replace the early surgical intervention with a more subtle hybrid approach, thus reducing not only the major surgical trauma but also been found to be cost-effective due to a shorter hospital stay. But a learning curve for performers is required for optimum results and also such procedures should be performed in a fully developed facility with an optimum surgical backup.

Morphological Characteristics of the Artery of the Atrioventricular Node by Congenital Heart Defects

The objective of the work is to study the topographic and anatomical characteristics of the atrioventricular node’s artery in complex congenital heart defects.The material for the work was the following:44 specimens including hearts of fetuses and children of the first three years having congenital defects and 50 specimens of the hearts of a similar age with normal development as the control.A complex of generally accepted morphological methods was used to identify the conductive system of the heart,its blood supply.According to the data obtained given congenital heart defects,the artery of the atrioventricular node arises from an artery,that determines the type of blood supply to the heart.With the full form of the common atrioventricular canal,the presence of the“U”-shaped bend of the coronary artery at the point of departure of the atrioventricular artery from it is inconstant,which is apparently due to the localization of the atrioventricular node in the embryonic position.The intensity of the lateral branches from the artery of the atrioventricular node to the heart partitions is determined by the hemodynamic features with congenital heart defects.

Congenital heart defects through 30 years

Aim: To assess basic trends in epidemiology of congenital heart defects (CHDs). Method: Population based prospective observational study. Material: CHDs in infants born alive in a Norwegian county 1982-2011. Results: In 828/71 217 infants (12 per 1000) a CHD was diagnosed. The prevalence increased from 8 to 12 per 1000 after introduction of early echocardiography in newborns with suspected CHD from 1986 (p = 0.0001). Ventricular septal defect (VSD) was the dominating CHD (474;57%). In 222 (27%) the CHDs were missed and diagnosed after discharge from hospital after birth. Twelve critical CHDs (causing death or requiring invasive procedures before 28 days of life) were missed. Prenatal diagnosis of critical CHDs increased from 4/67 (6%) born 1997-2006 to 4/11 (36%) born 2007-2011 (p = 0.01). In 177 (21%) a syndrome or extracardial defect occurred. The occurrence of CHDs associated with chromosomal disorders (60/73 (82%) trisomies) more than doubled from the cohort born in the first 10-year period 1982-1991 (0.6 per 1000) to the last 2002-2011 (1.4 per 1000) (p < 0.0001) in parallel with increasing births in women ≥ 35 years old in the population. 237 (29%) underwent therapeutic procedures (203 (86%) surgery, of whom 16 after initial catheter intervention, and 34 (14%) catheter intervention alone). 39/237 (16%) died, 101 (43%) were repaired and 97 (41%) had some minor residual defect. The death rate declined significantly from 65/532 (12%) born 1982-2001 to 11/296 (4%) born 2002-2011 (p = 0.0001). 37/76 (49%) deaths occurred within 28 days after birth. Conclusions: The rate of detection of CHDs increased substantially after introduction of echocardiography in newborns with suspected CHD, especially VSDs. Some critical CHDs were overlooked. The prenatal detection rate of such defects increased. The prevalence of CHDs with associated chromosomal disorders increased in parallel with increasing maternal age in the population. Most deaths occurred during the neonatal period. Increasing survival increases the load on long-term follow-up programmes.

The associations between resilience and socio-demographic factors in parents who care for their children with congenital heart disease

Objective To examine the resilience of parents of children with congenital heart disease and to investigate socio-demographic factors that may influence parents’resilience.Methods This is a web-based survey study using a cross-sectional design.A purposive sampling method was utilized to recruit 515 parents who care for children with congenital heart disease.Resilience was assessed using the Dispositional Resilience Scale-Ⅱ.Based on expert-interviews,a questionnaire was designed to collect socio-demographic data.Descriptive statistics,factor analysis,and linear regressions were used to analyze data.Results A total of 413 parents completed the survey study.The mean resilience score was 3.75(SD=0.61;range=1.89–4.89)with higher scores indicating higher resilience.The linear regression models demonstrated that parents who had lower education levels and lower gross household income had lower resilience(P<0.05).Conclusions Parents reported resilience that reflected their ability to cope with stressful events and mitigate stressors associated with having and caring for children with congenital heart disease.Lower education levels and lower gross household income are associated with lower resilience.To increase parents’resilience,nursing practice and nurse-led interventions should target screening and providing support for parents at-risk for lower resilience.As lower education level and financial hardship are factors that are difficult to modify through personal efforts,charitable foundations,federal and state governments should consider programs that would provide financial and health literacy support for parents at-risk for lower resilience.

Pulmonary Arterial Hypertension Medical Management of the Adult Patient with Congenital Heart Disease

Congenital heart disease(CHD)-associated pulmonary arterial hypertension(PAH)includes a heterogeneous patient population that can be characterized by the underlying cardiac malformation.CHD-associated PAH has an estimated prevalence of 5– 10% in adult patients,with an increasing number of patients surviving to adulthood because of advances in the surgical management and the development of pulmonary arterial hypertension(PAH)-targeted pharmacotherapy.Although limited data exist,targeted PAH pharmacotherapy has proven to be benefi cial in patients with CHD-associated PAH,with observed improvement in functional class,increase in exercise capacity,and improvement in quality of life and cardiopulmonary hemodynamics.Additionally,there has been increasing interest in the“treat-to-close”strategy.PAH-targeted pharmacotherapy may be used to optimize cardiopulmonary hemodynamics so as to improve patients’operability in repairing the cardiac defect.Although there have been signifi cant advances in the management of this disease state in the past 2 decades,mortality remains high,and ongoing clinical trials are needed to better understand the treat-to-close strategy.

A 49-year-old male with sleep-disordered breathing and nocturnal paroxysmal dyspnea after congenital heart defect correction

Rationale PH is a pathophysiological disorder involving multiple clinical conditions and is often concomitant with other cardiopulmonary diseases,and related differential diagnosis is quite tricky for its various etiologies.Patient characteristics A 49-year-old man presented with 1-year history of nocturnal paroxysmal dyspnea and was transferred to our hospital.

Hypertension and Heart Failure as Predictors of Mortality in an Adult Congenital Heart Defect Population

Early intervention to prevent premature mortality is vital for adults with congenital heart defects(CHD).Anatomic complexity and comorbid conditions are thought to contribute to CHD mortality.Since hypertension(HTN)and heart failure(HF)are the comorbid conditions among the most prevalent causes of death in the United States,and commonly accompany CHD,it is crucial to evaluate whether they are reliable predictors of mortality for adults with CHD(ACHD)independent of anatomic CHD complexity.A retrospective cross-sectional analysis of ACHD,aged 18–64,with concomitant HTN and/or HF and at least one health care encounter during 2008–2010 were assessed.Of 5,397 ACHD patients(18.3%HTN without HF,4.4%HF without HTN,8.3%with both),3.0%died(n=163)during the study period.Overall,the sample was 45.1%white,61.4%female,and 29.0%had a complex CHD.Among those who died,23.3%had HTN without HF,17.2%had HF without HTN,and 42.3%had both.Crude analyses revealed that older age,male gender,black race,and having public health insurance were associated with increased mortality during the three-year study period compared to ACHD patients who were younger,female gender,white race,and covered by private health insurance.ACHD patients diagnosed with non-complex CHD lesions(i.e.,shunts,valves,or shunts+valves)were at greater risk of dying compared to those with severe complex CHDs.When CHD type was assessed separately,those with valve lesions were more likely to die compared to those with complex CHD lesions.After adjustment for age,gender,race,insurance and CHD complexity,ACHD patients with HF,with or without HTN,were equally likely to die during the study period.However,ACHD patients with HF,without or without HTN,who had valve defects were more likely to die during the three-year study period compared to patients with complex CHDs.

Adult Congenital Heart Disease in the Veteran Population:A Case-Based Report

Simple forms of congenital heart disease can allow patients to go undiagnosed until they reach adulthood.Furthermore,improvements in care of patients with complex congenital heart disease are now allowing most patients to reach adulthood.As some patients with adult congenital heart disease can remain asymptomatic until later in life,it is possible for them to serve in the military and eventually fall under the care of Veterans Administration(VA)providers.Therefore it is important for providers,especially cardiologists at VA centers,to have fundamental understanding of the management of adult congenital heart disease.This article provides multiple cases of adult congenital heart disease experienced at a single VA medical center and reviews the anatomy,physiology,and surgical management of each condition.

Factors Affecting the Genetic Diagnostic Rate in Congenital Heart Disease

Background: Over 400 genes contribute to the development of congenital heart disease (CHD). Additionally,multisystemic manifestations accompanying syndromic CHD pose a higher risk of genetic diseases. This studyinvestigated the diagnostic yield of whole-exome sequencing (WES) in patients with sporadic syndromic CHDand the phenotypic factors affecting the genetic diagnostic rate. Methods: Sixty-four patients with sporadic syndromicCHD aged <18 years underwent WES between May 2018 and December 2020 in a single tertiary center,and the association between genetic testing data and extracardiac phenotypes was analyzed. Results: Extracardiacphenotypes were measured as 3.66 ± 3.05 (standard deviation, interquartile range: 2–5) items per patient. WESdetected diagnostic variants in 19 (29.7%) patients: seven (36.8%), seven (36.8%), and five (26.3%) with pathogenicvariants, likely pathogenic variants, and variants of unknown significance, respectively. Post-diagnosis surveillanceidentified the extracardiac phenotype in 54.5% (6/11) of patients. De novo variants accounted for 76.2%(15/19) of variants and autosomal dominant inheritance for 94.7% (18/19). Most diseases were ultra-rare. No significantdifferences were noted in cardiac and extracardiac phenotypes, single or combined (all P > 0.05), betweenthe groups with and without a diagnostic variant. However, patients with ≥3 extracardiac phenotypes had a significantlyhigher likelihood of having a diagnostic variant than those with ≤2 (38.3% vs. 5.9%, odds ratio = 9.93,95% confidence interval = 1.21–81.44, P = 0.013). Conclusions: The number of extracardiac phenotypes is importantin predicting the possibility of genetic diagnosis. Physicians will be able to select patients with a high probabilityof genetic diagnosis and provide appropriate genetic counseling based on the results of this study.

Lesion-based Patterns of Morbidity and Mortality in Hospitalized Adolescents with Congenital Heart Disease

Objective:The objective of this analysis is to describe the characteristics and morbidity during hospitalizations among adolescents with congenital heart disease(AdoCHD)from the Pediatric Health Information System(PHIS)database.Methods:The PHIS database was queried for all AdoCHD admissions aged 12–18 years(1/1/2004–12/31/2013).Major forms of CHD were identified by their International Classification of Diseases,ninth revision codes,further verified based on their secondary diagnosis and/or procedure codes.Patient characteristics,diagnoses,procedures and vital status were assessed.Results:In total,there were 4,267 adolescents admitted to 42 Children’s Hospitals,58.3%were males,24.6%single ventricle(SV)patients,64.1%bi-ventricle(BV),and 11.3%could not be classified.They accounted for 8,512 hospitalizations(41,240 total hospital days),of which 31.6%were intensive care unit(ICU)stays.ICU stay was similar for the SVand BV patients with similar duration of mechanical ventilation between the two groups.Overall,the most common CHD among in-patients was tetralogy of Fallot(TOF,36.4%).Larger proportion of the BVAdoCHD admissions were for elective surgical and electrophysiological procedures.There were 109(2.5%)heart transplantations(1.3%SV vs.0.6%BV)and 120 in-hospital deaths(2.8%)(1.1%SV vs.1.3%BV).Hypoplastic left heart syndrome was the most common diagnosis in transplanted patients(46%)and those who died(28%);TOF(29%)was frequent in 91(2.1%)patients who had cardiac arrests.Conclusions:Different hospitalization patterns exist for BV and SV AdoCHD.Recognizing this risk may encourage directing resources toward optimizing long-term care of CHD patients.