Cardiac Defects and Results of Cardiac Surgery in 22q11.2 Deletion Syndrome

ERIC Educational Resources Information Center

Carotti, Adriano; Digilio, Maria Cristina; Piacentini, Gerardo; Saffirio, Claudia; Di Donato, Roberto M.; Marino, Bruno

2008-01-01

Specific types and subtypes of cardiac defects have been described in children with 22q11.2 deletion syndrome as well as in other genetic syndromes. The conotruncal heart defects occurring in patients with 22q11.2 deletion syndrome include tetralogy of Fallot, pulmonary atresia with ventricular septal defect, truncus arteriosus, interrupted aortic…

Single-Cell Resolution of Temporal Gene Expression during Heart Development.

PubMed

DeLaughter, Daniel M; Bick, Alexander G; Wakimoto, Hiroko; McKean, David; Gorham, Joshua M; Kathiriya, Irfan S; Hinson, John T; Homsy, Jason; Gray, Jesse; Pu, William; Bruneau, Benoit G; Seidman, J G; Seidman, Christine E

2016-11-21

Activation of complex molecular programs in specific cell lineages governs mammalian heart development, from a primordial linear tube to a four-chamber organ. To characterize lineage-specific, spatiotemporal developmental programs, we performed single-cell RNA sequencing of >1,200 murine cells isolated at seven time points spanning embryonic day 9.5 (primordial heart tube) to postnatal day 21 (mature heart). Using unbiased transcriptional data, we classified cardiomyocytes, endothelial cells, and fibroblast-enriched cells, thus identifying markers for temporal and chamber-specific developmental programs. By harnessing these datasets, we defined developmental ages of human and mouse pluripotent stem-cell-derived cardiomyocytes and characterized lineage-specific maturation defects in hearts of mice with heterozygous mutations in Nkx2.5 that cause human heart malformations. This spatiotemporal transcriptome analysis of heart development reveals lineage-specific gene programs underlying normal cardiac development and congenital heart disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis.

PubMed

Harel, Itamar; Maezawa, Yoshiro; Avraham, Roi; Rinon, Ariel; Ma, Hsiao-Yen; Cross, Joe W; Leviatan, Noam; Hegesh, Julius; Roy, Achira; Jacob-Hirsch, Jasmine; Rechavi, Gideon; Carvajal, Jaime; Tole, Shubha; Kioussi, Chrissa; Quaggin, Susan; Tzahor, Eldad

2012-11-13

The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a previously undescribed player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.

Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments.

PubMed

Sun, RongRong; Liu, Min; Lu, Lei; Zheng, Yi; Zhang, Peiying

2015-07-01

The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/congenital-heart-defects-medications , 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described.

Ciona as a Simple Chordate Model for Heart Development and Regeneration

PubMed Central

Evans Anderson, Heather; Christiaen, Lionel

2016-01-01

Cardiac cell specification and the genetic determinants that govern this process are highly conserved among Chordates. Recent studies have established the importance of evolutionarily-conserved mechanisms in the study of congenital heart defects and disease, as well as cardiac regeneration. As a basal Chordate, the Ciona model system presents a simple scaffold that recapitulates the basic blueprint of cardiac development in Chordates. Here we will focus on the development and cellular structure of the heart of the ascidian Ciona as compared to other Chordates, principally vertebrates. Comparison of the Ciona model system to heart development in other Chordates presents great potential for dissecting the genetic mechanisms that underlie congenital heart defects and disease at the cellular level and might provide additional insight into potential pathways for therapeutic cardiac regeneration. PMID:27642586

Reproduction and Survival After Cardiac Defect Repair

ClinicalTrials.gov

2016-02-17

Cardiovascular Diseases; Heart Diseases; Defect, Congenital Heart; Aortic Valve Stenosis; Transposition of Great Vessels; Ductus Arteriosus, Patent; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Down Syndrome; Tetralogy of Fallot; Pulmonic Stenosis; Coarctation of Aorta

Care and Treatment for Congenital Heart Defects

MedlinePlus

... Physical Activity Recommendations for Heart Health • Tools & Resources Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

Maternal occupational pesticide exposure and risk of congenital heart defects in the National Birth Defects Prevention Study.

PubMed

Rocheleau, Carissa M; Bertke, Stephen J; Lawson, Christina C; Romitti, Paul A; Sanderson, Wayne T; Malik, Sadia; Lupo, Philip J; Desrosiers, Tania A; Bell, Erin; Druschel, Charlotte; Correa, Adolfo; Reefhuis, Jennita

2015-10-01

Congenital heart defects (CHDs) are common birth defects, affecting approximately 1% of live births. Pesticide exposure has been suggested as an etiologic factor for CHDs, but previous results were inconsistent. We examined maternal occupational exposure to fungicides, insecticides, and herbicides for 3328 infants with CHDs and 2988 unaffected control infants of employed mothers using data for 1997 through 2002 births from the National Birth Defects Prevention Study, a population-based multisite case-control study. Potential pesticide exposure from 1 month before conception through the first trimester of pregnancy was assigned by an expert-guided task-exposure matrix and job history details self-reported by mothers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Maternal occupational exposure to pesticides was not associated with CHDs overall. In examining specific CHD subtypes compared with controls, some novel associations were observed with higher estimated pesticide exposure: insecticides only and secundum atrial septal defect (OR = 1.8; 95% CI, 1.3-2.7, 40 exposed cases); both insecticides and herbicides and hypoplastic left heart syndrome (OR = 5.1; 95% CI, 1.7-15.3, 4 exposed cases), as well as pulmonary valve stenosis (OR = 3.6; 95% CI, 1.3-10.1, 5 exposed cases); and insecticides, herbicides, and fungicides and tetralogy of Fallot (TOF) (OR = 2.2; 95% CI, 1.2-4.0, 13 exposed cases). Broad pesticide exposure categories were not associated with CHDs overall, but examining specific CHD subtypes revealed some increased odds ratios. These results highlight the importance of examining specific CHDs separately. Because of multiple comparisons, additional work is needed to verify these associations. © 2014 Wiley Periodicals, Inc.

Maternal butalbital use and selected defects in the national birth defects prevention study.

PubMed

Browne, Marilyn L; Van Zutphen, Alissa R; Botto, Lorenzo D; Louik, Carol; Richardson, Sandra; Druschel, Charlotte M

2014-01-01

Butalbital is a barbiturate contained in combination products with caffeine and an analgesic prescribed for the treatment of migraine and tension-type headaches. Controversy exists as to whether butalbital should continue to be prescribed in the United States because of the potential for abuse, overuse headache, and withdrawal syndromes. Butalbital crosses the placenta but there is limited information about potential teratogenicity. To evaluate associations between butalbital and a wide range of specific birth defects. The National Birth Defects Prevention Study is an ongoing, case-control study of nonsyndromic, major birth defects conducted in 10 states. The detailed case classification and large number of cases in the National Birth Defects Prevention Study allowed us to examine the association between maternal self-reported butalbital use and specific birth defects. We conducted an analysis of 8373 unaffected controls and 21,090 case infants with estimated dates of delivery between 1997 and 2007; included were birth defects with 250 or more cases. An exploratory analysis examined groups with 100 to 249 cases. Seventy-three case mothers and 15 control mothers reported periconceptional butalbital use. Of 30 specific defect groups evaluated, adjusted odds ratios for maternal periconceptional butalbital use were statistically significant for 3 congenital heart defects: tetralogy of Fallot (adjusted odds ratio = 3.04; 95% confidence interval = 1.07-8.62), pulmonary valve stenosis (adjusted odds ratio = 5.73; 95% confidence interval = 2.25-14.62), and secundum-type atrial septal defect (adjusted odds ratio = 3.06; 95% confidence interval = 1.07-8.79). In the exploratory analysis, an elevated odds ratio was detected for 1 congenital heart defect, single ventricle. We observed relationships between maternal periconceptional butalbital use and certain congenital heart defects. These associations have not been reported before, and some may be spurious. Butalbital use was rare and despite the large size of the National Birth Defects Prevention Study, the number of exposed case and control infants was small. However, if confirmed in additional studies, our findings will be useful in weighing the risks and benefits of butalbital for the treatment of migraine and tension-type headaches. © Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies.

PubMed

Calcagni, Giulio; Adorisio, Rachele; Martinelli, Simone; Grutter, Giorgia; Baban, Anwar; Versacci, Paolo; Digilio, Maria Cristina; Drago, Fabrizio; Gelb, Bruce D; Tartaglia, Marco; Marino, Bruno

2018-04-01

RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. New short-term therapy with a mammalian target of rapamycin inhibitor has recently been used to prevent heart failure in these patients with a severe form of hypertrophic cardiomyopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk of thromboembolic complications in adult congenital heart disease: A literature review.

PubMed

Karsenty, Clement; Zhao, Alexandre; Marijon, Eloi; Ladouceur, Magalie

2018-05-30

Adult congenital heart disease (ACHD) is a constantly expanding population with challenging issues. Initial medical and surgical treatments are seldom curative, and the majority of patients still experience late sequelae and complications, especially thromboembolic events. These common and potentially life-threating adverse events are probably dramatically underdiagnosed. Better identification and understanding of thromboembolic risk factors are essential to prevent long-term related morbidities. In addition to specific situations associated with a high risk of thromboembolic events (Fontan circulation, cyanotic congenital heart disease), atrial arrhythmia has been recognized as an important risk factor for thromboembolic events in ACHD. Unlike in patients without ACHD, thromboembolic risk stratification scores, such as the CHA 2 DS 2 -VASc score, may not be applicable in ACHD. Overall, after a review of the scientific data published so far, it is clear that the complexity of the underlying congenital heart disease represents a major risk factor for thromboembolic events. As a consequence, prophylactic anticoagulation is indicated in patients with complex congenital heart disease and atrial arrhythmia, regardless of the other risk factors, as opposed to simple heart defects. The landscape of ACHD is an ongoing evolving process, and specific thromboembolic risk scores are needed, especially in the setting of simple heart defects; these should be coupled with specific trials or long-term follow-up of multicentre cohorts. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Understand Your Risk for Heart Failure

MedlinePlus

... Heart.org Arrhythmia About Arrhythmia Why Arrhythmia Matters Understand Your Risk for Arrhythmia Symptoms, Diagnosis & Monitoring of ... Heart Defects The Impact of Congenital Heart Defects Understand Your Risk for Congenital Heart Defects Symptoms & Diagnosis ...

Congenital heart defects in cats: A retrospective study of 162 cats (1996-2013).

PubMed

Tidholm, Anna; Ljungvall, Ingrid; Michal, Jenny; Häggström, Jens; Höglund, Katja

2015-12-01

To study the prevalence and distribution of congenital heart defects in cats presented at two referral centers in Sweden between 1996 and 2013. 162 client-owned cats with congenital heart defects. Case records of cats diagnosed with congenital heart disease were reviewed retrospectively. The overall prevalence of congenital heart disease was 0.2% of the total number of patient cats, and 8% of cats diagnosed with heart disease. A total of 182 heart defects were identified as 16 cats were diagnosed with more than one defect. Ventricular septal defect (VSD) was most prevalent, found in 50% of cats, followed by tricuspid valve dysplasia (11%), pulmonic stenosis (10%), atrial septal defect (10%), aortic stenosis (9%), mitral valve dysplasia (9%), tetralogy of Fallot (5%), patent ductus arteriosus (3%), common atrioventricular canal (2%), and the following defects that each accounted for 0.6% of cats: double chamber right ventricle, double outlet right ventricle, endocardial fibroelastosis, dextroposition of the aorta, persistent right aortic arch, and pulmonary atresia. The prevalence of congenital heart disease was 0.2% of the total number of patient cats, and 8% of cats diagnosed with heart disease. Ventricular septal defect was the most common congenital heart defect in this study. Copyright © 2014 Elsevier B.V. All rights reserved.

Tetralogy of Fallot

MedlinePlus

Tet; TOF; Congenital heart defect - tetralogy; Cyanotic heart disease - tetralogy; Birth defect - tetralogy ... The classic form includes four defects of the heart and its major blood vessels: Ventricular septal defect ( ...

Birth defects among a cohort of infants born to HIV-infected women on antiretroviral medication

PubMed Central

Watts, D. Heather; Huang, Sharon; Culnane, Mary; Kaiser, Kathleen A.; Scheuerle, Angela; Mofenson, Lynne; Stanley, Kenneth; Newell, Marie-Louise; Mandelbrot, Laurent; Delfraissy, Jean-Francois; Cunningham, Coleen K.

2011-01-01

Objective To determine rate of and risk factors for birth defects in infants born to HIV-infected women receiving nucleoside and protease inhibitor antiretroviral (ARV) therapy. Methods Birth defects were evaluated among infants on the Pediatric AIDS Clinical Trials Group 316 trial that studied addition of peripartum nevirapine to established ARV regimen for prevention of mother-to-child transmission. Maternal therapy was categorized by trimester of earliest exposure. Birth defects were coded using conventions of the Antiretroviral Pregnancy Registry. Results Birth defects were detected in 60/1414 (4.2%; 95% CI 3.3–5.4%) infants including 30/636 (4.7%; 95% CI 3.2–6.7%) with first trimester ARV exposure and 30/778 (3.9%; 95% CI 2.6–5.5%) with exposure only after the first trimester (P=0.51). Rates of classes of defects were similar between first trimester compared to later exposure groups except heart defects which occurred in 16 (2.5%; 95% CI 1.4–4.1%) with first trimester ARV exposure and in six (0.8%; 95% CI 0.3–1.7%) infants with later exposure (P=0.02). Exposure to ARV was not associated with specific types of heart defects. Two cases of cardiomyopathy were noted. Conclusion ARV use in early pregnancy was not associated with an increased risk of birth defects overall. The possible association of ARV exposure with heart defects requires further surveillance. PMID:21142844

Preparing Children for Heart Surgery

MedlinePlus

... Physical Activity Recommendations for Heart Health • Tools & Resources Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

Dextrocardia

MedlinePlus

Cyanotic heart defect - dextrocardia; Congenital heart defect - dextrocardia; Birth defect - dextrocardia ... During the early weeks of pregnancy, the baby’s heart develops. Sometimes, it turns so that it points ...

Potential implications of the helical heart in congenital heart defects.

PubMed

Corno, Antonio F; Kocica, Mladen J

2007-01-01

The anatomic and functional observations made by Francisco Torrent-Guasp, in particular his discovery of the helical ventricular myocardial band (HVMB), have challenged what has been taught to cardiologists and cardiac surgeons over centuries. A literature debate is ongoing, with interdependent articles and comments from supporters and critics. Adequate understanding of heart structure and function is obviously indispensable for the decision-making process in congenital heart defects. The HVMB described by Torrent-Guasp and the potential impact on the understanding and treatment of congenital heart defects has been analyzed in the following settings: embryology, ventriculo-arterial discordance (transposition of great arteries), Ebstein's anomaly, pulmonary valve regurgitation after repair of tetralogy of Fallot, Ross operation, and other congenital heart defects. The common structural spiral feature is only one of the elements responsible for the functional interaction of right and left ventricles, and understanding the form/function relationship in congenital heart defects is more difficult than for acquired heart disease because of the variety and complexity of congenital heart defects. Individuals involved in the care of patients with congenital heart defects have to be stimulated to consider further investigations and alternative surgical strategies.

Patent ductus arteriosus in mice with smooth muscle-specific Jag1 deletion

PubMed Central

Feng, Xuesong; Krebs, Luke T.; Gridley, Thomas

2010-01-01

The ductus arteriosus is an arterial vessel that shunts blood flow away from the lungs during fetal life, but normally occludes after birth to establish the adult circulation pattern. Failure of the ductus arteriosus to close after birth is termed patent ductus arteriosus and is one of the most common congenital heart defects. Mice with smooth muscle cell-specific deletion of Jag1, which encodes a Notch ligand, die postnatally from patent ductus arteriosus. These mice exhibit defects in contractile smooth muscle cell differentiation in the vascular wall of the ductus arteriosus and adjacent descending aorta. These defects arise through an inability to propagate the JAG1-Notch signal via lateral induction throughout the width of the vascular wall. Both heterotypic endothelial smooth muscle cell interactions and homotypic vascular smooth muscle cell interactions are required for normal patterning and differentiation of the ductus arteriosus and adjacent descending aorta. This new model for a common congenital heart defect provides novel insights into the genetic programs that underlie ductus arteriosus development and closure. PMID:21068062

Selected environmental risk factors and congenital heart defects.

PubMed

Kuciene, Renata; Dulskiene, Virginija

2008-01-01

The aim of the article is to review the published scientific literature and epidemiological studies about the effect of selected environmental risk factors on congenital heart defects in infants. According to recent reports, the prevalence of congenital heart defects is around 1% of live births. Congenital heart malformations are the leading cause of infant mortality. Unfortunately, the majority of the causes of heart defects remain unknown. These malformations are caused by interaction of genetic and environmental factors. The article reviews selected environmental risk factors: maternal illnesses and conditions associated with metabolic disorder (maternal diabetes, obesity, phenylketonuria), maternal lifestyle factors (alcohol use, smoking), which may increase the risk of congenital heart defects.

Prenatally diagnosed fetal lung lesions with associated conotruncal heart defects: is there a genetic association?

PubMed

Hüsler, Margaret R; Wilson, R Douglas; Rychik, Jack; Bebbington, Michael W; Johnson, Mark P; Mann, Stephanie E; Hedrick, Holly L; Adzick, Scott

2007-12-01

Congenital lung malformation can easily be diagnosed by prenatal ultrasound. Associated extrapulmonary malformations such as heart defects and chromosomal aberrations are rare. The objective of this study was to describe the natural history, outcome and other associated malformations in fetuses with lung lesions and an associated heart defect. Retrospective analysis of 4 cases of prenatally diagnosed fetal CCAMs and hybrid lesions with an associated heart defect and review of 8 cases in the literature. At a single referral center 1.9% of the fetuses with Congenital cystic adenomatoid malformation (CCAM) were diagnosed with an associated heart defect. Seven of the total 12 cases (58%) reviewed had a conotruncal heart abnormality. Chromosomal abnormalities were found in 5 (42%) of the cases. This retrospective review shows that karyotyping in fetal lung lesions with an associated heart defect or isolated large lung lesions is indicated. It also suggests that there is a subpopulation of fetuses with CCAMs who have conotruncal heart defects. This finding may suggest a common genetic background. Copyright (c) 2007 John Wiley & Sons, Ltd.

Remote Magnetic Navigation for Catheter Ablation in Patients With Congenital Heart Disease: A Review.

PubMed

Roy, Karine; Gomez-Pulido, Federico; Ernst, Sabine

2016-03-01

In patients with congenital heart disease, challenges to catheter-based arrhythmia interventions are unique and numerous given the complexity of the underlying defects, anatomic and surgical intervention variants including baffles, conduits, patches, and/or shunts. Remote magnetic navigation offers significant advantages in these cases that may present with limited vascular access or difficult access to the target cardiac chambers implicated by the previous surgical interventions. We reviewed the data available on the safety, feasibility, and effectiveness of magnetic navigation for the treatment of arrhythmia in congenital heart disease and discussed the specific challenges related to various congenital defects and repair with the potential advantages offered by magnetic navigation in these circumstances. © 2016 Wiley Periodicals, Inc.

Facts about Congenital Heart Defects

MedlinePlus

... Living With Heart Defects Data & Statistics Tracking & Research Articles & Key Findings Free Materials Multimedia and Tools Links to Other Websites Information For… Media Policy Makers Basics about Congenital Heart Defects Language: ...

Pediatric heart surgery

MedlinePlus

Heart surgery - pediatric; Heart surgery for children; Acquired heart disease; Heart valve surgery - children ... There are many kinds of heart defects. Some are minor, and others are more serious. Defects can occur inside the heart or in the large blood vessels ...

Adults with Congenital Heart Defects

MedlinePlus

... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Web Booklet: Adults With Congenital Heart Defects Updated:Aug ... topic from the list below to learn more. Web Booklet: Adults With Congenital Heart Defects Introduction Introduction: ...

A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs

USDA-ARS?s Scientific Manuscript database

Familial subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects in dogs and is an inherited defect of Newfoundlands, golden retrievers and human children. Although SAS is known to be inherited, specific genes involved in Newfoundlands with SAS have not been defined. We ...

Congenital Heart Defects (For Parents)

MedlinePlus

... or loses consciousness, call 911 . More treatments than ever are available for congenital heart defects, and most defects are treated successfully. Children with heart problems are best cared for by a team of specialists, which ...

Objectively assessed physical activity and sedentary behaviour does not differ between children and adolescents with and without a congenital heart defect: a pilot examination.

PubMed

Ewalt, Lauren A; Danduran, Michael J; Strath, Scott J; Moerchen, Victoria; Swartz, Ann M

2012-02-01

To objectively evaluate and describe physical activity levels in children with a stable congenital heart defect and compare those levels with children who do not have a congenital heart defect. We matched 21 pairs of children for gender and grade in school and gave them an accelerometer-based motion sensor to wear for 7 consecutive days. Physical activity levels did not differ between children with and without a congenital heart defect. During the 7 days of monitoring, children in this study spent most of their time in sedentary behaviours, that is, 6.7 hours of the 13 monitored hours, 54 minutes in moderate-intensity physical activity, and 12 minutes in vigorous-intensity physical activity. Less than one-fifth of all participants, with or without a congenital heart defect, accumulated sufficient physical activity to meet current physical activity recommendations for children and adolescents. Children with a stable congenital heart defect have activity behaviours that are similar to children without a congenital heart defect. Habitual physical activity in children with a congenital heart defect should be encouraged early on in life to develop strong physical activity habits that will hopefully follow them across their lifespan.

Maternal obesity and congenital heart defects: a population-based study123

PubMed Central

Mills, James L; Troendle, James; Conley, Mary R; Carter, Tonia; Druschel, Charlotte M

2010-01-01

Background: Obesity affects almost one-third of pregnant women and causes many complications, including neural tube defects. It is not clear whether the risk of congenital heart defects, the most common malformations, is also increased. Objective: This study was conducted to determine whether obesity is associated with an increased risk of congenital heart defects. Design: A population-based, nested, case-control study was conducted in infants born with congenital heart defects and unaffected controls from the cohort of all births (n = 1,536,828) between 1993 and 2003 in New York State, excluding New York City. The type of congenital heart defect, maternal body mass index (BMI; in kg/m2), and other risk factors were obtained from the Congenital Malformations Registry and vital records. Mothers of 7392 congenital heart defect cases and 56,304 unaffected controls were studied. Results: All obese women (BMI ≥ 30) were significantly more likely than normal-weight women (BMI: 19–24.9) to have children with a congenital heart defect [odds ratio (OR): 1.15; 95% CI: 1.07, 1.23; P < 0.0001]. Overweight women were not at increased risk (OR: 1.00; 95% CI: 0.94, 1.06). The risk in morbidly obese women (BMI ≥ 40) was higher (OR: 1.33; 95% CI: 1.15, 1.54; P = 0.0001) than that in obese women with a BMI of 30–39.9 (OR: 1.11; 95% CI: 1.04, 1.20; P = 0.004). There was a highly significant trend of increasing OR for congenital heart defects with increasing maternal obesity (P < 0.0001). The offspring of obese women had significantly higher ORs for atrial septal defects, hypoplastic left heart syndrome, aortic stenosis, pulmonic stenosis, and tetralogy of Fallot. Conclusions: Obese, but not overweight, women are at significantly increased risk of bearing children with a range of congenital heart defects, and the risk increases with increasing BMI. Weight reduction as a way to reduce risk should be investigated. PMID:20375192

Risk of Congenital Heart Defects after Ambient Heat Exposure Early in Pregnancy.

PubMed

Auger, Nathalie; Fraser, William D; Sauve, Reg; Bilodeau-Bertrand, Marianne; Kosatsky, Tom

2017-01-01

Congenital heart defects may be environmentally related, but the association with elevated ambient temperature has received little attention. We studied the relationship between outdoor heat during the first trimester of pregnancy and risk of congenital heart defects. We carried out a retrospective cohort study of 704,209 fetuses between 2 and 8 weeks postconception from April to September in Quebec, Canada, 1988-2012. We calculated the prevalence of congenital heart defects at birth according to the number of days women were exposed to maximum temperature ≥ 30°C. In log-binomial regression models, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) for the relationship of temperature with seven critical and eight noncritical heart defects, adjusted for pregnancy characteristics. Prevalence of congenital heart defects was 979.5 per 100,000 for 10 days or more of temperature ≥ 30°C compared with 878.9 per 100,000 for 0 days of exposure. Temperature was more precisely associated with noncritical than critical defects, which had lower prevalence. Fetuses exposed to 15 days of temperature ≥ 30°C between 2 and 8 weeks postconception had 1.06 times the risk of critical defects (95% CI: 0.67, 1.67) and 1.12 times the risk of noncritical defects (95% CI: 0.98, 1.29) relative to 0 days. Associations were higher for atrial septal defects (PR 1.37, 95% CI: 1.10, 1.70) than for other noncritical defects. For atrial septal defects, associations with elevated temperatures began the 3rd week postconception. Extreme heat exposure during the first trimester may be associated with noncritical heart defects, especially of the atrial septum. Citation: Auger N, Fraser WD, Sauve R, Bilodeau-Bertrand M, Kosatsky T. 2017. Risk of congenital heart defects after ambient heat exposure early in pregnancy. Environ Health Perspect 125:8-14; http://dx.doi.org/10.1289/EHP171.

Birth Defects Data and Statistics

MedlinePlus

... Septal Defect Atrioventricular Septal Defect Coarctation of the Aorta D-Transposition of the Great Arteries Hypoplastic Left ... Syndrome Disorders Gastroschisis Heart Defects Coarctation of the Aorta Hypoplastic left heart syndrome Tetralogy of Fallot Other ...

A template-based approach to semi-quantitative SPECT myocardial perfusion imaging: Independent of normal databases.

PubMed

Hughes, Tyler; Shcherbinin, Sergey; Celler, Anna

2011-07-01

Normal patient databases (NPDs) are used to distinguish between normal and abnormal perfusion in SPECT myocardial perfusion imaging (MPI) and have gained wide acceptance in the clinical environment, yet there are limitations to this approach. This study introduces a template-based method for semi-quantitative MPI, which attempts to overcome some of the NPD limitations. Our approach involves the construction of a 3D digital healthy heart template from the delineation of the patient's left ventricle in the SPECT image. This patient-specific template of the heart, filled with uniform activity, is then analytically projected and reconstructed using the same algorithm as the original image. Subsequent to generating bulls-eye maps for the patient image (PB) and the template image (TB), a ratio (PB/TB) is calculated, which produces a reconstruction-artifact corrected image (CB). Finally, a threshold is used to define defects within CB enabling measurements of the perfusion defect extent (EXT). The SPECT-based template (Ts) measurements were compared to those of a CT-based "ideal" template (TI). Twenty digital phantoms were simulated: male and female, each with one healthy heart and nine hearts with various defects. Four physical phantom studies were performed modeling a healthy heart and three hearts with different defects. The phantom represented a thorax with spine, lung, and left ventricle inserts. Images were acquired on General Electric's (GE) Infinia Hawkeye SPECT/CT camera using standard clinical MPI protocol. Finally, our method was applied to 14 patient MPI rest/stress studies acquired on the GE Infinia Hawkeye SPECT/CT camera and compared to the results obtained from Cedars-Sinai's QPS software. In the simulation studies, the true EXT correlated well with the TI (slope= 1.08; offset = -0.40%; r = 0.99) and Ts (slope = 0.90; offset = 0.27%; r = 0.99) methods with no significant differences between them. Similarly, strong correlations were measured for EXT obtained from QPS and the template method for patient studies (slope =0.91; offset = 0.45%; r = 0.98). Mean errors in extent for the Ts method using simulation, physical phantom, and patient data were 2.7% +/- 2.4%, 0.9% +/- 0.5%, 2.0% +/- 2.7%, respectively. The authors introduced a method for semi-quantitative SPECT MPI, which offers a patient-specific approach to define the perfusion defect regions within the heart, as opposed to the patient-averaged NPD methodology.

Single Ventricle Defects

MedlinePlus

... Your Risk • Symptoms & Diagnosis • Care & Treatment • Tools & Resources Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

Transient Early Embryonic Expression of Nkx2-5 Mutations Linked to Congenital Heart Defects in Human Causes Heart Defects in Xenopus laevis

PubMed Central

Bartlett, Heather L.; Sutherland, Lillian; Kolker, Sandra J.; Welp, Chelsea; Tajchman, Urszula; Desmarais, Vera; Weeks, Daniel L.

2007-01-01

Nkx2-5 is a homeobox containing transcription factor that is conserved and expressed in organisms that form hearts. Fruit flies lacking the gene (tinman) fail to form a dorsal vessel, mice that are homozygous null for Nkx2-5 form small, deformed hearts, and several human cardiac defects have been linked to dominant mutations in the Nkx2-5 gene. The Xenopus homologs (XNkx2-5) of two truncated forms of Nkx2-5 that have been identified in humans with congenital heart defects were used in the studies reported here. mRNAs encoding these mutations were injected into single cell Xenopus embryos, and heart development was monitored. Our results indicate that the introduction of truncated XNkx2-5 variants leads to three principle developmental defects. The atrial septum and the valve of the atrioventricular canal were both abnormal. In addition, video microscopic timing of heart contraction indicated that embryos injected with either mutant form of XNkx2-5 have conduction defects. PMID:17685485

Congenital Heart Defects and Receipt of Special Education Services.

PubMed

Riehle-Colarusso, Tiffany; Autry, Andrew; Razzaghi, Hilda; Boyle, Coleen A; Mahle, William T; Van Naarden Braun, Kim; Correa, Adolfo

2015-09-01

We investigated the prevalence of receipt of special education services among children with congenital heart defects (CHDs) compared with children without birth defects. Children born from 1982 to 2004 in metropolitan Atlanta with CHDs (n = 3744) were identified from a population-based birth defect surveillance program; children without birth defects (n = 860 715) were identified from birth certificates. Cohorts were linked to special education files for the 1992-2012 school years to identify special education services. Children with noncardiac defects or genetic syndromes were excluded; children with CHDs were classified by presence or absence of critical CHDs (ie, CHDs requiring intervention by age one year). We evaluated the prevalence of receipt of special education services and prevalence rate ratios using children without birth defects as a reference. Compared with children without birth defects, children with CHDs were 50% more likely to receive special education services overall (adjusted prevalence rate ratio [aPRR] = 1.5; 95% confidence interval [CI]: 1.4-1.7). Specifically, they had higher prevalence of several special education categories including: intellectual disability (aPRR = 3.8; 95% CI: 2.8-5.1), sensory impairment (aPRR = 3.0; 95% CI: 1.8-5.0), other health impairment (aPRR = 2.8; 95% CI: 2.2-3.5), significant developmental delay (aPRR = 1.9; 95% CI: 1.3-2.8), and specific learning disability (aPRR = 1.4; 95% CI: 1.1-1.7). For most special education services, the excess prevalence did not vary by presence of critical CHDs. Children with CHDs received special education services more often than children without birth defects. These findings highlight the need for special education services and the importance of developmental screening for all children with CHDs. Copyright © 2015 by the American Academy of Pediatrics.

3D-Printed Biodegradable Polymeric Vascular Grafts.

PubMed

Melchiorri, A J; Hibino, N; Best, C A; Yi, T; Lee, Y U; Kraynak, C A; Kimerer, L K; Krieger, A; Kim, P; Breuer, C K; Fisher, J P

2016-02-04

Congenital heart defect interventions may benefit from the fabrication of patient-specific vascular grafts because of the wide array of anatomies present in children with cardiovascular defects. 3D printing is used to establish a platform for the production of custom vascular grafts, which are biodegradable, mechanically compatible with vascular tissues, and support neotissue formation and growth. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estimated Maternal Pesticide Exposure from Drinking Water and Heart Defects in Offspring

PubMed Central

Kim, Jihye; Swartz, Michael D.; Langlois, Peter H.; Romitti, Paul A.; Weyer, Peter; Mitchell, Laura E.; Ramakrishnan, Anushuya; Malik, Sadia; Lupo, Philip J.; Feldkamp, Marcia L.; Meyer, Robert E.; Winston, Jennifer J.; Reefhuis, Jennita; Blossom, Sarah J.; Bell, Erin; Agopian, A. J.

2017-01-01

Our objective was to examine the relationship between estimated maternal exposure to pesticides in public drinking water and the risk of congenital heart defects (CHD). We used mixed-effects logistic regression to analyze data from 18,291 nonsyndromic cases with heart defects from the Texas Birth Defects Registry and 4414 randomly-selected controls delivered in Texas from 1999 through 2005. Water district-level pesticide exposure was estimated by linking each maternal residential address to the corresponding public water supply district’s measured atrazine levels. We repeated analyses among independent subjects from the National Birth Defects Prevention Study (NBDPS) (1620 nonsyndromic cases with heart defects and 1335 controls delivered from 1999 through 2005). No positive associations were observed between high versus low atrazine level and eight CHD subtypes or all included heart defects combined. These findings should be interpreted with caution, in light of potential misclassification and relatively large proportions of subjects with missing atrazine data. Thus, more consistent and complete monitoring and reporting of drinking water contaminants will aid in better understanding the relationships between pesticide water contaminants and birth defects. PMID:28786932

Estimated Maternal Pesticide Exposure from Drinking Water and Heart Defects in Offspring.

PubMed

Kim, Jihye; Swartz, Michael D; Langlois, Peter H; Romitti, Paul A; Weyer, Peter; Mitchell, Laura E; Luben, Thomas J; Ramakrishnan, Anushuya; Malik, Sadia; Lupo, Philip J; Feldkamp, Marcia L; Meyer, Robert E; Winston, Jennifer J; Reefhuis, Jennita; Blossom, Sarah J; Bell, Erin; Agopian, A J

2017-08-08

Our objective was to examine the relationship between estimated maternal exposure to pesticides in public drinking water and the risk of congenital heart defects (CHD). We used mixed-effects logistic regression to analyze data from 18,291 nonsyndromic cases with heart defects from the Texas Birth Defects Registry and 4414 randomly-selected controls delivered in Texas from 1999 through 2005. Water district-level pesticide exposure was estimated by linking each maternal residential address to the corresponding public water supply district's measured atrazine levels. We repeated analyses among independent subjects from the National Birth Defects Prevention Study (NBDPS) (1620 nonsyndromic cases with heart defects and 1335 controls delivered from 1999 through 2005). No positive associations were observed between high versus low atrazine level and eight CHD subtypes or all included heart defects combined. These findings should be interpreted with caution, in light of potential misclassification and relatively large proportions of subjects with missing atrazine data. Thus, more consistent and complete monitoring and reporting of drinking water contaminants will aid in better understanding the relationships between pesticide water contaminants and birth defects.

Coronary artery fistula

MedlinePlus

Congenital heart defect - coronary artery fistula; Birth defect heart - coronary artery fistula ... attaches to one of the chambers of the heart (the atrium or ventricle) or another blood vessel ( ...

Congenital Heart Defects in Adults : A Field Guide for Cardiologists

PubMed Central

Romfh, Anitra; Pluchinotta, Francesca Romana; Porayette, Prashob; Valente, Anne Marie; Sanders, Stephen P.

2013-01-01

Advances in cardiology and cardiac surgery allow a large proportion of patients with congenital heart defects to survive into adulthood. These patients frequently develop complications characteristic of the defect or its treatment. Consequently, adult cardiologists participating in the care of these patients need a working knowledge of the more common defects. Occasionally, patients with congenital heart defects such as atrial septal defect, Ebstein anomaly or physiologically corrected transposition of the great arteries present for the first time in adulthood. More often patients previously treated in pediatric cardiology centers have transitioned to adult congenital heart disease centers for ongoing care. Some of the more important defects in this category are tetralogy of Fallot, transposition of the great arteries, functionally single ventricle defects, and coarctation. Through this field guide, we provide an overview of the anatomy of selected defects commonly seen in an adult congenital practice using pathology specimens and clinical imaging studies. In addition, we describe the physiology, clinical presentation to the adult cardiologist, possible complications, treatment options, and outcomes. PMID:24294540

[Feasibility of sonography in the diagnosis of congenital heart diseases in dogs].

PubMed

Schneider, M; Schneider, I; Neu, H

1998-05-01

In ultrasound examination of the heart it is useful to combine the following techniques: echocardiography (in 2D and M-mode) gives information about morphology and motion of the heart. By using Doppler echocardiography (black and white or preferably colour) it is possible to evaluate bloodstreams and with contrast echocardiography shunts in the heart can be demonstrated. In our study (1994-1996) the following congenital heart defects were the most common in dogs: subaortic stenosis (SAS, 41%), pulmonic stenosis (PS, 19%), patent ductus arteriosus (PDA, 11%) and the combination of subaortic stenosis with pulmonic stenosis (11%). Echocardiography allows the morphologic evaluation of the primary defect in detail, for example the differentiation between aortic valve stenosis and subaortic stenosis. However the exact identification of the patent ductus arterious and of the morphology in pulmonic stenosis can remain difficult, especially in patients showing dyspnoe. In heart sonography quantitative measurements are available to graduate the defects, but guidelines for these measurements are not yet defined. The demonstration of secondary and combined defects, which are important for therapy is easily possible with heart ultrasound examination. Secondary insufficiencies are often seen at the mitral valve because of primary subaortic stenosis or patent ductus arteriosus and at the tricuspid valve because of pulmonic stenosis. For differentiation of combined heart defects (SAS with PS; SAS with PDA; PS with atrium septum defect) heart ultrasound is extremely valuable.

Type 2 diabetes mellitus induces congenital heart defects in murine embryos by increasing oxidative stress, endoplasmic reticulum stress, and apoptosis.

PubMed

Wu, Yanqing; Reece, E Albert; Zhong, Jianxiang; Dong, Daoyin; Shen, Wei-Bin; Harman, Christopher R; Yang, Peixin

2016-09-01

Maternal type 1 and 2 diabetes mellitus are strongly associated with high rates of severe structural birth defects, including congenital heart defects. Studies in type 1 diabetic embryopathy animal models have demonstrated that cellular stress-induced apoptosis mediates the teratogenicity of maternal diabetes leading to congenital heart defect formation. However, the mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects remain largely unknown. We aim to determine whether oxidative stress, endoplasmic reticulum stress, and excessive apoptosis are the intracellular molecular mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects. A mouse model of maternal type 2 diabetes mellitus was established by feeding female mice a high-fat diet (60% fat). After 15 weeks on the high-fat diet, the mice showed characteristics of maternal type 2 diabetes mellitus. Control dams were either fed a normal diet (10% fat) or the high-fat diet during pregnancy only. Female mice from the high-fat diet group and the 2 control groups were mated with male mice that were fed a normal diet. At E12.5, embryonic hearts were harvested to determine the levels of lipid peroxides and superoxide, endoplasmic reticulum stress markers, cleaved caspase 3 and 8, and apoptosis. E17.5 embryonic hearts were harvested for the detection of congenital heart defect formation using India ink vessel patterning and histological examination. Maternal type 2 diabetes mellitus significantly induced ventricular septal defects and persistent truncus arteriosus in the developing heart, along with increasing oxidative stress markers, including superoxide and lipid peroxidation; endoplasmic reticulum stress markers, including protein levels of phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated-IRE1α, phosphorylated-eIF2α, C/EBP homologous protein, and binding immunoglobulin protein; endoplasmic reticulum chaperone gene expression; and XBP1 messenger RNA splicing, as well as increased cleaved caspase 3 and 8 in embryonic hearts. Furthermore, maternal type 2 diabetes mellitus triggered excessive apoptosis in ventricular myocardium, endocardial cushion, and outflow tract of the embryonic heart. Similar to those observations in type 1 diabetic embryopathy, maternal type 2 diabetes mellitus causes heart defects in the developing embryo manifested with oxidative stress, endoplasmic reticulum stress, and excessive apoptosis in heart cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Vascular ring

MedlinePlus

... with aberrant subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... accounts for less than 1% of all congenital heart problems. The condition occurs as often in males ...

Infective Endocarditis

MedlinePlus

... material occurs within six months after the procedure. Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

The UNC-45 Chaperone Is Critical for Establishing Myosin-Based Myofibrillar Organization and Cardiac Contractility in the Drosophila Heart Model

PubMed Central

Melkani, Girish C.; Bodmer, Rolf; Ocorr, Karen; Bernstein, Sanford I.

2011-01-01

UNC-45 is a UCS (UNC-45/CRO1/She4P) class chaperone necessary for myosin folding and/or accumulation, but its requirement for maintaining cardiac contractility has not been explored. Given the prevalence of myosin mutations in eliciting cardiomyopathy, chaperones like UNC-45 are likely to be equally critical in provoking or modulating myosin-associated cardiomyopathy. Here, we used the Drosophila heart model to examine its role in cardiac physiology, in conjunction with RNAi-mediated gene silencing specifically in the heart in vivo. Analysis of cardiac physiology was carried out using high-speed video recording in conjunction with movement analysis algorithms. unc-45 knockdown resulted in severely compromised cardiac function in adults as evidenced by prolonged diastolic and systolic intervals, and increased incidence of arrhythmias and extreme dilation; the latter was accompanied by a significant reduction in muscle contractility. Structural analysis showed reduced myofibrils, myofibrillar disarray, and greatly decreased cardiac myosin accumulation. Cardiac unc-45 silencing also dramatically reduced life-span. In contrast, third instar larval and young pupal hearts showed mild cardiac abnormalities, as severe cardiac defects only developed during metamorphosis. Furthermore, cardiac unc-45 silencing in the adult heart (after metamorphosis) led to less severe phenotypes. This suggests that UNC-45 is mostly required for myosin accumulation/folding during remodeling of the forming adult heart. The cardiac defects, myosin deficit and decreased life-span in flies upon heart-specific unc-45 knockdown were significantly rescued by UNC-45 over-expression. Our results are the first to demonstrate a cardiac-specific requirement of a chaperone in Drosophila, suggestive of a critical role of UNC-45 in cardiomyopathies, including those associated with unfolded proteins in the failing human heart. The dilated cardiomyopathy phenotype associated with UNC-45 deficiency is mimicked by myosin knockdown suggesting that UNC-45 plays a crucial role in stabilizing myosin and possibly preventing human cardiomyopathies associated with functional deficiencies of myosin. PMID:21799905

Double aortic arch

MedlinePlus

Aortic arch anomaly; Double arch; Congenital heart defect - double aortic arch; Birth defect heart - double aortic arch ... aorta is a single arch that leaves the heart and moves leftward. In double aortic arch, some ...

Advances in the Care of Adults With Congenital Heart Disease.

PubMed

Nasr, Viviane G; Kussman, Barry D

2015-09-01

The significant decline in mortality among children and adolescents with congenital heart disease (CHD) is associated with an increasing prevalence of CHD in adults, particularly those with moderate to severe defects. As a significant percentage of adolescents and young adults are lost to follow-up in the transition from pediatric to adult care, they may present for elective procedures with substantial CHD-associated morbidity. In addition to the specific cardiac defect, the procedures performed, and the current pathophysiological status, several factors should be considered when managing the adult with CHD. These include the type of setting (adult vs pediatric institution); surgeon (pediatric vs adult cardiac surgeon); coexisting diseases associated with CHD, such as coronary artery disease, hepatic dysfunction, renal dysfunction, cerebrovascular accidents, myopathy, and coagulation disorders; acquired diseases of aging; pregnancy; and psychosocial functioning. The current status of the management of common and important congenital cardiac defects is also described. © The Author(s) 2014.

Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species

PubMed Central

Wythe, Joshua D.; Liu, Jiandong; Cartry, Jerome; Vogler, Georg; Mohapatra, Bhagyalaxmi; Otway, Robyn T.; Huang, Yu; King, Isabelle N.; Maillet, Marjorie; Zheng, Yi; Crawley, Timothy; Taghli-Lamallem, Ouarda; Semsarian, Christopher; Dunwoodie, Sally; Winlaw, David; Harvey, Richard P.; Fatkin, Diane; Towbin, Jeffrey A.; Molkentin, Jeffery D.; Srivastava, Deepak; Ocorr, Karen; Bruneau, Benoit G.

2011-01-01

Unraveling the gene regulatory networks that govern development and function of the mammalian heart is critical for the rational design of therapeutic interventions in human heart disease. Using the Drosophila heart as a platform for identifying novel gene interactions leading to heart disease, we found that the Rho-GTPase Cdc42 cooperates with the cardiac transcription factor Tinman/Nkx2-5. Compound Cdc42, tinman heterozygous mutant flies exhibited impaired cardiac output and altered myofibrillar architecture, and adult heart–specific interference with Cdc42 function is sufficient to cause these same defects. We also identified K+ channels, encoded by dSUR and slowpoke, as potential effectors of the Cdc42–Tinman interaction. To determine whether a Cdc42–Nkx2-5 interaction is conserved in the mammalian heart, we examined compound heterozygous mutant mice and found conduction system and cardiac output defects. In exploring the mechanism of Nkx2-5 interaction with Cdc42, we demonstrated that mouse Cdc42 was a target of, and negatively regulated by miR-1, which itself was negatively regulated by Nkx2-5 in the mouse heart and by Tinman in the fly heart. We conclude that Cdc42 plays a conserved role in regulating heart function and is an indirect target of Tinman/Nkx2-5 via miR-1. PMID:21690310

Novel de novo pathogenic variant in the NR2F2 gene in a boy with congenital heart defect and dysmorphic features.

PubMed

Upadia, Jariya; Gonzales, Patrick R; Robin, Nathaniel H

2018-04-16

The NR2F2 gene plays an important role in angiogenesis and heart development. Moreover, this gene is involved in organogenesis in many other organs in mouse models. Variants in this gene have been reported in a number of patients with nonsyndromic atrioventricular septal defect, and in one patient with congenital heart defect and dysmorphic features. Here we report an 11-month-old Caucasian male with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect. He was later found to have a pathogenic mutation in the NR2F2 gene by whole exome sequencing. This is the second instance in which an NR2F2 mutation has been identified in a child with a congenital heart defect and other anomalies. This case suggests that some variants in NR2F2 may cause syndromic forms of congenital heart defect. © 2018 Wiley Periodicals, Inc.

Down Syndrome with Complete Atrioventricular Septal Defect, Hypertrophic Cardiomyopathy, and Pulmonary Vein Stenosis.

PubMed

Mahadevaiah, Guruprasad; Gupta, Manoj; Ashwath, Ravi

2015-10-01

The prevalence of congenital heart disease in infants with Down syndrome is 40%, compared with 0.3% in children who have normal chromosomes. Atrioventricular and ventricular septal defects are often associated with chromosomal aberrations, such as in trisomy 21, whereas hypertrophic cardiomyopathy is chiefly thought to be secondary to specific gene mutations. We found only one reported case of congenital hypertrophic cardiomyopathy and atrioventricular septal defect in an infant with Down syndrome. Here, we report atrioventricular septal defect, hypertrophic cardiomyopathy, and pulmonary vein stenosis in a neonate with Down syndrome-an apparently unique combination. In addition, we discuss the relevant medical literature.

CHD's Impact on Females

MedlinePlus

... the test around the 18th week of pregnancy. Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

Pattern of congenital heart disease in Southern Yemeni children referred for echocardiography.

PubMed

Saleh, Hussein K

2009-06-01

To study the distribution of age, gender, and the relative frequency of congenital heart defects at the time of the diagnosis in Southern Yemeni children. This retrospective study focused on echocardiographic findings of 393 symptomatic children affected by congenital heart disease. It was conducted in the Echocardiography Department of a referral hospital for Aden city and surrounding governorates, Yemen, from January 2001 to December 2005. Out of 987 referred children, congenital heart defects were detected in 393 (39.8%); mean age was 3.45+/-4 years; of them, 48% males and 52% females. They were 85% non-cyanotic and 15% cyanotic. Patients comprised neonates, 5 (1.3%); infants under one year, 156 (39.7%), and children more than one year, 232 (59%). Most cyanotic patients (66%) presented during their first year of life, but only 8.5% were neonates. Most non-cyanotic (64%) presented after their first year mean age 3.9 years, none of them were neonates. The most frequent defects were: ventricular septal defect (26.5%), pulmonary stenosis (17.6%), patent ductus arteriosus (17.3%), and atrial septal defect (15.8%). Tetralogy of Fallot (8.9%) and transposition of great vessels (3.1%) were the most frequent cyanotic defects. The pattern of congenital heart diseases in Southern Yemen, is characterized by simple, potentially correctable heart defects, under-representation of cyanotic, and absence of critical defects that provokes high mortality during infancy.

Imaging techniques for visualizing and phenotyping congenital heart defects in murine models.

PubMed

Liu, Xiaoqin; Tobita, Kimimasa; Francis, Richard J B; Lo, Cecilia W

2013-06-01

Mouse model is ideal for investigating the genetic and developmental etiology of congenital heart disease. However, cardiovascular phenotyping for the precise diagnosis of structural heart defects in mice remain challenging. With rapid advances in imaging techniques, there are now high throughput phenotyping tools available for the diagnosis of structural heart defects. In this review, we discuss the efficacy of four different imaging modalities for congenital heart disease diagnosis in fetal/neonatal mice, including noninvasive fetal echocardiography, micro-computed tomography (micro-CT), micro-magnetic resonance imaging (micro-MRI), and episcopic fluorescence image capture (EFIC) histopathology. The experience we have gained in the use of these imaging modalities in a large-scale mouse mutagenesis screen have validated their efficacy for congenital heart defect diagnosis in the tiny hearts of fetal and newborn mice. These cutting edge phenotyping tools will be invaluable for furthering our understanding of the developmental etiology of congenital heart disease. Copyright © 2013 Wiley Periodicals, Inc.

Cardiomyocyte-Specific Telomere Shortening is a Distinct Signature of Heart Failure in Humans.

PubMed

Sharifi-Sanjani, Maryam; Oyster, Nicholas M; Tichy, Elisia D; Bedi, Kenneth C; Harel, Ofer; Margulies, Kenneth B; Mourkioti, Foteini

2017-09-07

Telomere defects are thought to play a role in cardiomyopathies, but the specific cell type affected by the disease in human hearts is not yet identified. The aim of this study was to systematically evaluate the cell type specificity of telomere shortening in patients with heart failure in relation to their cardiac disease, age, and sex. We studied cardiac tissues from patients with heart failure by utilizing telomere quantitative fluorescence in situ hybridization, a highly sensitive method with single-cell resolution. In this study, total of 63 human left ventricular samples, including 37 diseased and 26 nonfailing donor hearts, were stained for telomeres in combination with cardiomyocyte- or α-smooth muscle cell-specific markers, cardiac troponin T, and smooth muscle actin, respectively, and assessed for telomere length. Patients with heart failure demonstrate shorter cardiomyocyte telomeres compared with nonfailing donors, which is specific only to cardiomyocytes within diseased human hearts and is associated with cardiomyocyte DNA damage. Our data further reveal that hypertrophic hearts with reduced ejection fraction exhibit the shortest telomeres. In contrast to other reported cell types, no difference in cardiomyocyte telomere length is evident with age. However, under the disease state, telomere attrition manifests in both young and older patients with cardiac hypertrophy. Finally, we demonstrate that cardiomyocyte-telomere length is better sustained in women than men under diseased conditions. This study provides the first evidence of cardiomyocyte-specific telomere shortening in heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Genetic Counseling for Congenital Heart Defects

MedlinePlus

... Artery Disease Venous Thromboembolism Aortic Aneurysm More Genetic Counseling for Congenital Heart Defects Updated:Jan 19,2018 ... with congenital heart disease considers having children. Genetic counseling can help answer these questions and address your ...

Living with a Congenital Heart Defect

MedlinePlus

... to live as healthy a life as possible. Stories: Living with a Congenital Heart Defect William's Story ... Story Shandler's story Nicholas' Story Ken's Story William's Story William’s Story I was born with a heart ...

Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice

PubMed Central

Ye, Maoqing; Coldren, Chris; Liang, Xingqun; Mattina, Teresa; Goldmuntz, Elizabeth; Benson, D. Woodrow; Ivy, Dunbar; Perryman, M.B.; Garrett-Sinha, Lee Ann; Grossfeld, Paul

2010-01-01

Congenital heart defects comprise the most common form of major birth defects, affecting 0.7% of all newborn infants. Jacobsen syndrome (11q-) is a rare chromosomal disorder caused by deletions in distal 11q. We have previously determined that a wide spectrum of the most common congenital heart defects occur in 11q-, including an unprecedented high frequency of hypoplastic left heart syndrome (HLHS). We identified an ∼7 Mb ‘cardiac critical region’ in distal 11q that contains a putative causative gene(s) for congenital heart disease. In this study, we utilized chromosomal microarray mapping to characterize three patients with 11q- and congenital heart defects that carry interstitial deletions overlapping the 7 Mb cardiac critical region. We propose that this 1.2 Mb region of overlap harbors a gene(s) that causes at least a subset of the congenital heart defects that occur in 11q-. We demonstrate that one gene in this region, ETS-1 (a member of the ETS family of transcription factors), is expressed in the endocardium and neural crest during early mouse heart development. Gene-targeted deletion of ETS-1 in mice in a C57/B6 background causes, with high penetrance, large membranous ventricular septal defects and a bifid cardiac apex, and less frequently a non-apex-forming left ventricle (one of the hallmarks of HLHS). Our results implicate an important role for the ETS-1 transcription factor in mammalian heart development and should provide important insights into some of the most common forms of congenital heart disease. PMID:19942620

Congenital Heart Disease–Causing Gata4 Mutation Displays Functional Deficits In Vivo

PubMed Central

Misra, Chaitali; Sachan, Nita; McNally, Caryn Rothrock; Koenig, Sara N.; Nichols, Haley A.; Guggilam, Anuradha; Lucchesi, Pamela A.; Pu, William T.; Srivastava, Deepak; Garg, Vidu

2012-01-01

Defects of atrial and ventricular septation are the most frequent form of congenital heart disease, accounting for almost 50% of all cases. We previously reported that a heterozygous G296S missense mutation of GATA4 caused atrial and ventricular septal defects and pulmonary valve stenosis in humans. GATA4 encodes a cardiac transcription factor, and when deleted in mice it results in cardiac bifida and lethality by embryonic day (E)9.5. In vitro, the mutant GATA4 protein has a reduced DNA binding affinity and transcriptional activity and abolishes a physical interaction with TBX5, a transcription factor critical for normal heart formation. To characterize the mutation in vivo, we generated mice harboring the same mutation, Gata4 G295S. Mice homozygous for the Gata4 G295S mutant allele have normal ventral body patterning and heart looping, but have a thin ventricular myocardium, single ventricular chamber, and lethality by E11.5. While heterozygous Gata4 G295S mutant mice are viable, a subset of these mice have semilunar valve stenosis and small defects of the atrial septum. Gene expression studies of homozygous mutant mice suggest the G295S protein can sufficiently activate downstream targets of Gata4 in the endoderm but not in the developing heart. Cardiomyocyte proliferation deficits and decreased cardiac expression of CCND2, a member of the cyclin family and a direct target of Gata4, were found in embryos both homozygous and heterozygous for the Gata4 G295S allele. To further define functions of the Gata4 G295S mutation in vivo, compound mutant mice were generated in which specific cell lineages harbored both the Gata4 G295S mutant and Gata4 null alleles. Examination of these mice demonstrated that the Gata4 G295S protein has functional deficits in early myocardial development. In summary, the Gata4 G295S mutation functions as a hypomorph in vivo and leads to defects in cardiomyocyte proliferation during embryogenesis, which may contribute to the development of congenital heart defects in humans. PMID:22589735

Decoding the Long Noncoding RNA During Cardiac Maturation: A Roadmap for Functional Discovery.

PubMed

Touma, Marlin; Kang, Xuedong; Zhao, Yan; Cass, Ashley A; Gao, Fuying; Biniwale, Reshma; Coppola, Giovanni; Xiao, Xinshu; Reemtsen, Brian; Wang, Yibin

2016-10-01

Cardiac maturation during perinatal transition of heart is critical for functional adaptation to hemodynamic load and nutrient environment. Perturbation in this process has major implications in congenital heart defects. Transcriptome programming during perinatal stages is an important information but incomplete in current literature, particularly, the expression profiles of the long noncoding RNAs (lncRNAs) are not fully elucidated. From comprehensive analysis of transcriptomes derived from neonatal mouse heart left and right ventricles, a total of 45 167 unique transcripts were identified, including 21 916 known and 2033 novel lncRNAs. Among these lncRNAs, 196 exhibited significant dynamic regulation along maturation process. By implementing parallel weighted gene co-expression network analysis of mRNA and lncRNA data sets, several lncRNA modules coordinately expressed in a developmental manner similar to protein coding genes, while few lncRNAs revealed chamber-specific patterns. Out of 2262 lncRNAs located within 50 kb of protein coding genes, 5% significantly correlate with the expression of their neighboring genes. The impact of Ppp1r1b-lncRNA on the corresponding partner gene Tcap was validated in cultured myoblasts. This concordant regulation was also conserved in human infantile hearts. Furthermore, the Ppp1r1b-lncRNA/Tcap expression ratio was identified as a molecular signature that differentiated congenital heart defect phenotypes. The study provides the first high-resolution landscape on neonatal cardiac lncRNAs and reveals their potential interaction with mRNA transcriptome during cardiac maturation. Ppp1r1b-lncRNA was identified as a regulator of Tcap expression, with dynamic interaction in postnatal cardiac development and congenital heart defects. © 2016 American Heart Association, Inc.

Adverse outcome of using tilmicosin in a lamb with multiple ventricular septal defects.

PubMed

Christodoulopoulos, Georgios

2009-01-01

A 15-day-old, 6.08 kg, lamb was injected subcutaneously with tilmicosin 15 mg/kg body weight. Approximately 15 min later, the lamb died. During necropsy, the heart was found to have multiple ventricular septal defects. Death was attributed to sudden heart failure due to the cardiac effects of tilmicosin in a heart having congenital defects.

Maternal and infant genetic variants, maternal periconceptional use of selective serotonin reuptake inhibitors, and risk of congenital heart defects in offspring: population based study.

PubMed

Nembhard, Wendy N; Tang, Xinyu; Hu, Zhuopei; MacLeod, Stewart; Stowe, Zachary; Webber, Daniel

2017-03-06

Objective  To evaluate whether the association between maternal periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and increased risk of congenital heart defects in offspring is modified by maternal or infant genetic variants in folate, homocysteine, or transsulfuration pathways. Design  Population based study. DNA from mothers, fathers, and infants was genotyped with an Illumina GoldenGate custom single nucleotide polymorphism panel. A hybrid design based on a log linear model was used to calculate relative risks and Bayesian false discovery probabilities (BFDP) to identify polymorphisms associated with congenital heart defects modified by SSRI use. Data sources  Data from the US National Birth Defects Prevention Study on 1180 liveborn infants with congenital heart defects and 1644 controls, born 1997-2008. Main outcome measures  Cases included infants with selected congenital heart defects and control infants had no major defects. SSRI use was obtained from telephone interviews with mothers. Results  For women who reported taking SSRIs periconceptionally, maternal SHMT1 (rs9909104) GG and AGgenotypes were associated with a 5.9 and 2.4 increased risk of select congenital heart defects in offspring, respectively, versus the AA genotype (BFDP=0.69). Compared with the AA genotype, BHMT (rs492842 and rs542852) GG and AG genotypes were associated with twice the riskof congenital heart defects (BFDP=0.74 and 0.79, respectively). MGST1 (rs2075237) CC and ACgenotypes were associated with an increased risk compared with the GG genotype (8.0 and 2.8, respectively; BFDP=0.79). Single nucleotide polymorphism in infant genes in the folate (MTHFS rs12438477), homocysteine (TRDMT1 rs6602178 and GNMT rs11752813) and transsulfuration (GSTP1 rs7941395 and MGST1 rs7294985) pathways were also associated with an increased risk of congenital heart defects. Conclusions  Common maternal or infant genetic variants in folate, homocysteine, or transsulfuration pathways are associated with an increased risk of certain congenital heart defects among children of women taking SSRIs during cardiogenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Total Anomalous Pulmonary Venous Connection (TAPVC)

MedlinePlus

... Your Risk • Symptoms & Diagnosis • Care & Treatment • Tools & Resources Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

Are ECG abnormalities in Noonan syndrome characteristic for the syndrome?

PubMed

Raaijmakers, R; Noordam, C; Noonan, J A; Croonen, E A; van der Burgt, C J A M; Draaisma, J M T

2008-12-01

Of all patients with Noonan syndrome, 50-90% have one or more congenital heart defects. The most frequent occurring are pulmonary stenosis (PS) and hypertrophic cardiomyopathy. The electrocardiogram (ECG) of a patient with Noonan syndrome often shows a characteristic pattern, with a left axis deviation, abnormal R/S ratio over the left precordium, and an abnormal Q wave. The objective of this study was to determine if these ECG characteristics are an independent feature of the Noonan syndrome or if they are related to the congenital heart defect. A cohort study was performed with 118 patients from two university hospitals in the United States and in The Netherlands. All patients were diagnosed with definite Noonan syndrome and had had an ECG and echocardiography. Sixty-nine patients (58%) had characteristic abnormalities of the ECG. In the patient group without a cardiac defect (n = 21), ten patients had a characteristic ECG abnormality. There was no statistical relationship between the presence of a characteristic ECG abnormality and the presence of a cardiac defect (p = 0.33). Patients with hypertrophic cardiomyopathy had more ECG abnormalities in total (p = 0.05), without correlation with a specific ECG abnormality. We conclude that the ECG features in patients with Noonan syndrome are characteristic for the syndrome and are not related to a specific cardiac defect. An ECG is very useful in the diagnosis of Noonan syndrome; every child with a Noonan phenotype should have an ECG and echocardiogram for evaluation.

Congenital heart defects in Williams syndrome.

PubMed

Yuan, Shi-Min

2017-01-01

Yuan SM. Congenital heart defects in Williams syndrome. Turk J Pediatr 2017; 59: 225-232. Williams syndrome (WS), also known as Williams-Beuren syndrome, is a rare genetic disorder involving multiple systems including the circulatory system. However, the etiologies of the associated congenital heart defects in WS patients have not been sufficiently elucidated and represent therapeutic challenges. The typical congenital heart defects in WS were supravalvar aortic stenosis, pulmonary stenosis (both valvular and peripheral), aortic coarctation and mitral valvar prolapse. The atypical cardiovascular anomalies include tetralogy of Fallot, atrial septal defects, aortic and mitral valvular insufficiencies, bicuspid aortic valves, ventricular septal defects, total anomalous pulmonary venous return, double chambered right ventricle, Ebstein anomaly and arterial anomalies. Deletion of the elastin gene on chromosome 7q11.23 leads to deficiency or abnormal deposition of elastin during cardiovascular development, thereby leading to widespread cardiovascular abnormalities in WS. In this article, the distribution, treatment and surgical outcomes of typical and atypical cardiac defects in WS are discussed.

Rac1 modulates cardiomyocyte adhesion during mouse embryonic development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abu-Issa, Radwan, E-mail: rabuissa@umich.edu

2015-01-24

Highlights: • Conditional knockout of Rac1 using Nkx2.5 Cre line is lethal at E13.5. • The myocardium of the mutant is thin and disorganized. • The phenotype is not due to cardiomyocyte low proliferation or apoptosis. • The phenotype is due to specific defect in cardiomyocyte adhesion. - Abstract: Rac1, a member of the Rho subfamily of small GTPases, is involved in morphogenesis and differentiation of many cell types. Here we define a role of Rac1 in cardiac development by specifically deleting Rac1 in the pre-cardiac mesoderm using the Nkx2.5-Cre transgenic driver line. Rac1-conditional knockout embryos initiate heart development normallymore » until embryonic day 11.5 (E11.5); their cardiac mesoderm is specified, and the heart tube is formed and looped. However, by E12.5-E13.5 the mutant hearts start failing and embryos develop edema and hemorrhage which is probably the cause for the lethality observed soon after. The hearts of Rac1-cKO embryos exhibit disorganized and thin myocardial walls and defects in outflow tract alignment. No significant differences of cardiomyocyte death or proliferation were found between developing control and mutant embryos. To uncover the role of Rac1 in the heart, E11.5 primary heart cells were cultured and analyzed in vitro. Rac1-deficient cardiomyocytes were less spread, round and loosely attached to the substrate and to each other implying that Rac1-mediated signaling is required for appropriate cell–cell and/or cellmatrix adhesion during cardiac development.« less

Impact of noncardiac congenital and genetic abnormalities on outcomes in hypoplastic left heart syndrome.

PubMed

Patel, Angira; Hickey, Edward; Mavroudis, Constantine; Jacobs, Jeffrey P; Jacobs, Marshall L; Backer, Carl L; Gevitz, Melanie; Mavroudis, Constantine D

2010-06-01

Hypoplastic left heart syndrome may coexist with noncardiac congenital defects or genetic syndromes. We explored the impact of such lesions on outcomes after staged univentricular palliation. Society of Thoracic Surgeons database 2002 to 2006: Children diagnosed with hypoplastic left heart syndrome who underwent stage 1 Norwood (n = 1,236), stage 2 superior cavopulmonary anastamosis (n = 702) or stage 3 Fontan (n = 553) procedures were studied. In-hospital mortality, postoperative complications, and length of stay were compared at each stage between those with and without noncardiac-genetic defects. Congenital Heart Surgeons' Society database 1994 to 2001: All 703 infants enrolled in the Congenital Heart Surgeons' Society critical left ventricular outflow tract obstruction study who underwent primary stage 1 palliation were reviewed. The impact of noncardiac defects-syndromes on survival was explored using multivariable parametric models with bootstrap bagging. Society of Thoracic Surgeons database: Stage 1 in-hospital mortality (26% vs 20%, p = 0.04) and mean postoperative length of stay (42 versus 31 days, p < 0.0001) were greater, and postoperative complications significantly more prevalent in infants with noncardiac-genetic defects. Congenital Heart Surgeons' Society database: Noncardiac-genetic defects were present in 55 (8%). Early hazard for death after Norwood was significantly worse in infants with noncardiac defects-syndromes (p = 0.008). Chromosomal defects (n = 14) were highly unfavorable: the early risk of death was doubled (10-year survival 25 +/- 9% vs 54 +/- 2%, p = 0.005). Turner syndrome accounted for the majority of chromosomal defects in this population (11 of 14, 79%). Mode of death was rarely attributable to the noncardiac-genetic defect. Survival in hypoplastic left heart syndrome is strongly influenced by the presence of noncardiac abnormalities. Strategies to improve mortality in infants with noncardiac abnormalities should be explored. Presence of chromosomal defects, especially Turner syndrome, should enter decision-management options for parents and physicians. 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

A systematic review of trends and patterns of congenital heart disease in children in Nigeria from 1964-2015.

PubMed

Abdulkadir, Mohammed; Abdulkadir, Zainab

2016-06-01

Congenital heart diseases cause significant childhood morbidity and mortality. Several restricted studies have been conducted on the epidemiology in Nigeria. No truly nationwide data on patterns of congenital heart disease exists. To determine the patterns of congenital heart disease in children in Nigeria and examine trends in the occurrence of individual defects across 5 decades. We searched PubMed database, Google scholar, TRIP database, World Health Organisation libraries and reference lists of selected articles for studies on patterns of congenital heart disease among children in Nigeria between 1964 and 2015. Two researchers reviewed the papers independently and extracted the data. Seventeen studies were selected that included 2,953 children with congenital heart disease. The commonest congenital heart diseases in Nigeria are ventricular septal defect (40.6%), patent ductus arteriosus (18.4%), atrial septal defect (11.3%) and tetralogy of Fallot (11.8%). There has been a 6% increase in the burden of VSD in every decade for the 5 decades studied and a decline in the occurrence of pulmonary stenosis. Studies conducted in Northern Nigeria demonstrated higher proportions of atrial septal defects than patent ductus arteriosus. Ventricular septal defects are the commonest congenital heart diseases in Nigeria with a rising burden.

Adverse outcome of using tilmicosin in a lamb with multiple ventricular septal defects

PubMed Central

Christodoulopoulos, Georgios

2009-01-01

A 15-day-old, 6.08 kg, lamb was injected subcutaneously with tilmicosin 15 mg/kg body weight. Approximately 15 min later, the lamb died. During necropsy, the heart was found to have multiple ventricular septal defects. Death was attributed to sudden heart failure due to the cardiac effects of tilmicosin in a heart having congenital defects. PMID:19337615

Cardiovascular Conditions of Childhood

MedlinePlus

... Learn the symptoms, diagnosis and treatment for Kawasaki disease. Congenital Heart Defects If your child is born with ... and read personal stories of young stroke survivors. Congenital Heart Defects ... about children and heart disease. Login or Sign Up to save and share ...

Corresponding morphological and molecular indicators of crude oil toxicity to the developing hearts of mahi mahi

NASA Astrophysics Data System (ADS)

Edmunds, Richard C.; Gill, J. A.; Baldwin, David H.; Linbo, Tiffany L.; French, Barbara L.; Brown, Tanya L.; Esbaugh, Andrew J.; Mager, Edward M.; Stieglitz, John; Hoenig, Ron; Benetti, Daniel; Grosell, Martin; Scholz, Nathaniel L.; Incardona, John P.

2015-12-01

Crude oils from distinct geological sources worldwide are toxic to developing fish hearts. When oil spills occur in fish spawning habitats, natural resource injury assessments often rely on conventional morphometric analyses of heart form and function. The extent to which visible indicators correspond to molecular markers for cardiovascular stress is unknown for pelagic predators from the Gulf of Mexico. Here we exposed mahi (Coryphaena hippurus) embryos to field-collected crude oil samples from the 2010 Deepwater Horizon disaster. We compared visible heart defects (edema, abnormal looping, reduced contractility) to changes in expression of cardiac-specific genes that are diagnostic of heart failure in humans or associated with loss-of-function zebrafish cardiac mutants. Mahi exposed to crude oil during embryogenesis displayed typical symptoms of cardiogenic syndrome as larvae. Contractility, looping, and circulatory defects were evident, but larval mahi did not exhibit downstream craniofacial and body axis abnormalities. A gradation of oil exposures yielded concentration-responsive changes in morphometric and molecular responses, with relative sensitivity being influenced by age. Our findings suggest that 1) morphometric analyses of cardiac function are more sensitive to proximal effects of crude oil-derived chemicals on the developing heart, and 2) molecular indicators reveal a longer-term adverse shift in cardiogenesis trajectory.

Low dose trichloroethylene alters cytochrome P450 - 2C subfamily expression in the developing chick heart

PubMed Central

Makwana, Om; Ahles, Lauren; Lencinas, Alejandro; Selmin, Ornella I.; Runyan, Raymond B.

2013-01-01

Trichloroethylene (TCE) is an organic solvent and common environmental contaminant. TCE exposure is associated with heart defects in humans and animal models. Primary metabolism of TCE in adult rodent models is by specific hepatic cytochrome P450 enzymes (Lash et al., 2000). As association of TCE exposure with cardiac defects is in exposed embryos prior to normal liver development, we investigated metabolism of TCE in the early embryo. Developing chick embryos were dosed in ovo with environmentally relevant doses of TCE (8 ppb and 800 ppb) and RNA was extracted from cardiac and extra-cardiac tissue (whole embryo without heart). Real time PCR showed upregulation of CYP2H1 transcripts in response to TCE exposure in the heart. No detectable cytochrome expression was found in extra-cardiac tissue. As seen previously, the dose response was non-monotonic and 8ppb elicited stronger upregulation than 800 ppb. Immunostaining for CYP2C subfamily expression confirmed protein expression and showed localization in both myocardium and endothelium. TCE exposure increased protein expression in both tissues. These data demonstrate that the earliest embryonic expression of phase I detoxification enzymes is in the developing heart. Expression of these CYPs is likely to be relevant to the susceptibility of the developing heart to environmental teratogens. PMID:22855351

Corresponding morphological and molecular indicators of crude oil toxicity to the developing hearts of mahi mahi

PubMed Central

Edmunds, Richard C.; Gill, J. A.; Baldwin, David H.; Linbo, Tiffany L.; French, Barbara L.; Brown, Tanya L.; Esbaugh, Andrew J.; Mager, Edward M.; Stieglitz, John; Hoenig, Ron; Benetti, Daniel; Grosell, Martin; Scholz, Nathaniel L.; Incardona, John P.

2015-01-01

Crude oils from distinct geological sources worldwide are toxic to developing fish hearts. When oil spills occur in fish spawning habitats, natural resource injury assessments often rely on conventional morphometric analyses of heart form and function. The extent to which visible indicators correspond to molecular markers for cardiovascular stress is unknown for pelagic predators from the Gulf of Mexico. Here we exposed mahi (Coryphaena hippurus) embryos to field-collected crude oil samples from the 2010 Deepwater Horizon disaster. We compared visible heart defects (edema, abnormal looping, reduced contractility) to changes in expression of cardiac-specific genes that are diagnostic of heart failure in humans or associated with loss-of-function zebrafish cardiac mutants. Mahi exposed to crude oil during embryogenesis displayed typical symptoms of cardiogenic syndrome as larvae. Contractility, looping, and circulatory defects were evident, but larval mahi did not exhibit downstream craniofacial and body axis abnormalities. A gradation of oil exposures yielded concentration-responsive changes in morphometric and molecular responses, with relative sensitivity being influenced by age. Our findings suggest that 1) morphometric analyses of cardiac function are more sensitive to proximal effects of crude oil-derived chemicals on the developing heart, and 2) molecular indicators reveal a longer-term adverse shift in cardiogenesis trajectory. PMID:26658479

Cardiac Embryology and Molecular Mechanisms of Congenital Heart Disease: A Primer for Anesthesiologists.

PubMed

Kloesel, Benjamin; DiNardo, James A; Body, Simon C

2016-09-01

Congenital heart disease is diagnosed in 0.4% to 5% of live births and presents unique challenges to the pediatric anesthesiologist. Furthermore, advances in surgical management have led to improved survival of those patients, and many adult anesthesiologists now frequently take care of adolescents and adults who have previously undergone surgery to correct or palliate congenital heart lesions. Knowledge of abnormal heart development on the molecular and genetic level extends and improves the anesthesiologist's understanding of congenital heart disease. In this article, we aim to review current knowledge pertaining to genetic alterations and their cellular effects that are involved in the formation of congenital heart defects. Given that congenital heart disease can currently only occasionally be traced to a single genetic mutation, we highlight some of the difficulties that researchers face when trying to identify specific steps in the pathogenetic development of heart lesions.

Slit–Robo signalling in heart development

PubMed Central

Zhao, Juanjuan; Mommersteeg, Mathilda T M

2018-01-01

Abstract The Slit ligands and their Robo receptors are well-known for their roles during axon guidance in the central nervous system but are still relatively unknown in the cardiac field. However, data from different animal models suggest a broad involvement of the pathway in many aspects of heart development, from cardiac cell migration and alignment, lumen formation, chamber formation, to the formation of the ventricular septum, semilunar and atrioventricular valves, caval veins, and pericardium. Absence of one or more of the genes in the pathway results in defects ranging from bicuspid aortic valves to ventricular septal defects and abnormal venous connections to the heart. Congenital heart defects are the most common congenital malformations found in life new-born babies and progress in methods for large scale human genetic testing has significantly enhanced the identification of new causative genes involved in human congenital heart disease. Recently, loss of function variants in ROBO1 have also been linked to ventricular septal defects and tetralogy of Fallot in patients. Here, we will give an overview of the role of the Slit–Robo signalling pathway in Drosophila, zebrafish, and mouse heart development. The extent of these data warrant further attention on the SLIT–ROBO signalling pathway as a candidate for an array of human congenital heart defects. PMID:29538649

[Percutaneous intervention in the correction of congenital heart deffects (DCC): experience in as UMAE].

PubMed

Campos-García, Vicente; Ordóñez-Toquero, Guillermo; Monjaraz-Rodríguez, Sarain; Gómez-Conde, Eduardo

Congenital heart defects are common in infants and adults, affecting quality of life if not corrected. Unlike open surgery, percutaneous intervention allows correction with a high success rate and speedy recovery. In Mexico, there are not enough studies to describe their efficacy and safety. A cohort study was conducted in the Hospital "Manuel Avila Camacho", in Puebla, Mexico, including 149 patients with congenital heart defects repaired by percutaneous intervention, recording data from clinical records. The following were documented: post-guided fluoroscopy, hemodynamic changes, cardiac catheterization drilling anatomical changes, and complications six months later such as infection or bleeding at the puncture site, device migration, endocarditis, or death. SPSS was used, using descriptive and inferential statistics. The patients' congenital heart defects treated were ductus arteriosus, atrial septal defect, and aortic coarctation, with ductus arteriosus being recorded as the most frequent congenital heart defect. Primary angioplasties were performed in 75% and stenting in the rest. Anatomical corrections of congenital defects were successful in 96.4% of patients (p < 0.01), with minimal adverse effects (p < 0.01). We conclude that our hospital has good efficacy and safety in percutaneous intervention, comparable to published reports.

Velo-Cardio-Facial syndrome and DiGeorge sequence with meningomyelocele and deletions of the 22q11 region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nickel, R.E.; Pillers, D.M.; Merkens, M.

Approximately 5% of children with neural tube defects (NTDs) have a congenital heart defect and/or cleft lip and palate. The cause of isolated meningomyelocele, congenital heart defects, or cleft lip and palate has been largely thought to be multifactorial. However, chromosomal, teratogenic, and single gene causes of combinations of NTDs with congenital heart defects and/or cleft lip and palate have been reported. We report on 3 patients with meningomyelocele, congenital heart defects, and 22q11 deletions. Two of the children had the clinical diagnosis of velo-cardio-facial syndrome (VCFS); both have bifid uvula. The third child had DiGeorge sequence (DGS). The associationmore » of NTDs with 22q11 deletion has not been reported previously. An accurate diagnosis of the 22q11 deletion is critical as this micro-deletion and its associated clinical problems is transmitted as an autosomal dominant trait due to the inheritance of the deletion-bearing chromosome. We recommend that all children with NTDs and congenital heart defects, with or without cleft palate, have cytogenetic and molecular studies performed to detect 22q11 deletions. 31 refs., 3 figs.« less

Dysregulation of heart and brain specific micro-RNA in sudden infant death syndrome.

PubMed

Courts, Cornelius; Grabmüller, Melanie; Madea, Burkhard

2013-05-10

Channelopathic heart arrhythmias and dysfunctional autonomic regulation of respiration and arousal based on defects in the brainstem are assumed to be involved in the pathogenesis of SIDS. There is evidence that, apart from mutational alterations in associated genes, disruption of physiological processes and deficient responses to external stressors may be influenced by the dysregulation of organ specific micro-RNA expression. It is unknown, however, whether these small, non-coding regulatory RNA molecules are involved in any SIDS pathomechanism. In a case-control study of two series of fresh-frozen heart tissue (n=14) and formalin fixed, paraffin embedded brainstem tissue (n=11) from SIDS and respective control cases, differential expression of heart and brain specific miR-1/miR-133 and miR-124a/let-7b, respectively, was determined using quantitative PCR analysis. Our results show a significant upregulation of heart specific miR-1 and brainspecific let-7b in SIDS compared to control cases. This pilot study is first to analyze differential miRNA expression in SIDS. Our findings suggest that organ specific miRNA dysregulation may be associated with SIDS pathogenesis and establishes the feasibility of miRNA analysis in different kinds of preserved and archived SIDS tissues. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Opposite effects of catalase and MnSOD ectopic expression on stress induced defects and mortality in the desmin deficient cardiomyopathy model.

PubMed

Rapti, Kleopatra; Diokmetzidou, Antigoni; Kloukina, Ismini; Milner, Derek J; Varela, Aimilia; Davos, Constantinos H; Capetanaki, Yassemi

2017-09-01

Oxidative stress has been linked strongly to cell death and cardiac remodeling processes, all hallmarks of heart failure. Mice deficient for desmin (des-/-), the major muscle specific intermediate filament protein, develop dilated cardiomyopathy and heart failure characterized by mitochondrial defects and cardiomyocyte death. The cellular and biochemical alterations in the hearts of these mice strongly suggest that oxidative stress is one of the mechanisms contributing to the pathogenesis of the phenotype. Recently, we showed that indeed the desmin deficient cardiomyocytes are under increased oxidative stress. In order to verify these findings in vivo, we generated transgenic animals overexpressing SOD2 (MnSOD) and/or catalase in the heart and crossed them with des-/- mice, thus allowing us to evaluate the contribution of oxidative injury in inherited cardiomyopathies, as well as the therapeutic potential of antioxidant strategies. Moderate MnSOD and/or catalase overexpression in des-/- hearts leads to a marked decrease in intracellular reactive oxygen species (ROS), ameliorates mitochondrial and other ultrastructural defects, minimizes myocardial degeneration and leads to a significant improvement of cardiac function. Importantly, catalase overexpression increased the 50% survival rate of des-/- mice in an obligatory exercise to 100%. In contrast, MnSOD overexpression enhanced the lethality of des-/- mice, underscoring the importance of a fine balanced cellular redox status. Overall, the present study supports the contribution of oxidative stress in the development of des-/- cardiomyopathy and points to a well-considered antioxidant treatment as therapeutic for cardiomyopathies. Copyright © 2017 Elsevier Inc. All rights reserved.

Arrhythmias in Adults with Congenital Heart Disease: What Are Risk Factors for Specific Arrhythmias?

PubMed

Loomba, Rohit S; Buelow, Matthew W; Aggarwal, Saurabh; Arora, Rohit R; Kovach, Joshua; Ginde, Salil

2017-04-01

An increasing number of patients with congenital heart disease are now surviving into adulthood. This has also led to the emergence of complications from the underlying congenital heart disease, related surgical interventions, and associated combordities. While the prevalence of particular arrhythmias with specific congenital heart disease has been previously described, a detailed analysis of all lesions and a large number of comorbidities has not been previously published. Admissions with congenital heart disease were identified in the National Inpatient Sample. Associated comorbidities were also identified for these patients. Univariate analysis was done to compare those risk factors associated with specific arrhythmias in the setting of congenital heart disease. Next, regression analysis was done to identify what patient characteristics and comorbidities were associated with increased risk of specific arrhythmias. A total of 52,725,227 admissions were included in the analysis. Of these, 109,168 (0.21%) had congenital heart disease. Of those with congenital heart disease, 27,088 (25%) had an arrhythmia at some point. The most common arrhythmia in those with congenital heart disease was atrial fibrillation, which was noted in 86% of those with arrhythmia followed by atrial flutter which was noted in 20% of those with congenital heart disease. The largest burden of arrhythmia was found to be in those with tricuspid atresia with a 51% prevalence of arrhythmia in this group followed by Ebstein anomaly which had an arrhythmia prevalence of 39%. Increasing age, male gender, double outlet right ventricle, atrioventricular septal defect, heart failure, obstructive sleep apnea, transposition of the great arteries, congenitally corrected transposition, and tetralogy of Fallot were frequently noted to be independent risk factors of specific arrhythmias. Approximately, 25% of adult admissions with congenital heart disease are associated with arrhythmia. The burden of arrhythmia varies by the specific lesion and other risk factors as well. Understanding of these can help in risk stratification and can help devise strategies to lower this risk. © 2016 Wiley Periodicals, Inc.

DGCR6 at the proximal part of the DiGeorge critical region is involved in conotruncal heart defects

PubMed Central

Gao, Wenming; Higaki, Takashi; Eguchi-Ishimae, Minenori; Iwabuki, Hidehiko; Wu, Zhouying; Yamamoto, Eiichi; Takata, Hidemi; Ohta, Masaaki; Imoto, Issei; Ishii, Eiichi; Eguchi, Mariko

2015-01-01

Cardiac anomaly is one of the hallmarks of DiGeorge syndrome (DGS), observed in approximately 80% of patients. It often shows a characteristic morphology, termed as conotruncal heart defects. In many cases showing only the conotruncal heart defect, deletion of 22q11.2 region cannot be detected by fluorescence in situ hybridization (FISH), which is used to detect deletion in DGS. We investigated the presence of genomic aberrations in six patients with congenital conotruncal heart defects, who show no deletion at 22q11.2 in an initial screening by FISH. In these patients, no abnormalities were identified in the coding region of the TBX1 gene, one of the key genes responsible for the phenotype of DGS. However, when copy number alteration was analyzed by high-resolution array analysis, a small deletion or duplication in the proximal end of DiGeorge critical region was detected in two patients. The affected region contains the DGCR6 and PRODH genes. DGCR6 has been reported to affect the expression of the TBX1 gene. Our results suggest that altered dosage of gene(s) other than TBX1, possibly DGCR6, may also be responsible for the development of conotruncal heart defects observed in patients with DGS and, in particular, in those with stand-alone conotruncal heart defects. PMID:27081520

Time-frequency characterisation of paediatric heart sounds

NASA Astrophysics Data System (ADS)

Leung, Terence Sze-Tat

1998-08-01

The operation of the heart can be monitored by the sounds it emits. Structural defects or malfunction of the heart valves will cause additional abnormal sounds such as murmurs and ejection clicks. This thesis aims to characterise the heart sounds of three groups of children who either have an Atrial Septal Defect (ASD), a Ventricular Septal Defect (VSD), or are normal. Two aspects of heart sounds have been specifically investigated; the time-frequency analysis of systolic murmurs and the identification of splitting patterns in the second heart sound. The analysis is based on 42 paediatric heart sound recordings. Murmurs are sounds generated by turbulent flow of blood in the heart. They can be found in patients with both pathological and non-pathological conditions. The acoustic quality of the murmurs generated in each heart condition are different. The first aspect of this work is to characterise the three types of murmurs in the time- frequency domain. Modern time-frequency methods including, the Wigner-Ville Distribution, Smoothed Pseudo Wigner-Ville Distribution, Choi-Williams Distribution and spectrogram have been applied to characterise the murmurs. It was found that the three classes of murmurs exhibited different signatures in their time-frequency representations. By performing Discriminant Analysis, it was shown that spectral features extracted from the time- frequency representations can be used to distinguish between the three classes. The second aspect of the research is to identify splitting patterns in the second heart sound, which consists of two acoustic components due to the closure of the aortic valve and pulmonary valve. The aortic valve usually closes before the pulmonary valve, introducing a time delay known as 'split'. The split normally varies in duration over the respiratory cycle. In certain pathologies such as the ASD, the split becomes fixed over the respiration cycle. A technique based on adaptive signal decomposition is developed to measure the split and hence to identify the splitting pattern as either 'variable' or 'fixed'. This work has successfully characterised the murmurs and splitting patterns in the three groups of patients. Features extracted can be used for diagnostic purposes.

Strategies for Analyzing Cardiac Phenotypes in the Zebrafish Embryo

PubMed Central

Houk, Andrew R.; Yelon, Deborah

2017-01-01

The molecular mechanisms underlying cardiogenesis are of critical biomedical importance due to the high prevalence of cardiac birth defects. Over the past two decades, the zebrafish has served as a powerful model organism for investigating heart development, facilitated by its powerful combination of optical access to the embryonic heart and plentiful opportunities for genetic analysis. Work in zebrafish has identified numerous factors that are required for various aspects of heart formation, including the specification and differentiation of cardiac progenitor cells, the morphogenesis of the heart tube, cardiac chambers, and atrioventricular canal, and the establishment of proper cardiac function. However, our current roster of regulators of cardiogenesis is by no means complete. It is therefore valuable for ongoing studies to continue pursuit of additional genes and pathways that control the size, shape, and function of the zebrafish heart. An extensive arsenal of techniques is available to distinguish whether particular mutations, morpholinos, or small molecules disrupt specific processes during heart development. In this chapter, we provide a guide to the experimental strategies that are especially effective for the characterization of cardiac phenotypes in the zebrafish embryo. PMID:27312497

DNA methylation abnormalities in congenital heart disease.

PubMed

Serra-Juhé, Clara; Cuscó, Ivon; Homs, Aïda; Flores, Raquel; Torán, Núria; Pérez-Jurado, Luis A

2015-01-01

Congenital heart defects represent the most common malformation at birth, occurring also in ∼50% of individuals with Down syndrome. Congenital heart defects are thought to have multifactorial etiology, but the main causes are largely unknown. We have explored the global methylation profile of fetal heart DNA in comparison to blood DNA from control subjects: an absolute correlation with the type of tissue was detected. Pathway analysis revealed a significant enrichment of differential methylation at genes related to muscle contraction and cardiomyopathies in the developing heart DNA. We have also searched for abnormal methylation profiles on developing heart-tissue DNA of syndromic and non-syndromic congenital heart defects. On average, 3 regions with aberrant methylation were detected per sample and 18 regions were found differentially methylated between groups. Several epimutations were detected in candidate genes involved in growth regulation, apoptosis and folate pathway. A likely pathogenic hypermethylation of several intragenic sites at the MSX1 gene, involved in outflow tract morphogenesis, was found in a fetus with isolated heart malformation. In addition, hypermethylation of the GATA4 gene was present in fetuses with Down syndrome with or without congenital heart defects, as well as in fetuses with isolated heart malformations. Expression deregulation of the abnormally methylated genes was detected. Our data indicate that epigenetic alterations of relevant genes are present in developing heart DNA in fetuses with both isolated and syndromic heart malformations. These epimutations likely contribute to the pathogenesis of the malformation by cis-acting effects on gene expression.

Small heat shock proteins are necessary for heart migration and laterality determination in zebrafish

PubMed Central

Lahvic, Jamie L.; Ji, Yongchang; Marin, Paloma; Zuflacht, Jonah P.; Springel, Mark W.; Wosen, Jonathan E.; Davis, Leigh; Hutson, Lara D.; Amack, Jeffrey D.; Marvin, Martha J.

2013-01-01

Small heat shock proteins (sHsps) regulate cellular functions not only under stress, but also during normal development, when they are expressed in organ-specific patterns. Here we demonstrate that two small heat shock proteins expressed in embryonic zebrafish heart, hspb7 and hspb12, have roles in the development of left-right asymmetry. In zebrafish, laterality is determined by the motility of cilia in Kupffer’s vesicle (KV), where hspb7 is expressed; knockdown of hspb7 causes laterality defects by disrupting the motility of these cilia. In embryos with reduced hspb7, the axonemes of KV cilia have a 9+0 structure, while control embyros have a predominately 9+2 structure. Reduction of either hspb7 or hspb12 alters the expression pattern of genes that propagate the signals that establish left-right asymmetry: the nodal-related gene southpaw (spaw) in the lateral plate mesoderm, and its downstream targets pitx2, lefty1 and lefty2. Partial depletion of hspb7 causes concordant heart, brain and visceral laterality defects, indicating that loss of KV cilia motility leads causes coordinated but randomized laterality. Reducing hspb12 leads to similar alterations in the expression of downstream laterality genes, but at a lower penetrance. Simultaneous reduction of hspb7 and hspb12 randomizes heart, brain and visceral laterality, suggesting that these two genes have partially redundant functions in the establishment of left-right asymmetry. In addition, both hspb7 and hspb12 are expressed in the precardiac mesoderm and in the yolk syncytial layer, which supports the migration and fusion of mesodermal cardiac precursors. In embryos in which the reduction of hspb7 or hspb12 was limited to the yolk, migration defects predominated, suggesting that the yolk expression of these genes rather than heart expression is responsible for the migration defects. PMID:24140541

Changes in Motor Development During a 4-Year Follow-up on Children With Univentricular Heart Defects.

PubMed

Mäenpää, Heidi; Häkkinen, Arja; Sarajuuri, Anne

2016-01-01

To compare changes in motor development from 1 to 5 years of age among 18 children with hypoplastic left heart syndrome and 12 with univentricular heart to 42 children without heart defect. Motor development was assessed with the Alberta Infant Motor Scale and Movement Assessment Battery for Children (Movement ABC). Children with hypoplastic left heart syndrome or univentricular heart had significantly lower scores on the Alberta Infant Motor Scale test at the age of 1 and on the Movement ABC test at the age of 5 years compared with controls. Children with clear abnormalities on brain magnetic resonance imaging had lower scores compared with those with normal images or mild changes, and their relative motor scores decreased during follow-up. Some children with univentricular heart defects may benefit from physiotherapeutic interventions to support their motor development.

Mammalian Cardiovascular Patterning as Determined by Hemodynamic Forces and Blood Vessel Genetics

NASA Astrophysics Data System (ADS)

Anderson, Gregory Arthur

Cardiovascular development is a process that involves the timing of multiple molecular events, and numerous subtle three-dimensional conformational changes. Traditional developmental biology techniques have provided large quantities of information as to how these complex organ systems develop. However, the major drawback of the majority of current developmental biological imaging is that they are two-dimensional in nature. It is now well recognized that circulation of blood is required for normal patterning and remodeling of blood vessels. Normal blood vessel formation is dependent upon a complex network of signaling pathways, and genetic mutations in these pathways leads to impaired vascular development, heart failure, and lethality. As such, it is not surprising that mutant mice with aberrant cardiovascular patterning are so common, since normal development requires proper coordination between three systems: the heart, the blood, and the vasculature. This thesis describes the implementation of a three-dimensional imaging technique, optical projection tomography (OPT), in conjunction with a computer-based registration algorithm to statistically analyze developmental differences in groups of wild-type mouse embryos. Embryos that differ by only a few hours' gestational time are shown to have developmental differences in blood vessel formation and heart development progression that can be discerned. This thesis describes how we analyzed mouse models of cardiovascular perturbation by OPT to detect morphological differences in embryonic development in both qualitative and quantitative ways. Both a blood vessel specific mutation and a cardiac specific mutation were analyzed, providing evidence that developmental defects of these types can be quantified. Finally, we describe the implementation of OPT imaging to identify statistically significant phenotypes from three different mouse models of cardiovascular perturbation across a range of developmental time points. Image registration methods, combined with intensity- and deformation-based analyses are described and utilized to fully characterize myosin light chain 2a (Mlc2a), delta-like ligand 4 (Dll4), and Endoglin (Eng) mutant mouse embryos. We show that Eng mutant embryos are statistically similar to the Mlc2a phenotype, confirming that these mouse mutants suffer from a primary cardiac developmental defect. Thus, a loss of hemodynamic force caused by defective pumping of the heart is the primary developmental defect affecting these mice.

The Congenital Heart Disease Genetic Network Study: rationale, design, and early results.

PubMed

Gelb, Bruce; Brueckner, Martina; Chung, Wendy; Goldmuntz, Elizabeth; Kaltman, Jonathan; Kaski, Juan Pablo; Kim, Richard; Kline, Jennie; Mercer-Rosa, Laura; Porter, George; Roberts, Amy; Rosenberg, Ellen; Seiden, Howard; Seidman, Christine; Sleeper, Lynn; Tennstedt, Sharon; Kaltman, Jonathan; Schramm, Charlene; Burns, Kristin; Pearson, Gail; Rosenberg, Ellen

2013-02-15

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community's use of Pediatric Cardiac Genomics Consortium resources is welcome.

The Congenital Heart Disease Genetic Network Study

PubMed Central

2013-01-01

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community’s use of Pediatric Cardiac Genomics Consortium resources is welcome. PMID:23410879

The helical ventricular myocardial band of Torrent-Guasp: potential implications in congenital heart defects.

PubMed

Corno, Antonio F; Kocica, Mladen J; Torrent-Guasp, Francisco

2006-04-01

The new concepts of cardiac anatomy and physiology, based on the observations made by Francisco Torrent-Guasp's discovery of the helical ventricular myocardial band, can be useful in the context of the surgical strategies currently used to manage patients with congenital heart defects. The potential impact of the Torrent-Guasp's Heart on congenital heart defects have been analyzed in the following settings: ventriculo-arterial discordance (transposition of the great arteries), double (atrio-ventricular and ventriculo-arterial) discordance (congenitally corrected transposition of the great arteries), Ebstein's anomaly, pulmonary valve regurgitation after repair of tetralogy of Fallot, Ross operation, and complex intra-ventricular malformations. The functional interaction of right and left ventricles occurs not only through their arrangements in series but also thanks to the structural spiral features. Changes in size and function of either ventricle may influence the performance of the other ventricle. The variety and complexity of congenital heart defects make the recognition of the relationship between form and function a vital component, especially when compared to acquired disease. The new concepts of cardiac anatomy and function proposed by Francisco Torrent-Guasp, based on his observations, should stimulate further investigations of alternative surgical strategies by individuals involved with the management of patients with congenital heart defects.

Regional differences in right versus left congenital heart disease diagnoses in neonates in the United States.

PubMed

Nelson, Jennifer S; Strassle, Paula D

2018-03-01

Differences in the prevalence of left and right congenital heart defects (CHD) across the United States are unclear. This study evaluated the overall prevalence and the distribution of right versus left CHD across US regions and divisions in neonates. Newborns born from 2000 to 2014 diagnosed with CHD were identified using the National Inpatient Sample. Heart defects were stratified into right, left, and "neither" subtypes. The risk of right and left heart diagnoses between US Census regions and divisions was compared using multivariable binomial regression, adjusting for infant, and hospital characteristics. Two hundred forty thousand four hundred fifty-five newborns were included and 38,185 (15.9%) were classifiable as having either right or left subtypes. Between 2000 and 2014, the prevalence of right defects increased from 1.65 to 2.88 cases/1,000 live born infants (p < .0001), left defects increased from 0.47 to 0.75 cases/1,000 live born infants (p < .0001), and "neither" defects increased from 10.82 to 20.09 cases/1,000 live born infants (p < .0001). Newborns in the Northeast (RD adj .03, 95% CI .02, .03), Midwest (RD adj .02, 95% CI .02, .03), and South (RD adj .02, 95% CI .02, .02) were significantly more likely to have a right heart defect diagnosis compared to the West. When stratified by division, New England states had a significantly higher prevalence of right defects compared to the Pacific (RD adj .09, 95% CI .06, 0.11). No differences in the prevalence of left defects were seen. The prevalence of CHD diagnoses at birth in the US has increased, and regional differences in the prevalence of right defects appear to exist. © 2017 Wiley Periodicals, Inc.

Occurrence of Conotruncal Heart Birth Defects in Texas: A Comparison of Urban/Rural Classifications

ERIC Educational Resources Information Center

Langlois, Peter H.; Jandle, Leigh; Scheuerle, Angela; Horel, Scott A.; Carozza, Susan E.

2010-01-01

Purpose: (1) Determine if there is an association between 3 conotruncal heart birth defects and urban/rural residence of mother. (2) Compare results using different methods of measuring urban/rural status. Methods: Data were taken from the Texas Birth Defects Registry, 1999-2003. Poisson regression was used to compare crude and adjusted birth…

Pediatric heart surgery - discharge

MedlinePlus

... of the aorta repair - discharge; Heart surgery for children - discharge; Atrial septal defect repair - discharge; Ventricular septal ... discharge; Acquired heart disease - discharge; Heart valve surgery - ... Heart surgery - pediatric - discharge; Heart transplant - pediatric - ...

Conditional Creation and Rescue of Nipbl-Deficiency in Mice Reveals Multiple Determinants of Risk for Congenital Heart Defects

PubMed Central

Jacobs, Russell E.; Lopez-Burks, Martha E.; Choi, Hojae; Wikenheiser, Jamie; Hallgrimsson, Benedikt; Jamniczky, Heather A.; Fraser, Scott E.; Lander, Arthur D.; Calof, Anne L.

2016-01-01

Elucidating the causes of congenital heart defects is made difficult by the complex morphogenesis of the mammalian heart, which takes place early in development, involves contributions from multiple germ layers, and is controlled by many genes. Here, we use a conditional/invertible genetic strategy to identify the cell lineage(s) responsible for the development of heart defects in a Nipbl-deficient mouse model of Cornelia de Lange Syndrome, in which global yet subtle transcriptional dysregulation leads to development of atrial septal defects (ASDs) at high frequency. Using an approach that allows for recombinase-mediated creation or rescue of Nipbl deficiency in different lineages, we uncover complex interactions between the cardiac mesoderm, endoderm, and the rest of the embryo, whereby the risk conferred by genetic abnormality in any one lineage is modified, in a surprisingly non-additive way, by the status of others. We argue that these results are best understood in the context of a model in which the risk of heart defects is associated with the adequacy of early progenitor cell populations relative to the sizes of the structures they must eventually form. PMID:27606604

3D-manufactured patient-specific models of congenital heart defects for communication in clinical practice: feasibility and acceptability.

PubMed

Biglino, Giovanni; Capelli, Claudio; Wray, Jo; Schievano, Silvia; Leaver, Lindsay-Kay; Khambadkone, Sachin; Giardini, Alessandro; Derrick, Graham; Jones, Alexander; Taylor, Andrew M

2015-04-30

To assess the communication potential of three-dimensional (3D) patient-specific models of congenital heart defects and their acceptability in clinical practice for cardiology consultations. This was a questionnaire-based study in which participants were randomised into two groups: the 'model group' received a 3D model of the cardiac lesion(s) being discussed during their appointment, while the 'control group' had a routine visit. Outpatient clinic, cardiology follow-up visits. 103 parents of children with congenital heart disease were recruited (parental age: 43±8 years; patient age: 12±6 years). In order to have a 3D model made, patients needed to have a recent cardiac MRI examination; this was the crucial inclusion criterion. Questionnaires were administered to the participants before and after the visits and an additional questionnaire was administered to the attending cardiologist. Rating (1-10) for the liking of the 3D model, its usefulness and the clarity of the explanation received were recorded, as well as rating (1-10) of the parental understanding and their engagement according to the cardiologist. Furthermore, parental knowledge was assessed by asking them to mark diagrams, tick keywords and provide free text answers. The duration of consultations was recorded and parent feedback collected. Parents and cardiologists both found the models to be very useful and helpful in engaging the parents in discussing congenital heart defects. Parental knowledge was not associated with their level of education (p=0.2) and did not improve following their visit. Consultations involving 3D models lasted on average 5 min longer (p=0.02). Patient-specific models can enhance engagement with parents and improve communication between cardiologists and parents, potentially impacting on parent and patient psychological adjustment following treatment. However, in the short-term, parental understanding of their child's condition did not improve. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Congenital cardiac disease in the newborn infant: past, present, and future.

PubMed

Sadowski, Sharyl L

2009-03-01

Congenital heart defects are the most common of all congenital malformations, with a review of the literature reporting the incidence at 6 to 8 per 1000 live births. The Centers for Disease Control reports cyanotic heart defects occurred in 56.9 per 100,000 live births in the United States in 2005, with higher rates noted when maternal age exceeded 40 years. The incidence of congenital heart disease in premature infants is 12.5 per 1000 live births, excluding isolated patent ductus arteriosus and atrial septal defect. Despite advances in detection and treatment, congenital heart disease accounts for 3% of all infant deaths and 46% of death from congenital malformations. This article discusses the embryology, pathogenesis, clinical presentation, incidence, classifications, and management of congenital heart diseases.

Genetics Home Reference: Cantú syndrome

MedlinePlus

... syndrome is a rare condition characterized by excess hair growth (hypertrichosis), a distinctive facial appearance, heart defects, and ... problem with potassium channel function leads to excess hair growth, heart defects, and the other features of Cantú ...

[Change in our approach in the surgical management of congenital heart defects in patients with Down syndrome, 1974-2016].

PubMed

Hartyánszky, István; Bogáts, Gábor

2016-10-01

Congenital heart defects are frequently present in patients with Down syndrome. The authors analyzed the impact of changing approach in surgical management of congenital heart defect on the life expectancy of patients with Down syndrome. Between 1974 and 1997 the data of 359 children with Down syndrome were collected. Among them 255 patients had no surgery and the mortality in this group was 25.9%, whereas the mortality in the group of 104 patients who underwent palliative surgery was 8.6%. Surgical management of congenital heart defects provides the same life expectancy for these patients as compared to Down patients without cardiac defects. Primary reconstruction is the preferable surgical procedure in infancy that provides good results. Nowadays the number of the operated grown-up congenital heart disease patients with Down syndrome is increasing. During the last three years 82 grown-up congenital heart disease patients, including 4 patients with Down syndrome (aged between 24 and 60 years) were reconstructed successfully. Due to the successful surgery in infancy the population of grown-up congenital heart disease patients with Down syndrome is increasing. The cardiac surgeons are ready to do everything for the optimal life expectancy of these patients. However, management of special problems (indication and necessity of reoperation, optimal age) in patients with Down syndrome poses a great challenge for cardiologists and cardiac surgeons. Orv. Hetil., 2016, 157(40), 1601-1603.

Enlarged Heart

MedlinePlus

... rheumatic fever, a heart defect, infections (infectious endocarditis), connective tissue disorders, certain medications or radiation treatments for cancer, your heart may enlarge. Disease of the heart ...

Coronary Artery Formation Is Driven by Localized Expression of R-spondin3.

PubMed

Da Silva, Fabio; Rocha, Ana Sofia; Motamedi, Fariba Jian; Massa, Filippo; Basboga, Cem; Morrison, Harris; Wagner, Kay Dietrich; Schedl, Andreas

2017-08-22

Coronary arteries are essential to support the heart with oxygen, and coronary heart disease is one of the leading causes of death worldwide. The coronary arteries form at highly stereotyped locations and are derived from the primitive vascular plexus of the heart. How coronary arteries are remodeled and the signaling molecules that govern this process are poorly understood. Here, we have identified the Wnt-signaling modulator Rspo3 as a crucial regulator of coronary artery formation in the developing heart. Rspo3 is specifically expressed around the coronary stems at critical time points in their development. Temporal ablation of Rspo3 at E11.5 leads to decreased β-catenin signaling and a reduction in arterial-specific proliferation. As a result, the coronary stems are defective and the arterial tree does not form properly. These results identify a mechanism through which localized expression of RSPO3 induces proliferation of the coronary arteries at their stems and permits their formation. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Live dynamic analysis of the developing cardiovascular system in mice

NASA Astrophysics Data System (ADS)

Lopez, Andrew L.; Wang, Shang; Larin, Kirill V.; Larina, Irina V.

2017-02-01

The study of the developing cardiovascular system in mice is important for understanding human cardiogenesis and congenital heart defects. Our research focuses on imaging early development in the mouse embryo to specifically understand cardiovascular development under the regulation of dynamic factors like contractile force and blood flow using optical coherence tomography (OCT). We have previously developed an OCT based approach that combines static embryo culture and advanced image processing with computational modeling to live-image mouse embryos and obtain 4D (3D+time) cardiodynamic datasets. Here we present live 4D dynamic blood flow imaging of the early embryonic mouse heart in correlation with heart wall movement. We are using this approach to understand how specific mutations impact heart wall dynamics, and how this influences flow patterns and cardiogenesis. We perform studies in mutant embryos with cardiac phenotypes such as myosin regulatory light chain 2, atrial isoform (Mlc2a). This work is brings us closer to understanding the connections between dynamic mechanical factors and gene programs responsible for early cardiovascular development.

Early patterning and specification of cardiac progenitors in gastrulating mesoderm

PubMed Central

Devine, W Patrick; Wythe, Joshua D; George, Matthew; Koshiba-Takeuchi, Kazuko; Bruneau, Benoit G

2014-01-01

Mammalian heart development requires precise allocation of cardiac progenitors. The existence of a multipotent progenitor for all anatomic and cellular components of the heart has been predicted but its identity and contribution to the two cardiac progenitor ‘fields’ has remained undefined. Here we show, using clonal genetic fate mapping, that Mesp1+ cells in gastrulating mesoderm are rapidly specified into committed cardiac precursors fated for distinct anatomic regions of the heart. We identify Smarcd3 as a marker of early specified cardiac precursors and identify within these precursors a compartment boundary at the future junction of the left and right ventricles that arises prior to morphogenesis. Our studies define the timing and hierarchy of cardiac progenitor specification and demonstrate that the cellular and anatomical fate of mesoderm-derived cardiac cells is specified very early. These findings will be important to understand the basis of congenital heart defects and to derive cardiac regeneration strategies. DOI: http://dx.doi.org/10.7554/eLife.03848.001 PMID:25296024

Engineered chromosome-based genetic mapping establishes a 3.7 Mb critical genomic region for Down syndrome-associated heart defects in mice.

PubMed

Liu, Chunhong; Morishima, Masae; Jiang, Xiaoling; Yu, Tao; Meng, Kai; Ray, Debjit; Pao, Annie; Ye, Ping; Parmacek, Michael S; Yu, Y Eugene

2014-06-01

Trisomy 21 (Down syndrome, DS) is the most common human genetic anomaly associated with heart defects. Based on evolutionary conservation, DS-associated heart defects have been modeled in mice. By generating and analyzing mouse mutants carrying different genomic rearrangements in human chromosome 21 (Hsa21) syntenic regions, we found the triplication of the Tiam1-Kcnj6 region on mouse chromosome 16 (Mmu16) resulted in DS-related cardiovascular abnormalities. In this study, we developed two tandem duplications spanning the Tiam1-Kcnj6 genomic region on Mmu16 using recombinase-mediated genome engineering, Dp(16)3Yey and Dp(16)4Yey, spanning the 2.1 Mb Tiam1-Il10rb and 3.7 Mb Ifnar1-Kcnj6 regions, respectively. We found that Dp(16)4Yey/+, but not Dp(16)3Yey/+, led to heart defects, suggesting the triplication of the Ifnar1-Kcnj6 region is sufficient to cause DS-associated heart defects. Our transcriptional analysis of Dp(16)4Yey/+ embryos showed that the Hsa21 gene orthologs located within the duplicated interval were expressed at the elevated levels, reflecting the consequences of the gene dosage alterations. Therefore, we have identified a 3.7 Mb genomic region, the smallest critical genomic region, for DS-associated heart defects, and our results should set the stage for the final step to establish the identities of the causal gene(s), whose elevated expression(s) directly underlie this major DS phenotype.

What Are Congenital Heart Defects?

MedlinePlus

... surgery to close an atrial septal defect? This study tests a tool that allows surgeons to tell the difference between various types of heart tissue and avoid injury. To participate in this study, your child must be between 30 days and ...

c-Abl tyrosine kinase regulates cardiac growth and development.

PubMed

Qiu, Zhaozhu; Cang, Yong; Goff, Stephen P

2010-01-19

The c-Abl protein is a ubiquitously expressed nonreceptor tyrosine kinase involved in the development and function of many mammalian organ systems, including the immune system and bone. Here we show that homozygous Abl mutant embryos and newborns on the C57BL/6J background, but not on other backgrounds, display dramatically enlarged hearts and die perinatally. The heart defects can be largely rescued by cardiomyocyte-specific restoration of the full-length c-Abl protein. The cardiac hyperplasia phenotype is not caused by decreased apoptosis, but rather by abnormally increased cardiomyocyte proliferation during later stages of embryogenesis. Genes involved in cardiac stress and remodeling and cell cycle regulation are also up-regulated in the mutant hearts. These findings reveal an essential role for c-Abl in mammalian heart growth and development.

c-Abl tyrosine kinase regulates cardiac growth and development

PubMed Central

Qiu, Zhaozhu; Cang, Yong; Goff, Stephen P.

2009-01-01

The c-Abl protein is a ubiquitously expressed nonreceptor tyrosine kinase involved in the development and function of many mammalian organ systems, including the immune system and bone. Here we show that homozygous Abl mutant embryos and newborns on the C57BL/6J background, but not on other backgrounds, display dramatically enlarged hearts and die perinatally. The heart defects can be largely rescued by cardiomyocyte-specific restoration of the full-length c-Abl protein. The cardiac hyperplasia phenotype is not caused by decreased apoptosis, but rather by abnormally increased cardiomyocyte proliferation during later stages of embryogenesis. Genes involved in cardiac stress and remodeling and cell cycle regulation are also up-regulated in the mutant hearts. These findings reveal an essential role for c-Abl in mammalian heart growth and development. PMID:20080568

Ethnic and socioeconomic variation in incidence of congenital heart defects.

PubMed

Knowles, Rachel L; Ridout, Deborah; Crowe, Sonya; Bull, Catherine; Wray, Jo; Tregay, Jenifer; Franklin, Rodney C; Barron, David J; Cunningham, David; Parslow, Roger C; Brown, Katherine L

2017-06-01

Ethnic differences in the birth prevalence of congenital heart defects (CHDs) have been reported; however, studies of the contemporary UK population are lacking. We investigated ethnic variations in incidence of serious CHDs requiring cardiac intervention before 1 year of age. All infants who had a cardiac intervention in England and Wales between 1 January 2005 and 31 December 2010 were identified in the national congenital heart disease surgical audit and matched with paediatric intensive care admission records to create linked individual child records. Agreement in reporting of ethnic group by each audit was evaluated. For infants born 1 January 2006 to 31 December 2009, we calculated incidence rate ratios (IRRs) for CHDs by ethnicity and investigated age at intervention, antenatal diagnosis and area deprivation. We identified 5350 infants (2940 (55.0%) boys). Overall CHD incidence was significantly higher in Asian and Black ethnic groups compared with the White reference population (incidence rate ratios (IRR) (95% CIs): Asian 1.5 (1.4 to 1.7); Black 1.4 (1.3 to 1.6)); incidence of specific CHDs varied by ethnicity. No significant differences in age at intervention or antenatal diagnosis rates were identified but affected children from non-White ethnic groups were more likely to be living in deprived areas than White children. Significant ethnic variations exist in the incidence of CHDs, including for specific defects with high infant mortality. It is essential that healthcare provision mitigates ethnic disparity, including through timely identification of CHDs at screening, supporting parental choice and effective interventions. Future research should explore the factors underlying ethnic variation and impact on longer-term outcomes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Possible Common Aetiology behind Maternal Preeclampsia and Congenital Heart Defects in the Child: a Cardiovascular Diseases in Norway Project Study.

PubMed

Brodwall, Kristoffer; Leirgul, Elisabeth; Greve, Gottfried; Vollset, Stein Emil; Holmstrøm, Henrik; Tell, Grethe S; Øyen, Nina

2016-01-01

The aetiology of congenital heart defects (CHD) is mostly unknown, but maternal factors may modify the infant risk of CHD. We investigated the association between maternal preeclampsia and offspring risk of severe CHD in a nation-wide cohort study. Information on all births registered in the Medical Birth Registry of Norway, 1994-2009, was completed with information on CHD diagnoses from national health registries and the Cardiovascular Diseases in Norway Project (CVDNOR). Among 914 703 singleton births without chromosomal abnormalities, 32 864 (3.6%) were born after a pregnancy with preeclampsia. The preeclampsia was diagnosed before the 34th week of pregnancy (early-onset preeclampsia) in 2618 (8.0% of preeclamptic pregnancies). CHDs were diagnosed in 10 691 infants; of these, 2473 had severe CHD. The risk of severe CHD was compared between births with and without maternal preeclampsia and estimated with binomial log-linear regression. When adjusting for year of birth, maternal age, parity, and pregestational diabetes, the risk ratio (RR) for severe CHD in offspring of mothers with any preeclampsia was 1.3 [95% confidence interval (CI) 1.1, 1.5], and in pregnancies with early-onset preeclampsia, the RR was 2.8 (95% CI 1.8, 4.4). The association between early-onset preeclampsia and specific types of severe CHD was stronger for atrioventricular septal defects (AVSD), with adjusted RR 13.5 (95% CI 6.8, 26.8). Early-onset preeclampsia was strongly associated with infant risk of severe CHD, specifically; the risk of AVSD was 15-fold higher if the mother was diagnosed with early-onset preeclampsia, suggesting common aetiological factors for early-onset preeclampsia and erroneous fetal heart development. © 2015 John Wiley & Sons Ltd.

Ethnic and socioeconomic variation in incidence of congenital heart defects

PubMed Central

Knowles, Rachel L; Ridout, Deborah; Crowe, Sonya; Bull, Catherine; Wray, Jo; Tregay, Jenifer; Franklin, Rodney C; Barron, David J; Cunningham, David; Parslow, Roger C; Brown, Katherine L

2017-01-01

Introduction Ethnic differences in the birth prevalence of congenital heart defects (CHDs) have been reported; however, studies of the contemporary UK population are lacking. We investigated ethnic variations in incidence of serious CHDs requiring cardiac intervention before 1 year of age. Methods All infants who had a cardiac intervention in England and Wales between 1 January 2005 and 31 December 2010 were identified in the national congenital heart disease surgical audit and matched with paediatric intensive care admission records to create linked individual child records. Agreement in reporting of ethnic group by each audit was evaluated. For infants born 1 January 2006 to 31 December 2009, we calculated incidence rate ratios (IRRs) for CHDs by ethnicity and investigated age at intervention, antenatal diagnosis and area deprivation. Results We identified 5350 infants (2940 (55.0%) boys). Overall CHD incidence was significantly higher in Asian and Black ethnic groups compared with the White reference population (incidence rate ratios (IRR) (95% CIs): Asian 1.5 (1.4 to 1.7); Black 1.4 (1.3 to 1.6)); incidence of specific CHDs varied by ethnicity. No significant differences in age at intervention or antenatal diagnosis rates were identified but affected children from non-White ethnic groups were more likely to be living in deprived areas than White children. Conclusions Significant ethnic variations exist in the incidence of CHDs, including for specific defects with high infant mortality. It is essential that healthcare provision mitigates ethnic disparity, including through timely identification of CHDs at screening, supporting parental choice and effective interventions. Future research should explore the factors underlying ethnic variation and impact on longer-term outcomes. PMID:27986699

Maternal occupation and the risk of major birth defects: A follow-up analysis from the National Birth Defects Prevention Study

PubMed Central

Lin, Shao; Herdt-Losavio, Michele L.; Chapman, Bonnie R.; Munsie, Jean-Pierre; Olshan, Andrew F.; Druschel, Charlotte M.

2013-01-01

This study further examined the association between selected maternal occupations and a variety of birth defects identified from prior analysis and explored the effect of work hours and number of jobs held and potential interaction between folic acid and occupation. Data from a population-based, multi-center case-control study was used. Analyses included 45 major defects and specific sub-occupations under five occupational groups: healthcare workers, cleaners, scientists, teachers and personal service workers. Both logistic regression and Bayesian models (to minimize type-1 errors) were used, adjusted for potential confounders. Effect modification by folic acid was also assessed. More than any other occupation, nine different defects were positively associated with maids or janitors [odds ratio (OR) range: 1.72-3.99]. Positive associations were also seen between the following maternal occupations and defects in their children (OR range: 1.35-3.48): chemists/conotruncal heart and neural tube defects (NTDs), engineers/conotruncal defects, preschool teachers/cataracts and cleft lip with/without cleft palate (CL/P), entertainers/athletes/gastroschisis, and nurses/hydrocephalus and left ventricular outflow tract heart defects. Non-preschool teachers had significantly lower odds of oral clefts and gastroschisis in their offspring (OR range: 0.53-0.76). There was a suggestion that maternal folic acid use modified the effects with occupations including lowering the risk of NTDs and CL/P. No consistent patterns were found between maternal work hours or multiple jobs by occupation and the risk of birth defects. Overall, mothers working as maids, janitors, biologists, chemists, engineers, nurses, entertainers, child care workers and preschool teachers had increased risks of several malformations and non-preschool teachers had a lower risk of some defects. Maternal folic acid use reduced the odds of NTDs and CL/P among those with certain occupations. This hypothesis-generating study will provide clues for future studies with better exposure data. PMID:22695106

Increased Regurgitant Flow Causes Endocardial Cushion Defects in an Avian Embryonic Model of Congenital Heart Disease

PubMed Central

Ford, Stephanie M; McPheeters, Matthew T; Wang, Yves T; Ma, Pei; Gu, Shi; Strainic, James; Snyder, Christopher; Rollins, Andrew M; Watanabe, Michiko; Jenkins, Michael W

2017-01-01

Background The relationship between changes in endocardial cushion and resultant congenital heart diseases (CHD) has yet to be established. It has been shown that increased regurgitant flow early in embryonic heart development leads to endocardial cushion defects, but it remains unclear how abnormal endocardial cushions during the looping stages might affect the fully septated heart. The goal of this study was to reproducibly alter blood flow in vivo and then quantify the resultant effects on morphology of endocardial cushions in the looping heart and on CHDs in the septated heart. Methods Optical pacing was applied to create regurgitant flow in embryonic hearts, and optical coherence tomography (OCT) was utilized to quantify regurgitation and morphology. Embryonic quail hearts were optically paced at 3 Hz (180bpm, well above intrinsic rate 60–110bpm) at stage 13 of development (3–4 wks human) for 5 min. Pacing fatigued the heart and led to at least 1 hr of increased regurgitant flow. Resultant morphological changes were quantified with OCT imaging at stage 19 (cardiac looping – 4–5 wks human) or stage 35 (4 chambered heart – 8 wks human). Results All paced embryos imaged at stage 19 displayed structural changes in cardiac cushions. The amount of regurgitant flow immediately after pacing was inversely correlated with cardiac cushion size 24-hrs post pacing (p-value < 0.01). The embryos with the most regurgitant flow and smallest cushions after pacing had a decreased survival rate at 8 days (p<0.05), indicating that those most severe endocardial cushion defects were lethal. Of the embryos that survived to stage 35, 17/18 exhibited CHDs including valve defects, ventricular septal defects, hypoplastic ventricles, and common AV canal. Conclusion The data illustrate a strong inverse relationship in which regurgitant flow precedes abnormal and smaller cardiac cushions, resulting in the development of CHDs. PMID:28211263

Cor triatriatum dexter and atrial septal defect in a 43-year-old woman.

PubMed

Vukovic, Petar M; Kosevic, Dragana; Milicic, Miroslav; Jovovic, Ljiljana; Stojanovic, Ivan; Micovic, Slobodan

2014-08-01

Cor triatriatum dexter is a rare congenital heart anomaly in which a membrane divides the right atrium into 2 chambers. We report the case of a 43-year-old woman who had cor triatriatum dexter and a large atrial septal defect. During attempted percutaneous closure, the balloon disrupted the membrane and revealed that the defect had no inferior rim, precluding secure placement of an Amplatzer Septal Occluder. Surgical treatment subsequently proved to be successful. In patients with an incomplete membrane and a septal defect with well-defined rims, percutaneous treatment can be the first choice. In patients who have cor triatriatum dexter and unfavorable anatomic features or concomitant complex heart anomalies, open-heart surgery remains the gold standard for treatment.

Cor Triatriatum Dexter and Atrial Septal Defect in a 43-Year-Old Woman

PubMed Central

Kosevic, Dragana; Milicic, Miroslav; Jovovic, Ljiljana; Stojanovic, Ivan; Micovic, Slobodan

2014-01-01

Cor triatriatum dexter is a rare congenital heart anomaly in which a membrane divides the right atrium into 2 chambers. We report the case of a 43-year-old woman who had cor triatriatum dexter and a large atrial septal defect. During attempted percutaneous closure, the balloon disrupted the membrane and revealed that the defect had no inferior rim, precluding secure placement of an Amplatzer Septal Occluder. Surgical treatment subsequently proved to be successful. In patients with an incomplete membrane and a septal defect with well-defined rims, percutaneous treatment can be the first choice. In patients who have cor triatriatum dexter and unfavorable anatomic features or concomitant complex heart anomalies, open-heart surgery remains the gold standard for treatment. PMID:25120397

Hypoxia induced DNA damage in children with isolated septal defect and septal defect with great vessel anomaly of heart.

PubMed

G, Vidya; H Y, Suma; Bhat B, Vishnu; Chand, Parkash; Rao K, Ramachandra

2014-04-01

In Congenital Heart Disease (CHD), shunting of blood occurs through the anatomical defects which lead to mixing of oxygenated and deoxygenated blood. Chronic hypoxia which occurs due to the above said mechanism has the potency to cause DNA damage in children with CHD. In chronic hypoxia, there is a liberation of Reactive Oxygen Species (ROS) due to tissue injury as a result of ischemia and induction of hypoxia inducible factor - 1HIF-1 and p53 which in turn activates pro-apoptotic factors leading to alteration in the regulation of pro-apoptotic gene Blc-2 to be involved in causing the DNA damage. The extent of chronic hypoxia and the DNA damage depends on the nature of the anatomical heart defect. Hence, the present case-control study was conducted to find out the DNA damage in children with isolated septal defect and septal defect with great vessel anomaly of heart and to compare the same. The study group was categorized into those with isolated septal defects and septal defects associated with great vessel anomaly based on echo-cardiogram. Age and sex matched healthy children were taken as controls. Single-cell gel electrophoresis - Comet Assay of Alkaline Version was performed conventionally and the comets were analyzed using comet score software. The comet metrics was found to be statistically significant in children with isolated septal defect and septal defect with great vessel anomaly when compared with that of the controls. In addition, comet metrics also showed significantly increased DNA damage among children with septal defects associated with great vessel anomaly when compared to isolated septal defects. The data strongly suggests a linear correlation of severity of the anomaly involved with the degree of DNA damage as evidenced by lesser extent of DNA damage in isolated septal defect and greater in septal defect with great vessel anomaly.

Effectiveness of the critical congenital heart disease screening program for early diagnosis of cardiac abnormalities in newborn infants.

PubMed

Almawazini, Abdulmajid M; Hanafi, Hamdi K; Madkhali, Hasan A; Majrashi, Noura B

2017-10-01

To evaluate the effectiveness of critical congenital heart disease (CCHD) screening program for early diagnosis of cardiac anomalies in newborn infants.  Methods: This is a hospital-based prospective cross-sectional study conducted in the Pediatric and Neonatology Department, King Fahad Hospital at  Albaha, Saudi Arabia, between February 2016 and February 2017. Results: We screened 2961 (95.4%) of 3103 patients in a nursery unit; 142 (4.6%) patients were not screened. The test was positive in 114 (3.9%) patients and negative in 2847 (96.1%). There were 94 (3.2%) false positives and 20 (0.7%) true positives. Critical cardiac defects were diagnosed in 7 (0.2%) patients of all screened infants, and severe pulmonary hypertension was diagnosed in 13 (0.4%) patients. True negative results were found in 2841(96%) patients, and no cardiac defect was diagnosed, whereas false negative results were seen in 6 (0.2%) patients diagnosed with ventricular septal defect. The sensitivity was 77%, and the specificity was very high at 97%, with a positive predictive value of 18%, and a negative predictive value of 99.8% (95% confidence interval 13.78-19.18, p=0.0001). Conclusion: Pulse oximetry was found to be easy, safe, sensitive, and highly specific for diagnosis of CCHD.

Magnetic resonance imaging at a high field strength of ventricular septal defects in infants.

PubMed

Baker, E J; Ayton, V; Smith, M A; Parsons, J M; Ladusans, E J; Anderson, R H; Maisey, M N; Tynan, M; Fagg, N L; Deverall, P B

1989-10-01

Magnetic resonance imaging at a high field strength has potential benefits for the study of the heart in infants, which is when most congenital heart disease presents. Seventeen infants with various anatomical types of ventricular septal defect were studied by this technique. Good quality, high resolution, images were obtained in every case. There were no major practical problems. The morphology of the defects in all 17 hearts was displayed in great detail. In some instances, the interpretation of the images resembled that of equivalent images from cross sectional echocardiography. But this new technique allowed imaging in planes that cannot be obtained by echocardiography. One particularly valuable plane gave a face on view of the inlet and trabecular components of the septum. This allowed very precise localisation of defects in these areas. The relation between the defects and the atrioventricular and arterial valves was exceptionally well shown in various different imaging planes. One patient in the series had multiple trabecular defects that were clearly shown. Magnetic resonance imaging gives detailed morphological information about ventricular septal defects.

Retrospective review of congenital heart disease in 976 dogs.

PubMed

Oliveira, P; Domenech, O; Silva, J; Vannini, S; Bussadori, R; Bussadori, C

2011-01-01

Knowledge of epidemiology is important for recognition of cardiovascular malformations. Review the incidence of congenital heart defects in dogs in Italy and assess breed and sex predispositions. Nine hundred and seventy-six dogs diagnosed with congenital heart disease (CHD) of 4,480 dogs presented to Clinica Veterinaria Gran Sasso for cardiovascular examination from 1997 to 2010. A retrospective analysis of medical records regarding signalment, history, clinical examination, radiography, electrocardiography, echocardiography, angiography, and postmortem examination was performed. Breed and sex predisposition were assessed with the odds ratio test. CHD was observed in 21.7% of cases. A total of 1,132 defects were observed with single defects in 832 cases (85%), 2 concurrent defects in 132 cases (14%), and 3 concurrent defects in 12 cases (1%). The most common defects were pulmonic stenosis (PS; 32.1%), subaortic stenosis (SAS; 21.3%), and patent ductus arteriosus (20.9%), followed by ventricular septal defect (VSD; 7.5%), valvular aortic stenosis (AS; 5.7%), and tricuspid dysplasia (3.1%). SAS, PS, and VSD frequently were associated with other defects. Several breed and sex predispositions were identified. The results of this study are in accordance with previous studies, with slight differences. The breed and sex predilections identified may be of value for the diagnosis and screening of CHD in dogs. Additionally, the relatively high percentage of concurrent heart defects emphasizes the importance of accurate and complete examinations for identification. Because these data are from a cardiology referral center, a bias may exist. Copyright © 2011 by the American College of Veterinary Internal Medicine.

The heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome.

PubMed

Garrity, Deborah M; Childs, Sarah; Fishman, Mark C

2002-10-01

Holt-Oram syndrome is one of the autosomal dominant human "heart-hand" disorders, with a combination of upper limb malformations and cardiac defects. Holt-Oram syndrome is caused by mutations in the TBX5 gene, a member of a large family of T-box transcription factors that play important roles in cell-type specification and morphogenesis. In a screen for mutations affecting zebrafish cardiac function, we isolated the recessive lethal mutant heartstrings, which lacks pectoral fins and exhibits severe cardiac dysfunction, beginning with a slow heart rate and progressing to a stretched, non-functional heart. We mapped and cloned the heartstrings mutation and find it to encode the zebrafish ortholog of the TBX5 gene. The heartstrings mutation causes premature termination at amino acid 316. Homozygous mutant embryos never develop pectoral fin buds and do not express several markers of early fin differentiation. The total absence of any fin bud differentiation distinguishes heartstrings from most other mutations that affect zebrafish fin development, suggesting that Tbx5 functions very early in the pectoral fin induction pathway. Moderate reduction of Tbx5 by morpholino causes fin malformations, revealing an additional early requirement for Tbx5 in coordinating the axes of fin outgrowth. The heart of heartstrings mutant embryos appears to form and function normally through the early heart tube stage, manifesting only a slight bradycardia compared with wild-type siblings. However, the heart fails to loop and then progressively deteriorates, a process affecting the ventricle as well as the atrium. Relative to mammals, fish require lower levels of Tbx5 to produce malformed appendages and display whole-heart rather than atrial-predominant cardiac defects. However, the syndromic deficiencies of tbx5 mutation are remarkably well retained between fish and mammals.

A Matter of the Heart: The African Clawed Frog Xenopus as a Model for Studying Vertebrate Cardiogenesis and Congenital Heart Defects

PubMed Central

Hempel, Annemarie; Kühl, Michael

2016-01-01

The African clawed frog, Xenopus, is a valuable non-mammalian model organism to investigate vertebrate heart development and to explore the underlying molecular mechanisms of human congenital heart defects (CHDs). In this review, we outline the similarities between Xenopus and mammalian cardiogenesis, and provide an overview of well-studied cardiac genes in Xenopus, which have been associated with congenital heart conditions. Additionally, we highlight advantages of modeling candidate genes derived from genome wide association studies (GWAS) in Xenopus and discuss commonly used techniques. PMID:29367567

Septum primum atrial septal defect in an infant with hypoplastic left heart syndrome.

PubMed

Loar, Robert W; Burkhart, Harold M; Taggart, Nathaniel W

2014-08-01

Hypoplastic left heart syndrome (HLHS) is a form of congenital heart disease characterized by severe underdevelopment of the left heart, leading to inadequate systemic blood flow. Several different atrial septal morphologies are observed in HLHS, most commonly a secundum atrial septal defect, patent foramen ovale, intact septum, and leftward displacement of the superior attachment of the septum primum. It has been postulated that atrial septal development is associated with the development of the left heart. We present a case of a newborn infant with HLHS and the unusual finding of a primum ASD.

Usefulness of cutting balloon angioplasty for the treatment of congenital heart defects.

PubMed

Kusa, Jacek; Mazurak, Magdalena; Skierska, Agnieszka; Szydlowski, Leslaw; Czesniewicz, Pawel; Manka, Lukasz

2018-01-01

Patients with complex congenital heart defects may have different hemodynamic prob-lems which require a variety of interventional procedures including angioplasty which involves using high-pressure balloons. After failure of conventional balloon angioplasty, cutting balloon angioplasty is the next treatment option available. The purpose of this study was to evaluate the safety and efficacy of cutting balloon angioplasty in children with different types of congenital heart defects. Cutting balloon angioplasty was performed in 28 children with different congenital heart defects. The indication for cutting balloon angioplasty was: pulmonary artery stenosis in 17 patients, creating or dilatation of interatrial communication in 10 patients, and stenosis of left subclavian artery in 1 patient. In the pulmonary arteries group there was a significant decrease in systolic blood pressure (SBP) in the proximal part of the artery from the average 74.33 ± 20.4 mm Hg to 55 ± 16.7 mm Hg (p < 0.001). Distal to the stenosis there was an increase in SBP from 19.8 ± 3.82 mm Hg to 30.3 ± ± 13.3 mm Hg (p = 0.04). This result remained constant in the follow-up. In atrial septal defect/fenestra-tion group, cutting balloon angioplasty was performed after an unsuccessful classic Rashkind procedure. After cutting balloon angioplasty there was a significant widening of the interatrial communication. Cutting balloon angioplasty is a feasible and effective treatment option in different con-genital heart defects.

Parental overprotection and heart-focused anxiety in adults with congenital heart disease.

PubMed

Ong, Lephuong; Nolan, Robert P; Irvine, Jane; Kovacs, Adrienne H

2011-09-01

The care of adult patients with congenital heart disease (CHD) is challenging from a mental health perspective, as these patients continue to face a variety of biopsychosocial issues that may impact emotional functioning. Despite these issues, there are limited data on the psychosocial functioning of adults with CHD, and there are no data on the impact of parental overprotection on heart-focused anxiety in this patient population. The aim of this study was to examine the relationships between patient recollections of parental overprotection and current heart-focused anxiety in adults with CHD. A cross-sectional sample of 190 adult patients with CHD (51% male; mean age = 32.28, SD = 11.86 years) completed validated measures of perceived parental overprotection (Parental Bonding Instrument) and heart-focused anxiety (Cardiac Anxiety Questionnaire). The results indicated that perceived parental overprotection (β = 0.19, p = 0.02) and heart defect complexity (β = 0.17, p = 0.03) were significantly related to heart-focused anxiety. Contrary to hypotheses, perceived parental overprotection did not vary as a function of heart defect complexity (F (2, 169) = 0.02, p = 0.98). Perceived parental overprotection and heart defect complexity are associated with heart-focused anxiety in adults with congenital heart disease. These results can inform the development of clinical interventions aimed at improving the psychosocial adjustment of this patient population.

Association of maternal chronic disease with risk of congenital heart disease in offspring

PubMed Central

Chou, Hsin-Hsu; Chiou, Meng-Jiun; Liang, Fu-Wen; Chen, Lea-Hua; Lu, Tsung-Hsueh; Li, Chung-Yi

2016-01-01

Background: Information about known risk factors for congenital heart disease is scarce. In this population-based study, we aimed to investigate the relation between maternal chronic disease and congenital heart disease in offspring. Methods: The study cohort consisted of 1 387 650 live births from 2004 to 2010. We identified chronic disease in mothers and mild and severe forms of congenital heart disease in their offspring from Taiwan’s National Health Insurance medical claims. We used multivariable logistic regression analysis to assess the associations of all cases and specific types of congenital heart disease with various maternal chronic diseases. Results: For mothers with the following chronic diseases, the overall prevalence of congenital heart disease in their children was significantly higher than for mothers without these diseases: diabetes mellitus type 1 (adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 1.66–3.25), diabetes mellitus type 2 (adjusted OR 2.85, 95% CI 2.60–3.12), hypertension (adjusted OR 1.87, 95% CI 1.69–2.07), congenital heart defects (adjusted OR 3.05, 95% CI 2.45–3.80), anemia (adjusted OR 1.31, 95% CI 1.25–1.38), connective tissue disorders (adjusted OR 1.39, 95% CI 1.19–1.62), epilepsy (adjusted OR 1.37, 95% CI 1.08–1.74) and mood disorders (adjusted OR 1.25, 95% CI 1.11–1.41). The same pattern held for mild forms of congenital heart disease. A higher prevalence of severe congenital heart disease was seen only among offspring of mothers with congenital heart defects or type 2 diabetes. Interpretation: The children of women with several kinds of chronic disease appear to be at risk for congenital heart disease. Preconception counselling and optimum treatment of pregnant women with chronic disease would seem prudent. PMID:27729382

Association of maternal chronic disease with risk of congenital heart disease in offspring.

PubMed

Chou, Hsin-Hsu; Chiou, Meng-Jiun; Liang, Fu-Wen; Chen, Lea-Hua; Lu, Tsung-Hsueh; Li, Chung-Yi

2016-12-06

Information about known risk factors for congenital heart disease is scarce. In this population-based study, we aimed to investigate the relation between maternal chronic disease and congenital heart disease in offspring. The study cohort consisted of 1 387 650 live births from 2004 to 2010. We identified chronic disease in mothers and mild and severe forms of congenital heart disease in their offspring from Taiwan's National Health Insurance medical claims. We used multivariable logistic regression analysis to assess the associations of all cases and specific types of congenital heart disease with various maternal chronic diseases. For mothers with the following chronic diseases, the overall prevalence of congenital heart disease in their children was significantly higher than for mothers without these diseases: diabetes mellitus type 1 (adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 1.66-3.25), diabetes mellitus type 2 (adjusted OR 2.85, 95% CI 2.60-3.12), hypertension (adjusted OR 1.87, 95% CI 1.69-2.07), congenital heart defects (adjusted OR 3.05, 95% CI 2.45-3.80), anemia (adjusted OR 1.31, 95% CI 1.25-1.38), connective tissue disorders (adjusted OR 1.39, 95% CI 1.19-1.62), epilepsy (adjusted OR 1.37, 95% CI 1.08-1.74) and mood disorders (adjusted OR 1.25, 95% CI 1.11-1.41). The same pattern held for mild forms of congenital heart disease. A higher prevalence of severe congenital heart disease was seen only among offspring of mothers with congenital heart defects or type 2 diabetes. The children of women with several kinds of chronic disease appear to be at risk for congenital heart disease. Preconception counselling and optimum treatment of pregnant women with chronic disease would seem prudent. © 2016 Canadian Medical Association or its licensors.

4D Subject-Specific Inverse Modeling of the Chick Embryonic Heart Outflow Tract Hemodynamics

PubMed Central

Goenezen, Sevan; Chivukula, Venkat Keshav; Midgett, Madeline; Phan, Ly; Rugonyi, Sandra

2015-01-01

Blood flow plays a critical role in regulating embryonic cardiac growth and development, with altered flow leading to congenital heart disease. Progress in the field, however, is hindered by a lack of quantification of hemodynamic conditions in the developing heart. In this study, we present a methodology to quantify blood flow dynamics in the embryonic heart using subject-specific computational fluid dynamics (CFD) models. While the methodology is general, we focused on a model of the chick embryonic heart outflow tract (OFT), which distally connects the heart to the arterial system, and is the region of origin of many congenital cardiac defects. Using structural and Doppler velocity data collected from optical coherence tomography (OCT), we generated 4D (3D + time) embryo-specific CFD models of the heart OFT. To replicate the blood flow dynamics over time during the cardiac cycle, we developed an iterative inverse-method optimization algorithm, which determines the CFD model boundary conditions such that differences between computed velocities and measured velocities at one point within the OFT lumen are minimized. Results from our developed CFD model agree with previously measured hemodynamics in the OFT. Further, computed velocities and measured velocities differ by less than 15% at locations that were not used in the optimization, validating the model. The presented methodology can be used in quantifications of embryonic cardiac hemodynamics under normal and altered blood flow conditions, enabling an in depth quantitative study of how blood flow influences cardiac development. PMID:26361767

Prevalence and profile of congenital heart disease and pulmonary hypertension in Down syndrome in a pediatric cardiology service

PubMed Central

Mourato, Felipe Alves; Villachan, Lúcia Roberta R.; Mattos, Sandra da Silva

2014-01-01

OBJECTIVE: To determine the frequence and profile of congenital heart defects in Down syndrome patients referred to a pediatric cardiologic center, considering the age of referral, gender, type of heart disease diagnosed by transthoracic echocardiography and its association with pulmonary hypertension at the initial diagnosis. METHODS: Cross-sectional study with retrospective data collection of 138 patients with Down syndrome from a total of 17,873 records. Descriptive analysis of the data was performed, using Epi-Info version 7. RESULTS: Among the 138 patients with Down syndrome, females prevailed (56.1%) and 112 (81.2%) were diagnosed with congenital heart disease. The most common lesion was ostium secundum atrial septal defect, present in 51.8%, followed by atrioventricular septal defect, in 46.4%. Ventricular septal defects were present in 27.7%, while tetralogy of Fallot represented 6.3% of the cases. Other cardiac malformations corresponded to 12.5%. Pulmonary hypertension was associated with 37.5% of the heart diseases. Only 35.5% of the patients were referred before six months of age. CONCLUSIONS: The low percentage of referral until six months of age highlights the need for a better tracking of patients with Down syndrome in the context of congenital heart disease, due to the high frequency and progression of pulmonary hypertension. PMID:25119745

Genetics of Congenital Heart Disease: Past and Present.

PubMed

Muntean, Iolanda; Togănel, Rodica; Benedek, Theodora

2017-04-01

Congenital heart disease is the most common congenital anomaly, representing an important cause of infant morbidity and mortality. Congenital heart disease represents a group of heart anomalies that include septal defects, valve defects, and outflow tract anomalies. The exact genetic, epigenetic, or environmental basis of congenital heart disease remains poorly understood, although the exact mechanism is likely multifactorial. However, the development of new technologies including copy number variants, single-nucleotide polymorphism, next-generation sequencing are accelerating the detection of genetic causes of heart anomalies. Recent studies suggest a role of small non-coding RNAs, micro RNA, in congenital heart disease. The recently described epigenetic factors have also been found to contribute to cardiac morphogenesis. In this review, we present past and recent genetic discoveries in congenital heart disease.

Utility and Scope of Rapid Prototyping in Patients with Complex Muscular Ventricular Septal Defects or Double-Outlet Right Ventricle: Does it Alter Management Decisions?

PubMed

Bhatla, Puneet; Tretter, Justin T; Ludomirsky, Achi; Argilla, Michael; Latson, Larry A; Chakravarti, Sujata; Barker, Piers C; Yoo, Shi-Joon; McElhinney, Doff B; Wake, Nicole; Mosca, Ralph S

2017-01-01

Rapid prototyping facilitates comprehension of complex cardiac anatomy. However, determining when this additional information proves instrumental in patient management remains a challenge. We describe our experience with patient-specific anatomic models created using rapid prototyping from various imaging modalities, suggesting their utility in surgical and interventional planning in congenital heart disease (CHD). Virtual and physical 3-dimensional (3D) models were generated from CT or MRI data, using commercially available software for patients with complex muscular ventricular septal defects (CMVSD) and double-outlet right ventricle (DORV). Six patients with complex anatomy and uncertainty of the optimal management strategy were included in this study. The models were subsequently used to guide management decisions, and the outcomes reviewed. 3D models clearly demonstrated the complex intra-cardiac anatomy in all six patients and were utilized to guide management decisions. In the three patients with CMVSD, one underwent successful endovascular device closure following a prior failed attempt at transcatheter closure, and the other two underwent successful primary surgical closure with the aid of 3D models. In all three cases of DORV, the models provided better anatomic delineation and additional information that altered or confirmed the surgical plan. Patient-specific 3D heart models show promise in accurately defining intra-cardiac anatomy in CHD, specifically CMVSD and DORV. We believe these models improve understanding of the complex anatomical spatial relationships in these defects and provide additional insight for pre/intra-interventional management and surgical planning.

Chronic Hypoxemia in Children With Congenital Heart Defect Impairs Airway Epithelial Sodium Transport.

PubMed

Kaskinen, Anu K; Helve, Otto; Andersson, Sture; Kirjavainen, Turkka; Martelius, Laura; Mattila, Ilkka P; Rautiainen, Paula; Pitkänen, Olli M

2016-01-01

Ambient hypoxia impairs the airway epithelial Na transport, which is crucial in lung edema reabsorption. Whether chronic systemic hypoxemia affects airway Na transport has remained largely unknown. We have therefore investigated whether chronic systemic hypoxemia in children with congenital heart defect affects airway epithelial Na transport, Na transporter-gene expression, and short-term lung edema accumulation. Prospective, observational study. Tertiary care medical center responsible for nationwide pediatric cardiac surgery. Ninety-nine children with congenital heart defect or acquired heart disease (age range, 6 d to 14.8 yr) were divided into three groups based on their level of preoperative systemic hypoxemia: 1) normoxemic patients (SpO2% ≥ 95%; n = 44), 2) patients with cyanotic congenital heart defect and moderate hypoxemia (SpO2 86-94%; n = 16), and 3) patients with cyanotic congenital heart defect and profound systemic hypoxemia (SpO2 ≤ 85%; n = 39). Nasal transepithelial potential difference served as a surrogate measure for epithelial Na transport of the respiratory tract. Profoundly hypoxemic patients had 29% lower basal nasal transepithelial potential difference (p = 0.02) and 55% lower amiloride-sensitive nasal transepithelial potential difference (p = 0.0003) than normoxemic patients. In profoundly hypoxemic patients, nasal epithelial messenger RNA expressions of two airway Na transporters (amiloride-sensitive epithelial Na channel and β1- Na-K-ATPase) were not attenuated, but instead α1-Na-K-ATPase messenger RNA levels were higher (p = 0.03) than in the normoxemic patients, indicating that posttranscriptional factors may impair airway Na transport. The chest radiograph lung edema score increased after congenital cardiac surgery in profoundly hypoxemic patients (p = 0.0004) but not in patients with normoxemia or moderate hypoxemia. The impaired airway epithelial amiloride-sensitive Na transport activity in profoundly hypoxemic children with cyanotic congenital heart defect may hinder defense against lung edema after cardiac surgery.

Genetic and flow anomalies in congenital heart disease.

PubMed

Rugonyi, Sandra

2016-01-01

Congenital heart defects are the most common malformations in humans, affecting approximately 1% of newborn babies. While genetic causes of congenital heart disease have been studied, only less than 20% of human cases are clearly linked to genetic anomalies. The cause for the majority of the cases remains unknown. Heart formation is a finely orchestrated developmental process and slight disruptions of it can lead to severe malformations. Dysregulation of developmental processes leading to heart malformations are caused by genetic anomalies but also environmental factors including blood flow. Intra-cardiac blood flow dynamics plays a significant role regulating heart development and perturbations of blood flow lead to congenital heart defects in animal models. Defects that result from hemodynamic alterations, however, recapitulate those observed in human babies, even those due to genetic anomalies and toxic teratogen exposure. Because important cardiac developmental events, such as valve formation and septation, occur under blood flow conditions while the heart is pumping, blood flow regulation of cardiac formation might be a critical factor determining cardiac phenotype. The contribution of flow to cardiac phenotype, however, is frequently ignored. More research is needed to determine how blood flow influences cardiac development and the extent to which flow may determine cardiac phenotype.

Maternal occupational exposure to polycyclic aromatic hydrocarbons and congenital heart defects among offspring in the national birth defects prevention study.

PubMed

Lupo, Philip J; Symanski, Elaine; Langlois, Peter H; Lawson, Christina C; Malik, Sadia; Gilboa, Suzanne M; Lee, Laura J; Agopian, A J; Desrosiers, Tania A; Waters, Martha A; Romitti, Paul A; Correa, Adolfo; Shaw, Gary M; Mitchell, Laura E

2012-11-01

There is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) results in congenital heart defects (CHDs); however, to our knowledge, this relationship has not been examined in humans. Therefore, we conducted a case-control study assessing the association between estimated maternal occupational exposure to PAHs and CHDs in offspring. Data on CHD cases and control infants were obtained from the National Birth Defects Prevention Study for the period of 1997 to 2002. Exposure to PAHs was assigned by industrial hygienist consensus, based on self-reported maternal occupational histories from 1 month before conception through the third month of pregnancy. Logistic regression was used to evaluate the association between maternal occupational PAH exposure and specific CHD phenotypic subtypes among offspring. The prevalence of occupational PAH exposure was 4.0% in CHD case mothers (76/1907) and 3.6% in control mothers (104/2853). After adjusting for maternal age, race or ethnicity, education, smoking, folic acid supplementation, and study center, exposure was not associated with conotruncal defects (adjusted odds ratio [AOR], 0.98; 95% confidence interval [CI], 0.58-1.67), septal defects (AOR, 1.28; 95% CI, 0.86-1.90), or with any isolated CHD subtype. Our findings do not support an association between potential maternal occupational exposure to PAHs and various CHDs in a large, population-based study. For CHD phenotypic subtypes in which modest nonsignificant associations were observed, future investigations could be improved by studying populations with a higher prevalence of PAH exposure and by incorporating information on maternal and fetal genotypes related to PAH metabolism. Birth Defects Research (Part A), 2012. Copyright © 2012 Wiley Periodicals, Inc.

Health in adults with congenital heart disease.

PubMed

Cuypers, Judith A A E; Utens, Elisabeth M W J; Roos-Hesselink, Jolien W

2016-09-01

Since the introduction of cardiac surgery, the prospects for children born with a cardiac defect have improved spectacularly. Many reach adulthood and the population of adults with congenital heart disease is increasing and ageing. However, repair of congenital heart disease does not mean cure. Many adults with congenital heart disease encounter late complications. Late morbidity can be related to the congenital heart defect itself, but may also be the consequence of the surgical or medical treatment or longstanding alterations in hemodynamics, neurodevelopment and psychosocial development. This narrative review describes the cardiac and non-cardiac long-term morbidity in the adult population with congenital heart disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sequential segmental classification of feline congenital heart disease.

PubMed

Scansen, Brian A; Schneider, Matthias; Bonagura, John D

2015-12-01

Feline congenital heart disease is less commonly encountered in veterinary medicine than acquired feline heart diseases such as cardiomyopathy. Understanding the wide spectrum of congenital cardiovascular disease demands a familiarity with a variety of lesions, occurring both in isolation and in combination, along with an appreciation of complex nomenclature and variable classification schemes. This review begins with an overview of congenital heart disease in the cat, including proposed etiologies and prevalence, examination approaches, and principles of therapy. Specific congenital defects are presented and organized by a sequential segmental classification with respect to their morphologic lesions. Highlights of diagnosis, treatment options, and prognosis are offered. It is hoped that this review will provide a framework for approaching congenital heart disease in the cat, and more broadly in other animal species based on the sequential segmental approach, which represents an adaptation of the common methodology used in children and adults with congenital heart disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease.

PubMed

Peng, Ting; Wang, Li; Zhou, Shu-Feng; Li, Xiaotian

2010-12-01

A number of mutations in GATA4 and NKX2.5 have been identified to be causative for a subset of familial congenital heart defects (CHDs) and a small number of sporadic CHDs. In this study, we evaluated common GATA4 and NKX2.5 mutations in 135 Chinese pediatric patients with non-familial congenital heart defects. Two novel mutations in the coding region of GATA4 were identified, namely, 487C >T (Pro163Ser) in exon 1 in a child with tetralogy of Fallot and 1220C >A (Pro407Gln) in exon 6 in a pediatric patient with outlet membranous ventricular septal defect. We also found 848C >A (Pro283Gln) in exon 2 of the NKX2.5 gene in a pediatric patient with ventricular septal defect, patent ductus arteriosus and aortic isthmus stenosis. None of the mutations was detected in healthy control subjects (n = 114). This study suggests that GATA4 and NKX2.5 missense mutations may be associated with congenital heart defects in pediatric Chinese patients. Further clinical studies with large samples are warranted.

Hypertrophic cardiomyopathy

MedlinePlus

... heart, forcing the heart to work harder to pump blood. It also can make it harder for the heart to relax ... from defects in the genes that control heart muscle growth. Younger people are likely to ...

Folic acid supplementation and the occurrence of congenital heart defects, orofacial clefts, multiple births, and miscarriage.

PubMed

Bailey, Lynn B; Berry, Robert J

2005-05-01

Key research findings relative to the question of whether maternal use of folic acid before and during pregnancy reduces the chance that offspring will be born with a congenital heart defect or an orofacial cleft are reviewed in this paper. Observational studies in general support an association between maternal use of multivitamins containing folic acid and a reduction in the occurrence of congenital heart defects and orofacial clefts. Results from one randomized controlled trial (RCT) provide the strongest evidence that multivitamins prevent congenital heart defects, but this RCT did not provide evidence that multivitamins prevent orofacial clefts. In addition, most observational and interventional studies are not designed to detect an independent effect from folic acid. Early studies suggested that periconceptional multivitamin use was associated with an increased occurrence of both miscarriages and multiple births, which has resulted in a great deal of controversy about the safety of folic acid use during pregnancy. We also review reports that were designed to answer these questions with more definitive data. When more substantial evidence about the effect of periconceptional folic acid on the occurrence of congenital heart defects and orofacial clefts is reported, we will have additional support for promoting folic acid intervention programs. All women capable of becoming pregnant should continue to consume 400 mug/d of folic acid in addition to a healthy diet as advised.

Congenital Heart Information Network

MedlinePlus

... heart defects. Important Notice The Congenital Heart Information Network website is temporarily out of service. Please join ... and Uwe Baemayr for The Congenital Heart Information Network Exempt organization under Section 501(c)3. Copyright © ...

A Zebrafish Loss-of-Function Model for Human CFAP53 Mutations Reveals Its Specific Role in Laterality Organ Function.

PubMed

Noël, Emily S; Momenah, Tarek S; Al-Dagriri, Khalid; Al-Suwaid, Abdulrahman; Al-Shahrani, Safar; Jiang, Hui; Willekers, Sven; Oostveen, Yara Y; Chocron, Sonja; Postma, Alex V; Bhuiyan, Zahurul A; Bakkers, Jeroen

2016-02-01

Establishing correct left-right asymmetry during embryonic development is crucial for proper asymmetric positioning of the organs. Congenital heart defects, such as dextrocardia, transposition of the arteries, and inflow or outflow tract malformations, comprise some of the most common birth defects and may be attributed to incorrect establishment of body laterality. Here, we identify new patients with dextrocardia who have mutations in CFAP53, a coiled-coil domain containing protein. To elucidate the mechanism by which CFAP53 regulates embryonic asymmetry, we used genome editing to generate cfap53 zebrafish mutants. Zebrafish cfap53 mutants have specific defects in organ laterality and randomization of asymmetric gene expression. We show that cfap53 is required for cilia rotation specifically in Kupffer's vesicle, the zebrafish laterality organ, providing a mechanism by which patients with CFAP53 mutations develop dextrocardia and heterotaxy, and confirming previous evidence that left-right asymmetry in humans is regulated through cilia-driven fluid flow in a laterality organ. © 2015 WILEY PERIODICALS, INC.

Retrospective study of congenital heart defects in 151 dogs.

PubMed

Tidholm, A

1997-03-01

The case records of 151 dogs diagnosed with congenital heart disease were reviewed retrospectively. The most common defect was aortic stenosis, accounting for 35 per cent of all cases, followed by pulmonic stenosis (20 per cent), ventricular septal defect (12 per cent), patent ductus arteriosus (11 per cent), mitral valve dysplasia (8 per cent), tricuspid valve dysplasia (7 per cent), endocardial fibroelastosis (1.9 per cent) and tetralogy of Fallot (0.6 per cent). Fifty-one breeds were represented, with golden retrievers, German shepherd dogs and boxers predominating. No overall sex predilection was obvious. Seventy-five per cent of the dogs were asymptomatic at presentation. The defects most often associated with presenting symptoms, such as dyspnoea, syncope, ascites, failure to grow and depression, were mitral valve dysplasia, atrial septal defect, tricuspid valve dysplasia and endocardial fibroelastosis. The latter presented with the most severe signs of heart failure. In some cases of aortic stenosis and pulmonic stenosis, where the defect could not be accurately visualised with two-dimensional echocardiography, Doppler echocardiographic examination was needed for definitive diagnosis.

Abnormal lung function in adults with congenital heart disease: prevalence, relation to cardiac anatomy, and association with survival.

PubMed

Alonso-Gonzalez, Rafael; Borgia, Francesco; Diller, Gerhard-Paul; Inuzuka, Ryo; Kempny, Aleksander; Martinez-Naharro, Ana; Tutarel, Oktay; Marino, Philip; Wustmann, Kerstin; Charalambides, Menelaos; Silva, Margarida; Swan, Lorna; Dimopoulos, Konstantinos; Gatzoulis, Michael A

2013-02-26

Restrictive lung defects are associated with higher mortality in patients with acquired chronic heart failure. We investigated the prevalence of abnormal lung function, its relation to severity of underlying cardiac defect, its surgical history, and its impact on outcome across the spectrum of adult congenital heart disease. A total of 1188 patients with adult congenital heart disease (age, 33.1±13.1 years) undergoing lung function testing between 2000 and 2009 were included. Patients were classified according to the severity of lung dysfunction based on predicted values of forced vital capacity. Lung function was normal in 53% of patients with adult congenital heart disease, mildly impaired in 17%, and moderately to severely impaired in the remainder (30%). Moderate to severe impairment of lung function related to complexity of underlying cardiac defect, enlarged cardiothoracic ratio, previous thoracotomy/ies, body mass index, scoliosis, and diaphragm palsy. Over a median follow-up period of 6.7 years, 106 patients died. Moderate to severe impairment of lung function was an independent predictor of survival in this cohort. Patients with reduced force vital capacity of at least moderate severity had a 1.6-fold increased risk of death compared with patients with normal lung function (P=0.04). A reduced forced vital capacity is prevalent in patients with adult congenital heart disease; its severity relates to the complexity of the underlying heart defect, surgical history, and scoliosis. Moderate to severe impairment of lung function is an independent predictor of mortality in contemporary patients with adult congenital heart disease.

Wavelet packet-based insufficiency murmurs analysis method

NASA Astrophysics Data System (ADS)

Choi, Samjin; Jiang, Zhongwei

2007-12-01

In this paper, the aortic and mitral insufficiency murmurs analysis method using the wavelet packet technique is proposed for classifying the valvular heart defects. Considering the different frequency distributions between the normal sound and insufficiency murmurs in frequency domain, we used two properties such as the relative wavelet energy and the Shannon wavelet entropy which described the energy information and the entropy information at the selected frequency band, respectively. Then, the signal to murmur ratio (SMR) measures which could mean the ratio between the frequency bands for normal heart sounds and for aortic and mitral insufficiency murmurs allocated to 15.62-187.50 Hz and 187.50-703.12 Hz respectively, were employed as a classification manner to identify insufficiency murmurs. The proposed measures were validated by some case studies. The 194 heart sound signals with 48 normal and 146 abnormal sound cases acquired from 6 healthy volunteers and 30 patients were tested. The normal sound signals recorded by applying a self-produced wireless electric stethoscope system to subjects with no history of other heart complications were used. Insufficiency murmurs were grouped into two valvular heart defects such as aortic insufficiency and mitral insufficiency. These murmur subjects included no other coexistent valvular defects. As a result, the proposed insufficiency murmurs detection method showed relatively very high classification efficiency. Therefore, the proposed heart sound classification method based on the wavelet packet was validated for the classification of valvular heart defects, especially insufficiency murmurs.

Neighborhood Deprivation and Risk of Congenital Heart Defects, Neural Tube Defects and Orofacial Clefts: A Systematic Review and Meta-Analysis

PubMed Central

Deguen, Séverine; Kihal, Wahida; Jeanjean, Maxime; Padilla, Cindy; Zmirou-Navier, Denis

2016-01-01

Background We conducted this systematic review and meta-analysis to address the open question of a possible association between the socioeconomic level of the neighborhoods in which pregnant women live and the risk of Congenital Heart Defects (CHDs), Neural Tube Defects (NTDs) and OroFacial Clefts (OFCs). Methods We searched MEDLINE from its inception to December 20th, 2015 for case-control, cohort and ecological studies assessing the association between neighborhood socioeconomic level and the risk of CHDs, NTDs and the specific phenotypes Cleft Lip with or without Cleft Palate (CLP) and Cleft Palate (CP). Study-specific risk estimates were pooled according to random-effect and fixed-effect models. Results Out of 245 references, a total of seven case-control studies, two cohort studies and two ecological studies were assessed in the systematic review; all studies were enrolled in the meta-analysis with the exception of the two cohort studies. No significant association has been revealed between CHDs or NTDs and neighborhood deprivation index. For CLP phenotype subgroups, we found a significantly higher rate in deprived neighborhoods (Odds Ratios (OR) = 1.22, 95% CI: 1.10, 1.36) whereas this was not significant for CP phenotype subgroups (OR = 1.20, 95%CI: 0.89, 1.61). Conclusion In spite of the small number of epidemiological studies included in the present literature review, our findings suggest that neighborhood socioeconomic level where mothers live is associated only with an increased risk of CLP phenotype subgroups. This finding has methodological limitations that impede the formulation of firm conclusions, and further investigations should confirm this association. PMID:27783616

Pattern of congenital heart diseases in Rwandan children with genetic defects

PubMed Central

Teteli, Raissa; Uwineza, Annette; Butera, Yvan; Hitayezu, Janvier; Murorunkwere, Seraphine; Umurerwa, Lamberte; Ndinkabandi, Janvier; Hellin, Anne-Cécile; Jamar, Mauricette; Caberg, Jean-Hubert; Muganga, Narcisse; Mucumbitsi, Joseph; Rusingiza, Emmanuel Kamanzi; Mutesa, Leon

2014-01-01

Introduction Congenital heart diseases (CHD) are commonly associated with genetic defects. Our study aimed at determining the occurrence and pattern of CHD association with genetic defects among pediatric patients in Rwanda. Methods A total of 125 patients with clinical features suggestive of genetic defects were recruited. Echocardiography and standard karyotype studies were performed in all patients. Results CHDs were detected in the majority of patients with genetic defects. The commonest isolated CHD was ventricular septal defect found in many cases of Down syndrome. In total, chromosomal abnormalities represented the majority of cases in our cohort and were associated with various types of CHDs. Conclusion Our findings showed that CHDs are common in Rwandan pediatric patients with genetic defects. These results suggest that a routine echocardiography assessment combined with systematic genetic investigations including standard karyotype should be mandatory in patients presenting characteristic clinical features in whom CHD is suspected to be associated with genetic defect. PMID:25722758

Ventricular septal defect

MedlinePlus

... causing an irregular or slow heart rhythm) Delayed growth and development ( failure to thrive in infancy) Heart failure Infective endocarditis (bacterial infection of the heart) Pulmonary hypertension (high blood ...

[Self esteem of chronically ill children and adolescence exemplified by obesity and congenital heart defect].

PubMed

Sticker, Elisabeth; Schmidt, Claudia; Steins, Gisela

2003-01-01

Coping with a chronic illness challenges children and adolescents in addition to their normal developmental tasks. This double challenge probably endangers the development of a stable self-esteem. The present investigation explores the possibility whether these processes are different with respect to the kind of illness. Chronic illnesses such as obesity and congenital heart defects (CHD) serve as examples in comparing two samples (8-16 years): obesity (N = 54) as visible and partly controllable illness (with respect to the course of illness) vs. congenital heart disease (N = 56) as invisible and uncontrollable illness (with respect to the origin and course of illness). Self-esteem is measured by a scale (ALS) which focuses on the public areas "school" and "leisure time" and the private area "family". Children and adolescents with CHD (especially females) display an above-average positive self-esteem in all areas. Children and adolescents with obesity mainly display an average self-esteem, the females scoring above-average for the private area "family", the males scoring below-average for the public area "leisure time". Furthermore, leisure-time related self-esteem is significantly lower for obese than for CHD subjects. These specific relations implicate differential accentuations for intervention programs.

Using birth defects registry data to evaluate infant and childhood mortality associated with birth defects: an alternative to traditional mortality assessment using underlying cause of death statistics.

PubMed

Copeland, Glenn E; Kirby, Russell S

2007-11-01

Although birth defects are a leading cause of death in infancy and early childhood, the proportion of all deaths to children with clinically diagnosed birth defects is not well documented. The study is intended to measure the proportion of all deaths to infants and children under age 10 occurring to children with birth defects and how and why this proportion differs from the proportion of deaths due to an underlying cause of congenital anomalies using standard mortality statistics. A linked file of Michigan livebirths and deaths was combined with data from a comprehensive multisource birth defects registry of Michigan livebirths born during the years 1992 through 2000. The data were analyzed to determine the mortality rate for infants and children with birth defects and for children with no reported birth defect. Mortality risk ratios were calculated. The underlying causes of death for children with birth defects were also categorized and compared to cause- specific mortality rates for the general population. Congenital anomalies were the underlying cause of death for 17.8% of all infant deaths while infants with birth defects were 33.7% of all infant deaths in the study. Almost half of all Michigan deaths to children aged 1 to 2 were within the birth defects registry, though only 15.0% had an underlying cause of death of a congenital anomaly based upon standard mortality statistics. The mortality experience among children with birth defects was significantly higher than other children throughout the first 9 years of life, ranging from 4.6 for 5 year olds to 12.8 for children 1 to 2. Mortality risk ratios examined by cause of death for infants with birth defects were highest for other endocrine (28.1), other CNS (28.1), and heart (21.9) conditions. For children 1 through 9, the highest differential risk was seen for other perinatal conditions (39.0), other endocrine (29.7), other CNS (24.5), and heart (21.4). Childhood mortality analyses that incorporate birth defects registry data provide a more comprehensive picture of the full burden of birth defects on mortality in infant and children and can provide an effective mechanism for monitoring the survival and mortality risks of children with selected birth defects on a population basis.

Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome.

PubMed

Mlynarski, Elisabeth E; Xie, Michael; Taylor, Deanne; Sheridan, Molly B; Guo, Tingwei; Racedo, Silvia E; McDonald-McGinn, Donna M; Chow, Eva W C; Vorstman, Jacob; Swillen, Ann; Devriendt, Koen; Breckpot, Jeroen; Digilio, Maria Cristina; Marino, Bruno; Dallapiccola, Bruno; Philip, Nicole; Simon, Tony J; Roberts, Amy E; Piotrowicz, Małgorzata; Bearden, Carrie E; Eliez, Stephan; Gothelf, Doron; Coleman, Karlene; Kates, Wendy R; Devoto, Marcella; Zackai, Elaine; Heine-Suñer, Damian; Goldmuntz, Elizabeth; Bassett, Anne S; Morrow, Bernice E; Emanuel, Beverly S

2016-03-01

The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS; MIM #192430; 188400) is the most common microdeletion syndrome. The phenotypic presentation of 22q11DS is highly variable; approximately 60-75 % of 22q11DS patients have been reported to have a congenital heart defect (CHD), mostly of the conotruncal type, and/or aortic arch defect. The etiology of the cardiac phenotypic variability is not currently known for the majority of patients. We hypothesized that rare copy number variants (CNVs) outside the 22q11.2 deleted region may modify the risk of being born with a CHD in this sensitized population. Rare CNV analysis was performed using Affymetrix SNP Array 6.0 data from 946 22q11DS subjects with CHDs (n = 607) or with normal cardiac anatomy (n = 339). Although there was no significant difference in the overall burden of rare CNVs, an overabundance of CNVs affecting cardiac-related genes was detected in 22q11DS individuals with CHDs. When the rare CNVs were examined with regard to gene interactions, specific cardiac networks, such as Wnt signaling, appear to be overrepresented in 22q11DS CHD cases but not 22q11DS controls with a normal heart. Collectively, these data suggest that CNVs outside the 22q11.2 region may contain genes that modify risk for CHDs in some 22q11DS patients.

Early Evaluation of the Fetal Heart.

PubMed

Hernandez-Andrade, Edgar; Patwardhan, Manasi; Cruz-Lemini, Mónica; Luewan, Suchaya

2017-01-01

Evaluation of the fetal heart at 11-13 + 6 weeks of gestation is indicated for women with a family history of congenital heart defects (CHD), a previous child with CDH, or an ultrasound finding associated with cardiac anomalies. The accuracy for early detection of CHD is highly related to the experience of the operator. The 4-chamber view and outflow tracts are the most important planes for identification of an abnormal heart, and can be obtained in the majority of fetuses from 11 weeks of gestation onward. Transvaginal ultrasound is the preferred route for fetal cardiac examination prior to 12 weeks of gestation, whereas, after 12 weeks, the fetal heart can be reliably evaluated by transabdominal ultrasound. Cardiac defects, such as ventricular septal defects, tetralogy of Fallot, Ebstein's anomaly, or cardiac tumors, are unlikely to be identified at ≤14 weeks of gestation. Additional ultrasound techniques such as spatiotemporal image correlation and the evaluation of volumes by a fetal-heart expert can improve the detection of congenital heart disease. The evaluation of the fetal cardiac function at 11-13 + 6 weeks of gestation can be useful for early identification of fetuses at risk of anemia due to hemoglobinopathies, such as hemoglobin Bart's disease. © 2017 S. Karger AG, Basel.

Gerbode defect and multivalvular dysfunction: Complex complications in adult congenital heart disease.

PubMed

Ruivo, Catarina; Guardado, Joana; Montenegro Sá, Fernando; Saraiva, Fátima; Antunes, Alexandre; Correia, Joana; Morais, João

2017-07-01

We report a clinical case of a 40-year-old male with surgically corrected congenital heart disease (CHD) 10 years earlier: closure of ostium primum, mitral annuloplasty, and aortic valve and root surgery. The patient was admitted with acute heart failure. Transesophageal echocardiography (TEE) revealed a dysmorphic and severely incompetent aortic valve, a partial tear of the mitral valve cleft repair and annuloplasty ring dehiscence. A true left ventricular-to-right atrial shunt confirmed a direct Gerbode defect. The authors aim to discuss the diagnostic challenge of adult CHD, namely the key role of TEE on septal defects and valve regurgitations description. © 2017, Wiley Periodicals, Inc.

If Your Child Has a Heart Defect (For Parents)

MedlinePlus

... congenital heart disease are at risk for bacterial endocarditis, an infection of the tissue that lines the ... who have artificial heart valves or have had endocarditis before. Most children with heart problems, however, do ...

Temporally Distinct Six2-Positive Second Heart Field Progenitors Regulate Mammalian Heart Development and Disease.

PubMed

Zhou, Zhengfang; Wang, Jingying; Guo, Chaoshe; Chang, Weiting; Zhuang, Jian; Zhu, Ping; Li, Xue

2017-01-24

The embryonic process of forming a complex structure such as the heart remains poorly understood. Here, we show that Six2 marks a dynamic subset of second heart field progenitors. Six2-positive (Six2 + ) progenitors are rapidly recruited and assigned, and their descendants are allocated successively to regions of the heart from the right ventricle (RV) to the pulmonary trunk. Global ablation of Six2 + progenitors resulted in RV hypoplasia and pulmonary atresia. An early stage-specific ablation of a small subset of Six2 + progenitors did not cause any apparent structural defect at birth but rather resulted in adult-onset cardiac hypertrophy and dysfunction. Furthermore, Six2 expression depends in part on Shh signaling, and Shh deletion resulted in severe deficiency of Six2 + progenitors. Collectively, these findings unveil the chronological features of cardiogenesis, in which the mammalian heart is built sequentially by temporally distinct populations of cardiac progenitors, and provide insights into late-onset congenital heart disease. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate

PubMed Central

Burkhard, Silja Barbara

2018-01-01

Development of specialized cells and structures in the heart is regulated by spatially -restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue-sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development. Using our transcriptome map, we identified spatially restricted Wnt/β-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/β-catenin signaling controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially restricted molecular pathways critical for specific cardiac functions. PMID:29400650

Dual developmental role of transcriptional regulator Ets1 in Xenopus cardiac neural crest vs. heart mesoderm

PubMed Central

Nie, Shuyi; Bronner, Marianne E.

2015-01-01

Aims Ets1 is an important transcription factor that is expressed in both the cardiac neural crest (NC) and heart mesoderm of vertebrate embryos. Moreover, Ets1 deletion in humans results in congenital heart abnormalities. To clarify the functional contributions of Ets1 in cardiac NC vs. heart mesoderm, we performed tissue-targeted loss-of-function analysis to compare the relative roles of Ets1 in these two tissues during heart formation using Xenopus embryos as a model system. Methods and results We confirmed by in situ hybridization analysis that Ets1 is expressed in NC and heart mesoderm during embryogenesis. Using a translation-blocking antisense morpholino to knockdown Ets1 protein selectively in the NC, we observed defects in NC delamination from the neural tube, collective cell migration, as well as segregation of NC streams in the cranial and cardiac regions. Many cardiac NC cells failed to reach their destination in the heart, resulting in defective aortic arch artery formation. A different set of defects was noted when Ets1 knockdown was targeted to heart mesoderm. The formation of the primitive heart tube was dramatically delayed and the endocardial tissue appeared depleted. As a result, the conformation of the heart was severely disrupted. In addition, the outflow tract septum was missing, and trabeculae formation in the ventricle was abolished. Conclusion Our study shows that Ets1 is required in both the cardiac NC and heart mesoderm, albeit for different aspects of heart formation. Our results reinforce the suggestion that proper interaction between these tissues is critical for normal heart development. PMID:25691536

Tetralogy of Fallot associated with deletion in the DiGeorge region of chromosome 22 (22q11)

DOE Office of Scientific and Technical Information (OSTI.GOV)

D`Angelo, J.A.; Pillers, D.M.; Jett, P.L.

Cardiac conotruncal defects, such as Tetralogy of Fallot (TOF), are associated with DiGeorge syndrome which has been mapped to the q11 region of chromosome 22 and includes abnormalities of neural crest and branchial arch development. Patients with conotruncal defects and velo-cardio-facial syndrome may have defects in the 22q11 region but not show the complete DiGeorge phenotype consisting of cardiac, thymus, and parathyroid abnormalities. We report two neonates with TOF and small deletions in the DiGeorge region of chromosome 22 (46,XX,del(22)(q11.21q11.23) and 46,XY,del(22)(q11.2q11.2)) using both high-resolution cytogenetics and fluorescence in situ hybridization (FISH). The first patient is a female with TOFmore » and a family history of congenital heart disease. The mother has pulmonic stenosis and a right-sided aortic arch, one brother has TOF, and a second brother has a large VSD. The patient had intrauterine growth retardation and had thrombocytopenia due to maternal IgG platelet-directed autoantibody. Lymphocyte populations, both T and B cells, were reduced in number but responded normally to stimulation. The findings were not attributed to a DiGeorge phenotype. Although she had transient neonatal hypocalcemia, her parathyroid hormone level was normal. The patient was not dysmorphic in the newborn period but her mother had features consistent with velo-cardio-facial syndrome. The second patient was a male with TOF who was not dysmorphic and had no other significant clinical findings and no family history of heart disease. Lymphocyte testing did not reveal a specific immunodeficiency. No significant postnatal hypocalcemia was noted. These cases illustrate that there is a wide spectrum of clinical features associated with defects of the 22q11 region. We recommend karyotype analysis, including FISH probes specific to the DiGeorge region, in any patient with conotruncal cardiac defects.« less

Sulfamethoxazole/Trimethoprim (Bactrim or Septra) and Pregnancy

MedlinePlus

... defects, neural tube defects (opening in the spine), cleft lip or palate (lip or roof of mouth do not form correctly), and urinary tract defects. Trimethoprim might decrease the ... bifida, oral clefts and heart defects. It is recommended that pregnant ...

Parents' perceptions during the transition to home for their child with a congenital heart defect: How can we support families of children with hypoplastic left heart syndrome?

PubMed

March, Sarita

2017-07-01

The aim of the study was to explore the literature related to transitions in healthcare between the hospital and home that caregivers experience with a child who has a congenital heart defect (CHD), specifically related to hypoplastic left heart syndrome (HLHS). A systematic literature review was conducted searching OVID Medline, CINAHL, and PubMed to discover the caregivers' perceptions on their transitions between hospital care and home care of their child with a CHD. Articles included those with focus on the transitions of caregivers between hospital and home care for children with CHD. Excluded articles were studies focused on adolescents, transition to adult healthcare, mortality results, other diseases associated with CHDs, comparison of CHD treatments, feasibility studies, differences in care between hospitals, home monitoring, and comparison of videoconference and telephone home communication. Ten articles were selected. Many parents voiced their concerns with feeding their child, learning medical skills and knowledge, reported a disrupted relationship between parents and their child, and identified stress and anxiety associated with taking care of a child with a CHD. There were limited studies on caregivers' transitions with a child with HLHS, but there also was limited focus on the caregivers' experiences with transitions between hospital and home care for their child with any CHD. Research on the transition experience between hospital care and home care for caregivers of children born with a CHD, and a specific focus on HLHS from the caregivers' viewpoint, would provide insight into the perspective of caregivers during the numerous transitions. © 2017 Wiley Periodicals, Inc.

Effect of Congenital Heart Defects on Language Development in Toddlers with Down Syndrome

ERIC Educational Resources Information Center

Visootsak, J.; Hess, B.; Bakeman, R.; Adamson, L. B.

2013-01-01

Background: Down syndrome (DS, OMIM #190685) is the most commonly identified genetic form of intellectual disability with congenital heart defect (CHD) occurring in 50% of cases. With advances in surgical techniques and an increasing lifespan, this has necessitated a greater understanding of the neurodevelopmental consequences of CHDs. Herein, we…

Facts about Ventricular Septal Defect

MedlinePlus

... Living With Heart Defects Data & Statistics Tracking & Research Articles & Key Findings Free Materials Multimedia and Tools Links to Other Websites Information For… Media Policy Makers Facts about Ventricular Septal Defect Language: ...

Facts about Atrial Septal Defect

MedlinePlus

... Living With Heart Defects Data & Statistics Tracking & Research Articles & Key Findings Free Materials Multimedia and Tools Links to Other Websites Information For… Media Policy Makers Facts about Atrial Septal Defect Language: ...

Pulmonary atresia

MedlinePlus

... possible, but depend on the extent of the heart abnormalities that accompany the pulmonary valve defect. Potential treatments include: A thin, flexible tube (heart catheterization) to repair the problem Open heart surgery ...

Gia/Mthl5 is an aorta specific GPCR required for Drosophila heart tube morphology and normal pericardial cell positioning.

PubMed

Patel, Meghna V; Zhu, Jun-Yi; Jiang, Zhiping; Richman, Adam; VanBerkum, Mark F A; Han, Zhe

2016-06-01

G-protein signaling is known to be required for cell-cell contacts during the development of the Drosophila dorsal vessel. However, the identity of the G protein-coupled receptor (GPCR) that regulates this signaling pathway activity is unknown. Here we describe the identification of a novel cardiac specific GPCR, called Gia, for "GPCR in aorta". Gia is the only heart-specific GPCR identified in Drosophila to date and it is specifically expressed in cardioblasts that fuse at the dorsal midline to become the aorta. Gia is the only Drosophila gene so far identified for which expression is entirely restricted to cells of the aorta. Deletion of Gia led to a broken-hearted phenotype, characterized by pericardial cells dissociated from cardioblasts and abnormal distribution of cell junction proteins. Both phenotypes were similar to those observed in mutants of the heterotrimeric cardiac G proteins. Lack of Gia also led to defects in the alignment and fusion of cardioblasts in the aorta. Gia forms a protein complex with G-αo47A, the alpha subunit of the heterotrimeric cardiac G proteins and interacts genetically with G-αo47A during cardiac morphogenesis. Our study identified Gia as an essential aorta-specific GPCR that functions upstream of cardiac heterotrimeric G proteins and is required for morphological integrity of the aorta during heart tube formation. These studies lead to a redefinition of the bro phenotype, to encompass morphological integrity of the heart tube as well as cardioblast-pericardial cell spatial interactions. Copyright © 2016 Elsevier Inc. All rights reserved.

A Novel Alpha Cardiac Actin (ACTC1) Mutation Mapping to a Domain in Close Contact with Myosin Heavy Chain Leads to a Variety of Congenital Heart Defects, Arrhythmia and Possibly Midline Defects.

PubMed

Augière, Céline; Mégy, Simon; El Malti, Rajae; Boland, Anne; El Zein, Loubna; Verrier, Bernard; Mégarbané, André; Deleuze, Jean-François; Bouvagnet, Patrice

2015-01-01

A Lebanese Maronite family presented with 13 relatives affected by various congenital heart defects (mainly atrial septal defects), conduction tissue anomalies and midline defects. No mutations were found in GATA4 and NKX2-5. A set of 399 poly(AC) markers was used to perform a linkage analysis which peaked at a 2.98 lod score on the long arm of chromosome 15. The haplotype analysis delineated a 7.7 meganucleotides genomic interval which included the alpha-cardiac actin gene (ACTC1) among 36 other protein coding genes. A heterozygous missense mutation was found (c.251T>C, p.(Met84Thr)) in the ACTC1 gene which changed a methionine residue conserved up to yeast. This mutation was absent from 1000 genomes and exome variant server database but segregated perfectly in this family with the affection status. This mutation and 2 other ACTC1 mutations (p.(Glu101Lys) and p.(Met125Val)) which result also in congenital heart defects are located in a region in close apposition to a myosin heavy chain head region by contrast to 3 other alpha-cardiac actin mutations (p.(Ala297Ser),p.(Asp313His) and p.(Arg314His)) which result in diverse cardiomyopathies and are located in a totally different interaction surface. Alpha-cardiac actin mutations lead to congenital heart defects, cardiomyopathies and eventually midline defects. The consequence of an ACTC1 mutation may in part be dependent on the interaction surface between actin and myosin.

Current diagnosis and treatments for critical congenital heart defects

PubMed Central

ZENG, ZHANDONG; ZHANG, HONGWEI; LIU, FENGLI; ZHANG, NING

2016-01-01

Congenital heart defects (CHD) affect approximately 7% of infants, and account for 3% of all infant deaths. CHD is most often caused by the defects associated with ductus arteriosus, which is a vessel that usually closes shortly after birth. The types of CHD include tetralogy of fallot, hypoplastic left heart syndrome, pulmonary atresia, total anomalous pulmonary venous return, transposition of great arteries, tricuspid atresia and truncus arteriosus. There are some risk factors that can increase the chance of a fetus developing CHD such as prematurity, an existing CHD in a first-degree relative, genetic syndromes, infections in utero, maternal drug consumptions and disorders. CHD is diagnosed is through different techniques including pulse oximetry, echocardiograms and physical exams. In this review, we examined the current incidence of CHD, the risk factors associated with CHD, the current methods of diagnosis and surgical options used to repair the defects. PMID:27168772

Facts about Atrioventricular Septal Defect (AVSD)

MedlinePlus

... Living With Heart Defects Data & Statistics Tracking & Research Articles & Key Findings Free Materials Multimedia and Tools Links to Other Websites Information For… Media Policy Makers Facts about Atrioventricular Septal Defect (AVSD) ...

A Survey of Congenital Heart Disease and Other Organic Malformations Associated with Different Types of Orofacial Clefts in Eastern China

PubMed Central

Sun, Ting; Tian, Hua; Wang, Changqian; Yin, Ping; Zhu, Yaqin; Chen, Xianghua; Tang, Zhengde

2013-01-01

Background A high incidence of orofacial clefts is reported in China, but no data has shown the relation between cleft types and the incidence of other defects so far. The aim of this study is to assess the incidence of congenital heart diseases and other organic defects associated with different types of orofacial clefts. Methodology and Principal Findings All children with orofacial clefts, which were sought out from the Health Information System of Shanghai Ninth People's Hospital between 1st Jan 2009 and 30th Dec 2011, were enrolled in this study. All subjects underwent a thorough examination and grouped by the cleft phenotype. The numbers and types of other organic defects were recorded and analyzed statistically using SPSS 17.0. Of 2180 cases reported as having orofacial clefts, 657 (30.1%) had other congenital abnormalities, which were significantly more common in cleft palate (47.9% (329/687)) than that in cleft lip (10.6% (80/755)) or cleft lip and palate (33.6% (248/738)) (P<0.01). In subgroups, unilateral cleft lip and palate had a statistically higher incidence of associated abnormalities than bilateral cleft lip and palate (P<0.01). The most common malformation was congenital heart disease, which counted 45.1% (296/657) of all malformations. Disorders of the central nervous system (14.3%(94/657)) and Skeletal anomalies (13.1%(86/657)) were also frequently associated. Additionally, the most common defect in heart was atrial septal defect, which was 39.7% (118/296) of all congenital heart diseases. Conclusions and Significance As the high incidence of heart defects and other organic abnormalities in the children with cleft palate in Eastern China, special attention should be paid to them and echocardiography should be a proposed examination in the evaluation of children with cleft palate before any surgical correction being executed. PMID:23349958

A survey of congenital heart disease and other organic malformations associated with different types of orofacial clefts in Eastern China.

PubMed

Sun, Ting; Tian, Hua; Wang, Changqian; Yin, Ping; Zhu, Yaqin; Chen, Xianghua; Tang, Zhengde

2013-01-01

A high incidence of orofacial clefts is reported in China, but no data has shown the relation between cleft types and the incidence of other defects so far. The aim of this study is to assess the incidence of congenital heart diseases and other organic defects associated with different types of orofacial clefts. All children with orofacial clefts, which were sought out from the Health Information System of Shanghai Ninth People's Hospital between 1(st) Jan 2009 and 30(th) Dec 2011, were enrolled in this study. All subjects underwent a thorough examination and grouped by the cleft phenotype. The numbers and types of other organic defects were recorded and analyzed statistically using SPSS 17.0. Of 2180 cases reported as having orofacial clefts, 657 (30.1%) had other congenital abnormalities, which were significantly more common in cleft palate (47.9% (329/687)) than that in cleft lip (10.6% (80/755)) or cleft lip and palate (33.6% (248/738)) (P<0.01). In subgroups, unilateral cleft lip and palate had a statistically higher incidence of associated abnormalities than bilateral cleft lip and palate (P<0.01). The most common malformation was congenital heart disease, which counted 45.1% (296/657) of all malformations. Disorders of the central nervous system (14.3%(94/657)) and Skeletal anomalies (13.1%(86/657)) were also frequently associated. Additionally, the most common defect in heart was atrial septal defect, which was 39.7% (118/296) of all congenital heart diseases. As the high incidence of heart defects and other organic abnormalities in the children with cleft palate in Eastern China, special attention should be paid to them and echocardiography should be a proposed examination in the evaluation of children with cleft palate before any surgical correction being executed.

Loss of RNA expression and allele-specific expression associated with congenital heart disease

PubMed Central

McKean, David M.; Homsy, Jason; Wakimoto, Hiroko; Patel, Neil; Gorham, Joshua; DePalma, Steven R.; Ware, James S.; Zaidi, Samir; Ma, Wenji; Patel, Nihir; Lifton, Richard P.; Chung, Wendy K.; Kim, Richard; Shen, Yufeng; Brueckner, Martina; Goldmuntz, Elizabeth; Sharp, Andrew J.; Seidman, Christine E.; Gelb, Bruce D.; Seidman, J. G.

2016-01-01

Congenital heart disease (CHD), a prevalent birth defect occurring in 1% of newborns, likely results from aberrant expression of cardiac developmental genes. Mutations in a variety of cardiac transcription factors, developmental signalling molecules and molecules that modify chromatin cause at least 20% of disease, but most CHD remains unexplained. We employ RNAseq analyses to assess allele-specific expression (ASE) and biallelic loss-of-expression (LOE) in 172 tissue samples from 144 surgically repaired CHD subjects. Here we show that only 5% of known imprinted genes with paternal allele silencing are monoallelic versus 56% with paternal allele expression—this cardiac-specific phenomenon seems unrelated to CHD. Further, compared with control subjects, CHD subjects have a significant burden of both LOE genes and ASE events associated with altered gene expression. These studies identify FGFBP2, LBH, RBFOX2, SGSM1 and ZBTB16 as candidate CHD genes because of significantly altered transcriptional expression. PMID:27670201

Periconceptional Folic Acid Supplementation and Infant Risk of Congenital Heart Defects in Norway 1999-2009.

PubMed

Leirgul, Elisabeth; Gildestad, Trude; Nilsen, Roy Miodini; Fomina, Tatiana; Brodwall, Kristoffer; Greve, Gottfried; Vollset, Stein Emil; Holmstrøm, Henrik; Tell, Grethe S; Øyen, Nina

2015-09-01

The birth prevalence of congenital heart defects (CHDs) has decreased in Canada and Europe. Recommended intake of folic acid in pregnancy is a suggestive risk-reducing factor for CHDs. We investigated the association between periconceptional intake of folic acid supplements and infant risk of CHDs. Information on maternal intake of folic acid supplements before and during pregnancy in the Medical Birth Registry of Norway 1999-2009 was updated with information on CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. The association between folic acid intake and infant risk of CHD was estimated as relative risk (RR) with binomial log linear regression. Among 517 784 non-chromosomal singleton births, 6200 children were identified with CHD and 1153 with severe CHD. For all births, 18.4% of the mothers initiated folic acid supplements before pregnancy and 31.6% during pregnancy. The adjusted RR for severe CHD was 0.99 [95% confidence interval [CI] 0.86, 1.13] comparing periconceptional intake of folic acid with no intake. Specifically, RR for conotruncal defects was 0.99 [95% CI 0.80, 1.22], atrioventricular septal defects 1.19 [95% CI 0.78, 1.81], left ventricular outflow tract obstructions 1.02 [95% CI 0.78, 1.32], and right ventricular outflow tract obstructions 0.97 [95% CI 0.72, 1.29]. Birth prevalence of septal defects was higher in the group exposed to folic acid supplements with RR 1.19 [95% CI 1.10, 1.30]. Periconceptional folic acid supplement use showed no association with severe CHDs in the newborn. An unexpected association with an increased risk of septal defects warrants further investigation. © 2015 The Authors. Paediatric and Perinatal Epidemiology Published by John Wiley & Sons Ltd.

Syndromic Hirschsprung's disease and associated congenital heart disease: a systematic review.

PubMed

Duess, Johannes W; Puri, Prem

2015-08-01

Hirschsprung's disease (HD) occurs as an isolated phenotype in 70% of infants and is associated with additional congenital anomalies or syndromes in approximately 30% of patients. The cardiac development depends on neural crest cell proliferation and is closely related to the formation of the enteric nervous system. HD associated with congenital heart disease (CHD) has been reported in 5-8% of cases, with septation defects being the most frequently recorded abnormalities. However, the prevalence of HD associated with CHD in infants with syndromic disorders is not well documented. This systematic review was designed to determine the prevalence of CHD in syndromic HD. A systematic review of the literature using the keywords "Hirschsprung's disease", "aganglionosis", "congenital megacolon", "congenital heart disease" and "congenital heart defect" was performed. Resulting publications were reviewed for epidemiology and morbidity. Reference lists were screened for additional relevant studies. A total of fifty-two publications from 1963 to 2014 reported data on infants with HD associated with CHD. The overall reported prevalence of HD associated with CHD in infants without chromosomal disorders was 3%. In infants with syndromic disorders, the overall prevalence of HD associated with CHD ranged from 20 to 80 % (overall prevalence 51%). Septation defects were recorded in 57% (atrial septal defects in 29%, ventricular septal defects in 32%), a patent ductus arteriosus in 39%, vascular abnormalities in 16%, valvular heart defects in 4% and Tetralogy of Fallot in 7%. The prevalence of HD associated with CHD is much higher in infants with chromosomal disorders compared to infants without associated syndromes. A routine echocardiogram should be performed in all infants with syndromic HD to exclude cardiac abnormalities.

How to develop a business case to establish a neonatal pulse oximetry programme for screening of congenital heart defects.

PubMed

Ewer, Andrew K

2012-12-01

Pulse oximetry screening for critical congenital heart defects (CCHDs) is a highly specific, moderately sensitive test which is cost effective, acceptable to both clinical staff and parents and meets the criteria for universal screening. Pulse oximetry screening is gaining considerable worldwide support and last year was added to the recommended uniform screening panel in the USA following endorsement by the Health and Human Services Secretary. There is significant heterogeneity in published screening protocols and it is important to consider all available evidence and also take local factors into account when developing a screening programme, whether it is within an individual hospital, neonatal network or even at a national level. This paper presents available options based both on the published evidence and personal practice experience which will aid those considering the introduction of screening to make the right decisions both from a clinical and financial perspective. Copyright © 2012 Elsevier Ltd. All rights reserved.

Altering hemodynamics leads to congenital heart defects (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ford, Stephanie M.; McPheeters, Matthew T.; Wang, Yves T.; Gu, Shi; Doughman, Yong Qiu; Strainic, James P.; Rollins, Andrew M.; Watanabe, Michiko; Jenkins, Michael W.

2016-03-01

The role of hemodynamics in early heart development is poorly understood. In order to successfully assess the impact of hemodynamics on development, we need to monitor and perturb blood flow, and quantify the resultant effects on morphology. Here, we have utilized cardiac optical pacing to create regurgitant flow in embryonic hearts and OCT to quantify regurgitation percentage and resultant morphology. Embryonic quail in a shell-less culture were optically paced at 3 Hz (well above the intrinsic rate or 1.33-1.67 Hz) on day 2 of development (3-4 weeks human) for 5 minutes. The pacing fatigued the heart and led to a prolonged period (> 1 hour) of increased regurgitant flow. Embryos were kept alive until day 3 (cardiac looping - 4-5 weeks human) or day 8 (4 chambered heart - 8 weeks human) to quantify resultant morphologic changes with OCT. All paced embryos imaged at day 3 displayed cardiac defects. The extent of regurgitant flow immediately after pacing was correlated with cardiac cushion size 24-hours post pacing (p-value < 0.01) with higher regurgitation leading to smaller cushions. Almost all embryos (16/18) surviving to day 8 exhibited congenital heart defects (CHDs) including 11/18 with valve defects, 5/18 with ventricular septal defects and 5/18 with hypoplastic right ventricles. Our data suggests that regurgitant flow leads to smaller cushions, which develop into abnormal valves and septa. Our model produces similar phenotypes as found in our fetal alcohol syndrome and velo-cardio-facial/DiGeorge syndrome models suggesting that hemodynamics plays a role in these syndromes as well. Utilizing OCT and optical pacing to understand hemodynamics in development is an important step towards determining CHD mechanisms and ultimately developing earlier treatments.

Pacing-induced congenital heart defects assessed by OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ford, Stephanie M.; McPheeters, Matt T.; Wang, Yves T.; Gu, Shi; Doughman, Yong Qiu; Strainic, James P.; Rollins, Andrew M.; Watanabe, Michiko; Jenkins, Michael W.

2016-03-01

The role of hemodynamics in early heart development is poorly understood. In order to successfully assess the impact of hemodynamics on development, we need to monitor and perturb blood flow, and quantify the resultant effects on morphology. Here, we have utilized cardiac optical pacing to create regurgitant flow in embryonic hearts and OCT to quantify regurgitation percentage and resultant morphology. Embryonic quail in a shell-less culture were optically paced at 3 Hz (well above the intrinsic rate or 1.33-1.67 Hz) on day 2 of development (3-4 weeks human) for 5 minutes. The pacing fatigued the heart and led to a prolonged period (> 1 hour) of increased regurgitant flow. Embryos were kept alive until day 3 (cardiac looping - 4-5 weeks human) or day 8 (4 chambered heart - 8 weeks human) to quantify resultant morphologic changes with OCT. All paced embryos imaged at day 3 displayed cardiac defects. The extent of regurgitant flow immediately after pacing was correlated with cardiac cushion size 24-hours post pacing (p-value < 0.01) with higher regurgitation leading to smaller cushions. Almost all embryos (16/18) surviving to day 8 exhibited congenital heart defects (CHDs) including 11/18 with valve defects, 5/18 with ventricular septal defects and 5/18 with hypoplastic right ventricles. Our data suggests that regurgitant flow leads to smaller cushions, which develop into abnormal valves and septa. Our model produces similar phenotypes as found in our fetal alcohol syndrome and velo-cardio-facial/DiGeorge syndrome models suggesting that hemodynamics plays a role in these syndromes as well. Utilizing OCT and optical pacing to understand hemodynamics in development is an important step towards determining CHD mechanisms and ultimately developing earlier treatments.

Qualitative research of alternatively splice variants of fibronectin in different development stage of mice heart.

PubMed

Lu, Feng; Ma, Fang-Fang; Zhang, Wei; Li, Ying; Wei, Fei-Yu; Zhou, Lei

2015-12-01

Fibronectin (FN) plays vital roles in cell adhesion, differentiation, proliferation and migration. It is involved in the process of embryonic development and is highly conserved during evolution. The EIIIA and EIIIB of FN show a very high degree of homology among vertebrates. Embryos deleting both EIIIA and EIIIB displayed multiple embryonic cardiovascular defects, implying their crucial role during embryogenesis. The correlation of spliced EIIIB, EIIIA, and IIICS of FN to heart development was studied by observing their chronological expression in mice heart. C57 mice embryos at E11.5, E12.5, E13.5, E14.5, E15.5, E16.5, E17.5, E18.5, E19.5 days, postnatal day 1 (P1d), and adult male mice (3 months) were used. For each alternatively spliced FN1 domain (EIIIB, EIIIA and IIICS), primer pairs were designed for specific amplification. Total RNA was extracted from the heart tissue, reverse transcripted to cDNA, followed by RT-PCR with specific primers. The PCR amplification was verified by agarose gel electrophoresis, showing specific fragments of the expected sizes. In adult mice heart, only alternatively splice variants of EIIIA-, EIIIB-, IIICS+ were expressed. While in embryonic mice, spliced variant of EIIIA+/-, EIIIB+/-, IIICS+ were observed. The expression of EIIIA and EIIIB changed during heart development. FN is crucial for the normal development of the embryonic heart by modulating cardiac neural crest (CNC) proliferation and survival, and maintenance of CNC cells. FN1 gene seems to play a significant role by expression of highly conserved EIIIA and EIIIB in embryonic heart development.

In utero exposure to venlafaxine, a serotonin-norepinephrine reuptake inhibitor, increases cardiac anomalies and alters placental and heart serotonin signaling in the rat.

PubMed

Laurent, Laetitia; Huang, Chunwei; Ernest, Sheila R; Berard, Anick; Vaillancourt, Cathy; Hales, Barbara F

2016-12-01

Human studies are inconsistent with respect to an association between treatment with selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that in utero exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart serotonin signaling in the rat. Timed-pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression. Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the serotonin transporter (SERT/Slc6a4) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the serotonin 2B receptor (5-HT 2B /Htr2b) and of fibroblast growth factor 8 was induced in fetal hearts. In utero venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1044-1055, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A step-wise approach for analysis of the mouse embryonic heart using 17.6 Tesla MRI

PubMed Central

Gabbay-Benziv, Rinat; Reece, E. Albert; Wang, Fang; Bar-Shir, Amnon; Harman, Chris; Turan, Ozhan M.; Yang, Peixin; Turan, Sifa

2018-01-01

Background The mouse embryo is ideal for studying human cardiac development. However, laboratory discoveries do not easily translate into clinical findings partially because of histological diagnostic techniques that induce artifacts and lack standardization. Aim To present a step-wise approach using 17.6 T MRI, for evaluation of mice embryonic heart and accurate identification of congenital heart defects. Subjects 17.5-embryonic days embryos from low-risk (non-diabetic) and high-risk (diabetic) model dams. Study design Embryos were imaged using 17.6 Tesla MRI. Three-dimensional volumes were analyzed using ImageJ software. Outcome measures Embryonic hearts were evaluated utilizing anatomic landmarks to locate the four-chamber view, the left- and right-outflow tracts, and the arrangement of the great arteries. Inter- and intra-observer agreement were calculated using kappa scores by comparing two researchers’ evaluations independently analyzing all hearts, blinded to the model, on three different, timed occasions. Each evaluated 16 imaging volumes of 16 embryos: 4 embryos from normal dams, and 12 embryos from diabetic dams. Results Inter-observer agreement and reproducibility were 0.779 (95% CI 0.653–0.905) and 0.763 (95% CI 0.605–0.921), respectively. Embryonic hearts were structurally normal in 4/4 and 7/12 embryos from normal and diabetic dams, respectively. Five embryos from diabetic dams had defects: ventricular septal defects (n = 2), transposition of great arteries (n = 2) and Tetralogy of Fallot (n = 1). Both researchers identified all cardiac lesions. Conclusion A step-wise approach for analysis of MRI-derived 3D imaging provides reproducible detailed cardiac evaluation of normal and abnormal mice embryonic hearts. This approach can accurately reveal cardiac structure and, thus, increases the yield of animal model in congenital heart defect research. PMID:27569369

Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing inter-domain interactions within the ryanodine receptor

PubMed Central

Kobayashi, Shigeki; Yano, Masafumi; Suetomi, Takeshi; Ono, Makoto; Tateishi, Hiroki; Mochizuki, Mamoru; Xu, Xiaojuan; Uchinoumi, Hitoshi; Okuda, Shinichi; Yamamoto, Takeshi; Koseki, Noritaka; Kyushiki, Hiroyuki; Ikemoto, Noriaki; Matsuzaki, Masunori

2009-01-01

Objectives To investigate the effect of dantrolene, a drug generally used to treat Malignant Hyperthermia (MH), on the Ca2+ release and cardiomyocyte function in failing hearts. Background The N-terminal (N: 1-600) and Central (C: 2000-2500) domains of the ryanodine receptor (RyR), harbor many mutations associated with MH in skeletal muscle RyR (RyR1) and polymorphic ventricular tachycardia in cardiac RyR (RyR2). There is strong evidence that inter-domain interaction between these regions plays an important role in the mechanism of channel regulation. Methods Sarcoplasmic reticulum (SR) vesicles and cardiomyocytes were isolated from dog LV muscles (normal or rapid ventricular pacing for 4 weeks), for Ca2+ leak, transient, and spark assays. To assess the zipped or unzipped state of the interacting domains, the RyR was fluorescently labeled with methylcoumarin acetate in a site-directed manner. We employed a quartz-crystal microbalance technique to identify the dantrolene binding site within the RyR2. Results Dantrolene specifically bound to domain 601-620 in RyR2. In the SR isolated from pacing-induced dog failing hearts, the defective inter-domain interaction_(domain unzipping) has already occurred, causing spontaneous Ca2+ leak. Dantrolene suppressed both domain unzipping and the Ca2+ leak, showing identical drug concentration-dependence (IC50=0.3 μmol/L). In failing cardiomyocytes, both diastolic Ca2+ sparks and delayed afterdepolarization were frequently observed, but 1 μmol/L dantrolene inhibited both events. Conclusions Dantrolene corrects defective inter-domain interactions within RyR2 in failing hearts, inhibits spontaneous Ca2+ leak, in turn improves cardiomyocyte function in failing hearts. Thus, dantrolene may have a potential to treat heart failure, specifically targeting the RyR2. PMID:19460614

Congenital heart defect - corrective surgery

MedlinePlus

... repair; Tetralogy of Fallot repair; Coarctation of the aorta repair; Atrial septal defect repair; Ventricular septal defect ... has a blood vessel that runs between the aorta (the main artery to the body) and the ...

Atrioventricular Canal Defect

MedlinePlus

... birth (congenital). The condition is often associated with Down syndrome. Atrioventricular canal defect allows extra blood to flow ... baby's heart is developing. Some factors, such as Down syndrome, might increase the risk of atrioventricular canal defect. ...

Simultaneous transcatheter closure of intralobar pulmonary sequestration and patent ductus arteriosus in a patient with infantile Scimitar syndrome.

PubMed

Aslan, Eyüp; Tanıdır, İbrahim Cansaran; Saygı, Murat; Onan, Sertaç Hanedan; Güzeltaş, Alper

2015-03-01

Scimitar syndrome is a rare disease associated with a right lung sequestration vascularised by arteries arising from the abdominal aorta and abnormal venous drainage into the inferior vena cava. The infantile form is generally presented with severe heart failure, pulmonary hypertension and respiratory distress. It may be associated with various intracardiac defects, including atrial septal defects, ventricular septal defects, patent ductus arteriosus or more complicated structural congenital heart defects. Here, we present a 2-month-old girl with Scimitar syndrome whose pulmonary arterial pressure decreased after transcatheter patent ductus arteriosus closure and embolization of the anomalous systemic arterial supply.

An exploratory analysis of the relationship between ambient ...

EPA Pesticide Factsheets

Background: Associations between ozone (O3) and fine particulate matter (PM2.5) concentrations and birth outcomes have been previously demonstrated. We perform an exploratory analysis of O3 and PM2.5 concentrations during early pregnancy and multiple types of birth defects. Methods: Data on births were obtained from the Texas Birth Defects Registry and the National Birth Defects Prevention Study (NBDPS) in Texas. Air pollution concentrations were determined using a Bayesian hierarchical model that combined modeled air pollution concentrations with air monitoring data to create bias-corrected concentrations and matched to residential address at birth. Average air pollution concentrations during the first trimester were calculated. Results: The analysis generated hypotheses for future, confirmatory studies; although many of the observed associations between the air pollutants and birth defects were null. The hypotheses are provided by an observed association between O3 and craniosynostosis [adjusted OR 1.28 (95% CI 1.04, 1.58) per 13.3 ppb increase) and observed inverse associations between PM2.5 concentrations and septal heart defects and obstructive heart defects [adjusted ORs 0.79 (95% CI 0.75, 0.82) and 0.88 (95% CI 0.79, 0.97) per 5.0 µg/m3 increase, respectively] in the Texas Birth Defects Registry study. Septal heart defects and ventricular outflow tract obstructions were also examined using the NBDPS but the associations with PM2.5 were null [adj

Autophagy in health and disease: focus on the cardiovascular system.

PubMed

Mialet-Perez, Jeanne; Vindis, Cécile

2017-12-12

Autophagy is a highly conserved mechanism of lysosome-mediated protein and organelle degradation that plays a crucial role in maintaining cellular homeostasis. In the last few years, specific functions for autophagy have been identified in many tissues and organs. In the cardiovascular system, autophagy appears to be essential to heart and vessel homeostasis and function; however defective or excessive autophagy activity seems to contribute to major cardiovascular disorders including heart failure (HF) or atherosclerosis. Here, we review the current knowledge on the role of cardiovascular autophagy in physiological and pathophysiological conditions. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Split Tolerance in a Murine Model of Heterotopic En Bloc Chest Wall Transplantation

PubMed Central

Oh, Byoungchol; Furtmüller, Georg J.; Malek, Veronika; Fryer, Madeline L.; Brayton, Cory; Walczak, Piotr; Janowski, Miroslaw

2017-01-01

Background: Congenital and acquired chest wall deformities represent a significant challenge to functional reconstruction and may impact feasibility of heart transplantation for patients with end-stage organ failure. In the recent past, the concept of replacing like-with-like tissue by using vascularized composite allografts (VCA) has been enthusiastically employed for reconstruction of complex tissue defects. Methods: In this study, we introduce a novel murine model for en bloc chest wall, heart, and thymus transplantation and thereby the use of complex tissue allografts for reconstruction of both chest wall defects and also end-stage organ failure. Additionally, this model allows us to study the features of combined vascularized bone marrow (VBM), thymus, and heart transplantation on allograft survival and function. Heterotopic chest wall, thymus, and heart transplants were performed in untreated syngeneic and allogeneic combinations and in allogeneic combinations treated with costimulation blockade (CTLA4-Ig and MR-1). Results: Indefinite (ie, 150 d, N = 3) graft survival was observed in syngeneic controls. In untreated recipients of allogeneic grafts, the skin component was rejected after 10 (±1) days, whereas rejection of the heart occurred after 13 (± 1) days (N = 3). Costimulation blockade treatment prolonged survival of the heart and chest wall component (130 d, N = 3) as well as the VBM niche as evidenced by donor-specific chimerism (average: 2.35 ± 1.44%), whereas interestingly, the skin component was rejected after 13 (±1) days. Conclusion: Thus, this novel microsurgical model of VCA combined with solid organ transplantation is technically feasible and results in split tolerance when treated with costimulatory blockade. PMID:29632774

Utilisation of three-dimensional printed heart models for operative planning of complex congenital heart defects.

PubMed

Olejník, Peter; Nosal, Matej; Havran, Tomas; Furdova, Adriana; Cizmar, Maros; Slabej, Michal; Thurzo, Andrej; Vitovic, Pavol; Klvac, Martin; Acel, Tibor; Masura, Jozef

2017-01-01

To evaluate the accuracy of the three-dimensional (3D) printing of cardiovascular structures. To explore whether utilisation of 3D printed heart replicas can improve surgical and catheter interventional planning in patients with complex congenital heart defects. Between December 2014 and November 2015 we fabricated eight cardiovascular models based on computed tomography data in patients with complex spatial anatomical relationships of cardiovascular structures. A Bland-Altman analysis was used to assess the accuracy of 3D printing by comparing dimension measurements at analogous anatomical locations between the printed models and digital imagery data, as well as between printed models and in vivo surgical findings. The contribution of 3D printed heart models for perioperative planning improvement was evaluated in the four most representative patients. Bland-Altman analysis confirmed the high accuracy of 3D cardiovascular printing. Each printed model offered an improved spatial anatomical orientation of cardiovascular structures. Current 3D printers can produce authentic copies of patients` cardiovascular systems from computed tomography data. The use of 3D printed models can facilitate surgical or catheter interventional procedures in patients with complex congenital heart defects due to better preoperative planning and intraoperative orientation.

Illness Identity: A Novel Predictor for Healthcare Use in Adults With Congenital Heart Disease.

PubMed

Van Bulck, Liesbet; Goossens, Eva; Luyckx, Koen; Oris, Leen; Apers, Silke; Moons, Philip

2018-05-22

To optimize healthcare use of adults with congenital heart disease, all important predictors of healthcare utilization should be identified. Clinical and psychological characteristics (eg, age and depression) have been found to be associated with healthcare use. However, the concept of illness identity, which assesses the degree to which congenital heart disease is integrated into one's identity, has not yet been investigated in association with healthcare use. Hence, the purpose of the study is to examine the predictive value of illness identity for healthcare use. In this ambispective analytical observational cohort study, 216 adults with congenital heart disease were included. The self-reported Illness Identity Questionnaire was used to assess illness identity states: engulfment, rejection, acceptance, and enrichment. After 1 year, self-reported healthcare use for congenital heart disease or other reasons over the past 6 months was assessed including hospitalizations; visits to general practitioner; visits to medical specialists; and emergency room visits. Binary logistic and negative binomial regression analyses were conducted, adjusting for age, sex, disease complexity, and depressive and anxious symptoms. The more profoundly the heart defect dominated one's identity (ie, engulfment), the more likely this person was to be hospitalized (odds ratio=3.76; 95% confidence interval=1.43-9.86), to visit a medical specialist (odds ratio=2.32; 95% confidence interval=1.35-4.00) or a general practitioner (odds ratio=1.78; 95% confidence interval=1.01-3.17), because of their heart defect. Illness identity, more specifically engulfment, has a unique predictive value for the occurrence of healthcare encounters. This association deserves further investigation, in which the directionality of effects and the contribution of illness identity in terms of preventing inappropriate healthcare use should be determined. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Coronary anatomy in children with bicuspid aortic valves and associated congenital heart disease.

PubMed

Koenraadt, Wilke M C; Bartelings, Margot M; Bökenkamp, Regina; Gittenberger-de Groot, Adriana C; DeRuiter, Marco C; Schalij, Martin J; Jongbloed, Monique Rm

2018-03-01

In patients with bicuspid aortic valve (BAV), coronary anatomy is variable. High take-off coronary arteries have been described, but data are scarce, especially when associated with complex congenital heart disease (CHD). The purpose of this study was to describe coronary patterns in these patients. In 84 postmortem heart specimens with BAV and associated CHD, position and height of the coronary ostia were studied and related to BAV morphology. High take-off right (RCA) and left coronary arteries (LCA) were observed in 23% and 37% of hearts, respectively, most frequently in hearts with hypoplastic left ventricle (HLV) and outflow tract anomalies. In HLV, high take-off was observed in 18/40 (45%) more frequently of LCA (n=14) than RCA (n=6). In hearts with aortic hypoplasia, 8/13 (62%) had high take-off LCA and 6/13 (46%) high take-off RCA. High take-off was seen 19 times in 22 specimens with perimembranous ventricular septal defect (RCA 8, LCA 11). High take-off was associated with type 1A BAV (raphe between right and left coronary leaflets), more outspoken for the RCA. Separate ostia of left anterior descending coronary artery and left circumflex coronary artery were seen in four hearts (5%), not related to specific BAV morphology. High take-off coronary arteries, especially the LCA, occur more frequently in BAV with associated CHD than reported in normal hearts and isolated BAV. Outflow tract defects and HLV are associated with type 1A BAV and high take-off coronary arteries. Although it is unclear whether these findings in infants with detrimental outcome can be related to surviving adults, clinical awareness of variations in coronary anatomy is warranted. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Q Fever: Statistics and Epidemiology

MedlinePlus

... severe with complications requiring hospitalization that may include endocarditis (infection of the heart tissue), encephalitis (inflammation of ... people with a history of heart valve defects, endocarditis, or heart valve implants may increase the risk ...

Imaging of cardiovascular dynamics in early mouse embryos with swept source optical coherence tomography

NASA Astrophysics Data System (ADS)

Larina, Irina V.; Liebling, Michael; Dickinson, Mary E.; Larin, Kirill V.

2009-02-01

Congenital cardiovascular defects are very common, occurring in 1% of live births, and cardiovascular failures are the leading cause of birth defect-related deaths in infants. To improve diagnostics, prevention and treatment of cardiovascular abnormalities, we need to understand not only how cells form the heart and vessels but also how physical factors such as heart contraction and blood flow influence heart development and changes in the circulatory network. Mouse models are an excellent resource for studying cardiovascular development and disease because of the resemblance to humans, rapid generation time, and availability of mutants with cardiovascular defects linked to human diseases. In this work, we present results on development and application of Doppler Swept Source Optical Coherence Tomography (DSS-OCT) for imaging of cardiovascular dynamics and blood flow in the mouse embryonic heart and vessels. Our studies demonstrated that the spatial and temporal resolution of the DSS-OCT makes it possible to perform sensitive measurements of heart and vessel wall movements and to investigate how contractile waves facilitate the movement of blood through the circulatory system.

Minimum prevalence of chromosome 22q11 deletions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, D.I.; Cross, I.E.; Burn, J.

1994-09-01

Submicroscopic deletions from within chromosome 22q11 are associated with DiGeorge (DGS), velocardiofacial (VCFS) and conotruncal anomaly syndromes and isolated congenital heart defects. In 1993 our pediatric cardiologists clinically referred all children in whom a chromosome 22q11 deletion was suspected for fluorescent in situ hybridization studies using probes from the DGS critical region. 10 affected individuals have been identified to date from the children born in 1993 in the Northern Region served exclusively by our center. A further case, the subsequent pregnancy in one of these families was affected and terminated on the basis of a major heart malformation. In themore » years 1988-92, for which we have complete ascertainment, there were 1009 heart defects among 191,700 births (mean 202 per annum). Thus we estimate that chromosome 22q11 deletions were the cause of at least 5% of congenital heart disease. As not all children with chromosome 22q11 deletions have a heart defect, this gives an estimated minimum prevalence of 1/4000 live births.« less

The PTPN11 loss-of-function mutation Q510E-Shp2 causes hypertrophic cardiomyopathy by dysregulating mTOR signaling.

PubMed

Schramm, Christine; Fine, Deborah M; Edwards, Michelle A; Reeb, Ashley N; Krenz, Maike

2012-01-01

The identification of mutations in PTPN11 (encoding the protein tyrosine phosphatase Shp2) in families with congenital heart disease has facilitated mechanistic studies of various cardiovascular defects. However, the roles of normal and mutant Shp2 in the developing heart are still poorly understood. Furthermore, it remains unclear how Shp2 loss-of-function (LOF) mutations cause LEOPARD Syndrome (also termed Noonan Syndrome with multiple lentigines), which is characterized by congenital heart defects such as pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). In normal hearts, Shp2 controls cardiomyocyte size by regulating signaling through protein kinase B (Akt) and mammalian target of rapamycin (mTOR). We hypothesized that Shp2 LOF mutations dysregulate this pathway, resulting in HCM. For our studies, we chose the Shp2 mutation Q510E, a dominant-negative LOF mutation associated with severe early onset HCM. Newborn mice with cardiomyocyte-specific overexpression of Q510E-Shp2 starting before birth displayed increased cardiomyocyte sizes, heart-to-body weight ratios, interventricular septum thickness, and cardiomyocyte disarray. In 3-mo-old hearts, interstitial fibrosis was detected. Echocardiographically, ventricular walls were thickened and contractile function was depressed. In ventricular tissue samples, signaling through Akt/mTOR was hyperactivated, indicating that the presence of Q510E-Shp2 led to upregulation of this pathway. Importantly, rapamycin treatment started shortly after birth rescued the Q510E-Shp2-induced phenotype in vivo. If rapamycin was started at 6 wk of age, HCM was also ameliorated. We also generated a second mouse model in which cardiomyocyte-specific Q510E-Shp2 overexpression started after birth. In contrast to the first model, these mice did not develop HCM. In summary, our studies establish a role for mTOR signaling in HCM caused by Q510E-Shp2. Q510E-Shp2 overexpression in the cardiomyocyte population alone was sufficient to induce the phenotype. Furthermore, the pathomechanism was triggered pre- but not postnatally. However, postnatal rapamycin treatment could still reverse already established HCM, which may have important therapeutic implications.

N-Acetylcysteine prevents congenital heart defects induced by pregestational diabetes

PubMed Central

2014-01-01

Background Pregestational diabetes is a major risk factor of congenital heart defects (CHDs). Glutathione is depleted and reactive oxygen species (ROS) production is elevated in diabetes. In the present study, we aimed to examine whether treatment with N-acetylcysteine (NAC), which increases glutathione synthesis and inhibits ROS production, prevents CHDs induced by pregestational diabetes. Methods Female mice were treated with streptozotocin (STZ) to induce pregestational diabetes prior to breeding with normal males to produce offspring. Some diabetic mice were treated with N-acetylcysteine (NAC) in drinking water from E0.5 to the end of gestation or harvesting of the embryos. CHDs were identified by histology. ROS levels, cell proliferation and gene expression in the fetal heart were analyzed. Results Our data show that pregestational diabetes resulted in CHDs in 58% of the offspring, including ventricular septal defect (VSD), atrial septal defect (ASD), atrioventricular septal defects (AVSD), transposition of great arteries (TGA), double outlet right ventricle (DORV) and tetralogy of Fallot (TOF). Treatment with NAC in drinking water in pregestational diabetic mice completely eliminated the incidence of AVSD, TGA, TOF and significantly diminished the incidence of ASD and VSD. Furthermore, pregestational diabetes increased ROS, impaired cell proliferation, and altered Gata4, Gata5 and Vegf-a expression in the fetal heart of diabetic offspring, which were all prevented by NAC treatment. Conclusions Treatment with NAC increases GSH levels, decreases ROS levels in the fetal heart and prevents the development of CHDs in the offspring of pregestational diabetes. Our study suggests that NAC may have therapeutic potential in the prevention of CHDs induced by pregestational diabetes. PMID:24533448

Detection of a Heart Defect in the Fetus

MedlinePlus

... problems : There is a wide range of acceptable fetal heart rates (normal is between 120 and 160 but many ... usually go away shortly after birth. More important fetal heart problems include tachycardia (hear rate too fast) and bradycardia (heart rate too slow). ...

Between invisible defects and visible impact: the life experiences of adolescents and young adults with congenital heart disease.

PubMed

Chiang, Yueh-Tao; Chen, Chi-Wen; Su, Wen-Jen; Wang, Jou-Kou; Lu, Chun-Wei; Li, Yuh-Fen; Moons, Philip

2015-03-01

To describe the life experiences of adolescents and young adults with congenital heart disease. Owing to medical advances, most children with congenital heart disease are expected to survive into adulthood. The transitional development from adolescence to adult is the critical period for fostering self-care. Descriptive phenomenological study. Thirty-five patients of 15-24 years old with congenital heart disease were recruited from paediatric cardiology clinics by purposive sampling. They were individually interviewed between October 2012-February 2013 using a semi-structured interview guideline and joined adult congenital heart disease clinics at two medical centres in northern Taiwan. The data were analysed using descriptive phenomenological method developed by Giorgi. The essence of the life experience of adolescents and young adults with congenital heart disease involves a dynamic process of moving between invisible defects and coexistence with the disease. Six themes emerged: (1) invisible defects: the existence of imperfect understanding; (2) conflict: interpersonal frustrations; (3) imbalance: the loss of self-balance; (4) suffering: increasing anxiety; (5) encounters: meeting needs; and (6) coexistence: positive coping strategies. As patients with congenital heart disease transition from adolescence into adulthood, they must learn about their disease, overcome frustration and anxiety and develop self-care strategies for coexisting with congenital heart disease. Results of this study may serve as clinical care guidelines for adolescents and young adults with congenital heart disease and give a reference for developing transitional intervention strategies. © 2014 John Wiley & Sons Ltd.

Zic3 is required in the migrating primitive streak for node morphogenesis and left–right patterning

PubMed Central

Sutherland, Mardi J.; Wang, Shuyun; Quinn, Malgorzata E.; Haaning, Allison; Ware, Stephanie M.

2013-01-01

In humans, loss-of-function mutations in ZIC3 cause isolated cardiovascular malformations and X-linked heterotaxy, a disorder with abnormal left–right asymmetry of organs. Zic3 null mice recapitulate the human heterotaxy phenotype but also have early gastrulation defects, axial patterning defects and neural tube defects complicating an assessment of the role of Zic3 in cardiac development. Zic3 is expressed ubiquitously during critical stages of left–right patterning but its later expression in the developing heart remains controversial and the molecular mechanism(s) by which it causes heterotaxy are unknown. To define the temporal and spatial requirements, for Zic3 in left–right patterning, we generated conditional Zic3 mice and Zic3-LacZ-BAC reporter mice. The latter provide compelling evidence that Zic3 is expressed in the mouse node and absent in the heart. Conditional deletion using T-Cre identifies a requirement for Zic3 in the primitive streak and migrating mesoderm for proper left–right patterning and cardiac development. In contrast, Zic3 is not required in heart progenitors or the cardiac compartment. In addition, the data demonstrate abnormal node morphogenesis in Zic3 null mice and identify similar node dysplasia when Zic3 was specifically deleted from the migrating mesoderm and primitive streak. These results define the temporal and spatial requirements for Zic3 in node morphogenesis, left–right patterning and cardiac development and suggest the possibility that a requirement for Zic3 in node ultrastructure underlies its role in heterotaxy and laterality disorders. PMID:23303524

Type 0 Spinal Muscular Atrophy: Further Delineation of Prenatal and Postnatal Features in 16 Patients.

PubMed

Grotto, Sarah; Cuisset, Jean-Marie; Marret, Stéphane; Drunat, Séverine; Faure, Patricia; Audebert-Bellanger, Séverine; Desguerre, Isabelle; Flurin, Vincent; Grebille, Anne-Gaëlle; Guerrot, Anne-Marie; Journel, Hubert; Morin, Gilles; Plessis, Ghislaine; Renolleau, Sylvain; Roume, Joëlle; Simon-Bouy, Brigitte; Touraine, Renaud; Willems, Marjolaine; Frébourg, Thierry; Verspyck, Eric; Saugier-Veber, Pascale

2016-11-29

Spinal muscular atrophy (SMA) is caused by homozygous inactivation of the SMN1 gene. The SMN2 copy number modulates the severity of SMA. The 0SMN1/1SMN2 genotype, the most severe genotype compatible with life, is expected to be associated with the most severe form of the disease, called type 0 SMA, defined by prenatal onset. The aim of the study was to review clinical features and prenatal manifestations in this rare SMA subtype. SMA patients with the 0SMN1/1SMN2 genotype were retrospectively collected using the UMD-SMN1 France database. Data from 16 patients were reviewed. These 16 patients displayed type 0 SMA. At birth, a vast majority had profound hypotonia, severe muscle weakness, severe respiratory distress, and cranial nerves involvement (inability to suck/swallow, facial muscles weakness). They showed characteristics of fetal akinesia deformation sequence and congenital heart defects. Recurrent episodes of bradycardia were observed. Death occurred within the first month. At prenatal stage, decreased fetal movements were frequently reported, mostly only by mothers, in late stages of pregnancy; increased nuchal translucency was reported in about half of the cases; congenital heart defects, abnormal amniotic fluid volume, or joint contractures were occasionally reported. Despite a prenatal onset attested by severity at birth and signs of fetal akinesia deformation sequence, prenatal manifestations of type 0 SMA are not specific and not constant. As illustrated by the frequent association with congenital heart defects, type 0 SMA physiopathology is not restricted to motor neuron, highlighting that SMN function is critical for organogenesis.

Required, tissue-specific roles for Fgf8 in outflow tract formation and remodeling.

PubMed

Park, Eon Joo; Ogden, Lisa A; Talbot, Amy; Evans, Sylvia; Cai, Chen-Leng; Black, Brian L; Frank, Deborah U; Moon, Anne M

2006-06-01

Fibroblast growth factor 8 (Fgf8) is a secreted signaling protein expressed in numerous temporospatial domains that are potentially relevant to cardiovascular development. However, the pathogenesis of complex cardiac and outflow tract defects observed in Fgf8-deficient mice, and the specific source(s) of Fgf8 required for outflow tract formation and subsequent remodeling are unknown. A detailed examination of the timing and location of Fgf8 production revealed previously unappreciated expression in a subset of primary heart field cells; Fgf8 is also expressed throughout the anterior heart field (AHF) mesoderm and in pharyngeal endoderm at the crescent and early somite stages. We used conditional mutagenesis to examine the requirements for Fgf8 function in these different expression domains during heart and outflow tract morphogenesis. Formation of the primary heart tube and the addition of right ventricular and outflow tract myocardium depend on autocrine Fgf8 signaling in cardiac crescent mesoderm. Loss of Fgf8 in this domain resulted in decreased expression of the Fgf8 target gene Erm, and aberrant production of Isl1 and its target Mef2c in the anterior heart field, thus linking Fgf8 signaling with transcription factor networks that regulate survival and proliferation of the anterior heart field. We further found that mesodermal- and endodermal-derived Fgf8 perform specific functions during outflow tract remodeling: mesodermal Fgf8 is required for correct alignment of the outflow tract and ventricles, whereas activity of Fgf8 emanating from pharyngeal endoderm regulates outflow tract septation. These findings provide a novel insight into how the formation and remodeling of primary and anterior heart field-derived structures rely on Fgf8 signals from discrete temporospatial domains.

Dynamic Organization of lncRNA and Circular RNA Regulators Collectively Controlled Cardiac Differentiation in Humans.

PubMed

Li, Yongsheng; Zhang, Jinwen; Huo, Caiqin; Ding, Na; Li, Junyi; Xiao, Jun; Lin, Xiaoyu; Cai, Benzhi; Zhang, Yunpeng; Xu, Juan

2017-10-01

Advances in developmental cardiology have increased our understanding of the early aspects of heart differentiation. However, understanding noncoding RNA (ncRNA) transcription and regulation during this process remains elusive. Here, we constructed transcriptomes for both long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in four important developmental stages ranging from early embryonic to cardiomyocyte based on high-throughput sequencing datasets, which indicate the high stage-specific expression patterns of two ncRNA types. Additionally, higher similarities of samples within each stage were found, highlighting the divergence of samples collected from distinct cardiac developmental stages. Next, we developed a method to identify numerous lncRNA and circRNA regulators whose expression was significantly stage-specific and shifted gradually and continuously during heart differentiation. We inferred that these ncRNAs are important for the stages of cardiac differentiation. Moreover, transcriptional regulation analysis revealed that the expression of stage-specific lncRNAs is controlled by known key stage-specific transcription factors (TFs). In addition, circRNAs exhibited dynamic expression patterns independent from their host genes. Functional enrichment analysis revealed that lncRNAs and circRNAs play critical roles in pathways that are activated specifically during heart differentiation. We further identified candidate TF-ncRNA-gene network modules for each differentiation stage, suggesting the dynamic organization of lncRNAs and circRNAs collectively controlled cardiac differentiation, which may cause heart-related diseases when defective. Our study provides a foundation for understanding the dynamic regulation of ncRNA transcriptomes during heart differentiation and identifies the dynamic organization of novel key lncRNAs and circRNAs to collectively control cardiac differentiation. Copyright © 2017. Published by Elsevier B.V.

Interstitial deletion of 8q21-->22 associated with minor anomalies, congenital heart defect, and Dandy-Walker variant.

PubMed

Donahue, M L; Ryan, R M

1995-03-13

We describe an infant with a deletion of 8q21-->22 who had distinct clinical manifestations including minor facial anomalies, a congenital heart defect, a Dandy-Walker variant, and mild to moderate developmental delay. Her facial characteristics included small, wide-spaced eyes, asymmetric bilateral epicanthal folds, a broad nasal bridge, a "carp-shaped" mouth, micrognathia, and prominent, apparently low-set ears. Three other reports describe children with larger proximal deletions of 8q that include 8q21 and q22. These four children all have similar facial appearance. Of the others reported, one had a congenital heart defect and one had craniosynostosis. This case, in addition to the previously noted three cases, helps in delineating a recognizable syndrome.

Congenital cardiac malformations in relation to central venous access.

PubMed

Thompson, Christine

During the third and seventh weeks of gestation, teratogenic exposure may lead to fetal abnormality such as congenital heart defects or intrauterine death. Congenital heart defects are present from birth, but may appear at any time, or only revealed postmortem. Often defects are present by degree. Some defects are life-threatening, while other, less severe conditions, may have minimal physiological impact. Left superior vena cava exists in early embryonic development, but the vessel degenerates as the cardiovascular system matures. When not associated with other malformations, an incidence of persistent left-sided superior vena cava (PLSVC) has no clinical signs or symptoms. However, it may not be as innocuous as it appears due to its association with the cyanotic defect, tetralogy of Fallot (TOF). Using a case history as an illustration it can be shown that all cases of defect or chromosomal suspicion should be documented as there may be implications for future interventions.

Surgery of a cyanotic heart defect in an 11-year-old boy with thrombocytopenic thrombocytopathy and severe anemia due to a GATA-1 defect: hemostatic therapy.

PubMed

Hoefer, J; Streif, W; Kilo, J; Grimm, M; Berger, G; Velik-Salchner, C

2012-10-01

A child was admitted to our hospital for repair of a ventricular septal defect (VSD) characterized by a predominantly right-to-left shunt and a severe stenosis of the right ventricular outflow tract (Tetralogy of Fallot). Severe congenital anemia (hemoglobin 72 g/L), thrombocytopenia (42×G/L) and profound platelet dysfunction led a stem cell defect to be suspected. X-linked thrombocytopenia (GATA-1 mutation) was diagnosed. GATA-1 defect may complicate medical interventions due to excessive bleeding and partial or complete bone marrow failure. Maintaining a platelet count of 100 G/L and a maximal clot firmness (EXTEM-MCF) >50 mm allowed repair of the congenital heart defect without bleeding or hematological complications. Anemia and thrombocytopenia persisted after cardiac surgery, while the spontaneous bleeding tendency improved. © Georg Thieme Verlag KG Stuttgart · New York.

Healthy Heart Quizzes

MedlinePlus

... More Healthy Heart Quizzes Updated:Oct 30,2017 Cardiovascular Conditions • Conditions Home • Arrhythmia and Atrial Fibrillation • Cardiac Arrest • Cardiac Rehab • Cardiomyopathy • Cardiovascular Conditions of Childhood • Cholesterol • Congenital Heart Defects • Diabetes • ...

Ablation of PGC-1β Results in Defective Mitochondrial Activity, Thermogenesis, Hepatic Function, and Cardiac Performance

PubMed Central

Petrovic, Natasa; Kis, Adrienn; Feldmann, Helena M; Bjursell, Mikael; Parker, Nadeene; Curtis, Keira; Campbell, Mark; Hu, Ping; Zhang, Dongfang; Litwin, Sheldon E; Zaha, Vlad G; Fountain, Kimberly T; Boudina, Sihem; Jimenez-Linan, Mercedes; Blount, Margaret; Lopez, Miguel; Meirhaeghe, Aline; Bohlooly-Y, Mohammad; Storlien, Leonard; Strömstedt, Maria; Snaith, Michael; Orešič, Matej; Abel, E. Dale; Cannon, Barbara; Vidal-Puig, Antonio

2006-01-01

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1β (PGC-1β) has been implicated in important metabolic processes. A mouse lacking PGC-1β (PGC1βKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1βKO mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1β ablation was partially compensated by up-regulation of PGC-1α in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1βKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1β was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1βKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1βKO mice have impaired mitochondrial function. Lack of PGC-1β also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1β plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress. PMID:17090215

Pentamidine rescues contractility and rhythmicity in a Drosophila model of myotonic dystrophy heart dysfunction

PubMed Central

Chakraborty, Mouli; Selma-Soriano, Estela; Magny, Emile; Couso, Juan Pablo; Pérez-Alonso, Manuel; Charlet-Berguerand, Nicolas; Artero, Ruben; Llamusi, Beatriz

2015-01-01

ABSTRACT Up to 80% of individuals with myotonic dystrophy type 1 (DM1) will develop cardiac abnormalities at some point during the progression of their disease, the most common of which is heart blockage of varying degrees. Such blockage is characterized by conduction defects and supraventricular and ventricular tachycardia, and carries a high risk of sudden cardiac death. Despite its importance, very few animal model studies have focused on the heart dysfunction in DM1. Here, we describe the characterization of the heart phenotype in a Drosophila model expressing pure expanded CUG repeats under the control of the cardiomyocyte-specific driver GMH5-Gal4. Morphologically, expression of 250 CUG repeats caused abnormalities in the parallel alignment of the spiral myofibrils in dissected fly hearts, as revealed by phalloidin staining. Moreover, combined immunofluorescence and in situ hybridization of Muscleblind and CUG repeats, respectively, confirmed detectable ribonuclear foci and Muscleblind sequestration, characteristic features of DM1, exclusively in flies expressing the expanded CTG repeats. Similarly to what has been reported in humans with DM1, heart-specific expression of toxic RNA resulted in reduced survival, increased arrhythmia, altered diastolic and systolic function, reduced heart tube diameters and reduced contractility in the model flies. As a proof of concept that the fly heart model can be used for in vivo testing of promising therapeutic compounds, we fed flies with pentamidine, a compound previously described to improve DM1 phenotypes. Pentamidine not only released Muscleblind from the CUG RNA repeats and reduced ribonuclear formation in the Drosophila heart, but also rescued heart arrhythmicity and contractility, and improved fly survival in animals expressing 250 CUG repeats. PMID:26515653

The Pathogenesis of Atrial and Atrioventricular Septal Defects with Special Emphasis on the Role of the Dorsal Mesenchymal Protrusion

PubMed Central

Briggs, Laura E.; Kakarla, Jayant; Wessels, Andy

2012-01-01

Partitioning of the four-chambered heart requires the proper formation, interaction and fusion of several mesenchymal tissues derived from different precursor populations that together form the atrioventricular mesenchymal complex. This includes the major endocardial cushions and the mesenchymal cap of the septum primum, which are of endocardial origin, and the dorsal mesenchymal protrusion (DMP), which is derived from the Second Heart Field. Failure of these structures to develop and/or fully mature results in atrial septal defects (ASDs) and atrioventricular septal defects (AVSD). AVSDs are congenital malformations in which the atria are permitted to communicate due to defective septation between the inferior margin of the septum primum and the atrial surface of the common atrioventricular valve. The clinical presentation of AVSDs is variable and depends on both the size and/or type of defect; less severe defects may be asymptomatic while the most severe defect, if untreated, results in infantile heart failure. For many years, maldevelopment of the endocardial cushions was thought to be the sole etiology of AVSDs. More recent work, however, has demonstrated that perturbation of DMP development also results in AVSD. Here, we discuss in detail the formation of the DMP, its contribution to cardiac septation and describe the morphological features as well as potential etiologies of ASDs and AVSDs. PMID:22709652

Sequential en-face optical coherence tomography imaging and monitoring of Drosophila Melanogaster larval heart

NASA Astrophysics Data System (ADS)

Bradu, A.; Ma, Lisha; Bloor, J.; Podoleanu, A. GH.

2009-02-01

This article demonstrates two modalities to acquire information on cardiac function in larval Drosophila Melanogaster: in-vivo imaging and heartbeat monitoring. To achieve these goals a dedicated imaging instrument able to provide simultaneous en-face Optical Coherence Tomography (OCT) and Laser Scanning Confocal Microscopy (LSCM) images has been developed. With this dual imaging system, the heart can easily be located and visualised within the specimen and the change of the heart shape in a cardiac cycle monitored. The system can easily be switched to a stethoscopic regime, simply by interrupting the scanning of the light beam across the sample, after selecting the point of interest in the imaging regime. Here we have used targeted gene expression to knockdown the myospheroid (mys) gene in the larval heart using a specific RNAi construct. By knocking down a β integrin subunit encoded by mys we have recorded an enlarged heart chamber in both diastolic and systolic states. Also, the fraction of reduction of the chamber diameter was smaller in the knockdown heart. These phenotypic differences indicate that impaired cardiac contractility occurs in the heart where the integrin gene express level is reduced. As far as we are aware, this is for the first time when it is shown in Drosophila that integrins have a direct relationship to a dilated heart defect, and conseqThis article demonstrates two modalities to acquire information on cardiac function in larval Drosophila Melanogaster: in-vivo imaging and heartbeat monitoring. To achieve these goals a dedicated imaging instrument able to provide simultaneous en-face Optical Coherence Tomography (OCT) and Laser Scanning Confocal Microscopy (LSCM) images has been developed. With this dual imaging system, the heart can easily be located and visualised within the specimen and the change of the heart shape in a cardiac cycle monitored. The system can easily be switched to a stethoscopic regime, simply by interrupting the scanning of the light beam across the sample, after selecting the point of interest in the imaging regime. Here we have used targeted gene expression to knockdown the myospheroid (mys) gene in the larval heart using a specific RNAi construct. By knocking down a β integrin subunit encoded by mys we have recorded an enlarged heart chamber in both diastolic and systolic states. Also, the fraction of reduction of the chamber diameter was smaller in the knockdown heart. These phenotypic differences indicate that impaired cardiac contractility occurs in the heart where the integrin gene express level is reduced. As far as we are aware, this is for the first time when it is shown in Drosophila that integrins have a direct relationship to a dilated heart defect, and consequently we demonstrate the utility of Drosophila as model for the study of vertebrate heart disease. By monitoring the heartbeat we also demonstrated a reduction of the heart rate in Tropomyosin mutant compared to the wild type larva.uently we demonstrate the utility of Drosophila as model for the study of vertebrate heart disease. By monitoring the heartbeat we also demonstrated a reduction of the heart rate in Tropomyosin mutant compared to the wild type larva.

Current status of cardiovascular surgery in Japan 2013 and 2014: A report based on the Japan Cardiovascular Surgery Database. 2: Congenital heart surgery.

PubMed

Hirata, Yasutaka; Hirahara, Norimichi; Murakami, Arata; Motomura, Noboru; Miyata, Hiroaki; Takamoto, Shinichi

2018-01-01

We analyzed the mortality and morbidity of congenital heart surgery in Japan using the Japan Cardiovascular Surgery Database (JCVSD). Data regarding congenital heart surgery performed between January 2013 and December 2014 were obtained from JCVSD. The 20 most frequent procedures were selected and the mortality rates and major morbidities were analyzed. The mortality rates of atrial septal defect repair and ventricular septal defect repair were less than 1%, and the mortality rates of tetralogy of Fallot repair, complete atrioventricular septal defect repair, bidirectional Glenn, and total cavopulmonary connection were less than 2%. The mortality rates of the Norwood procedure and total anomalous pulmonary venous connection repair were more than 10%. The rates of unplanned reoperation, pacemaker implantation, chylothorax, deep sternal infection, phrenic nerve injury, and neurological deficit were shown for each procedure. Using JCVSD, the national data for congenital heart surgery, including postoperative complications, were analyzed. Further improvements of the database and feedback for clinical practice are required.

Review of Congenital Mitral Valve Stenosis: Analysis, Repair Techniques and Outcomes.

PubMed

Baird, Christopher W; Marx, Gerald R; Borisuk, Michele; Emani, Sitram; del Nido, Pedro J

2015-06-01

The spectrum of congenital mitral valve stenosis (MS) consists of a complex of defects that result in obstruction to left ventricular inflow. This spectrum includes patients with underdeveloped left heart structures (Fig. 1) to those with isolated congenital MS. The specific mitral valve defects can further be divided into categories based on the relationship to the mitral valve annulus including valvar, supravalvar and subvalvar components. Clinically, these patients present based on the degree of obstruction, associated mitral regurgitation, secondary pulmonary hypertension, associated lung disease and/or associated cardiac lesions. There are a number of factors that contribute to the successful outcomes in these patients including pre-operative imaging, aggressive surgical techniques and peri-operative management.

scaRNAs regulate splicing and vertebrate heart development.

PubMed

Patil, Prakash; Kibiryeva, Nataliya; Uechi, Tamayo; Marshall, Jennifer; O'Brien, James E; Artman, Michael; Kenmochi, Naoya; Bittel, Douglas C

2015-08-01

Alternative splicing (AS) plays an important role in regulating mammalian heart development, but a link between misregulated splicing and congenital heart defects (CHDs) has not been shown. We reported that more than 50% of genes associated with heart development were alternatively spliced in the right ventricle (RV) of infants with tetralogy of Fallot (TOF). Moreover, there was a significant decrease in the level of 12 small cajal body-specific RNAs (scaRNAs) that direct the biochemical modification of specific nucleotides in spliceosomal RNAs. We sought to determine if scaRNA levels influence patterns of AS and heart development. We used primary cells derived from the RV of infants with TOF to show a direct link between scaRNA levels and splice isoforms of several genes that regulate heart development (e.g., GATA4, NOTCH2, DAAM1, DICER1, MBNL1 and MBNL2). In addition, we used antisense morpholinos to knock down the expression of two scaRNAs (scarna1 and snord94) in zebrafish and saw a corresponding disruption of heart development with an accompanying alteration in splice isoforms of cardiac regulatory genes. Based on these combined results, we hypothesize that scaRNA modification of spliceosomal RNAs assists in fine tuning the spliceosome for dynamic selection of mRNA splice isoforms. Our results are consistent with disruption of splicing patterns during early embryonic development leading to insufficient communication between the first and second heart fields, resulting in conotruncal misalignment and TOF. Our findings represent a new paradigm for determining the mechanisms underlying congenital cardiac malformations. Copyright © 2015. Published by Elsevier B.V.

Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.

PubMed

Stennard, Fiona A; Costa, Mauro W; Lai, Donna; Biben, Christine; Furtado, Milena B; Solloway, Mark J; McCulley, David J; Leimena, Christiana; Preis, Jost I; Dunwoodie, Sally L; Elliott, David E; Prall, Owen W J; Black, Brian L; Fatkin, Diane; Harvey, Richard P

2005-05-01

The genetic hierarchies guiding lineage specification and morphogenesis of the mammalian embryonic heart are poorly understood. We now show by gene targeting that murine T-box transcription factor Tbx20 plays a central role in these pathways, and has important activities in both cardiac development and adult function. Loss of Tbx20 results in death of embryos at mid-gestation with grossly abnormal heart morphogenesis. Underlying these disturbances was a severely compromised cardiac transcriptional program, defects in the molecular pre-pattern, reduced expansion of cardiac progenitors and a block to chamber differentiation. Notably, Tbx20-null embryos showed ectopic activation of Tbx2 across the whole heart myogenic field. Tbx2 encodes a transcriptional repressor normally expressed in non-chamber myocardium, and in the atrioventricular canal it has been proposed to inhibit chamber-specific gene expression through competition with positive factor Tbx5. Our data demonstrate a repressive activity for Tbx20 and place it upstream of Tbx2 in the cardiac genetic program. Thus, hierarchical, repressive interactions between Tbx20 and other T-box genes and factors underlie the primary lineage split into chamber and non-chamber myocardium in the forming heart, an early event upon which all subsequent morphogenesis depends. Additional roles for Tbx20 in adult heart integrity and contractile function were revealed by in-vivo cardiac functional analysis of Tbx20 heterozygous mutant mice. These data suggest that mutations in human cardiac transcription factor genes, possibly including TBX20, underlie both congenital heart disease and adult cardiomyopathies.

Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy

PubMed Central

Fang, Xi; Wu, Tongbin; Liu, Canzhao; Veevers, Jennifer; Stroud, Matthew J.; Zhang, Zhiyuan; Ma, Xiaolong; Mu, Yongxin; Lao, Dieu-Hung; Dalton, Nancy D.; Gu, Yusu; Wang, Celine; Wang, Michael; Liang, Yan; Ouyang, Kunfu; Peterson, Kirk L.; Evans, Sylvia M.

2017-01-01

Defective protein quality control (PQC) systems are implicated in multiple diseases. Molecular chaperones and co-chaperones play a central role in functioning PQC. Constant mechanical and metabolic stress in cardiomyocytes places great demand on the PQC system. Mutation and downregulation of the co-chaperone protein BCL-2–associated athanogene 3 (BAG3) are associated with cardiac myopathy and heart failure, and a BAG3 E455K mutation leads to dilated cardiomyopathy (DCM). However, the role of BAG3 in the heart and the mechanisms by which the E455K mutation leads to DCM remain obscure. Here, we found that cardiac-specific Bag3-KO and E455K-knockin mice developed DCM. Comparable phenotypes in the 2 mutants demonstrated that the E455K mutation resulted in loss of function. Further experiments revealed that the E455K mutation disrupted the interaction between BAG3 and HSP70. In both mutants, decreased levels of small heat shock proteins (sHSPs) were observed, and a subset of proteins required for cardiomyocyte function was enriched in the insoluble fraction. Together, these observations suggest that interaction between BAG3 and HSP70 is essential for BAG3 to stabilize sHSPs and maintain cardiomyocyte protein homeostasis. Our results provide insight into heart failure caused by defects in BAG3 pathways and suggest that increasing BAG3 protein levels may be of therapeutic benefit in heart failure. PMID:28737513

Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy.

PubMed

Fang, Xi; Bogomolovas, Julius; Wu, Tongbin; Zhang, Wei; Liu, Canzhao; Veevers, Jennifer; Stroud, Matthew J; Zhang, Zhiyuan; Ma, Xiaolong; Mu, Yongxin; Lao, Dieu-Hung; Dalton, Nancy D; Gu, Yusu; Wang, Celine; Wang, Michael; Liang, Yan; Lange, Stephan; Ouyang, Kunfu; Peterson, Kirk L; Evans, Sylvia M; Chen, Ju

2017-08-01

Defective protein quality control (PQC) systems are implicated in multiple diseases. Molecular chaperones and co-chaperones play a central role in functioning PQC. Constant mechanical and metabolic stress in cardiomyocytes places great demand on the PQC system. Mutation and downregulation of the co-chaperone protein BCL-2-associated athanogene 3 (BAG3) are associated with cardiac myopathy and heart failure, and a BAG3 E455K mutation leads to dilated cardiomyopathy (DCM). However, the role of BAG3 in the heart and the mechanisms by which the E455K mutation leads to DCM remain obscure. Here, we found that cardiac-specific Bag3-KO and E455K-knockin mice developed DCM. Comparable phenotypes in the 2 mutants demonstrated that the E455K mutation resulted in loss of function. Further experiments revealed that the E455K mutation disrupted the interaction between BAG3 and HSP70. In both mutants, decreased levels of small heat shock proteins (sHSPs) were observed, and a subset of proteins required for cardiomyocyte function was enriched in the insoluble fraction. Together, these observations suggest that interaction between BAG3 and HSP70 is essential for BAG3 to stabilize sHSPs and maintain cardiomyocyte protein homeostasis. Our results provide insight into heart failure caused by defects in BAG3 pathways and suggest that increasing BAG3 protein levels may be of therapeutic benefit in heart failure.

Prune belly syndrome and heart defect in one of monozygotic twins, following exposure to Tigan and Bendectin.

PubMed

Greene, C; Wilson, A; Shapira, E

1985-01-01

One of twins was born with prune belly syndrome and congenital heart defect following exposure to Bendectin and Tigan. Red cell antigens and HLA typing were compatible with monozygosity. The possible associations of the prune belly syndrome to monozygotic twinning or to teratogenic agents is considered in light of this patient and review of the literature.

Williams Syndrome Transcription Factor is critical for neural crest cell function in Xenopus laevis

PubMed Central

Barnett, Chris; Yazgan, Oya; Kuo, Hui-Ching; Malakar, Sreepurna; Thomas, Trevor; Fitzgerald, Amanda; Harbour, Billy; Henry, Jonathan J.; Krebs, Jocelyn E.

2012-01-01

Williams Syndrome Transcription Factor (WSTF) is one of ~25 haplodeficient genes in patients with the complex developmental disorder Williams Syndrome (WS). WS results in visual/spatial processing defects, cognitive impairment, unique behavioral phenotypes, characteristic “elfin” facial features, low muscle tone and heart defects. WSTF exists in several chromatin remodeling complexes and has roles in transcription, replication, and repair. Chromatin remodeling is essential during embryogenesis, but WSTF’s role in vertebrate development is poorly characterized. To investigate the developmental role of WSTF, we knocked down WSTF in Xenopus laevis embryos using a morpholino that targets WSTF mRNA. BMP4 shows markedly increased and spatially aberrant expression in WSTF-deficient embryos, while SHH, MRF4, PAX2, EPHA4 and SOX2 expression are severely reduced, coupled with defects in a number of developing embryonic structures and organs. WSTF-deficient embryos display defects in anterior neural development. Induction of the neural crest, measured by expression of the neural crest-specific genes SNAIL and SLUG, is unaffected by WSTF depletion. However, at subsequent stages WSTF knockdown results in a severe defect in neural crest migration and/or maintenance. Consistent with a maintenance defect, WSTF knockdowns display a specific pattern of increased apoptosis at the tailbud stage in regions corresponding to the path of cranial neural crest migration. Our work is the first to describe a role for WSTF in proper neural crest function, and suggests that neural crest defects resulting from WSTF haploinsufficiency may be a major contributor to the pathoembryology of WS. PMID:22691402

Limb-body wall defect: experience of a reference service of fetal medicine from Southern Brazil.

PubMed

Gazolla, Ana C; da Cunha, André C; Telles, Jorge A B; Betat, Rosilene da S; Romano, Mayara A; Marshall, Isabel; Gobatto, Amanda M; de H Bicca, Anna M; Arcolini, Camila P; Dal Pai, Thaís K V; Vieira, Luciane R; Targa, Luciano V; Betineli, Ildo; Zen, Paulo R G; Rosa, Rafael F M

2014-10-01

Limb-body wall defect is a rare condition characterized by a combination of large and complex defects of the ventral thorax and abdominal wall with craniofacial and limb anomalies. The aim of this study was to describe the experience of our fetal medicine service, a reference from Southern Brazil, with prenatally diagnosed patients with a limb-body wall defect in a 3 years period. Only patients who fulfilled the criteria suggested by Hunter et al. (2011) were included in the study. Clinical data and results of radiological and cytogenetic evaluation were collected from their medical records. Our sample was composed of 8 patients. Many of their mothers were younger than 25 years (50%) and in their first pregnancy (62.5%). It is noteworthy that one patient was referred due to suspected anencephaly and another due to a twin pregnancy with an embryonic sac. Craniofacial defects were verified in three patients (37.5%), thoracic/abdominal abnormalities in 6 (75%) and limb defects in eight (100%). Congenital heart defects were observed in five patients (62.5%). One of them presented a previously undescribed complex heart defect. The results disclosed that complementary exams, such as MRI and echocardiography, are important to better define the observed defects. Some of them, such as congenital heart defects, may be more common than previously reported. This definition is essential for the proper management of the pregnancy and genetic counseling of the family. The birth of these children must be planned with caution and for the prognosis a long survival possibility, despite unlikely and rare, must be considered. © 2014 Wiley Periodicals, Inc.

Detection of congenital heart defects throughout pregnancy; impact of first trimester ultrasound screening for cardiac abnormalities.

PubMed

Eleftheriades, Makarios; Tsapakis, Elsa; Sotiriadis, Alexandros; Manolakos, Emmanouil; Hassiakos, Demetrios; Botsis, Demetrios

2012-12-01

To evaluate prospectively the efficacy to screen for congenital heart defects (CHD) during the first trimester nuchal translucency (NT) ultrasound examination by assessing the four chambers' view of fetal heart. Pregnancies that were examined prospectively by ultrasound in the first trimester (11th-14th week), the second (19th-24th week) and third trimester were included in the study. 3774 fetuses were examined and fetal heart was assessed during the NT scan by examining the four chambers view. Detailed echocardiography was performed during the anomaly and growth scans. Diagnosis of congenital heart defects (CHD) was further confirmed by a fetal cardiologist. The four chambers view was obtained in 99.52% of the cases. CHD were diagnosed in 29 fetuses (0.77%). Thirteen cases (44.8%) were detected during the 11-13 weeks' scan, 14 cases (48.3%) during the anomaly scan, 1 CHD (3.5%) during the third trimester scan and 1 case (3.5%) postpartum. Assessment of the four chambers of fetal heart early in pregnancy was feasible and allowed the detection of 45% of CHD. Additional parameters of fetal cardiac anatomy during the NT scan may further improve the detection rate providing pregnancy management information early in the first trimester.

Congenital defects of the pericardium.

PubMed

Drury, Nigel E; De Silva, Ravi J; Hall, Roger M O; Large, Stephen R

2007-04-01

Congenital defects of the pericardium are rare, but when they are reported they are frequently associated with other cardiac lesions. We describe a case of partial pericardial defect found incidentally at surgery for closure of an ostium primum atrial septal defect. Proposed mechanisms of pericardial defect development are discussed and we suggest that associations with congenital and acquired heart disease are mostly circumstantial.

Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

PubMed

Cheung, Carlos Chun Ho; Soon, Choong Yee; Chuang, Chia-Lin; Phillips, Anthony R J; Zhang, Shaoping; Cooper, Garth J S

2015-09-01

Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P < 0.0001) at concentrations that only moderately impaired function of control hearts. To our knowledge, this is the first report describing the acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Essential but partially redundant roles for POU4F1/Brn-3a and POU4F2/Brn-3b transcription factors in the developing heart

PubMed Central

Maskell, Lauren J; Qamar, Kashif; Babakr, Aram A; Hawkins, Thomas A; Heads, Richard J; Budhram-Mahadeo, Vishwanie S

2017-01-01

Congenital heart defects contribute to embryonic or neonatal lethality but due to the complexity of cardiac development, the molecular changes associated with such defects are not fully understood. Here, we report that transcription factors (TFs) Brn-3a (POU4F1) and Brn-3b (POU4F2) are important for normal cardiac development. Brn-3a directly represses Brn-3b promoter in cardiomyocytes and consequently Brn-3a knockout (KO) mutant hearts express increased Brn-3b mRNA during mid-gestation, which is linked to hyperplastic growth associated with elevated cyclin D1, a known Brn-3b target gene. However, during late gestation, Brn-3b can cooperate with p53 to enhance transcription of pro-apoptotic genes e.g. Bax, thereby increasing apoptosis and contribute to morphological defects such as non-compaction, ventricular wall/septal thinning and increased crypts/fissures, which may cause lethality of Brn-3a KO mutants soon after birth. Despite this, early embryonic lethality in e9.5 double KO (Brn-3a−/− : Brn-3b−/−) mutants indicate essential functions with partial redundancy during early embryogenesis. High conservation between mammals and zebrafish (ZF) Brn-3b (87%) or Brn-3a (76%) facilitated use of ZF embryos to study potential roles in developing heart. Double morphant embryos targeted with morpholino oligonucleotides to both TFs develop significant cardiac defects (looping abnormalities and valve defects) suggesting essential roles for Brn-3a and Brn-3b in developing hearts. PMID:28594399

Spectrum Of Congenital Heart Disease In Full Term Neonates.

PubMed

Bibi, Saima; Hussain Gilani, Syed Yasir; Bibi, Shawana

2018-01-01

Congenital heart disease is a significant problem world over especially in neonates. Early diagnosis and prompt interventions in neonatal period precludes the mortality associated with this disorder. The objective of this study was to highlight the diversity of congenital cardiac defects in our region so that appropriate interventions are devised to minimize significant morbidity and mortality associated with this disorder. This descriptive cross-sectional study was conducted at the Neonatology Unit of Department of Paediatrics, Ayub Teaching Hospital from January 2015 to December 2016. Approval of ethical committee was taken. All fullterm neonates of either gender who presented in department of neonatology including those delivered in hospital or received from other sources (private settings, home deliveries), diagnosed as having congenital heart disease on echocardiography were included in the study. Preterm neonates of either gender were excluded from the study. Patient characteristics were recorded in a designed proforma. Data was entered in SPSS version 20 and analysed. A total of 89 neonates were included in the study. Mean age of presentation was 6.34±7.058 days and range of 1-28 days. There was a male preponderance with 57 (64%) male patients as compared to 32 (36%) female patients. Ventricular septal defect (VSD) was the commonest cardiac lesion being present in 34 (38.2%) patients. Other defects included complex congenital heart disease in 8 (9%), atrial septal defect (ASD) and transposition of great arteries (TGA) in 7 (7.9%) each, atrioventricular septal defect (AVSD) in 6 (6.7%) and Fallots's tetralogy (TOF) and hypoplastic left heart syndrome in 5 (5.6%) each.. Congenital heart disease is a problem of profound importance. It constitutes approximately one third of the total major congenital malformations. There is a diversity of cardiac lesions in our region that warrant early and prompt interventions so that the disease is recognized and treated at the earliest to reduce morbidity and mortality.

Search for Rare Copy-Number Variants in Congenital Heart Defects Identifies Novel Candidate Genes and a Potential Role for FOXC1 in Patients With Coarctation of the Aorta.

PubMed

Sanchez-Castro, Marta; Eldjouzi, Hadja; Charpentier, Eric; Busson, Pierre-François; Hauet, Quentin; Lindenbaum, Pierre; Delasalle-Guyomarch, Béatrice; Baudry, Adrien; Pichon, Olivier; Pascal, Cécile; Lefort, Bruno; Bajolle, Fanny; Pezard, Philippe; Schott, Jean-Jacques; Dina, Christian; Redon, Richard; Gournay, Véronique; Bonnet, Damien; Le Caignec, Cédric

2016-02-01

Congenital heart defects are the most frequent malformations among newborns and a frequent cause of morbidity and mortality. Although genetic variation contributes to congenital heart defects, their precise molecular bases remain unknown in the majority of patients. We analyzed, by high-resolution array comparative genomic hybridization, 316 children with sporadic, nonsyndromic congenital heart defects, including 76 coarctation of the aorta, 159 transposition of the great arteries, and 81 tetralogy of Fallot, as well as their unaffected parents. We identified by array comparative genomic hybridization, and validated by quantitative real-time polymerase chain reaction, 71 rare de novo (n=8) or inherited (n=63) copy-number variants (CNVs; 50 duplications and 21 deletions) in patients. We identified 113 candidate genes for congenital heart defects within these CNVs, including BTRC, CHRNB3, CSRP2BP, ERBB2, ERMARD, GLIS3, PLN, PTPRJ, RLN3, and TCTE3. No de novo CNVs were identified in patients with transposition of the great arteries in contrast to coarctation of the aorta and tetralogy of Fallot (P=0.002; Fisher exact test). A search for transcription factor binding sites showed that 93% of the rare CNVs identified in patients with coarctation of the aorta contained at least 1 gene with FOXC1-binding sites. This significant enrichment (P<0.0001; permutation test) was not observed for the CNVs identified in patients with transposition of the great arteries and tetralogy of Fallot. We hypothesize that these CNVs may alter the expression of genes regulated by FOXC1. Foxc1 belongs to the forkhead transcription factors family, which plays a critical role in cardiovascular development in mice. These data suggest that deregulation of FOXC1 or its downstream genes play a major role in the pathogenesis of coarctation of the aorta in humans. © 2015 American Heart Association, Inc.

Mice Carrying a Hypomorphic Evi1 Allele Are Embryonic Viable but Exhibit Severe Congenital Heart Defects

PubMed Central

Bard-Chapeau, Emilie A.; Szumska, Dorota; Jacob, Bindya; Chua, Belinda Q. L.; Chatterjee, Gouri C.; Zhang, Yi; Ward, Jerrold M.; Urun, Fatma; Kinameri, Emi; Vincent, Stéphane D.; Ahmed, Sayadi; Bhattacharya, Shoumo; Osato, Motomi; Perkins, Archibald S.; Moore, Adrian W.; Jenkins, Nancy A.; Copeland, Neal G.

2014-01-01

The ecotropic viral integration site 1 (Evi1) oncogenic transcription factor is one of a number of alternative transcripts encoded by the Mds1 and Evi1 complex locus (Mecom). Overexpression of Evi1 has been observed in a number of myeloid disorders and is associated with poor patient survival. It is also amplified and/or overexpressed in many epithelial cancers including nasopharyngeal carcinoma, ovarian carcinoma, ependymomas, and lung and colorectal cancers. Two murine knockout models have also demonstrated Evi1's critical role in the maintenance of hematopoietic stem cell renewal with its absence resulting in the death of mutant embryos due to hematopoietic failure. Here we characterize a novel mouse model (designated Evi1fl3) in which Evi1 exon 3, which carries the ATG start, is flanked by loxP sites. Unexpectedly, we found that germline deletion of exon3 produces a hypomorphic allele due to the use of an alternative ATG start site located in exon 4, resulting in a minor Evi1 N-terminal truncation and a block in expression of the Mds1-Evi1 fusion transcript. Evi1δex3/δex3 mutant embryos showed only a mild non-lethal hematopoietic phenotype and bone marrow failure was only observed in adult Vav-iCre/+, Evi1fl3/fl3 mice in which exon 3 was specifically deleted in the hematopoietic system. Evi1δex3/δex3 knockout pups are born in normal numbers but die during the perinatal period from congenital heart defects. Database searches identified 143 genes with similar mutant heart phenotypes as those observed in Evi1δex3/δex3 mutant pups. Interestingly, 42 of these congenital heart defect genes contain known Evi1-binding sites, and expression of 18 of these genes are also effected by Evi1 siRNA knockdown. These results show a potential functional involvement of Evi1 target genes in heart development and indicate that Evi1 is part of a transcriptional program that regulates cardiac development in addition to the development of blood. PMID:24586749

Endothelial deletion of Ino80 disrupts coronary angiogenesis and causes congenital heart disease.

PubMed

Rhee, Siyeon; Chung, Jae I; King, Devin A; D'amato, Gaetano; Paik, David T; Duan, Anna; Chang, Andrew; Nagelberg, Danielle; Sharma, Bikram; Jeong, Youngtae; Diehn, Maximilian; Wu, Joseph C; Morrison, Ashby J; Red-Horse, Kristy

2018-01-25

During development, the formation of a mature, well-functioning heart requires transformation of the ventricular wall from a loose trabecular network into a dense compact myocardium at mid-gestation. Failure to compact is associated in humans with congenital diseases such as left ventricular non-compaction (LVNC). The mechanisms regulating myocardial compaction are however still poorly understood. Here, we show that deletion of the Ino80 chromatin remodeler in vascular endothelial cells prevents ventricular compaction in the developing mouse heart. This correlates with defective coronary vascularization, and specific deletion of Ino80 in the two major coronary progenitor tissues-sinus venosus and endocardium-causes intermediate phenotypes. In vitro, endothelial cells promote myocardial expansion independently of blood flow in an Ino80-dependent manner. Ino80 deletion increases the expression of E2F-activated genes and endothelial cell S-phase occupancy. Thus, Ino80 is essential for coronary angiogenesis and allows coronary vessels to support proper compaction of the heart wall.

Prenatal diagnosis of congenital fetal heart abnormalities and clinical analysis.

PubMed

Li, Hui; Wei, Jun; Ma, Ying; Shang, Tao

2005-09-01

To study the value of detecting fetal congenital heart disease (CHD) using the five transverse planes technique of fetal echocardiography. Nine hundred and eighty-two high-risk pregnancies for fetal CHD were included in this study, the fetal heart was scanned with the five transverse planes technique of fetal echocardiography described by Yagel, autopsy was conducted when pregnancy was terminated. Blood from fetal heart was collected for fetal chromosome analysis. A close follow-up was given for normal fetal heart pregnancies and neonatal echocardiography was performed to check the accuracy of prenatal diagnosis. (1) Forty-six cases (4.68%) were found to have fetal heart abnormalities in this study, 69.56% of them were diagnosed by single four-chamber view, another 30.43% fetal CHD were found by combining other views; (2) Forty-one parents of prenatal fetuses with CHD chose to terminate pregnancy, thirty-two of them gave consent to conduct autopsy, 93.75% of which yielded unanimous conclusion between prenatal fetal echocardiography and autopsy; (3) Thirty-two of 46 cases underwent fetal chromosome analysis, 8 cases (25%) were found to have abnormal chromosome; (4) Five cases were found to have right ventricle and atrium a little bigger than those on the left side, with the unequal condition being the same after birth, but there were no clinical manifestations and they are healthy for the time being; (5) Nine hundred and thirty-six cases were not found with abnormality in this study, but one case was diagnosed with ventricular septal defect after birth, one case was diagnosed with patent ductus arteriosus, one case had atrial septal defect after birth. (1) The detected CHD rate was 4.68% by screening fetal heart with five transverse planes according to Yagel's description of high risk population basis for CHD. The coinciding rate of prenatal diagnosis and autopsy was 93.75%; (2) The sensitivity of detecting fetal heart abnormality is 92%, the specificity is 99.6% using the five transverse planes technique of fetal echocardiography; (3) Fetuses with mild or moderate disproportion of right and left side in the heart are potentially healthy babies.

Class IA phosphoinositide 3-kinase regulates heart size and physiological cardiac hypertrophy.

PubMed

Luo, Ji; McMullen, Julie R; Sobkiw, Cassandra L; Zhang, Li; Dorfman, Adam L; Sherwood, Megan C; Logsdon, M Nicole; Horner, James W; DePinho, Ronald A; Izumo, Seigo; Cantley, Lewis C

2005-11-01

Class I(A) phosphoinositide 3-kinases (PI3Ks) are activated by growth factor receptors, and they regulate, among other processes, cell growth and organ size. Studies using transgenic mice overexpressing constitutively active and dominant negative forms of the p110alpha catalytic subunit of class I(A) PI3K have implicated the role of this enzyme in regulating heart size and physiological cardiac hypertrophy. To further understand the role of class I(A) PI3K in controlling heart growth and to circumvent potential complications from the overexpression of dominant negative and constitutively active proteins, we generated mice with muscle-specific deletion of the p85alpha regulatory subunit and germ line deletion of the p85beta regulatory subunit of class I(A) PI3K. Here we show that mice with cardiac deletion of both p85 subunits exhibit attenuated Akt signaling in the heart, reduced heart size, and altered cardiac gene expression. Furthermore, exercise-induced cardiac hypertrophy is also attenuated in the p85 knockout hearts. Despite such defects in postnatal developmental growth and physiological hypertrophy, the p85 knockout hearts exhibit normal contractility and myocardial histology. Our results therefore provide strong genetic evidence that class I(A) PI3Ks are critical regulators for the developmental growth and physiological hypertrophy of the heart.

Heart disease in patients with pulmonary embolism.

PubMed

Pesavento, Raffaele; Piovella, Chiara; Prandoni, Paolo

2010-09-01

Several heart diseases are promoters of left-side cardiac thrombosis and could lead to arterial embolism. The same mechanism may be responsible for right-side cardiac thrombosis and therefore be a direct source of pulmonary embolism. Yasuoka et al. showed a higher incidence of perfusion defects in lung scan in patients with spontaneous echocontrast in the right atrium than in those without it (40% and 7% respectively; P=0.006). We recently assessed the prevalence of heart diseases in 11.236 consecutive patients older than 60 years discharged from Venetian hospitals with a diagnosis of pulmonary embolism. We observed a higher prevalence of all-cause heart diseases (odds ratio 1.26; 95% confidence interval, 1.13-1.40) in patients with a diagnosis of pulmonary embolism alone (secondary or unprovoked) compared with those discharged with a diagnosis of pulmonary embolism associated with deep vein thrombosis, generating the hypothesis that some specific heart diseases in older patients could themselves be a possible source of pulmonary emboli. Further prospective studies are required to confirm these findings, which have the potential to open new horizons for the interpretation and management of venous thromboembolic disease.

Maternal bond with cardiosurgically treated infant. Qualitative analysis of mothers' narratives.

PubMed

Sikora, Karolina; Janusz, Bernadetta

2014-01-01

The aim of this work is to describe the experience of being a mother by women who together with their children stay on the ward after cardiac surgical correction of congenital heart defects. The research material consisted of the narratives of mothers whose children were born with a heart defect and surgically treated. Four women aged 21-30 years were participants of this study. The age of the subjects' children ranged from 5 weeks to 1 year and three months. The heart defects with which the children were born were hypoplastic left heart syndrome (HLHS ) or atrioventricular canal defect. The research was carried out using the narrative interview. Qualitative analysis was carried out according to the rules of thematic analysis. The results of the research confirm that cardiac treatment can have a significant impact on maternal care patterns and the mother-infant bonding process. Intermittent contact with an infant can lead to loss of control over what happens to the child and the loss of a sense of competence to care for him. Medical staff face the challenge of supporting the parents of hospitalized children in the process of building relationships with a sick infant. The actions of doctors and nurses to enable parents to care for a baby can help foster their sense of competence and responsibility.

Cardiac Hemodynamics in the Pathogenesis of Congenital Heart Disease and Aortic Valve Calcification

NASA Astrophysics Data System (ADS)

Nigam, Vishal

2011-11-01

An improved understanding of the roles of hemodynamic forces play in cardiac development and the pathogenesis of cardiac disease will have significant scientific and clinical impact. I will focus on the role of fluid dynamics in congenital heart disease and aortic valve calcification. Congenital heart defects are the most common form of birth defect. Aortic valve calcification/stenosis is the third leading cause of adult heart disease and the most common form of acquired valvular disease in developed countries. Given the high incidence of these diseases and their associated morbidity and mortality, the potential translational impact of an improved understanding of cardiac hemodynamic forces is very large. Division of Pediatric Cardiology, Rady Children's Hospital, San Diego

Dynamic three-dimensional display of common congenital cardiac defects from reconstruction of two-dimensional echocardiographic images.

PubMed

Hsieh, K S; Lin, C C; Liu, W S; Chen, F L

1996-01-01

Two-dimensional echocardiography had long been a standard diagnostic modality for congenital heart disease. Further attempts of three-dimensional reconstruction using two-dimensional echocardiographic images to visualize stereotypic structure of cardiac lesions have been successful only recently. So far only very few studies have been done to display three-dimensional anatomy of the heart through two-dimensional image acquisition because such complex procedures were involved. This study introduced a recently developed image acquisition and processing system for dynamic three-dimensional visualization of various congenital cardiac lesions. From December 1994 to April 1995, 35 cases were selected in the Echo Laboratory here from about 3000 Echo examinations completed. Each image was acquired on-line with specially designed high resolution image grazmber with EKG and respiratory gating technique. Off-line image processing using a window-architectured interactive software package includes construction of 2-D ehcocardiographic pixel to 3-D "voxel" with conversion of orthogonal to rotatory axial system, interpolation, extraction of region of interest, segmentation, shading and, finally, 3D rendering. Three-dimensional anatomy of various congenital cardiac defects was shown, including four cases with ventricular septal defects, two cases with atrial septal defects, and two cases with aortic stenosis. Dynamic reconstruction of a "beating heart" is recorded as vedio tape with video interface. The potential application of 3D display of the reconstruction from 2D echocardiographic images for the diagnosis of various congenital heart defects has been shown. The 3D display was able to improve the diagnostic ability of echocardiography, and clear-cut display of the various congenital cardiac defects and vavular stenosis could be demonstrated. Reinforcement of current techniques will expand future application of 3D display of conventional 2D images.

Bmp2 and Notch cooperate to pattern the embryonic endocardium.

PubMed

Papoutsi, T; Luna-Zurita, L; Prados, B; Zaffran, S; de la Pompa, J L

2018-05-31

Signaling interactions between myocardium and endocardium pattern embryonic cardiac regions, instructing their development to fulfill specific functions in the mature heart. We show that ectopic Bmp2 expression in the mouse chamber myocardium changes the transcriptional signature of adjacent chamber endocardial cells into valve tissue, and enables them to undergo epithelial-mesenchyme transition. This induction is independent of valve myocardium specification and requires high levels of Notch1 activity. Biochemical experiments suggest that Bmp2-mediated Notch1 induction is achieved through transcriptional activation of the Notch ligand Jag1, and physical interaction of Smad1/5 with the intracellular domain of the Notch1 receptor. Thus, widespread myocardial Bmp2 and endocardial Notch signaling drive presumptive ventricular endocardium to differentiate into valve endocardium. Understanding the molecular basis of valve development is instrumental to designing therapeutic strategies for congenital heart valve defects. © 2018. Published by The Company of Biologists Ltd.

Heart morphogenesis gene regulatory networks revealed by temporal expression analysis.

PubMed

Hill, Jonathon T; Demarest, Bradley; Gorsi, Bushra; Smith, Megan; Yost, H Joseph

2017-10-01

During embryogenesis the heart forms as a linear tube that then undergoes multiple simultaneous morphogenetic events to obtain its mature shape. To understand the gene regulatory networks (GRNs) driving this phase of heart development, during which many congenital heart disease malformations likely arise, we conducted an RNA-seq timecourse in zebrafish from 30 hpf to 72 hpf and identified 5861 genes with altered expression. We clustered the genes by temporal expression pattern, identified transcription factor binding motifs enriched in each cluster, and generated a model GRN for the major gene batteries in heart morphogenesis. This approach predicted hundreds of regulatory interactions and found batteries enriched in specific cell and tissue types, indicating that the approach can be used to narrow the search for novel genetic markers and regulatory interactions. Subsequent analyses confirmed the GRN using two mutants, Tbx5 and nkx2-5 , and identified sets of duplicated zebrafish genes that do not show temporal subfunctionalization. This dataset provides an essential resource for future studies on the genetic/epigenetic pathways implicated in congenital heart defects and the mechanisms of cardiac transcriptional regulation. © 2017. Published by The Company of Biologists Ltd.

Gastrointestinal system malformations in children are associated with congenital heart defects.

PubMed

Orün, Utku Arman; Bilici, Meki; Demirçeken, Fulya G; Tosun, Mahya; Ocal, Burhan; Cavuşoğlu, Yusuf Hakan; Erdoğan, Derya; Senocak, Filiz; Karademir, Selmin

2011-03-01

To determine the frequency of congenital heart defects (CHD) in children with gastrointestinal malformations (GISM) and mortality rates in patients with GISM. Two hundred and forty two consecutive children patients with GISM followed up in Pediatric Surgery Clinics of our hospital were examined for cardiovascular anomaly by the Department of Pediatric Cardiology, and the CHD incidence was investigated by examining the records of the patients retrospectively. Chi-square test was used for the statistical analysis of data. Two hundred and forty two patients with gastrointestinal system malformations were included in the study. Of 242 patients, 135 (55.8%) were male and 107 (44.2%) were female, and their age range was 0-15 years. The most frequent GISM were anorectal malformations (43.2%), atresia involving stomach, ileum or colon (21%) and esophageal atresia/tracheoesophageal fistula (18.3%). Congenital heart defects were observed in 28.5% of the participants. The most frequent defects were as follows; atrial septal defect (31 patients, 44.9%) a, ventricular septal defect (17 patients, 24.6%) and patent ductus arteriosus (5 patients, 7.2%). There was no significant difference (p>0.05) in mortality rate in patients with CHD (16.7%) and without CHD (13.3%) undergoing operations for GISM. We would like to emphasize the importance of the earliest possible cardiological evaluation of all patients with gastrointestinal system malformations.

Impact of patient-specific factors, irradiated left ventricular volume, and treatment set-up errors on the development of myocardial perfusion defects after radiation therapy for left-sided breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evans, Elizabeth S.; Prosnitz, Robert G.; Yu Xiaoli

2006-11-15

Purpose: The aim of this study was to assess the impact of patient-specific factors, left ventricle (LV) volume, and treatment set-up errors on the rate of perfusion defects 6 to 60 months post-radiation therapy (RT) in patients receiving tangential RT for left-sided breast cancer. Methods and Materials: Between 1998 and 2005, a total of 153 patients were enrolled onto an institutional review board-approved prospective study and had pre- and serial post-RT (6-60 months) cardiac perfusion scans to assess for perfusion defects. Of the patients, 108 had normal pre-RT perfusion scans and available follow-up data. The impact of patient-specific factors onmore » the rate of perfusion defects was assessed at various time points using univariate and multivariate analysis. The impact of set-up errors on the rate of perfusion defects was also analyzed using a one-tailed Fisher's Exact test. Results: Consistent with our prior results, the volume of LV in the RT field was the most significant predictor of perfusion defects on both univariate (p = 0.0005 to 0.0058) and multivariate analysis (p = 0.0026 to 0.0029). Body mass index (BMI) was the only significant patient-specific factor on both univariate (p = 0.0005 to 0.022) and multivariate analysis (p = 0.0091 to 0.05). In patients with very small volumes of LV in the planned RT fields, the rate of perfusion defects was significantly higher when the fields set-up 'too deep' (83% vs. 30%, p = 0.059). The frequency of deep set-up errors was significantly higher among patients with BMI {>=}25 kg/m{sup 2} compared with patients of normal weight (47% vs. 28%, p = 0.068). Conclusions: BMI {>=}25 kg/m{sup 2} may be a significant risk factor for cardiac toxicity after RT for left-sided breast cancer, possibly because of more frequent deep set-up errors resulting in the inclusion of additional heart in the RT fields. Further study is necessary to better understand the impact of patient-specific factors and set-up errors on the development of RT-induced perfusion defects.« less

CHARACTERIZING THE ROLE OF THE NELL1 GENE IN CARDIOVASCULAR DEVELOPMENT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, L. Y.; Culiat, C.

Nell1{sup 6R} is a chemically-induced point mutation in a novel cell-signaling gene, Nell1, which results in truncation of the protein and degradation of the Nell16R transcript. Earlier studies revealed that loss of Nell1 function reduces expression of numerous extracellular matrix (ECM) proteins required for differentiation of bone and cartilage precursor cells, thereby causing severe skull and spinal defects. Since skeletal and cardiovascular development are closely linked biological processes, this research focused on: a) examining Nell16R mutant mice for cardiovascular defects, b) determining Nell1 expression in fetal and adult hearts, and c) establishing how ECM genes affected by Nell1 infl uencemore » heart development. Structural heart defects in Nell16R mutant fetuses were analyzed by heart length and width measurements and standard histological methods (haematoxylin and eosin staining). Nell1 expression was assayed in fetal and adult hearts using reverse transcription polymerase chain reaction (RT-PCR). A comprehensive bioinformatics analysis using public databases (Stanford SOURCE Search, Integrated Cartilage Gene Database, Mouse Genome Informatics, and NCBI UniGene) was undertaken to investigate the relationship between cardiovascular development and each of twentyeight genes affected by Nell1. Nell1-defi cient mice have signifi cantly enlarged hearts (particularly the heart width), dramatically reduced blood fl ow out of the heart and unexpanded lungs. Isolation of total RNAs from hearts of adult (control and heterozygote) and fetal (control and homozygous mutant) mice have been completed and RT-PCR assays are in progress. The bioinformatics analysis showed that the majority of genes with reduced expression in Nell1-defi cient mice are normally expressed in the heart (79%; 22/28), blood vessels (71%; 20/28) and bone marrow (61%; 17/28). Moreover, mouse mutations in seven of these genes (Col15a1, Osf-2, Bmpr1a, Pkd1, Mfge8, Ptger4, Col5a1) manifest abnormalities in cardiovascular development. These data demonstrate for the fi rst time that Nell1 has a role in early mammalian cardiovascular development, mediated by its regulation of ECM proteins necessary for normal cell growth and differentiation. In addition, understanding the mechanisms by which Nell1 and its associated ECM genes affect the cardiovascular system can provide future strategies for the treatment of heart and blood vessel defects.« less

Interstitial deletion of 8q21{yields}22 associated with minor anomalies, congenital heart defect, and Dandy-Walker variant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donahue, M.L.; Ryan, R.M.

1995-03-13

We describe an infant with a deletion of 8q21{yields}22 who had distinct clinical manifestations including minor facial anomalies, a congenital heart defect, a Dandy-Walker variant, and mild to moderate developmental delay. Her facial characteristics included small, wide-spaced eyes, asymmetric bilateral epicanthal folds, a broad nasal bridge, a {open_quotes}carp-shaped{close_quotes} mouth, micrognathia, and prominent, apparently low-set ears. Three other reports describe children with larger proximal deletions of 8q that include 8q21 and q22. These four children all have similar facial appearance. Of the others reported, one had a congenital heart defect and one had craniosynostosis. This case, in addition to the previouslymore » noted three cases, helps in delineating a recognizable syndrome. 12 refs., 3 figs., 1 tab.« less

The BMP pathway acts to directly regulate Tbx20 in the developing heart

PubMed Central

Mandel, Elizabeth M.; Kaltenbrun, Erin; Callis, Thomas E.; Zeng, Xin-Xin I.; Marques, Sara R.; Yelon, Deborah; Wang, Da-Zhi; Conlon, Frank L.

2010-01-01

TBX20 has been shown to be essential for vertebrate heart development. Mutations within the TBX20 coding region are associated with human congenital heart disease, and the loss of Tbx20 in a wide variety of model systems leads to cardiac defects and eventually heart failure. Despite the crucial role of TBX20 in a range of cardiac cellular processes, the signal transduction pathways that act upstream of Tbx20 remain unknown. Here, we have identified and characterized a conserved 334 bp Tbx20 cardiac regulatory element that is directly activated by the BMP/SMAD1 signaling pathway. We demonstrate that this element is both necessary and sufficient to drive cardiac-specific expression of Tbx20 in Xenopus, and that blocking SMAD1 signaling in vivo specifically abolishes transcription of Tbx20, but not that of other cardiac factors, such as Tbx5 and MHC, in the developing heart. We further demonstrate that activation of Tbx20 by SMAD1 is mediated by a set of novel, non-canonical, high-affinity SMAD-binding sites located within this regulatory element and that phospho-SMAD1 directly binds a non-canonical SMAD1 site in vivo. Finally, we show that these non-canonical sites are necessary and sufficient for Tbx20 expression in Xenopus, and that reporter constructs containing these sites are expressed in a cardiac-specific manner in zebrafish and mouse. Collectively, our findings define Tbx20 as a direct transcriptional target of the BMP/SMAD1 signaling pathway during cardiac maturation. PMID:20460370

Heparan Sulfate Expression in the Neural Crest is Essential for Mouse Cardiogenesis

PubMed Central

Pan, Yi; Carbe, Christian; Pickhinke, Ute; Kupich, Sabine; Ohlig, Stefanie; Frye, Maike; Seelige, Ruth; Pallerla, Srinivas R.; Moon, Anne M.; Lawrence, Roger; Esko, Jeffrey D.; Zhang, Xin; Grobe, Kay

2015-01-01

Impaired heparan sulfate (HS) synthesis in vertebrate development causes complex malformations due to the functional disruption of multiple HS-binding growth factors and morphogens. Here, we report developmental heart defects in mice bearing a targeted disruption of the HS-generating enzyme GlcNAc N-Deacetylase/GlcN N-Sulfotransferase 1 (NDST1), including ventricular septal defects (VSD), persistent truncus arteriosus (PTA), double outlet right ventricle (DORV), and retroesophageal right subclavian artery (RERSC). These defects closely resemble cardiac anomalies observed in mice made deficient in the cardiogenic regulator fibroblast growth factor 8 (FGF8). Consistent with this, we show that HS-dependent FGF8/FGF-receptor2C assembly and FGF8-dependent ERK-phosphorylation are strongly reduced in NDST1−/− embryonic cells and tissues. Moreover, WNT1-Cre/LoxP-mediated conditional targeting of NDST function in neural crest cells (NCCs) revealed that their impaired HS-dependent development contributes strongly to the observed cardiac defects. These findings raise the possibility that defects in HS biosynthesis may contribute to congenital heart defects in humans that represent the most common type of birth defect. PMID:24200809

Nutrition and growth in congenital heart disease: a challenge in children.

PubMed

Medoff-Cooper, Barbara; Ravishankar, Chitra

2013-03-01

Growth failure secondary to feeding problems after complex neonatal cardiac surgery is well documented, but not well understood. The purpose of this review is to describe feeding and growth pattern in children with congenital heart defects. Nearly half of the infants with univentricular heart defects require supplementation with nasogastric or gastrostomy tube at discharge from neonatal surgery. Feeding challenges contribute to parental stress, and persist beyond infancy. These infants are 'stunted' with both weight and height being below normal. Nearly a quarter of these infants meet the definition of 'failure to thrive' in the first year of life. Short stature is a significant problem for many of these children, and has an impact on neurodevelopmental outcomes. A structured nutritional program can have a positive impact on growth in the interstage period prior to the superior cavopulmonary connection. Optimizing nutritional intake has been targeted as a key component of the National Pediatric Cardiology Quality Improvement Collaborative. This initiative has enabled the development of best practices that have the potential to mitigate poor growth in children with congenital heart defects.

Mitochondrial Metabolism in Aging Heart

PubMed Central

Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

2016-01-01

Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

Color vision abnormalities in type II diabetes: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study II report no 2

PubMed Central

Gella, Laxmi; Raman, Rajiv; Kulothungan, Vaitheeswaran; Pal, Swakshyar Saumya; Ganesan, Suganeswari; Srinivasan, Sangeetha; Sharma, Tarun

2017-01-01

Purpose: The purpose of this study is to assess color vision abnormalities in a cohort of subjects with type II diabetes and elucidate associated risk factors. Methods: Subjects were recruited from follow-up cohort of Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study I. Six hundred and seventy-three eyes of 343 subjects were included from this population-based study. All subjects underwent detailed ophthalmic evaluation, including the Farnsworth-Munsell 100 hue test. Results: The prevalence of impaired color vision (ICV) was 43% (CI: 39.2–46.7). Risk factors for ICV were higher heart rate (odds ratio [OR]: 1.043, [1.023–1.064]) and a higher intraocular pressure (IOP) (OR: 1.086, [1.012–1.165]). Subjects with clinically significant macular edema (CSME) had three times higher chance of having ICV. C1, C2, and C3 are the commonly found Early Treatment Diabetic Retinopathy Study (ETDRS) patterns. The moment of inertia method showed that the angle did not reveal any specific pattern of color vision defect. Although the major and minor radii were high in those with ICV, we did not observe polarity. Confusion index was high in subjects with ICV, indicating a severe color vision defect. Conclusions: The prevalence of ICV was 43% among subjects with type II diabetes. The most commonly observed patterns were increasing severities of the blue–yellow defect on ETDRS patterns, but no specific pattern was observed at the moment of inertia analysis. The presence of CSME, a higher heart rate, and IOP was significant risk factors for ICV. This functional impairment in color vision could significantly contribute to morbidity among subjects with diabetes. PMID:29044066

Color vision abnormalities in type II diabetes: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study II report no 2.

PubMed

Gella, Laxmi; Raman, Rajiv; Kulothungan, Vaitheeswaran; Pal, Swakshyar Saumya; Ganesan, Suganeswari; Srinivasan, Sangeetha; Sharma, Tarun

2017-10-01

The purpose of this study is to assess color vision abnormalities in a cohort of subjects with type II diabetes and elucidate associated risk factors. Subjects were recruited from follow-up cohort of Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study I. Six hundred and seventy-three eyes of 343 subjects were included from this population-based study. All subjects underwent detailed ophthalmic evaluation, including the Farnsworth-Munsell 100 hue test. The prevalence of impaired color vision (ICV) was 43% (CI: 39.2-46.7). Risk factors for ICV were higher heart rate (odds ratio [OR]: 1.043, [1.023-1.064]) and a higher intraocular pressure (IOP) (OR: 1.086, [1.012-1.165]). Subjects with clinically significant macular edema (CSME) had three times higher chance of having ICV. C1, C2, and C3 are the commonly found Early Treatment Diabetic Retinopathy Study (ETDRS) patterns. The moment of inertia method showed that the angle did not reveal any specific pattern of color vision defect. Although the major and minor radii were high in those with ICV, we did not observe polarity. Confusion index was high in subjects with ICV, indicating a severe color vision defect. The prevalence of ICV was 43% among subjects with type II diabetes. The most commonly observed patterns were increasing severities of the blue-yellow defect on ETDRS patterns, but no specific pattern was observed at the moment of inertia analysis. The presence of CSME, a higher heart rate, and IOP was significant risk factors for ICV. This functional impairment in color vision could significantly contribute to morbidity among subjects with diabetes.

Postnatal Cardiac Autonomic Nervous Control in Pediatric Congenital Heart Disease

PubMed Central

Nederend, Ineke; Jongbloed, Monique R. M.; de Geus, Eco J. C.; Blom, Nico A.; ten Harkel, Arend D. J.

2016-01-01

Congenital heart disease is the most common congenital defect. During childhood, survival is generally good but, in adulthood, late complications are not uncommon. Abnormal autonomic control in children with congenital heart disease may contribute considerably to the pathophysiology of these long term sequelae. This narrative review of 34 studies aims to summarize current knowledge on function of the autonomic nervous system in children with a congenital heart defect. Large scale studies that measure both branches of the nervous system for prolonged periods of time in well-defined patient cohorts in various phases of childhood and adolescence are currently lacking. Pending such studies, there is not yet a good grasp on the extent and direction of sympathetic and parasympathetic autonomic function in pediatric congenital heart disease. Longitudinal studies in homogenous patient groups linking autonomic nervous system function and clinical outcome are warranted. PMID:29367565

Maternal residential proximity to chlorinated solvent emissions and birth defects in offspring: a case-control study.

PubMed

Brender, Jean D; Shinde, Mayura U; Zhan, F Benjamin; Gong, Xi; Langlois, Peter H

2014-11-19

Some studies have noted an association between maternal occupational exposures to chlorinated solvents and birth defects in offspring, but data are lacking on the potential impact of industrial air emissions of these solvents on birth defects. With data from the Texas Birth Defects Registry for births occurring in 1996-2008, we examined the relation between maternal residential proximity to industrial air releases of chlorinated solvents and birth defects in offspring of 60,613 case-mothers and 244,927 control-mothers. Maternal residential exposures to solvent emissions were estimated with metrics that took into account residential distances to industrial sources and annual amounts of chemicals released. Logistic regression was used to generate odds ratios and 95% confidence intervals for the associations between residential proximity to emissions of 14 chlorinated solvents and selected birth defects, including neural tube, oral cleft, limb deficiency, and congenital heart defects. All risk estimates were adjusted for year of delivery and maternal age, education, race/ethnicity, and public health region of residence. Relative to exposure risk values of 0, neural tube defects were associated with maternal residential exposures (exposure risk values >0) to several types of chlorinated solvents, most notably carbon tetrachloride (adjusted odds ratio [aOR] 1.42, 95% confidence interval [CI] 1.09, 1.86); chloroform (aOR 1.40, 95% CI 1.04, 1.87); ethyl chloride (aOR 1.39, 95% CI 1.08, 1.79); 1,1,2-trichloroethane (aOR 1.56, 95% CI 1.11, 2.18); and 1,2,3-trichloropropane (aOR 1.49, 95% CI 1.08, 2.06). Significant associations were also noted between a few chlorinated solvents and oral cleft, limb deficiency, and congenital heart defects. We observed stronger associations between some emissions and neural tube, oral cleft, and heart defects in offspring of mothers 35 years or older, such as spina bifida with carbon tetrachloride (aOR 2.49, 95% CI 1.09, 5.72), cleft palate with 1,2-dichloroethane (aOR 1.93, 95% 1.05, 3.54), cleft lip with or without cleft palate with ethyl chloride (aOR 1.81, 95% CI 1.06, 3.07), and obstructive heart defects with trichloroethylene (aOR 1.43, 95% CI 1.08, 1.88). These findings suggest that maternal residential proximity to industrial emissions of chlorinated solvents might be associated with selected birth defects in offspring, especially among older mothers.

[Surgery of grown up congenital heart disease. About 540 cases].

PubMed

Haddad, A; Bourezak, R; Aouiche, M; Ait Mohand, R; Hamzaoui, A; Bourezak, S E

2015-09-01

With advances in recent decades in the field of congenital heart disease both for imaging in medical therapy, a large number of heart disease is diagnosed before birth. Many of them benefit from surgery and reach adulthood, they do not require further action. Some of them develop later in their lives other problems requiring reoperation in adulthood. This sparked the birth of a subspecialty within the department of congenital heart disease: GUCH Unit "grown up congenital heart disease". In developing countries, little heart are detected in childhood, a minority of them are operated and very few reach adulthood or with minor heart disease or become advanced enough then inoperable. Only part may still take advantage of surgery at this age. The aim of our study is to describe the spectrum and characteristics of congenital heart disease in adulthood in Algiers a center of cardiovascular surgery. A retrospective descriptive study of patients aged 15 and above operated for congenital heart defects between 1995 and 2011. Five hundred and forty patients aged 15 to 76years (29±10 years), including 314 women and 226 men are operated congenital heart defects between 1995 and 2011. The left-right shunts represent two thirds of heart disease, represented mainly (50%) by the atrial septal defect. Barriers to the ejection of the left heart represent one forth of cases with a predominance of subvalvular aortic stenosis. We find the native heart whose survival is considered exceptional in adulthood in the absence of surgery, such as tetralogy of Fallot, aortopulmonary windows wide, double outlet right ventricle and atrioventricular canal that take advantage of always surgery. The results are encouraging with low perioperative mortality (2%). The approach of congenital heart disease in developing countries is different from that of developed countries. Efforts need to be made in early detection and monitoring of congenital heart disease and improve access to surgery centers in close collaboration with pediatricians, cardiologists and obstetricians. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

CARDIAC OPERATIONS WITH EXTRACORPOREAL CIRCULATION

PubMed Central

Kay, Jerome Harold; Anderson, Robert M.; Lewis, Reuben R.; Meihaus, John; Magidson, Oscar; Snyder, Edward N.; Bennett, Louis C.; Bernstein, Sol; Amsden, Neal

1959-01-01

In a series of 50 patients for whom a heart-lung machine was used for periods as long as 70 minutes during operations to correct structural defects of the heart, there were no deaths attributable to the machine. Seven patients died. Two of them had high pressure ventricular septal defects with bidirectional shunts; a third patient with the same lesion recovered after repair. One patient died of cardiac tamponade when a large blood clot formed about the entire heart in a loosely closed pericardial sac. Others died of various causes. The development of subacute bacterial endocarditis in one patient led to a change in sterilization of apparatus. PMID:13662856

Toward a practical template-based approach to semiquantitative SPECT myocardial perfusion imaging.

PubMed

Hughes, Tyler; Celler, Anna

2012-03-01

Our template-based quantitative perfusion single photon emission computed tomography (SPECT) method (T-QPS) performs semiquantitative analysis for myocardial perfusion imaging (MPI) without the use of normal databases. However, in its current form, T-QPS requires extensive calculations, which limits its clinical application. In the interest of clinical feasibility, the authors examine the trade-off between accuracy and processing time as the method is simplified. The T-QPS method uses the reconstructed SPECT image of the patient to create a 3D digital template of his∕her healthy heart. This template is then projected, reconstructed, and sampled into the bulls-eye map domain. A ratio of the patient and template images produces a final corrected image in which a threshold is applied to identify perfusion defects. In principle, the template should be constructed with the heart and all extracardiac activity, and the projection step should include primary and scatter components; however, this leads to lengthy calculations. In an attempt to shorten the processing time, the authors analyzed the performance of four template (T) generation methods: T(P-HRT), T(PS-HRT), T(P-HRTBKG), and T(PS-HRTBKG), where P and S represent primary and scattered photons included in the projection step, respectively; and HRT and HRTBKG represent template constructed with the heart only and the heart with background activity, respectively. Forty-eight thorax phantoms and 21 randomly selected patient studies were analyzed using each approach. All studies used GE's Infinia Hawkeye SPECT∕CT system and followed a standard cardiac acquisition protocol. Approximate processing times for the T(P-HRT), T(PS-HRT), T(P-HRTBKG), and T(PS-HRTBKG) methods were less than a minute, 2-3 h, less than a minute and 3-4 h, respectively. In both the simulation and patient studies, a significant reduction in the quality of perfusion defect definition was exhibited by the T(P-HRT) method relative to the other three methods. The optimal method with respect to perfusion defect definition and processing time was T(P-HRTBKG) with a sensitivity, specificity, and accuracy in spatially defining the perfusion defects (simulation study) of 80%, 84%, and 83%, respectively. The T-QPS method using T(P-HRTBKG) leads to accurate and fast semiquantitative analysis of SPECT MPI, without the use of normal databases.

SHP-2 acts via ROCK to regulate the cardiac actin cytoskeleton

PubMed Central

Langdon, Yvette; Tandon, Panna; Paden, Erika; Duddy, Jennifer; Taylor, Joan M.; Conlon, Frank L.

2012-01-01

Noonan syndrome is one of the most common causes of human congenital heart disease and is frequently associated with missense mutations in the protein phosphatase SHP-2. Interestingly, patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), juvenile myelomonocytic leukemia (JMML) and LEOPARD syndrome frequently carry a second, somatically introduced subset of missense mutations in SHP-2. To determine the cellular and molecular mechanisms by which SHP-2 regulates heart development and, thus, understand how Noonan-associated mutations affect cardiogenesis, we introduced SHP-2 encoding the most prevalent Noonan syndrome and JMML mutations into Xenopus embryos. Resulting embryos show a direct relationship between a Noonan SHP-2 mutation and its ability to cause cardiac defects in Xenopus; embryos expressing Noonan SHP-2 mutations exhibit morphologically abnormal hearts, whereas those expressing an SHP-2 JMML-associated mutation do not. Our studies indicate that the cardiac defects associated with the introduction of the Noonan-associated SHP-2 mutations are coupled with a delay or arrest of the cardiac cell cycle in M-phase and a failure of cardiomyocyte progenitors to incorporate into the developing heart. We show that these defects are a result of an underlying malformation in the formation and polarity of cardiac actin fibers and F-actin deposition. We show that these defects can be rescued in culture and in embryos through the inhibition of the Rho-associated, coiled-coil-containing protein kinase 1 (ROCK), thus demonstrating a direct relationship between SHP-2N308D and ROCK activation in the developing heart. PMID:22278918

3D characterization of EMT cell density in developing cardiac cushions using optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yu, Siyao; Gu, Shi; Zhao, Xiaowei; Liu, Yehe; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

2017-02-01

Congenital heart defects (CHDs) are the most common birth defect, affecting between 4 and 75 per 1,000 live births depending on the inclusion criteria. Many of these defects can be traced to defects of cardiac cushions, critical structures during development that serve as precursors to many structures in the mature heart, including the atrial and ventricular septa, and all four sets of cardiac valves. Epithelial-mesenchymal transition (EMT) is the process through which cardiac cushions become populated with cells. Altered cushion size or altered cushion cell density has been linked to many forms of CHDs, however, quantitation of cell density in the complex 3D cushion structure poses a significant challenge to conventional histology. Optical coherence tomography (OCT) is a technique capable of 3D imaging of the developing heart, but typically lacks the resolution to differentiate individual cells. Our goal is to develop an algorithm to quantitatively characterize the density of cells in the developing cushion using 3D OCT imaging. First, in a heart volume, the atrioventricular (AV) cushions were manually segmented. Next, all voxel values in the region of interest were pooled together to generate a histogram. Finally, two populations of voxels were classified using either K-means classification, or a Gaussian mixture model (GMM). The voxel population with higher values represents cells in the cushion. To test the algorithm, we imaged and evaluated avian embryonic hearts at looping stages. As expected, our result suggested that the cell density increases with developmental stages. We validated the technique against scoring by expert readers.

SHP-2 acts via ROCK to regulate the cardiac actin cytoskeleton.

PubMed

Langdon, Yvette; Tandon, Panna; Paden, Erika; Duddy, Jennifer; Taylor, Joan M; Conlon, Frank L

2012-03-01

Noonan syndrome is one of the most common causes of human congenital heart disease and is frequently associated with missense mutations in the protein phosphatase SHP-2. Interestingly, patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), juvenile myelomonocytic leukemia (JMML) and LEOPARD syndrome frequently carry a second, somatically introduced subset of missense mutations in SHP-2. To determine the cellular and molecular mechanisms by which SHP-2 regulates heart development and, thus, understand how Noonan-associated mutations affect cardiogenesis, we introduced SHP-2 encoding the most prevalent Noonan syndrome and JMML mutations into Xenopus embryos. Resulting embryos show a direct relationship between a Noonan SHP-2 mutation and its ability to cause cardiac defects in Xenopus; embryos expressing Noonan SHP-2 mutations exhibit morphologically abnormal hearts, whereas those expressing an SHP-2 JMML-associated mutation do not. Our studies indicate that the cardiac defects associated with the introduction of the Noonan-associated SHP-2 mutations are coupled with a delay or arrest of the cardiac cell cycle in M-phase and a failure of cardiomyocyte progenitors to incorporate into the developing heart. We show that these defects are a result of an underlying malformation in the formation and polarity of cardiac actin fibers and F-actin deposition. We show that these defects can be rescued in culture and in embryos through the inhibition of the Rho-associated, coiled-coil-containing protein kinase 1 (ROCK), thus demonstrating a direct relationship between SHP-2(N308D) and ROCK activation in the developing heart.

Interrupted Aortic Arch Associated with Absence of Left Common Carotid Artery: Imaging with MDCT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onbas, Omer; Olgun, Hasim; Ceviz, Naci

2006-06-15

Interrupted aortic arch (IAA) is a rare severe congenital heart defect defined as complete luminal and anatomic discontinuity between ascending and descending aorta. Although its association with various congenital heart defects has been reported, absence of left common carotid artery (CCA) in patients with IAA has not been reported previously. We report a case of IAA associated with the absence of left CCA which was clearly shown on multidetector-row spiral CT.

Experiences of informational needs and received information following a prenatal diagnosis of congenital heart defect

PubMed Central

Bergman, Gunnar; Wadensten, Barbro; Mattsson, Elisabet

2016-01-01

Abstract Objective To explore the need for information and what information was actually received following prenatal diagnosis of a congenital heart defect, in a country where termination of pregnancy beyond 22 weeks of gestation is not easily possible because of legal constraints. Methods Twenty‐six Swedish‐speaking pregnant women (n = 14) and partners (n = 12) were consecutively recruited for semi‐structured telephone interviews following the prenatal diagnosis of a congenital heart defect. Data were analyzed using content analysis. Results Although high satisfaction with the specialist information was described, the information was considered overwhelming and complex. Objective, honest, and detailed information about multiple subjects were needed, delivered repeatedly, and supplemented by written information/illustrations. Eighteen respondents had used the Internet to search for information and identified issues involving searching difficulties, low quality, and that it was too complex, insufficient, or unspecific. Those who terminated their pregnancy criticized that there was a lack of information about termination of pregnancy, both from health professionals and online sources, resulting in unanswered questions and unpreparedness. Conclusion Individuals faced with a prenatal diagnosis of a congenital heart defect need individualized and repeated information. These needs are not all adequately met, as individuals are satisfied with the specialist consultation but left with unanswered questions regarding pregnancy termination. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. PMID:26991536

Experiences of informational needs and received information following a prenatal diagnosis of congenital heart defect.

PubMed

Carlsson, Tommy; Bergman, Gunnar; Wadensten, Barbro; Mattsson, Elisabet

2016-06-01

To explore the need for information and what information was actually received following prenatal diagnosis of a congenital heart defect, in a country where termination of pregnancy beyond 22 weeks of gestation is not easily possible because of legal constraints. Twenty-six Swedish-speaking pregnant women (n = 14) and partners (n = 12) were consecutively recruited for semi-structured telephone interviews following the prenatal diagnosis of a congenital heart defect. Data were analyzed using content analysis. Although high satisfaction with the specialist information was described, the information was considered overwhelming and complex. Objective, honest, and detailed information about multiple subjects were needed, delivered repeatedly, and supplemented by written information/illustrations. Eighteen respondents had used the Internet to search for information and identified issues involving searching difficulties, low quality, and that it was too complex, insufficient, or unspecific. Those who terminated their pregnancy criticized that there was a lack of information about termination of pregnancy, both from health professionals and online sources, resulting in unanswered questions and unpreparedness. Individuals faced with a prenatal diagnosis of a congenital heart defect need individualized and repeated information. These needs are not all adequately met, as individuals are satisfied with the specialist consultation but left with unanswered questions regarding pregnancy termination. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

Birth Defects & Other Health Conditions

MedlinePlus

... Congenital heart defects and CCHD Congenital syphilis Congenital Zika syndrome Coxsackie infection and your baby Cystic fibrosis ... families in our new awareness campaign video. GO Zika services near you Visit Zika Care Connect to ...

Assessing bottled water nitrate concentrations to evaluate total drinking water nitrate exposure and risk of birth defects.

PubMed

Weyer, Peter J; Brender, Jean D; Romitti, Paul A; Kantamneni, Jiji R; Crawford, David; Sharkey, Joseph R; Shinde, Mayura; Horel, Scott A; Vuong, Ann M; Langlois, Peter H

2014-12-01

Previous epidemiologic studies of maternal exposure to drinking water nitrate did not account for bottled water consumption. The objective of this National Birth Defects Prevention Study (NBDPS) (USA) analysis was to assess the impact of bottled water use on the relation between maternal exposure to drinking water nitrate and selected birth defects in infants born during 1997-2005. Prenatal residences of 1,410 mothers reporting exclusive bottled water use were geocoded and mapped; 326 bottled water samples were collected and analyzed using Environmental Protection Agency Method 300.0. Median bottled water nitrate concentrations were assigned by community; mothers' overall intake of nitrate in mg/day from drinking water was calculated. Odds ratios for neural tube defects, limb deficiencies, oral cleft defects, and heart defects were estimated using mixed-effects models for logistic regression. Odds ratios (95% CIs) for the highest exposure group in offspring of mothers reporting exclusive use of bottled water were: neural tube defects [1.42 (0.51, 3.99)], limb deficiencies [1.86 (0.51, 6.80)], oral clefts [1.43 (0.61, 3.31)], and heart defects [2.13, (0.87, 5.17)]. Bottled water nitrate had no appreciable impact on risk for birth defects in the NBDPS.

Assessing bottled water nitrate concentrations to evaluate total drinking water nitrate exposure and risk of birth defects

PubMed Central

Weyer, Peter J.; Brender, Jean D.; Romitti, Paul A.; Kantamneni, Jiji R.; Crawford, David; Sharkey, Joseph R.; Shinde, Mayura; Horel, Scott A.; Vuong, Ann M.; Langlois, Peter H.

2016-01-01

Previous epidemiologic studies of maternal exposure to drinking water nitrate did not account for bottled water consumption. The objective of this National Birth Defects Prevention Study (NBDPS) (USA) analysis was to assess the impact of bottled water use on the relation between maternal exposure to drinking water nitrate and selected birth defects in infants born during 1997–2005. Prenatal residences of 1,410 mothers reporting exclusive bottled water use were geocoded and mapped; 326 bottled water samples were collected and analyzed using Environmental Protection Agency Method 300.0. Median bottled water nitrate concentrations were assigned by community; mothers’ overall intake of nitrate in mg/day from drinking water was calculated. Odds ratios for neural tube defects, limb deficiencies, oral cleft defects, and heart defects were estimated using mixed-effects models for logistic regression. Odds ratios (95% CIs) for the highest exposure group in offspring of mothers reporting exclusive use of bottled water were: neural tube defects [1.42 (0.51, 3.99)], limb deficiencies [1.86 (0.51, 6.80)], oral clefts [1.43 (0.61, 3.31)], and heart defects [2.13, (0.87, 5.17)]. Bottled water nitrate had no appreciable impact on risk for birth defects in the NBDPS. PMID:25473985

Histone deacetylase is required for the activation of Wnt/β-catenin signaling crucial for heart valve formation in zebrafish embryos.

PubMed

Kim, Young-Seop; Kim, Myoung-Jin; Koo, Tae-Hee; Kim, Jun-Dae; Koun, Soonil; Ham, Hyung Jin; Lee, You Mie; Rhee, Myungchull; Yeo, Sang-Yeob; Huh, Tae-Lin

2012-06-22

During vertebrate heart valve formation, Wnt/β-catenin signaling induces BMP signals in atrioventricular canal (AVC) myocardial cells and underlying AVC endocardial cells then undergo endothelial-mesenchymal transdifferentiation (EMT) by receiving this BMP signals. Histone deacetylases (HDACs) have been implicated in numerous developmental processes by regulating gene expression. However, their specific roles in controlling heart valve development are largely unexplored. To investigate the role of HDACs in vertebrate heart valve formation, we treated zebrafish embryos with trichostatin A (TSA), an inhibitor of class I and II HDACs, from 36 to 48 h post-fertilization (hpf) during which heart looping and valve formation occur. Following TSA treatment, abnormal linear heart tube development was observed. In these embryos, expression of AVC myocardial bmp4 and AVC endocardial notch1b genes was markedly reduced with subsequent failure of EMT in the AVC endocardial cells. However, LiCl-mediated activation of Wnt/β-catenin signaling was able to rescue defective heart tube formation, bmp4 and notch1b expression, and EMT in the AVC region. Taken together, our results demonstrated that HDAC activity plays a pivotal role in vertebrate heart tube formation by activating Wnt/β-catenin signaling which induces bmp4 expression in AVC myocardial cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Facts about Hypoplastic Left Heart Syndrome

MedlinePlus

... Septal Defect Atrioventricular Septal Defect Coarctation of the Aorta D-Transposition of the Great Arteries Hypoplastic Left ... is very small. The ascending portion of the aorta is underdeveloped or is too small. Often, babies ...

Natural history and clinical outcome of "uncorrected" scimitar syndrome patients: a multicenter study of the italian society of pediatric cardiology.

PubMed

Vida, Vladimiro L; Padrini, Maddalena; Boccuzzo, Giovanna; Agnoletti, Gabriella; Bondanza, Sara; Butera, Gianfranco; Chiappa, Enrico; Marasini, Maurizio; Pilati, Mara; Pongiglione, Giacomo; Prandstraller, Daniela; Russo, Maria Giovanna; Castaldi, Biagio; Santoro, Giuseppe; Spadoni, Isabella; Stellin, Giovanni; Milanesi, Ornella

2013-07-01

To analyze the clinical status of patients with "uncorrected" scimitar syndrome in a multicenter Italian study. The natural history of scimitar syndrome was analyzed in 44 affected individuals (from 9 Italian centers). The median age at diagnosis was 1.05 years (range, 1 day-41 years). Thirty-three patients (75%) had an isolated form; 11 patients (25%) had associated congenital heart diseases. Twenty-two patients (50%) were symptomatic at diagnosis, including respiratory symptoms (n=20) and congestive heart failure (n=6). Patients with associated congenital heart defects had a higher prevalence of congestive heart failure (4 of 11 [36.4%] vs 2 of 33 [6.1%]; P=.027), pulmonary arterial hypertension (7 of 11 [63.6%] vs 2 of 33 [6.1%]; P=.027) than patients with isolated forms. Ten patients (22.7%) underwent correction of associated cardiac defects, leaving the anomalous pulmonary venous drainage intact. The median length of follow-up after diagnosis was 6.4 years (range, 0.2-27.5 years). Two patients died, both with associated cardiac defects and severe pulmonary arterial hypertension. Of 42 survivors, 39 (92.8%) were asymptomatic at the last follow-up visit; 3 patients still complained respiratory symptoms. There was no difference between isolated and associated forms of the disease. In most patients, scimitar syndrome presented as an isolated lesion with a benign outcome. Nonetheless, when associated with other cardiac defects and pulmonary arterial hypertension, there was an increased risk of congestive heart failure and mortality. Correction of associated cardiac defects (transforming "associated" into "isolated" forms), together with the therapeutic occlusion of anomalous arterial supply to the lung, led to a benign outcome comparable to that in primarily isolated forms. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Pulmonary Hypertension Overview

MedlinePlus

... well as sleep apnea, are common causes of secondary pulmonary hypertension. Other causes include the following: Congestive heart failure Birth defects in the heart Chronic pulmonary thromboembolism (blood clots in the pulmonary arteries) Acquired immunodeficiency syndrome ( ...

Jarcho-Levin syndrome presenting with diaphragmatic hernia.

PubMed

Onay, O S; Kinik, S T; Otgün, Y; Arda, I S; Varan, B

2008-08-01

Jarcho-Levin syndrome (spondylothoracic or spondylocostal dysostosis) is an eponym that is used to define individuals with a short neck, short trunk, and short stature and multiple vertebral anomalies. The prognosis is directly related to respiratory complications. Reported findings associated with Jarcho-Levin syndrome include congenital heart defects, abdominal wall malformations, genitourinary malformations, upper limb anomalies, and neural tube defects. We report on a 6-day-old girl who presented with an incomplete form of Jarcho-Levin syndrome with late-presenting congenital diaphragmatic hernia and congenital heart disease.

New Lethal Skeletal Dysplasia with Dandy-Walker Malformation, Congenital Heart Defects, Abnormal Thumbs, Hypoplastic Genitalia, and Distinctive Facies

PubMed Central

Stevens, Cathy A.; Lachman, Ralph S.

2011-01-01

We report on two sibs with a lethal form of bone dysplasia with distinctive skeletal findings including rhizomelic and mesomelic limb shortening, hooked clavicles, dumbbell femurs, and absence of talus and calcaneus ossification. Other clinical features include Dandy-Walker malformation, congenital heart defects, joint contractures, genital hypoplasia, and distinctive facial features. These sibs appear to have a previously undescribed skeletal dysplasia, which is most likely inherited in an autosomal recessive fashion. PMID:20602491

Genetics Home Reference: critical congenital heart disease

MedlinePlus

... into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination ... defects classified as CCHD include coarctation of the aorta , double-outlet right ventricle, D-transposition of the ...

Novel Therapeutic Strategies for Reducing Right Heart Failure Associated Mortality in Fibrotic Lung Diseases

PubMed Central

Levy, Matthew; Oyenuga, Olusegun

2015-01-01

Fibrotic lung diseases carry a significant mortality burden worldwide. A large proportion of these deaths are due to right heart failure and pulmonary hypertension. Underlying contributory factors which appear to play a role in the mechanism of progression of right heart dysfunction include chronic hypoxia, defective calcium handling, hyperaldosteronism, pulmonary vascular alterations, cyclic strain of pressure and volume changes, elevation of circulating TGF-β, and elevated systemic NO levels. Specific therapies targeting pulmonary hypertension include calcium channel blockers, endothelin (ET-1) receptor antagonists, prostacyclin analogs, phosphodiesterase type 5 (PDE5) inhibitors, and rho-kinase (ROCK) inhibitors. Newer antifibrotic and anti-inflammatory agents may exert beneficial effects on heart failure in idiopathic pulmonary fibrosis. Furthermore, right ventricle-targeted therapies, aimed at mitigating the effects of functional right ventricular failure, include β-adrenoceptor (β-AR) blockers, angiotensin-converting enzyme (ACE) inhibitors, antioxidants, modulators of metabolism, and 5-hydroxytryptamine-2B (5-HT2B) receptor antagonists. Newer nonpharmacologic modalities for right ventricular support are increasingly being implemented. Early, effective, and individualized therapy may prevent overt right heart failure in fibrotic lung disease leading to improved outcomes and quality of life. PMID:26583148

Myocardin-related transcription factors are required for cardiac development and function

PubMed Central

Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

2016-01-01

Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks. PMID:26386146

Analysis of Craniocardiac Malformations in Xenopus using Optical Coherence Tomography

PubMed Central

Deniz, Engin; Jonas, Stephan; Hooper, Michael; N. Griffin, John; Choma, Michael A.; Khokha, Mustafa K.

2017-01-01

Birth defects affect 3% of children in the United States. Among the birth defects, congenital heart disease and craniofacial malformations are major causes of mortality and morbidity. Unfortunately, the genetic mechanisms underlying craniocardiac malformations remain largely uncharacterized. To address this, human genomic studies are identifying sequence variations in patients, resulting in numerous candidate genes. However, the molecular mechanisms of pathogenesis for most candidate genes are unknown. Therefore, there is a need for functional analyses in rapid and efficient animal models of human disease. Here, we coupled the frog Xenopus tropicalis with Optical Coherence Tomography (OCT) to create a fast and efficient system for testing craniocardiac candidate genes. OCT can image cross-sections of microscopic structures in vivo at resolutions approaching histology. Here, we identify optimal OCT imaging planes to visualize and quantitate Xenopus heart and facial structures establishing normative data. Next we evaluate known human congenital heart diseases: cardiomyopathy and heterotaxy. Finally, we examine craniofacial defects by a known human teratogen, cyclopamine. We recapitulate human phenotypes readily and quantify the functional and structural defects. Using this approach, we can quickly test human craniocardiac candidate genes for phenocopy as a critical first step towards understanding disease mechanisms of the candidate genes. PMID:28195132

Congenital heart defects in oculodentodigital dysplasia: Report of two cases.

PubMed

Izumi, Kosuke; Lippa, Andrew M; Wilkens, Alisha; Feret, Holly A; McDonald-McGinn, Donna M; Zackai, Elaine H

2013-12-01

Oculodentodigital dysplasia is caused by mutations in the GJA1 gene. Oculodentodigital dysplasia presents with a spectrum of clinical features including craniofacial, ocular, dental, and limb anomalies. Although recent findings implicate the major role of GJA1 during cardiac organogenesis, congenital heart defects are infrequently reported in oculodentodigital dysplasia. Here we report on two patients with GJA1 mutations presenting with cardiac malformations and type III syndactyly. Patient 1 presented with pulmonary atresia, an intact septum, right ventricular hypoplasia and tricuspid stenosis. The infant had a small nose, thin columella and bilateral 4-5 syndactyly of the fingers. A de novo c.226C>T (p.Arg76Cys) mutation was identified. Patient 2 presented at 6 months with a ventricular septal defect. The child had hypoplastic alae nasi with a thin columella and bilateral 4-5 syndactyly of the digits. A de novo missense mutation, c.145C>G (p.Gln49Glu) was found. Our two patients underscore the importance of cardiac evaluations as part of the initial workup for patients with findings of oculodentodigital dysplasia. Conversely, those patients with type III syndactyly and congenital heart defect should be screened for GJA1 mutations. © 2013 Wiley Periodicals, Inc.

When Your Baby Has a Birth Defect

MedlinePlus

... as heart defects, cleft lip and palate, or cerebral palsy. Still, you may find yourself being both the ... the NICU Gene Therapy and Children Down Syndrome Cerebral Palsy Spina Bifida Prenatal Genetic Counseling What Is a ...

Medical therapy in adults with congenital heart disease.

PubMed

Book, Wendy M; Shaddy, Robert E

2014-01-01

Heart failure is a common late complication in adults with congenital heart defects, both repaired and unrepaired. The onset of clinical heart failure is associated with increased morbidity and mortality. Some patients with congenital heart disease may benefit from medications shown to improve survival in the population with acquired heart failure, but these same therapies may be of no benefit to other patients. Further studies are needed to better guide the choice of medical therapies. Copyright © 2014 Elsevier Inc. All rights reserved.

[CLINICAL CHARACTERISTICS OF CONGENITAL HEART DISEASES ASSOCIATED WITH CONNECTIVE TISSUE DISPLASIA AT CHILDREN LIVING IN EAST REGION OF KAZAKHSTAN].

PubMed

Madiyeva, M; Rymbayeva, T

2017-11-01

The frequency of the combination of congenital heart defects (CHD) and connective tissue dysplasia remains poorly understood. And connective tissue dysplasia enhance severity the clinical of CHD. The aim of the study was to conduct a clinical and laboratory analysis of combinations of congenital heart defects and connective tissue dysplasia in children of Semey and to determine the risk for the development of these pathologies. The object of the study is the children of Semey (East Kazakhstan) aged 1-14 with congenital heart defects (CHD), with connective tissue dysplasia, healthy children and their mothers. Definition complex clinical and laboratory studies in children with CHD and connective tissue dysplasia, and their mothers. In children with CHD, the frequency of external and visceral signs of dysplasia was high. In 88.1% of cases in children with CHD was diagnosed 2-3 degrees of dysplasia. Was found difference in the microelement composition of blood serum and of hemostasis in children with CHD were expressed by hypofibrinogenemia, hypocalcemia, hypomagnesemia. Excess of the frequency of signs of dysplasia in mothers over the control group to consider dysplasia as a factor that influences the clinical of CHD.

Meis2 is essential for cranial and cardiac neural crest development.

PubMed

Machon, Ondrej; Masek, Jan; Machonova, Olga; Krauss, Stefan; Kozmik, Zbynek

2015-11-06

TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging. We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2α-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities. Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.

Proteomic-based detection of a protein cluster dysregulated during cardiovascular development identifies biomarkers of congenital heart defects.

PubMed

Nath, Anjali K; Krauthammer, Michael; Li, Puyao; Davidov, Eugene; Butler, Lucas C; Copel, Joshua; Katajamaa, Mikko; Oresic, Matej; Buhimschi, Irina; Buhimschi, Catalin; Snyder, Michael; Madri, Joseph A

2009-01-01

Cardiovascular development is vital for embryonic survival and growth. Early gestation embryo loss or malformation has been linked to yolk sac vasculopathy and congenital heart defects (CHDs). However, the molecular pathways that underlie these structural defects in humans remain largely unknown hindering the development of molecular-based diagnostic tools and novel therapies. Murine embryos were exposed to high glucose, a condition known to induce cardiovascular defects in both animal models and humans. We further employed a mass spectrometry-based proteomics approach to identify proteins differentially expressed in embryos with defects from those with normal cardiovascular development. The proteins detected by mass spectrometry (WNT16, ST14, Pcsk1, Jumonji, Morca2a, TRPC5, and others) were validated by Western blotting and immunoflorescent staining of the yolk sac and heart. The proteins within the proteomic dataset clustered to adhesion/migration, differentiation, transport, and insulin signaling pathways. A functional role for several proteins (WNT16, ADAM15 and NOGO-A/B) was demonstrated in an ex vivo model of heart development. Additionally, a successful application of a cluster of protein biomarkers (WNT16, ST14 and Pcsk1) as a prenatal screen for CHDs was confirmed in a study of human amniotic fluid (AF) samples from women carrying normal fetuses and those with CHDs. The novel finding that WNT16, ST14 and Pcsk1 protein levels increase in fetuses with CHDs suggests that these proteins may play a role in the etiology of human CHDs. The information gained through this bed-side to bench translational approach contributes to a more complete understanding of the protein pathways dysregulated during cardiovascular development and provides novel avenues for diagnostic and therapeutic interventions, beneficial to fetuses at risk for CHDs.

Proteomic-Based Detection of a Protein Cluster Dysregulated during Cardiovascular Development Identifies Biomarkers of Congenital Heart Defects

PubMed Central

Nath, Anjali K.; Krauthammer, Michael; Li, Puyao; Davidov, Eugene; Butler, Lucas C.; Copel, Joshua; Katajamaa, Mikko; Oresic, Matej; Buhimschi, Irina; Buhimschi, Catalin; Snyder, Michael; Madri, Joseph A.

2009-01-01

Background Cardiovascular development is vital for embryonic survival and growth. Early gestation embryo loss or malformation has been linked to yolk sac vasculopathy and congenital heart defects (CHDs). However, the molecular pathways that underlie these structural defects in humans remain largely unknown hindering the development of molecular-based diagnostic tools and novel therapies. Methodology/Principal Findings Murine embryos were exposed to high glucose, a condition known to induce cardiovascular defects in both animal models and humans. We further employed a mass spectrometry-based proteomics approach to identify proteins differentially expressed in embryos with defects from those with normal cardiovascular development. The proteins detected by mass spectrometry (WNT16, ST14, Pcsk1, Jumonji, Morca2a, TRPC5, and others) were validated by Western blotting and immunoflorescent staining of the yolk sac and heart. The proteins within the proteomic dataset clustered to adhesion/migration, differentiation, transport, and insulin signaling pathways. A functional role for several proteins (WNT16, ADAM15 and NOGO-A/B) was demonstrated in an ex vivo model of heart development. Additionally, a successful application of a cluster of protein biomarkers (WNT16, ST14 and Pcsk1) as a prenatal screen for CHDs was confirmed in a study of human amniotic fluid (AF) samples from women carrying normal fetuses and those with CHDs. Conclusions/Significance The novel finding that WNT16, ST14 and Pcsk1 protein levels increase in fetuses with CHDs suggests that these proteins may play a role in the etiology of human CHDs. The information gained through this bed-side to bench translational approach contributes to a more complete understanding of the protein pathways dysregulated during cardiovascular development and provides novel avenues for diagnostic and therapeutic interventions, beneficial to fetuses at risk for CHDs. PMID:19156209

Inheritance Analysis of Congenital Left Ventricular Outflow Tract Obstruction Malformations: Segregation, Multiplex Relative Risk, and Heritability

PubMed Central

McBride, Kim L.; Pignatelli, Ricardo; Lewin, Mark; Ho, Trang; Fernbach, Susan; Menesses, Andres; Lam, Wilbur; Leal, Suzanne M.; Kaplan, Norman; Schliekelman, Paul; Towbin, Jeffrey A.; Belmont, John W.

2006-01-01

The left ventricular outflow tract (LVOTO) malformations, aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic left heart (HLH) constitute a mechanistically defined subgroup of congenital heart defects that have substantial evidence for a genetic component. Evidence from echocardiography studies has shown that bicuspid aortic valve (BAV) is found frequently in relatives of children with LVOTO defects. However, formal inheritance analysis has not been performed. We ascertained 124 families by an index case with AVS, COA, or HLH. A total of 413 relatives were enrolled in the study, of which 351 had detailed echocardiography exams for structural heart defects and measurements of a variety of aortic arch, left ventricle, and valve structures. LVOTO malformations were noted in 30 relatives (18 BAV, 5 HLH, 3 COA, and 3 AVS), along with significant congenital heart defects (CHD) in 2 others (32/413; 7.7%). Relative risk for first-degree relatives in this group was 36.9, with a heritability of 0.71–0.90. Formal segregation analysis suggests that one or more minor loci with rare dominant alleles may be operative in a subset of families. Multiplex relative risk analysis, which estimates number of loci, had the highest maximum likelihood score in a model with 2 loci (range of 1–6 in the lod-1 support interval). Heritability of several aortic arch measurements and aortic valve was significant. These data support a complex but most likely oligogenic pattern of inheritance. A combination of linkage and association study designs is likely to enable LVOTO risk gene identification. This data can also provide families with important information for screening asymptomatic relatives for potentially harmful cardiac defects. PMID:15690347

Left cardiac isomerism in the Sonic hedgehog null mouse.

PubMed

Hildreth, Victoria; Webb, Sandra; Chaudhry, Bill; Peat, Jonathan D; Phillips, Helen M; Brown, Nigel; Anderson, Robert H; Henderson, Deborah J

2009-06-01

Sonic hedgehog (Shh) is a secreted morphogen necessary for the production of sidedness in the developing embryo. In this study, we describe the morphology of the atrial chambers and atrioventricular junctions of the Shh null mouse heart. We demonstrate that the essential phenotypic feature is isomerism of the left atrial appendages, in combination with an atrioventricular septal defect and a common atrioventricular junction. These malformations are known to be frequent in humans with left isomerism. To confirm the presence of left isomerism, we show that Pitx2c, a recognized determinant of morphological leftness, is expressed in the Shh null mutants on both the right and left sides of the inflow region, and on both sides of the solitary arterial trunk exiting from the heart. It has been established that derivatives of the second heart field expressing Isl1 are asymmetrically distributed in the developing normal heart. We now show that this population is reduced in the hearts from the Shh null mutants, likely contributing to the defects. To distinguish the consequences of reduced contributions from the second heart field from those of left-right patterning disturbance, we disrupted the movement of second heart field cells into the heart by expressing dominant-negative Rho kinase in the population of cells expressing Isl1. This resulted in absence of the vestibular spine, and presence of atrioventricular septal defects closely resembling those seen in the hearts from the Shh null mutants. The primary atrial septum, however, was well formed, and there was no evidence of isomerism of the atrial appendages, suggesting that these features do not relate to disruption of the contributions made by the second heart field. We demonstrate, therefore, that the Shh null mouse is a model of isomerism of the left atrial appendages, and show that the recognized associated malformations found at the venous pole of the heart in the setting of left isomerism are likely to arise from the loss of the effects of Shh in the establishment of laterality, combined with a reduced contribution made by cells derived from the second heart field.

Rare copy number variants in a population-based investigation of hypoplastic right heart syndrome.

PubMed

Dimopoulos, Aggeliki; Sicko, Robert J; Kay, Denise M; Rigler, Shannon L; Druschel, Charlotte M; Caggana, Michele; Browne, Marilyn L; Fan, Ruzong; Romitti, Paul A; Brody, Lawrence C; Mills, James L

2017-01-20

Hypoplastic right heart syndrome (HRHS) is a rare congenital defect characterized by underdevelopment of the right heart structures commonly accompanied by an atrial septal defect. Familial HRHS reports suggest genetic factor involvement. We examined the role of copy number variants (CNVs) in HRHS. We genotyped 32 HRHS cases identified from all New York State live births (1998-2005) using Illumina HumanOmni2.5 microarrays. CNVs were called with PennCNV and prioritized if they were ≥20 Kb, contained ≥10 SNPs and had minimal overlap with CNVs from in-house controls, the Database of Genomic Variants, HapMap3, and Childrens Hospital of Philadelphia database. We identified 28 CNVs in 17 cases; several encompassed genes important for right heart development. One case had a 2p16-2p23 duplication spanning LBH, a limb and heart development transcription factor. Lbh mis-expression results in right ventricular hypoplasia and pulmonary valve defects. This duplication also encompassed SOS1, a factor associated with pulmonary valve stenosis in Noonan syndrome. Sos1 -/- mice display thin and poorly trabeculated ventricles. In another case, we identified a 1.5 Mb deletion associated with Williams-Beuren syndrome, a disorder that includes valvular malformations. A third case had a 24 Kb deletion upstream of the TGFβ ligand ITGB8. Embryos genetically null for Itgb8, and its intracellular interactant Band 4.1B, display lethal cardiac phenotypes. To our knowledge, this is the first study of CNVs in HRHS. We identified several rare CNVs that overlap genes related to right ventricular wall and valve development, suggesting that genetics plays a role in HRHS and providing clues for further investigation. Birth Defects Research 109:16-26, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Congenital heart defect causing mutation in Nkx2.5 displays in vivo functional deficit.

PubMed

Zakariyah, Abeer F; Rajgara, Rashida F; Veinot, John P; Skerjanc, Ilona S; Burgon, Patrick G

2017-04-01

The Nkx2.5 gene encodes a transcription factor that plays a critical role in heart development. In humans, heterozygous mutations in NKX2.5 result in congenital heart defects (CHDs). However, the molecular mechanisms by which these mutations cause the disease remain unknown. NKX2.5-R142C is a mutation that was reported to be associated with atrial septal defect (ASD) and atrioventricular (AV) block in 13-patients from one family. The R142C mutation is located within both the DNA-binding domain and the nuclear localization sequence of NKX2.5 protein. The pathogenesis of CHDs in humans with R142C point mutation is not well understood. To examine the functional deficit associated with this mutation in vivo, we generated and characterized a knock-in mouse that harbours the human mutation R142C. Systematic structural and functional examination of the embryonic, newborn, and adult mice revealed that the homozygous embryos Nkx2.5 R141C/R141C are developmentally arrested around E10.5 with delayed heart morphogenesis and downregulation of Nkx2.5 target genes, Anf, Mlc2v, Actc1 and Cx40. Histological examination of Nkx2.5 R141C/+ newborn hearts showed that 36% displayed ASD, with at least 80% 0f adult heterozygotes displaying a septal defect. Moreover, heterozygous Nkx2.5 R141C/+ newborn mice have downregulation of ion channel genes with 11/12 adult mice manifesting a prolonged PR interval that is indicative of 1st degree AV block. Collectively, the present study demonstrates that mice with the R141C point mutation in the Nkx2.5 allele phenocopies humans with the NKX2.5 R142C point mutation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Arteriovenous Malformations

MedlinePlus

Arteriovenous malformations (AVMs) are defects in your vascular system. The vascular system includes arteries, veins, and capillaries. Arteries carry blood away from the heart to other organs; veins carry blood back to the heart. Capillaries connect the arteries and veins. An ...

Diving into the world of alcohol teratogenesis: a review of zebrafish models of fetal alcohol spectrum disorder.

PubMed

Fernandes, Yohaan; Buckley, Desire M; Eberhart, Johann K

2018-04-01

The term fetal alcohol spectrum disorder (FASD) refers to the entire suite of deleterious outcomes resulting from embryonic exposure to alcohol. Along with other reviews in this special issue, we provide insight into how animal models, specifically the zebrafish, have informed our understanding of FASD. We first provide a brief introduction to FASD. We discuss the zebrafish as a model organism and its strengths for alcohol research. We detail how zebrafish has been used to model some of the major defects present in FASD. These include behavioral defects, such as social behavior as well as learning and memory, and structural defects, disrupting organs such as the brain, sensory organs, heart, and craniofacial skeleton. We provide insights into how zebrafish research has aided in our understanding of the mechanisms of ethanol teratogenesis. We end by providing some relatively recent advances that zebrafish has provided in characterizing gene-ethanol interactions that may underlie FASD.

Functional study of DAND5 variant in patients with Congenital Heart Disease and laterality defects.

PubMed

Cristo, Fernando; Inácio, José M; de Almeida, Salomé; Mendes, Patrícia; Martins, Duarte Saraiva; Maio, José; Anjos, Rui; Belo, José A

2017-07-24

Perturbations on the Left-Right axis establishment lead to laterality defects, with frequently associated Congenital Heart Diseases (CHDs). Indeed, in the last decade, it has been reported that the etiology of isolated cases of CHDs or cases of laterality defects with associated CHDs is linked with variants of genes involved in the Nodal signaling pathway. With this in mind, we analyzed a cohort of 38 unrelated patients with Congenital Heart Defects that can arise from initial perturbations in the formation of the Left-Right axis and 40 unrelated ethnically matched healthy individuals as a control population. Genomic DNA was extracted from buccal epithelial cells, and variants screening was performed by PCR and direct sequencing. A Nodal-dependent luciferase assay was conducted in order to determine the functional effect of the variant found. In this work, we report two patients with a DAND5 heterozygous non-synonymous variant (c.455G > A) in the functional domain of the DAND5 protein (p.R152H), a master regulator of Nodal signaling. Patient 1 presents left isomerism, ventricular septal defect with overriding aorta and pulmonary atresia, while patient 2 presents ventricular septal defect with overriding aorta, right ventricular hypertrophy and pulmonary atresia (a case of extreme tetralogy of Fallot phenotype). The functional analysis assay showed a significant decrease in the activity of this variant protein when compared to its wild-type counterpart. Altogether, our results provide new insight into the molecular mechanism of the laterality defects and related CHDs, priming for the first time DAND5 as one of multiple candidate determinants for CHDs in humans.

Is depressed myocyte contractility centrally involved in heart failure?

PubMed

Houser, Steven R; Margulies, Kenneth B

2003-03-07

This review examines the evidence for and against the hypothesis that abnormalities in cardiac contractility initiate the heart failure syndrome and drive its progression. There is substantial evidence that the contractility of failing human hearts is depressed and that abnormalities of basal Ca2+ regulation and adrenergic regulation of Ca2+ signaling are responsible. The cellular and molecular defects that cause depressed myocyte contractility are not well established but seem to culminate in abnormal sarcoplasmic reticulum uptake, storage, and release. There are also strong links between Ca2+ regulation, Ca2+ signaling pathways, hypertrophy, and heart failure that need to be more clearly delineated. There is not substantial direct evidence for a causative role for depressed contractility in the initiation and progression of human heart failure, and some studies show that heart failure can occur without depressed myocyte contractility. Stronger support for a causal role for depressed contractility in the initiation of heart failure comes from animal studies where maintaining or improving contractility can prevent heart failure. Recent clinical studies in humans also support the idea that beneficial heart failure treatments, such as beta-adrenergic antagonists, involve improved contractility. Current or previously used heart failure treatments that increase contractility, primarily by increasing cAMP, have generally increased mortality. Novel heart failure therapies that increase or maintain contractility or adrenergic signaling by selectively modulating specific molecules have produced promising results in animal experiments. How to reliably implement these potentially beneficial inotropic therapies in humans without introducing negative side effects is the major unanswered question in this field.

Myocardial-specific R-spondin3 drives proliferation of the coronary stems primarily through the Leucine Rich Repeat G Protein coupled receptor LGR4.

PubMed

Da Silva, Fabio; Massa, Filippo; Motamedi, Fariba Jian; Vidal, Valerie; Rocha, Ana Sofia; Gregoire, Elodie P; Cai, Chen-Leng; Wagner, Kay Dietrich; Schedl, Andreas

2018-05-31

Coronary artery anomalies are common congenital disorders with serious consequences in adult life. Coronary circulation begins when the coronary stems form connections between the aorta and the developing vascular plexus. We recently identified the WNT signaling modulator R-spondin 3 (Rspo3), as a crucial regulator of coronary stem proliferation. Using expression analysis and tissue-specific deletion we now demonstrate that Rspo3 is primarily produced by cardiomyocytes. Moreover, we have employed CRISPR/Cas9 technology to generate novel Lgr4-null alleles that showed a significant decrease in coronary stem proliferation and thus phenocopied the coronary artery defects seen in Rspo3 mutants. Interestingly, Lgr4 mutants displayed slightly hypomorphic right ventricles, an observation also made after myocardial specific deletion of Rspo3. These results shed new light on the role of Rspo3 in heart development and demonstrate that LGR4 is the principal R-spondin 3 receptor in the heart. Copyright © 2018 Elsevier Inc. All rights reserved.

Building a comprehensive team for the longitudinal care of single ventricle heart defects: Building blocks and initial results.

PubMed

Texter, Karen; Davis, Jo Ann M; Phelps, Christina; Cheatham, Sharon; Cheatham, John; Galantowicz, Mark; Feltes, Timothy F

2017-07-01

With increasing survival of children with HLHS and other single ventricle lesions, the complexity of medical care for these patients is substantial. Establishing and adhering to best practice models may improve outcome, but requires careful coordination and monitoring. In 2013 our Heart Center began a process to build a comprehensive Single Ventricle Team designed to target these difficult issues. Comprehensive Single Ventricle Team in 2014 was begun, to standardize care for children with single ventricle heart defects from diagnosis to adulthood within our institution. The team is a multidisciplinary group of providers committed to improving outcomes and quality of life for children with single ventricle heart defects, all functioning within the medical home of our heart center. Standards of care were developed and implemented in five target areas to standardize medical management and patient and family support. Under the team 100 patients have been cared for. Since 2014 a decrease in interstage mortality for HLHS were seen. Using a team approach and the tools of Quality Improvement they have been successful in reaching high protocol compliance for each of these areas. This article describes the process of building a successful Single Ventricle team, our initial results, and lessons learned. Additional study is ongoing to demonstrate the effects of these interventions on patient outcomes. © 2017 Wiley Periodicals, Inc.

Risk comparison for prenatal use of analgesics and selected birth defects, National Birth Defects Prevention Study 1997-2011.

PubMed

Interrante, Julia D; Ailes, Elizabeth C; Lind, Jennifer N; Anderka, Marlene; Feldkamp, Marcia L; Werler, Martha M; Taylor, Lockwood G; Trinidad, James; Gilboa, Suzanne M; Broussard, Cheryl S

2017-10-01

To compare the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or opioids to the use of acetaminophen without NSAIDs or opioids with respect to associations with birth defects. We used data from the National Birth Defects Prevention Study (1997-2011). Exposure was self-reported maternal analgesic use from the month before through the third month of pregnancy (periconceptional). Adjusted odds ratios (aORs) were calculated to examine associations with 16 birth defects. Compared to acetaminophen, mothers reporting NSAIDs were significantly more likely to have offspring with gastroschisis, hypospadias, cleft palate, cleft lip with cleft palate, cleft lip without cleft palate, anencephaly, spina bifida, hypoplastic left heart syndrome, pulmonary valve stenosis, and tetralogy of Fallot (aOR range, 1.2-1.6). Opioids were associated with tetralogy of Fallot, perimembranous ventricular septal defect, and ventricular septal defect with atrial septal defect (aOR range, 1.8-2.3), whereas use of both opioids and NSAIDs was associated with gastroschisis, cleft palate, spina bifida, hypoplastic left heart syndrome, and pulmonary valve stenosis (aOR range, 2.0-2.9). Compared to periconceptional use of acetaminophen, selected birth defects occurred more frequently among infants of women using NSAIDs and/or opioids. However, we could not definitely determine whether these risks relate to the drugs or to indications for treatment. Published by Elsevier Inc.

Pitx2c attenuation results in cardiac defects and abnormalities of intestinal orientation in developing Xenopus laevis.

PubMed

Dagle, John M; Sabel, Jaime L; Littig, Jennifer L; Sutherland, Lillian B; Kolker, Sandra J; Weeks, Daniel L

2003-10-15

The experimental manipulation of early embryologic events, resulting in the misexpression of the homeobox transcription factor pitx2, is associated with subsequent defects of laterality in a number of vertebrate systems. To clarify the role of one pitx2 isoform, pitx2c, in determining the left-right axis of amphibian embryos, we examined the heart and gut morphology of Xenopus laevis embryos after attenuating pitx2c mRNA levels using chemically modified antisense oligonucleotides. We demonstrate that the partial depletion of pitx2c mRNA in these embryos results in alteration of both cardiac morphology and intestinal coiling. The most common cardiac abnormality seen was a failure of rightward migration of the outflow tract, while the most common intestinal laterality phenotype seen was a full reversal in the direction of coiling, each present in 23% of embryos injected with the pitx2c antisense oligonucleotide. An abnormality in either the heart or gut further predisposed to a malformation in the other. In addition, a number of other cardiac anomalies were observed after pitx2c mRNA attenuation, including abnormalities of atrial septation, extracellular matrix restriction, relative atrial-ventricular chamber positioning, and restriction of ventricular development. Many of these findings correlate with cardiac defects previously reported in pitx2 null and hypomorphic mice, but can now be assigned specifically to attenuation of the pitx2c isoform in Xenopus.

Successful total correction of congenital interruption of the aortic arch and ventricular septal defect

PubMed Central

Singh, M. P.; Bentall, H. H.; Oakley, C. M.

1970-01-01

Successful surgical correction of the complex anomaly of interruption of the aortic arch and intracardiac ventricular septal defect is reported. The patient was a boy 5 years old when he first came under treatment. The total correction was performed in two stages. At the first operation, at the age of 7 years, continuity of the aortic arch was achieved by insertion of a Teflon graft, employing left heart bypass. The ventricular septal defect was closed at the age of 13 years on total cardiopulmonary bypass. Two and half years after the total correction the boy is alive and well. The difficulties in diagnosing the condition are discussed. The role of left heart bypass is emphasized. Images PMID:5489187

AcvR1-mediated BMP signaling in second heart field is required for arterial pole development: implications for myocardial differentiation and regional identity.

PubMed

Thomas, Penny S; Rajderkar, Sudha; Lane, Jamie; Mishina, Yuji; Kaartinen, Vesa

2014-06-15

BMP signaling plays an essential role in second heart field-derived heart and arterial trunk development, including myocardial differentiation, right ventricular growth, and interventricular, outflow tract and aortico-pulmonary septation. It is mediated by a number of different BMP ligands, and receptors, many of which are present simultaneously. The mechanisms by which they regulate morphogenetic events and degree of redundancy amongst them have still to be elucidated. We therefore assessed the role of BMP Type I receptor AcvR1 in anterior second heart field-derived cell development, and compared it with that of BmpR1a. By removing Acvr1 using the driver Mef2c[AHF]-Cre, we show that AcvR1 plays an essential role in arterial pole morphogenesis, identifying defects in outflow tract wall and cushion morphology that preceded a spectrum of septation defects from double outlet right ventricle to common arterial trunk in mutants. Its absence caused dysregulation in gene expression important for myocardial differentiation (Isl1, Fgf8) and regional identity (Tbx2, Tbx3, Tbx20, Tgfb2). Although these defects resemble to some degree those in the equivalent Bmpr1a mutant, a novel gene knock-in model in which Bmpr1a was expressed in the Acvr1 locus only partially restored septation in Acvr1 mutants. These data show that both BmpR1a and AcvR1 are needed for normal heart development, in which they play some non-redundant roles, and refine our understanding of the genetic and morphogenetic processes underlying Bmp-mediated heart development important in human congenital heart disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci

PubMed Central

2013-01-01

Background Congenital heart defects (CHD) is the most common cause of death from a congenital structure abnormality in newborns and is often associated with fetal loss. There are many types of CHD. Human genetic studies have identified genes that are responsible for the inheritance of a particular type of CHD and for some types of CHD previously thought to be sporadic. However, occasionally different members of the same family might have anatomically distinct defects — for instance, one member with atrial septal defect, one with tetralogy of Fallot, and one with ventricular septal defect. Our objective is to identify susceptibility loci for CHD in families affected by distinct defects. The occurrence of these apparently discordant clinical phenotypes within one family might hint at a genetic framework common to most types of CHD. Results We performed a genome-wide linkage analysis using MOD score analysis in families with diverse CHD. Significant linkage was obtained in two regions, at chromosome 15 (15q26.3, Pempirical = 0.0004) and at chromosome 18 (18q21.2, Pempirical = 0.0005). Conclusions In these two novel regions four candidate genes are located: SELS, SNRPA1, and PCSK6 on 15q26.3, and TCF4 on 18q21.2. The new loci reported here have not previously been described in connection with CHD. Although further studies in other cohorts are needed to confirm these findings, the results presented here together with recent insight into how the heart normally develops will improve the understanding of CHD. PMID:23705960

Cardiac phenotyping in ex vivo murine embryos using microMRI.

PubMed

Cleary, Jon O; Price, Anthony N; Thomas, David L; Scambler, Peter J; Kyriakopoulou, Vanessa; McCue, Karen; Schneider, Jürgen E; Ordidge, Roger J; Lythgoe, Mark F

2009-10-01

Microscopic MRI (microMRI) is an emerging technique for high-throughput phenotyping of transgenic mouse embryos, and is capable of visualising abnormalities in cardiac development. To identify cardiac defects in embryos, we have optimised embryo preparation and MR acquisition parameters to maximise image quality and assess the phenotypic changes in chromodomain helicase DNA-binding protein 7 (Chd7) transgenic mice. microMRI methods rely on tissue penetration with a gadolinium chelate contrast agent to reduce tissue T(1), thus improving signal-to-noise ratio (SNR) in rapid gradient echo sequences. We investigated 15.5 days post coitum (dpc) wild-type CD-1 embryos fixed in gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) solutions for either 3 days (2 and 4 mM) or 2 weeks (2, 4, 8 and 16 mM). To assess penetration of the contrast agent into heart tissue and enable image contrast simulations, T(1) and T(*) (2) were measured in heart and background agarose. Compared to 3-day, 2-week fixation showed reduced mean T(1) in the heart at both 2 and 4 mM concentrations (p < 0.0001), resulting in calculated signal gains of 23% (2 mM) and 29% (4 mM). Using T(1) and T(*) (2) values from 2-week concentrations, computer simulation of heart and background signal, and ex vivo 3D gradient echo imaging, we demonstrated that 2-week fixed embryos in 8 mM Gd-DTPA in combination with optimised parameters (TE/TR/alpha/number of averages: 9 ms/20 ms/60 degrees /7) produced the largest SNR in the heart (23.2 +/- 1.0) and heart chamber contrast-to-noise ratio (CNR) (27.1 +/- 1.6). These optimised parameters were then applied to an MRI screen of embryos heterozygous for the gene Chd7, implicated in coloboma of the eye, heart defects, atresia of the choanae, retardation of growth, genital/urinary abnormalities, ear abnormalities and deafness (CHARGE) syndrome (a condition partly characterised by cardiovascular birth defects in humans). A ventricular septal defect was readily identified in the screen, consistent with the human phenotype. (c) 2009 John Wiley & Sons, Ltd.

77 FR 49001 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

...: Stem Cells, Heart Regeneration, Congenital Heart Defect and Cardiac Valve Disease. Date: September 10... Program Nos. 93.306, Comparative Medicine; 93.333, Clinical Research, 93.306, 93.333, 93.337, 93.393-93...

Ventricular Septal Defect (VSD)

MedlinePlus

... hears a murmur while listening to your baby's heart with a stethoscope. Sometimes VSDs can be detected by ultrasound before ... murmur your doctor hears when listening to your heart with a stethoscope. When to see a doctor Call your doctor ...

Inflammation and Heart Disease

MedlinePlus

... Cholesterol This content was last reviewed July 2015. Cardiovascular Conditions • Conditions Home • Arrhythmia and Atrial Fibrillation • Cardiac Arrest • Cardiac Rehab • Cardiomyopathy • Cardiovascular Conditions of Childhood • Cholesterol • Congenital Heart Defects • Diabetes • ...

Travel and Heart Disease

MedlinePlus

... to the Terms and Conditions and Privacy Policy Cardiovascular Conditions • Conditions Home • Arrhythmia and Atrial Fibrillation • Cardiac Arrest • Cardiac Rehab • Cardiomyopathy • Cardiovascular Conditions of Childhood • Cholesterol • Congenital Heart Defects • Diabetes • ...

[Combined G-banded karyotyping and multiplex ligation-dependent probe amplification for the detection of chromosomal abnormalities in fetuses with congenital heart defects].

PubMed

Liu, Yang; Xie, Jiansheng; Geng, Qian; Xu, Zhiyong; Wu, Weiqin; Luo, Fuwei; Li, Suli; Wang, Qin; Chen, Wubin; Tan, Hongxi; Zhang, Hu

2017-02-10

To assess the value of G-banded karyotyping in combination with multiplex ligation-dependent probe amplification (MLPA) as a tool for the detection of chromosomal abnormalities in fetuses with congenital heart defects. The combined method was used to analyze 104 fetuses with heart malformations identified by ultrasonography. Abnormal findings were confirmed with chromosomal microarray analysis (CMA). Nineteen (18%) fetuses were found to harbor chromosomal aberrations by G-banded karyotyping and MLPA. For 93 cases, CMA has detected abnormalities in 14 cases including 10 pathogenic copy number variations (CNVs) and 4 CNVs of uncertain significance (VOUS). MLPA was able to detect all of the pathogenic CNVs and 1 VOUS CNV. Combined use of G-banded karyotyping and MLPA is a rapid, low-cost and effective method to detect chromosomal abnormalities in fetuses with various heart malformations.

Effect of Tbx1 knock-down on cardiac performance in zebrafish.

PubMed

Zhang, Li-feng; Gui, Yong-hao; Wang, Yue-xiang; Jiang, Qiu; Song, Hou-yan

2010-05-05

Tbx1 is the major candidate gene for DiGeorge syndrome (DGS). Similar to defects observed in DGS patients, the structures disrupted in Tbx1(-/-) animal models are derived from the neural crest cells during development. Although the morphological phenotypes of some Tbx1 knock-down animal models have been well described, analysis of the cardiac performance is limited. Therefore, myocardial performance was explored in Tbx1 morpholino injected zebrafish embryos. To elucidate these issues, Tbx1 specific morpholino was used to reduce the function of Tbx1 in zebrafish. The differentiation of the myocardial cells was observed using whole mount in situ hybridization. Heart rates were observed and recorded under the microscope from 24 to 72 hours post fertilization (hpf). The cardiac performance was analyzed by measuring ventricular shortening fraction and atrial shortening fraction. Tbx1 morpholino injected embryos were characterized by defects in the pharyngeal arches, otic vesicle, aortic arches and thymus. In addition, Tbx1 knock down reduced the amount of pharyngeal neural crest cells in zebrafish. Abnormal cardiac morphology was visible in nearly 20% of the Tbx1 morpholino injected embryos. The hearts in these embryos did not loop or loop incompletely. Importantly, cardiac performance and heart rate were reduced in Tbx1 morpholino injected embryos. Tbx1 might play an essential role in the development of pharyngeal neural crest cells in zebrafish. Cardiac performance is impaired by Tbx1 knock down in zebrafish.

Mesenchymal stem cell-derived inflammatory fibroblasts mediate interstitial fibrosis in the aging heart.

PubMed

Trial, JoAnn; Entman, Mark L; Cieslik, Katarzyna A

2016-02-01

Pathologic fibrosis in the aging mouse heart is associated with dysregulated resident mesenchymal stem cells (MSC) arising from reduced stemness and aberrant differentiation into dysfunctional inflammatory fibroblasts. Fibroblasts derived from aging MSC secrete higher levels of 1) collagen type 1 (Col1) that directly contributes to fibrosis, 2) monocyte chemoattractant protein-1 (MCP-1) that attracts leukocytes from the blood and 3) interleukin-6 (IL-6) that facilitates transition of monocytes into myeloid fibroblasts. The transcriptional activation of these proteins is controlled via the farnesyltransferase (FTase)-Ras-Erk pathway. The intrinsic change in the MSC phenotype acquired by advanced age is specific for the heart since MSC originating from bone wall (BW-MSC) or fibroblasts derived from them were free of these defects. The potential therapeutic interventions other than clinically approved strategies based on findings presented in this review are discussed as well. This article is a part of a Special Issue entitled "Fibrosis and Myocardial Remodeling". Copyright © 2015 Elsevier Ltd. All rights reserved.

Advances in the Study of Heart Development and Disease Using Zebrafish

PubMed Central

Brown, Daniel R.; Samsa, Leigh Ann; Qian, Li; Liu, Jiandong

2016-01-01

Animal models of cardiovascular disease are key players in the translational medicine pipeline used to define the conserved genetic and molecular basis of disease. Congenital heart diseases (CHDs) are the most common type of human birth defect and feature structural abnormalities that arise during cardiac development and maturation. The zebrafish, Danio rerio, is a valuable vertebrate model organism, offering advantages over traditional mammalian models. These advantages include the rapid, stereotyped and external development of transparent embryos produced in large numbers from inexpensively housed adults, vast capacity for genetic manipulation, and amenability to high-throughput screening. With the help of modern genetics and a sequenced genome, zebrafish have led to insights in cardiovascular diseases ranging from CHDs to arrhythmia and cardiomyopathy. Here, we discuss the utility of zebrafish as a model system and summarize zebrafish cardiac morphogenesis with emphasis on parallels to human heart diseases. Additionally, we discuss the specific tools and experimental platforms utilized in the zebrafish model including forward screens, functional characterization of candidate genes, and high throughput applications. PMID:27335817

Maternal Residential Exposure to Agricultural Pesticides and ...

EPA Pesticide Factsheets

Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. We conducted a case-control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003-2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20-44 weeks (n=304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for four categories of exposure (90th percentiles) compared to unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status. We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR (95% CI) (highest exposure vs. unexposed) for tracheal esophageal fistula/esophageal atresia = 1.98 (0.69, 5.66), and OR for atr

Outcome of adults with Eisenmenger syndrome treated with drugs specific to pulmonary arterial hypertension: A French multicentre study.

PubMed

Hascoet, Sebastien; Fournier, Emmanuelle; Jaïs, Xavier; Le Gloan, Lauriane; Dauphin, Claire; Houeijeh, Ali; Godart, Francois; Iriart, Xavier; Richard, Adelaïde; Radojevic, Jelena; Amedro, Pascal; Bosser, Gilles; Souletie, Nathalie; Bernard, Yvette; Moceri, Pamela; Bouvaist, Hélène; Mauran, Pierre; Barre, Elise; Basquin, Adeline; Karsenty, Clement; Bonnet, Damien; Iserin, Laurence; Sitbon, Olivier; Petit, Jérôme; Fadel, Elie; Humbert, Marc; Ladouceur, Magalie

2017-05-01

The relationship between pulmonary arterial hypertension-specific drug therapy (PAH-SDT) and mortality in Eisenmenger syndrome (ES) is controversial. To investigate outcomes in patients with ES, and their relationship with PAH-SDT. Retrospective, observational, nationwide, multicentre cohort study. We included 340 patients with ES: genetic syndrome (n=119; 35.3%); pretricuspid defect (n=75; 22.1%). Overall, 276 (81.2%) patients received PAH-SDT: monotherapy (endothelin receptor antagonist [ERA] or phosphodiesterase 5 inhibitor [PDE5I]) 46.7%; dual therapy (ERA+PDE5I) 40.9%; triple therapy (ERA+PDE5I+prostanoid) 9.1%. Median PAH-SDT duration was 5.5 years [3.0-9.1 years]. Events (death, lung or heart-lung transplantation) occurred in 95 (27.9%) patients at a median age of 40.5 years [29.4-47.6]. The cumulative occurrence of events was 16.7% [95% confidence interval 12.8-21.6%] and 46.4% [95% confidence interval 38.2-55.4%] at age 40 and 60 years, respectively. With age at evaluation or time since PAH diagnosis as time scales, cumulative occurrence of events was lower in patients taking one or two PAH-SDTs (P=0.0001 and P=0.004, respectively), with the largest differences in the post-tricuspid defect subgroup (P<0.001 and P<0.02, respectively) versus patients without PAH-SDT. By multivariable Cox analysis, with time since PAH diagnosis as time scale, New York Heart Association/World Health Organization functional class III/IV, lower peripheral arterial oxygen saturation and pretricuspid defect were associated with a higher risk of events (P=0.002, P=0.01 and P=0.04, respectively), and one or two PAH-SDTs with a lower risk of events (P=0.009). Outcomes are poor in ES, but seem better with PAH-SDT. ES with pretricuspid defects has worse outcomes despite the delayed disease onset. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Alarm!!! A UFO inside the heart.

PubMed

Santoro, Giuseppe; Castaldi, Biagio; Iacono, Carola; Giugno, Luca; Gaio, Gianpiero; Russo, Maria G

2012-10-01

An 8-year-old asymptomatic child was referred for surgical repair of coronary sinus atrial septal defect resulting in significant left-to-right shunt and right chamber volume overload. The septal fenestration was located near to its drainage site into the right atrium. Due to this seemingly favourable anatomy, transcatheter closure of the septal defect was performed using an Amplatzer Septal Occluder device. The echocardiographic postprocedural evaluation imaged the occluding device almost perpendicular to the atrial septum, seemingly floating above the mitral valve orifice, like an alien spaceship inside the heart.

Transcatheter intervention for the treatment of congenital cardiac defects.

PubMed Central

Grifka, R G

1997-01-01

Cardiac catheterization has an illustrious history, originating in 1929 when Werner Forsmann, a surgical resident, performed a heart catheterization on himself. Transcatheter interventional procedures have been performed since the 1960s. The 1st intracardiac procedure to become standard therapy was a balloon atrial septostomy. Skeptics attacked this innovative procedure. However, the balloon septostomy procedure soon became the standard emergency procedure for certain congenital heart defects, and was the impetus for other investigators in the field of transcatheter intervention. We will discuss transcatheter treatment for congenital vascular stenoses and vascular occlusion. Images PMID:9456482

Mutations in the Caenorhabditis elegans orthologs of human genes required for mitochondrial tRNA modification cause similar electron transport chain defects but different nuclear responses.

PubMed

Navarro-González, Carmen; Moukadiri, Ismaïl; Villarroya, Magda; López-Pascual, Ernesto; Tuck, Simon; Armengod, M-Eugenia

2017-07-01

Several oxidative phosphorylation (OXPHOS) diseases are caused by defects in the post-transcriptional modification of mitochondrial tRNAs (mt-tRNAs). Mutations in MTO1 or GTPBP3 impair the modification of the wobble uridine at position 5 of the pyrimidine ring and cause heart failure. Mutations in TRMU affect modification at position 2 and cause liver disease. Presently, the molecular basis of the diseases and why mutations in the different genes lead to such different clinical symptoms is poorly understood. Here we use Caenorhabditis elegans as a model organism to investigate how defects in the TRMU, GTPBP3 and MTO1 orthologues (designated as mttu-1, mtcu-1, and mtcu-2, respectively) exert their effects. We found that whereas the inactivation of each C. elegans gene is associated with a mild OXPHOS dysfunction, mutations in mtcu-1 or mtcu-2 cause changes in the expression of metabolic and mitochondrial stress response genes that are quite different from those caused by mttu-1 mutations. Our data suggest that retrograde signaling promotes defect-specific metabolic reprogramming, which is able to rescue the OXPHOS dysfunction in the single mutants by stimulating the oxidative tricarboxylic acid cycle flux through complex II. This adaptive response, however, appears to be associated with a biological cost since the single mutant worms exhibit thermosensitivity and decreased fertility and, in the case of mttu-1, longer reproductive cycle. Notably, mttu-1 worms also exhibit increased lifespan. We further show that mtcu-1; mttu-1 and mtcu-2; mttu-1 double mutants display severe growth defects and sterility. The animal models presented here support the idea that the pathological states in humans may initially develop not as a direct consequence of a bioenergetic defect, but from the cell's maladaptive response to the hypomodification status of mt-tRNAs. Our work highlights the important association of the defect-specific metabolic rewiring with the pathological phenotype, which must be taken into consideration in exploring specific therapeutic interventions.

Gata4-Dependent Differentiation of c-Kit+ Derived Endothelial Cells Underlies Artefactual Cardiomyocyte Regeneration in the Heart.

PubMed

Maliken, Bryan D; Kanisicak, Onur; Karch, Jason; Khalil, Hadi; Fu, Xing; Boyer, Justin G; Prasad, Vikram; Zheng, Yi; Molkentin, Jeffery D

2018-04-17

Background -While c-Kit + adult progenitor cells were initially reported to produce new cardiomyocytes in the heart, recent genetic evidence suggests that such events are exceedingly rare. However, to determine if these rare events represent true de novo cardiomyocyte formation we deleted the necessary cardiogenic transcription factors Gata4 and Gata6 from c-Kit-expressing cardiac progenitor cells (CPCs). Methods - Kit allele-dependent lineage tracing and fusion analysis was performed in mice following simultaneous Gata4 and Gata6 cell-type specific deletion to examine rates of putative de novo cardiomyocyte formation from c-Kit + cells. Bone marrow transplantation experiments were used to define the contribution of Kit allele-derived hematopoietic cells versus Kit lineage-dependent cells endogenous to the heart in contributing to apparent de novo lineage-traced cardiomyocytes. A Tie2 CreERT2 transgene was also used to examine the global impact of Gata4 deletion on the mature cardiac endothelial cell network, which was further evaluated with select angiogenesis assays. Results -Deletion of Gata4 in Kit lineage-derived endothelial cells or in total endothelial cells using the Tie2 CreERT2 transgene, but not from bone morrow cells, resulted in profound endothelial cell expansion, defective endothelial cell differentiation, leukocyte infiltration into the heart and a dramatic increase in Kit allele-dependent lineage-traced cardiomyocytes. However, this increase in labeled cardiomyocytes was an artefact of greater leukocyte-cardiomyocyte cellular fusion due to defective endothelial cell differentiation in the absence of Gata4 Conclusions -Past identification of presumed de novo cardiomyocyte formation in the heart from c-Kit + cells using Kit allele lineage tracing appears to be an artefact of labeled leukocyte fusion with cardiomyocytes. Deletion of Gata4 from c-Kit + endothelial progenitor cells or adult endothelial cells negatively impacted angiogenesis and capillary network integrity.

African-Americans and Heart Disease, Stroke

MedlinePlus

... website This content was last reviewed July 2015. Cardiovascular Conditions • Conditions Home • Arrhythmia and Atrial Fibrillation • Cardiac Arrest • Cardiac Rehab • Cardiomyopathy • Cardiovascular Conditions of Childhood • Cholesterol • Congenital Heart Defects • Diabetes • ...

Protect Your Heart in the Heat

MedlinePlus

... Activity for Stroke Survivors Heatstroke vs Stroke infographic Cardiovascular Conditions • Conditions Home • Arrhythmia and Atrial Fibrillation • Cardiac Arrest • Cardiac Rehab • Cardiomyopathy • Cardiovascular Conditions of Childhood • Cholesterol • Congenital Heart Defects • Diabetes • ...

Sleep Apnea and Heart Disease, Stroke

MedlinePlus

... tea. This content was last reviewed July 2015. Cardiovascular Conditions • Conditions Home • Arrhythmia and Atrial Fibrillation • Cardiac Arrest • Cardiac Rehab • Cardiomyopathy • Cardiovascular Conditions of Childhood • Cholesterol • Congenital Heart Defects • Diabetes • ...

Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort.

PubMed

Rappazzo, Kristen M; Warren, Joshua L; Meyer, Robert E; Herring, Amy H; Sanders, Alison P; Brownstein, Naomi C; Luben, Thomas J

2016-04-01

Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. We conducted a case-control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003 to 2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20 to 44 weeks (n = 304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for four categories of exposure (<10(th) , 10-50(th) , 50-90(th) , and >90(th) percentiles) compared with unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status. We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR [95% confidence interval] [highest exposure vs. unexposed] for tracheal esophageal fistula/esophageal atresia = 1.98 [0.69, 5.66], and OR for atrial septal defects: 1.70 [1.34, 2.14]). Our results provide some evidence of associations between residential exposure to agricultural pesticides and several birth defects phenotypes. Birth Defects Research (Part A) 106:240-249, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Birth defects among children born to HIV-infected women: Pediatric AIDS Clinical Trials Protocols 219 and 219C

PubMed Central

Brogly, Susan B.; Abzug, Mark J.; Watts, D. Heather; Cunningham, Coleen K.; Williams, Paige L.; Oleske, James; Conway, Daniel; Sperling, Rhoda S.; Spiegel, Hans; Van Dyke, Russell B.

2010-01-01

Background Some studies have detected associations between in utero antiretroviral therapy (ARV) exposure and birth defects but evidence is inconclusive. Methods 2,202 HIV-exposed children enrolled in the Pediatric AIDS Clinical Trials Group 219 and 219C protocols before one year of age were included. Birth defects were classified using the Metropolitan Atlanta Congenital Defects Program (MACDP) coding. Logistic regression models were used to evaluate associations between first trimester in utero ARV exposure and birth defects. Results 117 live-born children had birth defects for a prevalence of 5.3% (95% CI: 4.4, 6.3). Prevalence did not differ by HIV infection status or overall ARV exposure; rates were 4.8% (95% CI: 3.7, 6.1) and 5.8% (95% CI: 4.2, 7.8) in children without and with first trimester ARV exposure, respectively. The defect rate was higher among children with first trimester efavirenz exposure (5/32, 15.6%) versus children without first trimester efavirenz exposure [adjusted odds ratio (aOR)=4.31 (95% CI: 1.56, 11.86)]. Protective effects of first trimester zidovudine exposure on musculoskeletal defects were detected [aOR=0.24 (95% CI: 0.08, 0.69)], while a higher risk of heart defects was found [aOR=2.04 (95% CI: 1.03, 4.05)]. Conclusion The prevalence of birth defects was higher in this cohort of HIV-exposed children than in other pediatric cohorts. There was no association with overall ARV exposure, but there were some associations with specific agents including efavirenz. Additional studies are needed to rule out confounding and to evaluate newer ARV agents. PMID:20539252

Facts about dextro-Transposition of the Great Arteries (d-TGA)

MedlinePlus

... Septal Defect Atrioventricular Septal Defect Coarctation of the Aorta D-Transposition of the Great Arteries Hypoplastic Left ... the heart – the main pulmonary artery and the aorta – are switched in position, or “transposed.” What is ...

Using optical coherence tomography to rapidly phenotype and quantify congenital heart defects associated with prenatal alcohol exposure

PubMed Central

Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Noonan, Amanda I.; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

2014-01-01

Background The most commonly used method to analyze congenital heart defects involves serial sectioning and histology. However, this is often a time-consuming process where the quantification of cardiac defects can be difficult due to problems with accurate section registration. Here we demonstrate the advantages of using optical coherence tomography, a comparatively new and rising technology, to phenotype avian embryo hearts in a model of Fetal Alcohol Syndrome where a binge-like quantity of alcohol/ethanol was introduced at gastrulation. Results The rapid, consistent imaging protocols allowed for the immediate identification of cardiac anomalies, including ventricular septal defects and misaligned/missing vessels. Interventricular septum thicknesses and vessel diameters for three of the five outflow arteries were also significantly reduced. Outflow and atrio-ventricular valves were segmented using image processing software and had significantly reduced volumes compared to controls. This is the first study to our knowledge that has 3-D reconstructed the late-stage cardiac valves in precise detail in order to examine their morphology and dimensions. Conclusion We believe therefore that OCT, with its ability to rapidly image and quantify tiny embryonic structures in high resolution, will serve as an excellent and cost-effective preliminary screening tool for developmental biologists working with a variety of experimental/disease models. PMID:25546089

Platelet abnormalities in adults with severe pulmonary arterial hypertension related to congenital heart defects (Eisenmenger syndrome).

PubMed

Remková, Anna; Šimková, Iveta; Valkovičová, Tatiana; Kaldarárová, Monika

2016-12-01

Patients with severe pulmonary arterial hypertension suffer from life-threatening thrombotic and bleeding complications. The aim of this study was to compare selected platelet, endothelial, and coagulation parameters in healthy volunteers and patients with severe pulmonary arterial hypertension because of congenital heart defects. The study included healthy volunteers (n = 50) and patients with cyanotic congenital heart defects classified as Eisenmenger syndrome (n = 41). We investigated platelet count, mean platelet volume, and platelet aggregation - spontaneous and induced by various concentrations of five agonists. Von Willebrand factor (vWF), fibrinogen, factor VIII and XII, plasminogen activator inhibitor, antithrombin, D-dimer, and antiphospholipid antibodies were also investigated. We found a decreased platelet count [190 (147-225) vs. 248 (205-295) 10 l, P < 0.0001], higher mean platelet volume [10.9 (10.1-12.0) vs. 10.2 (9.4-10.4) fl, P < 0.0001], and significantly decreased platelet aggregation (induced by five agonists, in various concentrations) in patients with Eisenmenger syndrome compared with controls. These changes were accompanied by an increase of plasma vWF antigen [141.6 (108.9-179.1) vs. 117.4 (9.2-140.7) IU/dl, P = 0.022] and serum anti-β2-glycoprotein [2.07 (0.71-3.41) vs. 0.47 (0.18-0.99) U/ml, P < 0.0001]. Eisenmenger syndrome is accompanied by platelet abnormalities. Thrombocytopenia with increased platelet size is probably due to a higher platelet turnover associated with platelet activation. Impaired platelet aggregation can reflect specific platelet behaviour in patients with Eisenmenger syndrome. These changes can be related both to bleeding and to thrombotic events. A higher vWF antigen may be a consequence of endothelial damage in Eisenmenger syndrome, but the cause for an increase of anti-β2-glycoprotein is unknown.

STAR (Simple Targeted Arterial Rendering) Technique: a Novel and Simple Method to Visualize the Fetal Cardiac Outflow Tracts

PubMed Central

Yeo, Lami; Romero, Roberto; Jodicke, Cristiano; Kim, Sun Kwon; Gonzalez, Juan M.; Oggè, Giovanna; Lee, Wesley; Kusanovic, Juan Pedro; Vaisbuch, Edi; Hassan, Sonia S.

2010-01-01

Objective To describe a novel and simple technique (STAR: Simple Targeted Arterial Rendering) to visualize the fetal cardiac outflow tracts from dataset volumes obtained with spatiotemporal image correlation (STIC) and applying a new display technology (OmniView). Methods We developed a technique to image the outflow tracts by drawing three dissecting lines through the four-chamber view of the heart contained in a STIC volume dataset. Each line generated the following plane: 1) Line 1: ventricular septum “en face” with both great vessels (pulmonary artery anterior to the aorta); 2) Line 2: pulmonary artery with continuation into the longitudinal view of the ductal arch; and 3) Line 3: long axis view of the aorta arising from the left ventricle. The pattern formed by all 3 lines intersecting approximately through the crux of the heart resembles a “star”. The technique was then tested in 50 normal hearts (15.3 – 40.4 weeks of gestation). To determine if the technique could identify planes that departed from the normal images, we tested the technique in 4 cases with proven congenital heart defects (ventricular septal defect, transposition of great vessels, tetralogy of Fallot, and pulmonary atresia with intact ventricular septum). Results The STAR technique was able to generate the intended planes in all 50 normal cases. In the abnormal cases, the STAR technique allowed identification of the ventricular septal defect, demonstrated great vessel anomalies, and displayed views that deviated from what was expected from the examination of normal hearts. Conclusions This novel and simple technique can be used to visualize the outflow tracts and ventricular septum “en face” in normal fetal hearts. The inability to obtain expected views or the appearance of abnormal views in the generated planes should raise the index of suspicion for congenital heart disease involving the great vessels and/or the ventricular septum. The STAR technique may simplify examination of the fetal heart and could reduce operator dependency. PMID:20878672

Sequential Ligand-Dependent Notch Signaling Activation Regulates Valve Primordium Formation and Morphogenesis.

PubMed

MacGrogan, Donal; D'Amato, Gaetano; Travisano, Stanislao; Martinez-Poveda, Beatriz; Luxán, Guillermo; Del Monte-Nieto, Gonzalo; Papoutsi, Tania; Sbroggio, Mauro; Bou, Vanesa; Gomez-Del Arco, Pablo; Gómez, Manuel Jose; Zhou, Bin; Redondo, Juan Miguel; Jiménez-Borreguero, Luis J; de la Pompa, José Luis

2016-05-13

The Notch signaling pathway is crucial for primitive cardiac valve formation by epithelial-mesenchymal transition, and NOTCH1 mutations cause bicuspid aortic valve; however, the temporal requirement for the various Notch ligands and receptors during valve ontogeny is poorly understood. The aim of this study is to determine the functional specificity of Notch in valve development. Using cardiac-specific conditional targeted mutant mice, we find that endothelial/endocardial deletion of Mib1-Dll4-Notch1 signaling, possibly favored by Manic-Fringe, is specifically required for cardiac epithelial-mesenchymal transition. Mice lacking endocardial Jag1, Notch1, or RBPJ displayed enlarged valve cusps, bicuspid aortic valve, and septal defects, indicating that endocardial Jag1 to Notch1 signaling is required for post-epithelial-mesenchymal transition valvulogenesis. Valve dysmorphology was associated with increased mesenchyme proliferation, indicating that Jag1-Notch1 signaling restricts mesenchyme cell proliferation non-cell autonomously. Gene profiling revealed upregulated Bmp signaling in Jag1-mutant valves, providing a molecular basis for the hyperproliferative phenotype. Significantly, the negative regulator of mesenchyme proliferation, Hbegf, was markedly reduced in Jag1-mutant valves. Hbegf expression in embryonic endocardial cells could be readily activated through a RBPJ-binding site, identifying Hbegf as an endocardial Notch target. Accordingly, addition of soluble heparin-binding EGF-like growth factor to Jag1-mutant outflow tract explant cultures rescued the hyperproliferative phenotype. During cardiac valve formation, Dll4-Notch1 signaling leads to epithelial-mesenchymal transition and cushion formation. Jag1-Notch1 signaling subsequently restrains Bmp-mediated valve mesenchyme proliferation by sustaining Hbegf-EGF receptor signaling. Our studies identify a mechanism of signaling cross talk during valve morphogenesis involved in the origin of congenital heart defects associated with reduced NOTCH function. © 2016 American Heart Association, Inc.

Obstructive heart defects associated with candidate genes, maternal obesity, and folic acid supplementation.

PubMed

Tang, Xinyu; Cleves, Mario A; Nick, Todd G; Li, Ming; MacLeod, Stewart L; Erickson, Stephen W; Li, Jingyun; Shaw, Gary M; Mosley, Bridget S; Hobbs, Charlotte A

2015-06-01

Right-sided and left-sided obstructive heart defects (OHDs) are subtypes of congenital heart defects, in which the heart valves, arteries, or veins are abnormally narrow or blocked. Previous studies have suggested that the development of OHDs involved a complex interplay between genetic variants and maternal factors. Using the data from 569 OHD case families and 1,644 control families enrolled in the National Birth Defects Prevention Study (NBDPS) between 1997 and 2008, we conducted an analysis to investigate the genetic effects of 877 single nucleotide polymorphisms (SNPs) in 60 candidate genes for association with the risk of OHDs, and their interactions with maternal use of folic acid supplements, and pre-pregnancy obesity. Applying log-linear models based on the hybrid design, we identified a SNP in methylenetetrahydrofolate reductase (MTHFR) gene (C677T polymorphism) with a main genetic effect on the occurrence of OHDs. In addition, multiple SNPs in betaine-homocysteine methyltransferase (BHMT and BHMT2) were also identified to be associated with the occurrence of OHDs through significant main infant genetic effects and interaction effects with maternal use of folic acid supplements. We also identified multiple SNPs in glutamate-cysteine ligase, catalytic subunit (GCLC) and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) that were associated with elevated risk of OHDs among obese women. Our findings suggested that the risk of OHDs was closely related to a combined effect of variations in genes in the folate, homocysteine, or glutathione/transsulfuration pathways, maternal use of folic acid supplements and pre-pregnancy obesity. © 2015 Wiley Periodicals, Inc.

Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development.

PubMed

Zhao, Chengtian; Andreeva, Viktoria; Gibert, Yann; LaBonty, Melissa; Lattanzi, Victoria; Prabhudesai, Shubhangi; Zhou, Yi; Zon, Leonard; McCann, Kathleen L; Baserga, Susan; Yelick, Pamela C

2014-01-01

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome.

Association between left ventricular perfusion defects and myocardial deformation indexes in heart transplantation recipients.

PubMed

D'Andrea, Antonello; De Rimini, Maria Luisa; America, Raffaella; Cirillo, Chiara; Riegler, Lucia; Limongelli, Giuseppe; D'Alto, Michele; Salerno, Gemma; Maiello, Ciro; Muto, Pietro; Russo, Maria Giovanna; Calabrò, Raffaele; Bossone, Eduardo; Pacileo, Giuseppe

2017-10-01

The aim of the study was to analyze possible correlations between strain echocardiography (STE) and PET myocardial perfusion in a population of heart transplantation (HTx) recipients showing preserved left ventricular (LV) ejection fraction. By STE, LV global longitudinal strain (LV GLS) was lower in HTx. PET showed no transient or chronic ischemia in 83 of 115 HTx (73%). Fixed perfusion defects were observed in 17% of HTx and reversible ischemia in 10%. Significant coronary stenosis was observed only in 10 cases. GLS was independently associated with age at HTx and fixed perfusion defects (HR 0.41; P<.001). Such relationships underline STE ability to early identify HTx pts with subclinical myocardial dysfunction during long-term follow-up. © 2017, Wiley Periodicals, Inc.

[Neurological and psychomotor development of foetuses and children with congenital heart disease--causes and prevalence of disorders and long-term prognosis].

PubMed

Herberg, U; Hövels-Gürich, H

2012-06-01

Children with severe congenital heart defects (CHD) requiring open heart surgery in the first year of life are at high risk for developing neurological and psychomotor abnormalities. Depending on the type and severity of the CHD, between 15 and over 50% of these children have deficits, which are usually confined to distinct domains of development, although formal intelligence tends to be normal. Children with mild CHD, who comprise the majority of congenital heart defects, have a far better developmental prognosis than those with complex CHD. This review concentrates on the impact of severe CHD on the developing brain of the foetus and infant. It also provides a summary of recent clinical and neuroimaging studies, and an overview of the long-term neurological prognosis. Advanced neuroimaging modalities indicate that, related to altered cerebral blood flow and oxygenation, foetuses with severe CHD show delayed third trimester brain maturation and increased vulnerability for hypoxic injury. Morphological and neurological abnormalities are present before surgery, commonly affecting the white matter. In the long-term, impaired neurological and developmental outcomes are related to the combination of prenatal, perinatal and additional perioperative risk factors. Therefore, new therapeutic approaches aim to optimise the intra- and perinatal management of foetuses and newborns with congenital heart defects. Identification and avoidance of risk factors, early neurodevelopmental assessment and therapy may optimise the long-term outcome in this high-risk population. © Georg Thieme Verlag KG Stuttgart · New York.

Partial rescue of defects in Cited2-deficient embryos by HIF-1alpha heterozygosity.

PubMed

Xu, Bing; Doughman, Yongqiu; Turakhia, Mona; Jiang, Weihong; Landsettle, Chad E; Agani, Faton H; Semenza, Gregg L; Watanabe, Michiko; Yang, Yu-Chung

2007-01-01

Hypoxia inducible factor-1 (HIF-1) initiates key cellular and tissue responses to physiological and pathological hypoxia. Evidence from in vitro and structural analyses supports a critical role for Cited2 in down-regulating HIF-1-mediated transcription by competing for binding with oxygen-sensitive HIF-1alpha to transcriptional co-activators CBP/p300. We previously detected elevated expression of HIF-1 target genes in Cited2(-/-) embryonic hearts, indicating that Cited2 inhibits HIF-1 transactivation in vivo. In this study, we show for the first time that highly hypoxic cardiac regions in mouse embryos corresponded to the sites of defects in Cited2(-/-) embryos and that defects of the outflow tract, interventricular septum, cardiac vasculature, and hyposplenia were largely rescued by HIF-1alpha haploinsufficiency. The hypoxia of the outflow tract and interventricular septum peaked at E13.5 and dissipated by E15.5 in wild-type hearts, but persisted in E15.5 Cited2(-/-) hearts. The persistent hypoxia and abnormal vasculature in the myocardium of interventricular septum in E15.5 Cited2(-/-) hearts were rescued with decreased HIF-1alpha gene dosage. Accordingly, mRNA levels of HIF-1-responsive genes were reduced in Cited2(-/-) embryonic hearts by HIF-1alpha heterozygosity. These findings suggest that a precise level of HIF-1 transcriptional activity critical for normal development is triggered by differential hypoxia and regulated through feedback inhibition by Cited2.

The CHARGE Association: Implications for Teachers.

ERIC Educational Resources Information Center

Jones, Thomas W.; Dunne, Michele T.

1988-01-01

CHARGE association is described as a diagnostic label for a group of congenital malformations, including coloboma, heart defects, atresia choanae, retarded postnatal growth/central nervous system defects, genital hypoplasia, and ear deformities. Etiology and characteristics of the CHARGE association are discussed, along with implications for…

Change in prevalence of congenital defects in children with Prader-Willi syndrome.

PubMed

Torrado, M; Foncuberta, M E; Perez, M F de Castro; Gravina, L P; Araoz, H V; Baialardo, E; Chertkoff, L P

2013-02-01

The aim of this study was to assess the prevalence of congenital defects observed in patients with Prader-Willi syndrome (PWS) and to compare this prevalence with that described in the general population. In addition, these findings were correlated with the different etiologic subtypes. A total of 180 children with PWS followed for 13 years were included in this study. Diagnosis was confirmed by the methylation test, and genetic subtypes were established by using fluorescence in situ hybridization or multiplex ligation-dependent probe amplification and microsatellite analyses. The prevalence of congenital defects was compared with national and international registries of congenital defects in the general population (Estudio Colaborativo Latinoamericano de Malformaciones Congénitas, European Surveillance of Congenital Anomalies, and the New York Registry). Twenty-two percent of the patients presented congenital defects with a risk of 5.4 to 18.7 times higher than that of the general population. The most frequent congenital defects were heart defects, renoureteral malformations, vertebral anomalies, hip dysplasia, clubfoot, and agenesis/hypoplasia of the corpus callosum. Each of these congenital defects was significantly more frequent in the children with PWS than in the general population. The congenital heart defects were more frequent in girls than in boys with PWS. No significant differences were found when the defects were correlated with the different etiologic subtypes. An increased prevalence of congenital defects was found in our PWS patients. This finding suggests the need for further studies in PWS children that allow physicians to detect the congenital defects found in this series and, thus, to anticipate complications, with the ultimate aim of enhancing the management of PWS patients.

The Complex Genetic Basis of Congenital Heart Defects

PubMed Central

Akhirome, Ehiole; Walton, Nephi A.; Nogee, Julie M.; Jay, Patrick Y.

2017-01-01

Twenty years ago, chromosomal abnormalities were the only identifiable genetic causes of a small fraction of congenital heart defects (CHD). Today, a de novo or inherited genetic abnormality can be identified as pathogenic in one-third of cases. We refer to them here as monogenic causes, insofar as the genetic abnormality has a readily detectable, large effect. What explains the other two-thirds? This review considers a complex genetic basis. That is, a combination of genetic mutations or variants that individually may have little or no detectable effect contribute to the pathogenesis of a heart defect. Genes in the embryo that act directly in cardiac developmental pathways have received the most attention, but genes in the mother that establish the gestational milieu via pathways related to metabolism and aging also have an effect. A growing body of evidence highlights the pathogenic significance of genetic interactions in the embryo and maternal effects that have a genetic basis. The investigation of CHD as guided by a complex genetic model could help estimate risk more precisely and logically lead to a means of prevention. PMID:28381817

A Rare de novo Interstitial Duplication at 4p15.2 in a Boy with Severe Congenital Heart Defects, Limb Anomalies, Hypogonadism, and Global Developmental Delay.

PubMed

Liang, Liyang; Xie, Yingjun; Shen, Yiping; Yin, Qibin; Yuan, Haiming

2016-01-01

Proximal 4p deletion syndrome is a relatively rare genetic condition characterized by dysmorphic facial features, limb anomalies, minor congenital heart defects, hypogonadism, cafe-au-lait spots, developmental delay, tall and thin habitus, and intellectual disability. At present, over 20 cases of this syndrome have been published. However, duplication of the same region in proximal 4p has never been reported. Here, we describe a 2-year-5-month-old boy with severe congenital heart defects, limb anomalies, hypogonadism, distinctive facial features, pre- and postnatal developmental delay, and mild cognitive impairments. A de novo 4.5-Mb interstitial duplication at 4p15.2p15.1 was detected by chromosomal microarray analysis. Next-generation sequencing was employed and confirmed the duplication, but revealed no additional pathogenic variants. Several candidate genes in this interval responsible for the complex clinical phenotype were identified, such as RBPJ, STIM2, CCKAR, and LGI2. The results suggest a novel contiguous gene duplication syndrome. © 2016 S. Karger AG, Basel.

No turning, a mouse mutation causing left-right and axial patterning defects.

PubMed

Melloy, P G; Ewart, J L; Cohen, M F; Desmond, M E; Kuehn, M R; Lo, C W

1998-01-01

Patterning along the left/right axes helps establish the orientation of visceral organ asymmetries, a process which is of fundamental importance to the viability of an organism. A linkage between left/right and axial patterning is indicated by the finding that a number of genes involved in left/right patterning also play a role in anteroposterior and dorsoventral patterning. We have recovered a spontaneous mouse mutation causing left/right patterning defects together with defects in anteroposterior and dorsoventral patterning. This mutation is recessive lethal and was named no turning (nt) because the mutant embryos fail to undergo embryonic turning. nt embryos exhibit cranial neural tube closure defects and malformed somites and are caudally truncated. Development of the heart arrests at the looped heart tube stage, with cardiovascular defects indicated by ballooning of the pericardial sac and the pooling of blood in various regions of the embryo. Interestingly, in nt embryos, the direction of heart looping was randomized. Nodal and lefty, two genes that are normally expressed only in the left lateral plate mesoderm, show expression in the right and left lateral plate mesoderm. Lefty, which is normally also expressed in the floorplate, is not found in the prospective floor plate of nt embryos. This suggests the possibility of notochordal defects. This was confirmed by histological analysis and the examination of sonic hedgehog, Brachyury, and HNF-3 beta gene expression. These studies showed that the notochord is present in the early nt embryo, but degenerates as development progresses. Overall, these findings support the hypothesis that the notochord plays an active role in left/right patterning. Our results suggest that nt may participate in this process by modulating the notochordal expression of HNF-3 beta.

[Artificial heart--turbo type blood pump for long-term use].

PubMed

Akamatsu, Teruaki

2003-05-01

Shortage of donor heart for transplantation necessitates long-term artificial assist heart. Turbo-pump is smaller, simpler and cheaper than the pulsatile displacement type pump, but the turbo-pump has defect of thrombus formation at the shaft seal. Our centrifugal pump with magnetically suspended impellers overcomes this defect and is ready for clinical trials now. The structures and functions are described and are compared with the other newly-developed pump of the same kinds with us. And also the pumps of centrifugal type and axial-type, of which impellers are supported by pivots, are reviewed briefly from the stand point for long-term use. Other pumps are referred too: pumps with hydrodynamic bearing and a pump with the shaft seal which is washed and cooled by saline solution.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furforo, L.; Rittler, M.; Slavutsky, I.R.

We report on a girl with developmental delay, macrocephaly, facial asymmetry, small downturned palpebral fissures, high and narrow palate, micrognathia, short neck, a heart defect, and unilateral renal agenesis. Cytogenetic analysis showed a proximal tandem duplication of the long arm of chromosome one (1q12{r_arrow}q21.3). This abnormality was suggested by G-and C-banding but it was specifically characterized by fluorescent in situ hybridization (FISH). Clinical findings in our patient are compared with those of the literature in an attempt to delineate the phenotype in patients with proximal 1q duplication. 12 refs., 4 figs., 1 tab.

Alteration of gene expression by alcohol exposure at early neurulation.

PubMed

Zhou, Feng C; Zhao, Qianqian; Liu, Yunlong; Goodlett, Charles R; Liang, Tiebing; McClintick, Jeanette N; Edenberg, Howard J; Li, Lang

2011-02-21

We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables. Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos. This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube defects during early neurulation.

Atrial Septal Defect (For Kids)

MedlinePlus

... eventually become the walls and chambers of the baby's heart. If a problem happens during this process, a ... was exposed to chemicals or drugs while the baby was growing inside her. For ... who have ASDs have their heart murmur found by their regular doctor. Then they ...

The uses of two-dimensional Doppler echocardiographic techniques preoperatively and postoperatively in a ventricular septal defect caused by penetrating trauma.

PubMed

Goldman, A P; Kotler, M N; Goldberg, S E; Parameswaran, R; Parry, W

1985-12-01

Doppler echocardiography was used to determine the site and size of a ventricular septal defect in a patient with a penetrating wound of the heart. Additional physiological measurements by Doppler study, including pulmonary artery pressure and degree of left-to-right shunting, were helpful in deciding on surgical closure of the defect as the definitive therapy in this patient. Associated intracardiac defects (e.g., mitral or tricuspid regurgitation) can be excluded by Doppler echocardiography.

Congenital heart disease and chromossomopathies detected by the karyotype

PubMed Central

Trevisan, Patrícia; Rosa, Rafael Fabiano M.; Koshiyama, Dayane Bohn; Zen, Tatiana Diehl; Paskulin, Giorgio Adriano; Zen, Paulo Ricardo G.

2014-01-01

OBJECTIVE: To review the relationship between congenital heart defects and chromosomal abnormalities detected by the karyotype. DATA SOURCES: Scientific articles were searched in MEDLINE database, using the descriptors "karyotype" OR "chromosomal" OR "chromosome" AND "heart defects, congenital". The research was limited to articles published in English from 1980 on. DATA SYNTHESIS: Congenital heart disease is characterized by an etiologically heterogeneous and not well understood group of lesions. Several researchers have evaluated the presence of chromosomal abnormalities detected by the karyotype in patients with congenital heart disease. However, most of the articles were retrospective studies developed in Europe and only some of the studied patients had a karyotype exam. In this review, only one study was conducted in Latin America, in Brazil. It is known that chromosomal abnormalities are frequent, being present in about one in every ten patients with congenital heart disease. Among the karyotype alterations in these patients, the most important is the trisomy 21 (Down syndrome). These patients often have associated extra-cardiac malformations, with a higher risk of morbidity and mortality, which makes heart surgery even more risky. CONCLUSIONS: Despite all the progress made in recent decades in the field of cytogenetic, the karyotype remains an essential tool in order to evaluate patients with congenital heart disease. The detailed dysmorphological physical examination is of great importance to indicate the need of a karyotype. PMID:25119760

in vitro Models if Human Embryonic Mesenchymal Transitions in Morphogenesis

EPA Science Inventory

Our ability to predict human developmental consequences produced by exposure to environmental chemicals is limited by the current experimental and computational models.Human heart defects are among the most common type of birth defects and affect 1% of children (~40,000 children)...

A unique phenotype in a patient with a rare triplication of the 22q11.2 region and new clinical insights of the 22q11.2 microduplication syndrome: a report of two cases.

PubMed

Vaz, Sara O; Pires, Renato; Pires, Luís M; Carreira, Isabel M; Anjos, Rui; Maciel, Paula; Mota-Vieira, Luisa

2015-08-22

The rearrangements of the 22q11.2 chromosomal region, most frequently deletions and duplications, have been known to be responsible for multiple congenital anomaly disorders. These rearrangements are implicated in syndromes that have some phenotypic resemblances. While the 22q11.2 deletion, also known as DiGeorge/Velocardiofacial syndrome, has common features that include cardiac abnormalities, thymic hypoplasia, characteristic face, hypocalcemia, cognitive delay, palatal defects, velopharyngeal insufficiency, and other malformations, the microduplication syndrome is largely undetected. This is mainly because phenotypic appearance is variable, milder, less characteristic and unpredictable. In this paper, we report the clinical evaluation and follow-up of two patients affected by 22q11.2 rearrangements, emphasizing new phenotypic features associated with duplication and triplication of this genomic region. Patient 1 is a 24 year-old female with 22q11.2 duplication who has a heart defect (ostium secundum atrial septal defect) and supernumerary teeth (hyperdontia), a feature previously not reported in patients with 22q11.2 microduplication syndrome. Her monozygotic twin sister, who died at the age of one month, had a different heart defect (truncus arteriousus). Patient 2 is a 20 year-old female with a 22q11.2 triplication who had a father with 22q11.2 duplication. In comparison to the first case reported in the literature, she has an aggravated phenotype characterized by heart defects (restrictive VSD and membranous subaortic stenosis), and presented other facial dysmorphisms and urogenital malformations (ovarian cyst). Additionally, she has a hemangioma planum on the right side of her face, a feature of Sturge-Weber syndrome. In this report, we described hyperdontia as a new feature of 22q11.2 microdeletion syndrome. Moreover, this syndrome was diagnosed in a patient who had a deceased monozygotic twin affected with a different heart defect, which corresponds to a phenotypic discordance never reported in the literature. Case 2 is the second clinical report of 22q11.2 triplication and presents an aggravated phenotype in contrast to the patient previously reported.

Histone Deacetylases 5 and 9 Govern Responsiveness of the Heart to a Subset of Stress Signals and Play Redundant Roles in Heart Development

PubMed Central

Chang, Shurong; McKinsey, Timothy A.; Zhang, Chun Li; Richardson, James A.; Hill, Joseph A.; Olson, Eric N.

2004-01-01

The adult heart responds to stress signals by hypertrophic growth, which is often accompanied by activation of a fetal cardiac gene program and eventual cardiac demise. We showed previously that histone deacetylase 9 (HDAC9) acts as a suppressor of cardiac hypertrophy and that mice lacking HDAC9 are sensitized to cardiac stress signals. Here we report that mice lacking HDAC5 display a similar cardiac phenotype and develop profoundly enlarged hearts in response to pressure overload resulting from aortic constriction or constitutive cardiac activation of calcineurin, a transducer of cardiac stress signals. In contrast, mice lacking either HDAC5 or HDAC9 show a hypertrophic response to chronic β-adrenergic stimulation identical to that of wild-type littermates, suggesting that these HDACs modulate a specific subset of cardiac stress response pathways. We also show that compound mutant mice lacking both HDAC5 and HDAC9 show a propensity for lethal ventricular septal defects and thin-walled myocardium. These findings reveal central roles for HDACs 5 and 9 in the suppression of a subset of cardiac stress signals as well as redundant functions in the control of cardiac development. PMID:15367668

Histone deacetylases 5 and 9 govern responsiveness of the heart to a subset of stress signals and play redundant roles in heart development.

PubMed

Chang, Shurong; McKinsey, Timothy A; Zhang, Chun Li; Richardson, James A; Hill, Joseph A; Olson, Eric N

2004-10-01

The adult heart responds to stress signals by hypertrophic growth, which is often accompanied by activation of a fetal cardiac gene program and eventual cardiac demise. We showed previously that histone deacetylase 9 (HDAC9) acts as a suppressor of cardiac hypertrophy and that mice lacking HDAC9 are sensitized to cardiac stress signals. Here we report that mice lacking HDAC5 display a similar cardiac phenotype and develop profoundly enlarged hearts in response to pressure overload resulting from aortic constriction or constitutive cardiac activation of calcineurin, a transducer of cardiac stress signals. In contrast, mice lacking either HDAC5 or HDAC9 show a hypertrophic response to chronic beta-adrenergic stimulation identical to that of wild-type littermates, suggesting that these HDACs modulate a specific subset of cardiac stress response pathways. We also show that compound mutant mice lacking both HDAC5 and HDAC9 show a propensity for lethal ventricular septal defects and thin-walled myocardium. These findings reveal central roles for HDACs 5 and 9 in the suppression of a subset of cardiac stress signals as well as redundant functions in the control of cardiac development.

Health-related quality of life of mothers of children with congenital heart disease in a sub-Saharan setting: cross-sectional comparative study.

PubMed

Sileshi, Lidia; Tefera, Endale

2017-10-26

While the Health Related Quality of Life of the children with congenital heart defects is primarily affected, caring for a child with birth defect has an impact on the family's quality of life as well. Understanding the level of quality of life of the parents, which is likely to vary in different cultural settings, beliefs and parental educational status may help to implement educational programs and other interventional measures that may improve the HRQOL of parents of such children. This cross-sectional comparative study reports the health-related quality of life of mothers of children with congenital heart diseases in a sub-Saharan setting. Mean age of the mothers in the study group was 32.2 ± 7.1 years where as that of the control group was 30.5 ± 6.5 years (p = .054). One hundred-four children had congenital cardiac lesions classified as mild to moderate while 31 patients had severe lesions. On average, mothers in the study group showed poor performance on the Short Form-36 (SF-36) with statistically significant differences on all sub-scales including general health perception, physical functioning, role physical, role emotional, social functioning, bodily pain, vitality and mental health. Severity of the congenital heart defect was not associated with statistically significant difference in the health-related quality of life of the mothers. Mothers of children with congenital heart disease in our study have significantly lower quality of life in all domains of SF-36 compared to the control group. Planning and devising a strategy to support these mothers may need to be part of management and clinical care of children with congenital heart diseases.

Thrombus formation in the interrupted segment of the aorta.

PubMed

Karavelioğlu, Yusuf; Kalçık, Macit; Yetim, Mucahit; Doğan, Tolga; Gölbaşı, Zehra

2017-06-01

Interrupted aorta is a very rare heart defect in which there is a gap between the ascending and the descending thoracic aorta. It is usually associated with other cardiac anomalies, including ventricular septal defect, ductus arteriosus, and truncus arteriosus. Severe cases present with serious complications such as hypertension, heart failure, or intracranial hemorrhage. Neurological complications are very rare form of presentation and commonly associated with intracranial aneurysms. We have reported a case of interrupted aorta who presented with transient ischemic attack due to thrombus formation in the interrupted segment of the aorta. © 2017, Wiley Periodicals, Inc.

The natural history of congenitally corrected transposition of the great arteries.

PubMed

Huhta, James

2011-01-01

The natural history of congenitally corrected transposition of the great arteries is of clinical/surgical importance once the fetus is born without heart block or signs of heart failure. Without significant tricuspid valve malformation, associated defects such as ventricular septal defect and left ventricular outflow obstruction can be repaired surgically. The mortality and long-term outcome appear to be linked strongly with the severity of tricuspid valve regurgitation. Some patients with an intact ventricular septum and no right ventricular dysfunction will live long lives without detection, and some women will successfully complete pregnancy.

["Open" surgery of mitral heart diseases complicated by pulmonary hypertension].

PubMed

Abdumazhidov, Kh A; Guliamov, D S; Amanov, A A

2000-01-01

Under analysis were the results of 386 operations on the "open" heart made for mitral diseases complicated by pulmonary hypertension of different degrees. Prosthetics of the mitral valve was performed in 251 patients, in 135 patients the so-called "organ-saving" correction of the defect was fulfilled. The decision on the method of the defect correction depends on the anatomical particularities, morphological alterations of the valvular apparatus. The main place among the causes of postoperative lethality (9-11%) is occupied by cardiac insufficiency and renohepatic failure which are noted mainly in patients of the IVth functional class.

Ambient air pollution and congenital heart defects in Lanzhou, China

NASA Astrophysics Data System (ADS)

Jin, Lan; Qiu, Jie; Zhang, Yaqun; Qiu, Weitao; He, Xiaochun; Wang, Yixuan; Sun, Qingmei; Li, Min; Zhao, Nan; Cui, Hongmei; Liu, Sufen; Tang, Zhongfeng; Chen, Ya; Yue, Li; Da, Zhenqiang; Xu, Xiaoying; Huang, Huang; Liu, Qing; Bell, Michelle L.; Zhang, Yawei

2015-07-01

Congenital heart defects are the most prevalent type of birth defects. The association of air pollution with congenital heart defects is not well understood. We investigated a cohort of 8969 singleton live births in Lanzhou, China during 2010-2012. Using inverse distance weighting, maternal exposures to particulate matter with diameters ≤10 μm (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were estimated as a combination of monitoring station levels for time spent at home and in a work location. We used logistic regression to estimate the associations, adjusting for maternal age, education, income, BMI, disease, folic acid intake and therapeutic drug use, and smoking; season of conception, fuel used for cooking and temperature. We found significant positive associations of Patent Ductus Arteriosus (PDA) with PM10 during the 1st trimester, 2nd trimester and the entire pregnancy (OR 1st trimester = 3.96, 95% confidence interval (CI): 1.36, 11.53; OR 2nd trimester = 3.59, 95% CI: 1.57, 8.22; OR entire pregnancy = 2.09, 95% CI: 1.21, 3.62, per interquartile range (IQR) increment for PM10 (IQR = 71.2, 61.6, and 27.4 μg m-3, respectively)), and associations with NO2 during 2nd trimester and the entire pregnancy (OR 2nd trimester = 1.92, 95% CI: 1.11, 3.34; OR entire pregnancy = 2.32, 95% Cl: 1.14, 4.71, per IQR increment for NO2 (IQR = 13.4 and 10.9 μg m-3, respectively)). The associations for congenital malformations of the great arteries and pooled cases showed consistent patterns. We also found positive associations for congenital malformations of cardiac septa with PM10 exposures in the 2nd trimester and the entire pregnancy, and SO2 exposures in the entire pregnancy. Results indicate a health burden from maternal exposures to air pollution, with increased risk of congenital heart defects.

Targeted deletion of RIC8A in mouse neural precursor cells interferes with the development of the brain, eyes, and muscles.

PubMed

Kask, Keiu; Tikker, Laura; Ruisu, Katrin; Lulla, Sirje; Oja, Eva-Maria; Meier, Riho; Raid, Raivo; Velling, Teet; Tõnissoo, Tambet; Pooga, Margus

2018-04-01

Autosomal recessive disorders such as Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, and the muscle-eye-brain disease are characterized by defects in the development of patient's brain, eyes, and skeletal muscles. These syndromes are accompanied by brain malformations like type II lissencephaly in the cerebral cortex with characteristic overmigrations of neurons through the breaches of the pial basement membrane. The signaling pathways activated by laminin receptors, dystroglycan and integrins, control the integrity of the basement membrane, and their malfunctioning may underlie the pathologies found in the rise of defects reminiscent of these syndromes. Similar defects in corticogenesis and neuromuscular disorders were found in mice when RIC8A was specifically removed from neural precursor cells. RIC8A regulates a subset of G-protein α subunits and in several model organisms, it has been reported to participate in the control of cell division, signaling, and migration. Here, we studied the role of RIC8A in the development of the brain, muscles, and eyes of the neural precursor-specific conditional Ric8a knockout mice. The absence of RIC8A severely affected the attachment and positioning of radial glial processes, Cajal-Retzius' cells, and the arachnoid trabeculae, and these mice displayed additional defects in the lens, skeletal muscles, and heart development. All the discovered defects might be linked to aberrancies in cell adhesion and migration, suggesting that RIC8A has a crucial role in the regulation of cell-extracellular matrix interactions and that its removal leads to the phenotype characteristic to type II lissencephaly-associated diseases. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 374-390, 2018. © 2018 Wiley Periodicals, Inc.

Crosstalk between AhR and wnt/β-catenin signal pathways in the cardiac developmental toxicity of PM2.5 in zebrafish embryos.

PubMed

Zhang, Hang; Yao, Yugang; Chen, Yang; Yue, Cong; Chen, Jiahong; Tong, Jian; Jiang, Yan; Chen, Tao

2016-04-29

Recent studies have shown an association between congenital heart defects and air fine particle matter (PM2.5), but the molecular mechanisms remain elusive. It is well known that a number of organic compounds in PM2.5 can act as AhR agonists, and activation of AhR can antagonize Wnt/β-catenin signaling. Therefore, we hypothesized that PM2.5 could activate AhR and then repress the expression of wnt/β-catenin targeted genes essential for cardiogenesis, resulting in heart defects. To test this hypothesis, we investigated the effects of extractable organic matter (EOM) from PM2.5 on AhR and Wnt/β-catenin signal pathways in zebrafish embryos. We confirmed that EOM could cause malformations in the heart and decreased heart rate in zebrafish embryos at 72hpf, and found that the EOM-induced heart defects were rescued in embryos co-exposed with EOM plus AhR antagonist CH223191 or β-catenin agonist CHIR99021. We further found that EOM had increased the expression levels of AhR targeted genes (Cyp1a1, Cyp1b1 and Ahrra) and reduced the mRNA levels of β-catenin targeted genes (axin2, nkx2.5 and sox9b). The mRNA expression level of Rspo2, a β-catenin upstream gene, was also decreased in embryos exposed to EOM. Supplementation with CH223191 or CHIR99021 attenuated most of the EOM-induced expression changes of genes involved in both AhR and wnt/β-catenin signal pathways. However, the mRNA expression level of AhR inhibitor Ahrrb, which did not change by EOM treatment alone, was increased in embryos co-exposed to EOM plus CH223191 or CHIR99021. We conclude that the activation of AhR by EOM from PM2.5 might repress wnt/β-catenin signaling, leading to heart defects in zebrafish embryos. Furthermore, our results indicate that the cardiac developmental toxicity of PM2.5 might be prevented by targeting AhR or wnt/β-catenin signaling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Expression of hLAMP-1-Positive Particles During Early Heart Development in the Chick.

PubMed

Abd-Elhamid, T H; Conway, M L; Sinning, A R

2017-10-01

Heart development requires coordinated activity of various factors, the disturbance of which can lead to congenital heart defects. Heart lectin-associated matrix protein-1 (hLAMP-1) is a matrix protein expressed within Hensen's node at Hamburger-Hamilton (HH) stage 4, in the lateral mesoderm by HH stages 5-6 and enhanced within the left pre-cardiac field at HH stage 7. At HH stages 15-16, hLAMP-1 expression is observed in the atrioventricular canal and the outflow tract. Also, the role of hLAMP-1 in induction of mesenchyme formation in chick heart has been well documented. To further elucidate the role of this molecule in heart development, we examined its expression patterns during HH stages 8-14 in the chick. In this regard, we immunostained sections of the heart during HH stages 8-14 with antibodies specific to hLAMP-1. Our results showed prominent expression of hLAMP-1-positive particles in the extracellular matrix associated with the pre-cardiac mesoderm, the endoderm, ectoderm as well as neuroectoderm at HH stages 8-9. After formation of the linear heart tube at HH stage 10, the expression of hLAMP-1-stained particles disappears in those regions of original contact between the endoderm and heart forming fields due to rupture of the dorsal mesocardium while their expression becomes confined to the arterial and venous poles of the heart tube. This expression pattern is maintained until HH stage 14. This expression pattern suggests that hLAMP-1 may be involved in the formation of the endocardial tube. © 2017 Blackwell Verlag GmbH.

A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs.

PubMed

Stern, Joshua A; White, Stephen N; Lehmkuhl, Linda B; Reina-Doreste, Yamir; Ferguson, Jordan L; Nascone-Yoder, Nanette M; Meurs, Kathryn M

2014-09-01

Familial subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects in dogs and is an inherited defect of Newfoundlands, golden retrievers and human children. Although SAS is known to be inherited, specific genes involved in Newfoundlands with SAS have not been defined. We hypothesized that SAS in Newfoundlands is inherited in an autosomal dominant pattern and caused by a single genetic variant. We studied 93 prospectively recruited Newfoundland dogs, and 180 control dogs of 30 breeds. By providing cardiac screening evaluations for Newfoundlands we conducted a pedigree evaluation, genome-wide association study and RNA sequence analysis to identify a proposed pattern of inheritance and genetic loci associated with the development of SAS. We identified a three-nucleotide exonic insertion in phosphatidylinositol-binding clathrin assembly protein (PICALM) that is associated with the development of SAS in Newfoundlands. Pedigree evaluation best supported an autosomal dominant pattern of inheritance and provided evidence that equivocally affected individuals may pass on SAS in their progeny. Immunohistochemistry demonstrated the presence of PICALM in the canine myocardium and area of the subvalvular ridge. Additionally, small molecule inhibition of clathrin-mediated endocytosis resulted in developmental abnormalities within the outflow tract (OFT) of Xenopus laevis embryos. The ability to test for presence of this PICALM insertion may impact dog-breeding decisions and facilitate reduction of SAS disease prevalence in Newfoundland dogs. Understanding the role of PICALM in OFT development may aid in future molecular and genetic investigations into other congenital heart defects of various species.

The effects of carbaryl on the development of zebrafish (Danio rerio) embryos.

PubMed

Schock, Elizabeth N; Ford, Windsor C; Midgley, Kirsten J; Fader, Joseph G; Giavasis, Michael N; McWhorter, Michelle L

2012-12-01

In the United States, Sevin(™) brand insecticide is one of the most commonly used insecticides. The active ingredient in Sevin(™), carbaryl (1-napthyl-N-methylcarbamate), is a known acetylcholinesterase (AChE) inhibitor that prevents the breakdown of acetylcholine to acetate and choline at the synapse. While carbaryl successfully causes the death of insects by paralysis, it has also been shown to have negative effects on the development of several nontarget species. To study the effects of carbaryl on nontarget species, zebrafish (Danio rerio) were used, as they are a good model for both toxicology and development studies. Our study suggests that carbaryl induces changes in morphology, specifically in embryo size and shape. Additionally, carbaryl causes defects in heart formation that is characterized by a decrease in heart rate and a developmental delay/defect in cardiac looping. A significant decrease in the number of spinal cord neurons present was also observed. Further investigation showed that there was an increase in cell death in carbaryl-treated embryos. The results indicate that carbaryl may have a greater environmental impact than initially intended. Our study, which was conducted solely by undergraduates at a liberal arts college, indicates that carbaryl may be detrimental to the development of nontarget species.

[Value of chest x-ray films in the diagnosis of congenital heart defects in infants].

PubMed

Koczyński, A

1982-01-01

The respiratory distress and suspicion of the heart defects in newborns and infants is indicated by x-ray chest examinations. The right interpretation of the x-ray pictures is very important but it must be followed by other diagnostic procedures. In every child it is possible to take the linear measurements of the great vessels and arteries in parahilar lung areas as well as the heart and chest in two dimensions from x-ray plain films. The measurements let to establish the indices: cardio-thoracic (ICP), vasculo-cardiac (IVC) and sagittal one (IS), which play important role in radiological evaluation of the chest. It results from the investigated material, that the evaluation of the pulmonary vascular pattern and the indices particularly facilitate the diagnosis of heart deformities coexisting with higher blood flow in pulmonary circulation. Nevertheless the measurements and the indices play the relative role in establishing of the final opinion about the chest and should be considered together with clinical and cardiological data.

Rescue of neonatal cardiac dysfunction in mice by administration of cardiac progenitor cells in utero

PubMed Central

Liu, Xiaoli; Hall, Sean R. R.; Wang, Zhihong; Huang, He; Ghanta, Sailaja; Di Sante, Moises; Leri, Annarosa; Anversa, Piero; Perrella, Mark A.

2015-01-01

Striated preferentially expressed gene (Speg) is a member of the myosin light chain kinase family. We previously showed that disruption of the Speg gene locus in mice leads to a dilated cardiomyopathy with immature-appearing cardiomyocytes. Here we show that cardiomyopathy of Speg−/− mice arises as a consequence of defects in cardiac progenitor cell (CPC) function, and that neonatal cardiac dysfunction can be rescued by in utero injections of wild-type CPCs into Speg−/− foetal hearts. CPCs harvested from Speg−/− mice display defects in clone formation, growth and differentiation into cardiomyocytes in vitro, which are associated with cardiac dysfunction in vivo. In utero administration of wild-type CPCs into the hearts of Speg−/− mice results in CPC engraftment, differentiation and myocardial maturation, which rescues Speg−/− mice from neonatal heart failure and increases the number of live births by fivefold. We propose that in utero administration of CPCs may have future implications for treatment of neonatal heart diseases. PMID:26593099

Possible association of Down syndrome and exstrophy-epispadias complex: report of two new cases and review of the literature.

PubMed

Reutter, Heiko; Bökenkamp, Arend; Ebert, Anne-Karolin; Rösch, Wolfgang; Boemers, Thomas M; Nöthen, Markus M; Ludwig, Michael

2009-07-01

In the past, several midline defects have been associated with Down syndrome (DS) on a regular basis, e.g. heart defects, cleft lip and palate, neural tube defects, omphalocele and anal atresia. The exstrophy-epispadias complex (EEC) represents a rare midline defect, rarely described in association with DS. Here, we report on the co-occurrence of DS and EEC in two, so far, unreported cases and present a review of the literature. We suggest that EEC represents a rare but inherent part in the spectrum of DS-associated midline defects.

Holt-oram syndrome associated with double outlet right ventricle: A rare association

PubMed Central

Singh, Bhupinder; Kariyappa, Mallesh; Vijayalakshmi, Ishwarappa Balekundri; Nanjappa, Manjunath C

2013-01-01

Holt-Oram syndrome is a rare inherited disorder that causes abnormalities of the hands, arms, and the heart. Most commonly, there are defects in the carpal bones of the wrist and in the bones of the thumb along with cardiac defects such as atrial or ventricular septal defects. We report a case of Holt-Oram syndrome with a rare association of double outlet right ventricle. PMID:23626447

Redundant roles of Sox17 and Sox18 in early cardiovascular development of mouse embryos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakamoto, Youhei; Hara, Kenshiro; Kanai-Azuma, Masami

Sox7, -17 and -18 constitute the Sox subgroup F (SoxF) of HMG box transcription factor genes, which all are co-expressed in developing vascular endothelial cells in mice. Here we characterized cardiovascular phenotypes of Sox17/Sox18-double and Sox17-single null embryos during early-somite stages. Whole-mount PECAM staining demonstrated the aberrant heart looping, enlarged cardinal vein and mild defects in anterior dorsal aorta formation in Sox17 single-null embryos. The Sox17/Sox18 double-null embryos showed more severe defects in formation of anterior dorsal aorta and head/cervical microvasculature, and in some cases, aberrant differentiation of endocardial cells and defective fusion of the endocardial tube. However, the posteriormore » dorsal aorta and allantoic microvasculature was properly formed in all of the Sox17/Sox18 double-null embryos. The anomalies in both anterior dorsal aorta and head/cervical vasculature corresponded with the weak Sox7 expression sites. This suggests the region-specific redundant activities of three SoxF members along the anteroposterior axis of embryonic vascular network.« less

A case of severe type of cerebro-costo-mandibular syndrome.

PubMed

Matić, Aleksandra; Velisavljev-Filipović, Gordana; Lovrenski, Jovan; Gajdobranski, Djordje

2016-01-01

Cerebro-costo-mandibular syndrome (CCMS) is a rare disorder, with only 75 cases described in the literature to date. CCMS is characterized by association of micrognathia and specific multiple rib defects. It is accompanied by mental deficiency in considerable number of cases. Sometimes, there are associated anomalies and problems, such as spine deformities, brain, heart, kidney or ear anomalies, feeding difficulties, delayed psychomotor development, and growth impairment. Depending on severity of deformities and consecutive respiratory insufficiency, in about 35–50% of CCMS cases, death occurs during the first year of life. These cases are referred to as severe types of CCMS. In this paper we present a female infant with severe type of CCMS. Diagnosis was established in the first day of life, based on micrognathia and findings of posterior rib-gap defects on the chest X-ray, accompanied by dyspnea. Progressive severe respiratory insufficiency caused by chest and air-way deformities and exacerbated by episodes of pneumonia, led to respiratory failure and death at the age of 7.5 months. CCMS should be considered in every infant with micrognathia and rib-gap defects on chest X-ray.

UDP-glucose Dehydrogenase Polymorphisms from Patients with Congenital Heart Valve Defects Disrupt Enzyme Stability and Quaternary Assembly*

PubMed Central

Hyde, Annastasia S.; Farmer, Erin L.; Easley, Katherine E.; van Lammeren, Kristy; Christoffels, Vincent M.; Barycki, Joseph J.; Bakkers, Jeroen; Simpson, Melanie A.

2012-01-01

Cardiac valve defects are a common congenital heart malformation and a significant clinical problem. Defining molecular factors in cardiac valve development has facilitated identification of underlying causes of valve malformation. Gene disruption in zebrafish revealed a critical role for UDP-glucose dehydrogenase (UGDH) in valve development, so this gene was screened for polymorphisms in a patient population suffering from cardiac valve defects. Two genetic substitutions were identified and predicted to encode missense mutations of arginine 141 to cysteine and glutamate 416 to aspartate, respectively. Using a zebrafish model of defective heart valve formation caused by morpholino oligonucleotide knockdown of UGDH, transcripts encoding the UGDH R141C or E416D mutant enzymes were unable to restore cardiac valve formation and could only partially rescue cardiac edema. Characterization of the mutant recombinant enzymes purified from Escherichia coli revealed modest alterations in the enzymatic activity of the mutants and a significant reduction in the half-life of enzyme activity at 37 °C. This reduction in activity could be propagated to the wild-type enzyme in a 1:1 mixed reaction. Furthermore, the quaternary structure of both mutants, normally hexameric, was destabilized to favor the dimeric species, and the intrinsic thermal stability of the R141C mutant was highly compromised. The results are consistent with the reduced function of both missense mutations significantly reducing the ability of UGDH to provide precursors for cardiac cushion formation, which is essential to subsequent valve formation. The identification of these polymorphisms in patient populations will help identify families genetically at risk for valve defects. PMID:22815472

Right heart failure: toward a common language.

PubMed

Mehra, Mandeep R; Park, Myung H; Landzberg, Michael J; Lala, Anuradha; Waxman, Aaron B

2014-02-01

In this perspective, the International Right Heart Foundation Working Group moves a step forward to develop a common language to describe the development and defects that exemplify the common syndrome of right heart failure. We first propose fundamental definitions of the distinctive components of the right heart circulation and provide consensus on a universal definition of right heart failure. These definitions will form the foundation for describing a uniform nomenclature for right heart circulatory failure with a view to foster collaborative research initiatives and conjoint education in an effort to provide insight into echanisms of disease unique to the right heart. © 2014 Published by International Society for the Heart and Lung Transplantation on behalf of International Society for Heart and Lung Transplantation.

Detection of chromosomal abnormalities and the 22q11 microdeletion in fetuses with congenital heart defects.

PubMed

Lv, Wei; Wang, Shuyu

2014-11-01

Chromosomal abnormalities and the 22q11 microdeletion are implicated in congenital heart defects (CHDs). This study was designed to detect these abnormalities in fetuses and determine the effect of genetic factors on CHD etiology. Between January 2010 and December 2011, 113 fetuses with CHD treated at the Beijing Obstetrics and Gynecology Hospital were investigated, using chromosome karyotyping of either amniotic fluid cell or umbilical cord blood cell samples. Fetuses with a normal result were then investigated for the 22q11 microdeletion by fluorescence in situ hybridization. Of the 113 patients, 12 (10.6%) exhibited chromosomal abnormalities, while 6 (5.3%) of the remaining 101 cases presented with a 22q11 microdeletion. The incidence of chromosomal abnormalities was significantly higher in the group of fetuses presenting with extracardiac malformations in addition to CHD (P<0.001), although the detection of the 22q11 microdeletion was not significantly different between the two groups (P=0.583). In addition, all fetuses with the 22q11 microdeletion occurred de novo. In conclusion, genetic factors are important in the etiology of CHD. Where fetuses present with cardiac defects, additional chromosomal analysis is required to detect extracardiac abnormalities. Fetuses with heart defects should also be considered for 22q11 microdeletion detection to evaluate fetal prognosis, particularly prior to surgery.

Evolution of membrane oxygenator technology for utilization during pediatric cardiopulmonary bypass.

PubMed

Melchior, Richard W; Sutton, Steven W; Harris, William; Dalton, Heidi J

2016-01-01

The development of the membrane oxygenator for pediatric cardiopulmonary bypass has been an incorporation of ideology and technological advancements with contributions by many investigators throughout the past two centuries. With the pursuit of this technological achievement, the ability to care for mankind in the areas of cardiac surgery has been made possible. Heart disease can affect anyone within the general population, but one such segment that it can affect from inception includes children. Currently, congenital heart defects are the most common birth defects nationally and worldwide. A large meta-analysis study from 1930 to 2010 was conducted in review of published medical literature totaling 114 papers with a study population of 24,091,867 live births, and divulged a staggering incidence of congenital heart disease involving 164,396 subjects with diverse cardiac illnesses. The prevalence of these diseases increased from 0.6 per 1,000 live births from 1930-1934 to 9.1 per 1,000 live births after 1995. These data reveal an emphasis on a growing public health issue regarding congenital heart disease. This discovery displays a need for heightened awareness in the scientific and medical industrial community to accelerate investigative research on emerging cardiovascular devices in an effort to confront congenital anomalies. One such device that has evolved over the past several decades is the pediatric membrane oxygenator. The pediatric membrane oxygenator, in conjunction with the heart lung machine, assists in the repair of most congenital cardiac defects. Numerous children born with congenital heart disease with or without congestive heart failure have experienced improved clinical outcomes in quality of life, survival, and mortality as a result of the inclusion of this technology during their cardiac surgical procedure. The purpose of this review is to report a summary of the published medical and scientific literature related to development of the pediatric membrane oxygenator from its conceptual evolutionary stages to artificially supporting whole body perfusion in the modern pediatric cardiac surgical setting.

Xenopus as a Model Organism for Birth Defects – Congenital Heart Disease and Heterotaxy

PubMed Central

Duncan, Anna R.; Khokha, Mustafa K.

2016-01-01

Congenital heart disease is the leading cause of birth defects, affecting 9 out of 1000 newborns each year. A particularly severe form of congenital heart disease is heterotaxy, a disorder of left-right development. Despite aggressive surgical management, patients with heterotaxy have poor survival rates and severe morbidity due to their complex congenital heart disease. Recent genetic analysis of affected patients has found novel candidate genes for heterotaxy although their underlying mechanisms remain unknown. In this review, we discuss the importance and challenges of birth defects research including high locus heterogeneity and few second alleles that make defining disease causality difficult. A powerful strategy moving forward is to analyze these candidate genes in a high-throughput human disease model. Xenopus is ideal for these studies. We present multiple examples demonstrating the power of Xenopus in discovery new biology from the analysis of candidate heterotaxy genes such as GALNT11, NEK2 and BCOR. These genes have diverse roles in embryos and have led to a greater understanding of complex signaling pathways and basic developmental biology. It is our hope that the mechanistic analysis of these candidate genes in Xenopus enabled by next generation sequencing of patients will provide clinicians with a greater understanding of patient pathophysiology allowing more precise and personalized medicine, to help them more effectively in the future. PMID:26910255

3D Visualization of Developmental Toxicity of 2,4,6-Trinitrotoluene in Zebrafish Embryogenesis Using Light-Sheet Microscopy

PubMed Central

Eum, Juneyong; Kwak, Jina; Kim, Hee Joung; Ki, Seoyoung; Lee, Kooyeon; Raslan, Ahmed A.; Park, Ok Kyu; Chowdhury, Md Ashraf Uddin; Her, Song; Kee, Yun; Kwon, Seung-Hae; Hwang, Byung Joon

2016-01-01

Environmental contamination by trinitrotoluene is of global concern due to its widespread use in military ordnance and commercial explosives. Despite known long-term persistence in groundwater and soil, the toxicological profile of trinitrotoluene and other explosive wastes have not been systematically measured using in vivo biological assays. Zebrafish embryos are ideal model vertebrates for high-throughput toxicity screening and live in vivo imaging due to their small size and transparency during embryogenesis. Here, we used Single Plane Illumination Microscopy (SPIM)/light sheet microscopy to assess the developmental toxicity of explosive-contaminated water in zebrafish embryos and report 2,4,6-trinitrotoluene-associated developmental abnormalities, including defects in heart formation and circulation, in 3D. Levels of apoptotic cell death were higher in the actively developing tissues of trinitrotoluene-treated embryos than controls. Live 3D imaging of heart tube development at cellular resolution by light-sheet microscopy revealed trinitrotoluene-associated cardiac toxicity, including hypoplastic heart chamber formation and cardiac looping defects, while the real time PCR (polymerase chain reaction) quantitatively measured the molecular changes in the heart and blood development supporting the developmental defects at the molecular level. Identification of cellular toxicity in zebrafish using the state-of-the-art 3D imaging system could form the basis of a sensitive biosensor for environmental contaminants and be further valued by combining it with molecular analysis. PMID:27869673

Echocardiography findings in clinically confirmed congenital rubella syndrome cases seen at the University of Port Harcourt Teaching Hospital, Nigeria.

PubMed

Otaigbe, B E; Tabansi, P N; Agbedey, G O

2012-01-01

Congenital rubella syndrome (CRS) is known to affect thousands of children in the developing world because rubella vaccination is not available routinely in most of these countries. Among its many manifestations only congenital heart disease is life threatening. This study was undertaken to ascertain the cases of echocardiographic determined congenital heart disease in clinically confirmed CRS cases. Data of patients with clinically confirmed CRS seen over a period of 5 years in the Paediatric cardiology clinic of the University of Port Harcourt Teaching Hospital was retrieved and analysed. Seven cases (2.8 % of total cardiac cases) were seen. 6 (85.7%) cases had at least one murmur on auscultation. Patent ductus arteriosus was the commonest cardiac defect seen either in isolation or incombination with a VSD or ASD. Only one child had no cardiac defect. 4 (57.1%) of them had been admitted for heart failure at least once and 2 (28.6 %) were on anti-failure regimen, one of whom had cardiac surgery one month ago. In view of the fact that 6 (85.7%) of the patients with CRS had at least one congenital heart defect, we advocate routine echocardiography on patients with CRS to ensure early treatment and reduce mortality and morbidity.We also advocate that rubella vaccination be given routinely in developing countries.

Retrospective study of 156 atrial septal defects in dogs and cats (2001-2005).

PubMed

Chetboul, V; Charles, V; Nicolle, A; Sampedrano, C Carlos; Gouni, V; Pouchelon, J-L; Tissier, R

2006-05-01

Atrial septal defect (ASD) is a common congenital heart disease (CHD) in humans, but considered relatively rare in veterinary medicine. However, modern echocardiographic and Doppler techniques currently offer a good view of the morphology of the interatrial septum, thus facilitating earlier detection of ASD in awake animals. In this context, we carried out a retrospective study of cases of recently diagnosed ASD in dogs and cats at the Cardiology Unit of Alfort (2001-2005) using echocardiography combined with colour Doppler mode. ASD was diagnosed in 156 animals and represented 37.7% of all canine and feline CHDs (n = 414). ASD was the most common CHD after mitral dysplasia in both species. Boxer and Domestic shorthair were the most common canine and feline breeds affected. Most defects (98.7%) were secundum-type ASD, without clinical signs in 73.7% of cases. The most common clinical signs included systolic murmur heard over the left heart base (20.2%), exercise intolerance (7.0%), syncope (5.3%), dyspnoea (2.6%) and cough (2.6%). Animals that presented a systolic heart murmur over the left base had a significantly larger ASD than others (P < 0.05). These data suggest that the incidence of ASD is higher than previously assumed. ASD should be suspected, for example, in instances of left basal systolic heart murmur, although its clinical and haemodynamic consequences are usually minor.

Technological advances shed light on left ventricular cardiac disturbances in cystic fibrosis.

PubMed

Sayyid, Zahra N; Sellers, Zachary M

2017-07-01

Cystic fibrosis (CF), the most common autosomal recessive lethal disease in Caucasians, causes chronic pulmonary disease and can lead to cor pulmonale with right ventricular dysfunction. The presence of the cystic fibrosis transmembrane conductance regulator (CFTR) in cardiac myocardia has prompted debate regarding possible defective ion channel-induced cardiomyopathy. Clinical heart disease in CF is considered rare and is restricted to case reports. It has been unclear if this is due to the lack of physiological importance of CFTR in the heart, the relatively short lifespan of those with CF, or a technical inability to detect subclinical disease. Extensive echocardiographic investigations have yielded contradictory results, leading to the dogma that left ventricular defects in CF occur secondary to lung disease. In this review, we consider why studies examining heart function in CF have not provided clarity on this topic. We then focus on data from new echocardiographic and magnetic resonance imaging technology, which are providing greater insight into cardiac function in CF and demonstrating that, in addition to secondary effects from pulmonary disease, there may be an intrinsic primary defect in the CF heart. With advancing lifespans and activity levels, understanding the risk of cardiac disease is vital to minimizing morbidity in adults with CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Later Competence and Adaptation in Infants Who Survive Severe Heart Defects.

ERIC Educational Resources Information Center

O'Dougherty, Margaret; And Others

1983-01-01

Describes a model of risk potential for developmental outcome that was based on cardiac, medical, surgical, and family stress factors in 31 children with transposition of the great arteries. All children had undergone reparative open heart surgery utilizing cardiopulmonary bypass during infancy. (Author/RH)

Down Syndrome: A Cardiovascular Perspective

ERIC Educational Resources Information Center

Vis, J. C.; Duffels, M. G. J.; Winter, M. M.; Weijerman, M. E.; Cobben, J. M.; Huisman, S. A.; Mulder, B. J. M.

2009-01-01

This review focuses on the heart and vascular system in patients with Down syndrome. A clear knowledge on the wide spectrum of various abnormalities associated with this syndrome is essential for skillful management of cardiac problems in patients with Down syndrome. Epidemiology of congenital heart defects, cardiovascular aspects and…

Burden and impact of congenital syndromes and comorbidities among adults with congenital heart disease.

PubMed

Bracher, Isabelle; Padrutt, Maria; Bonassin, Francesca; Santos Lopes, Bruno; Gruner, Christiane; Stämpfli, Simon F; Oxenius, Angela; De Pasquale, Gabriella; Seeliger, Theresa; Lüscher, Thomas F; Attenhofer Jost, Christine; Greutmann, Matthias

2017-08-01

Our aim was to assess the overall burden of congenital syndromes and non-cardiac comorbidities among adults with congenital heart disease and to assess their impact on circumstances of living and outcomes. Within a cohort of 1725 adults with congenital heart defects (65% defects of moderate or great complexity) followed at a single tertiary care center, congenital syndromes and comorbidities were identified by chart review. Their association with arrhythmias, circumstances of living and survival was analyzed. Within the study cohort, 232 patients (13%) had a genetic syndrome, 51% at least one comorbidity and 23% ≥2 comorbidities. Most prevalent comorbidities were systemic arterial hypertension (11%), thyroid dysfunction (9%), psychiatric disorders (9%), neurologic disorders (7%), chronic lung disease (7%), and previous stroke (6%). In contrast to higher congenital heart defect complexity, the presence of comorbidities had no impact on living circumstances but patients with comorbidities were less likely to work full-time. Atrial arrhythmias were more common among patients with moderate/great disease complexity and those with comorbidities but were less common among patients with congenital syndromes (p<0.01 for all comparisons). Patients with ≥2 comorbidities had lower survival estimates compared to those with ≤1 comorbidity (p=0.013). Congenital syndromes and comorbidities are highly prevalent in adults with congenital heart disease followed at specialist centers and add to the overall complexity of care. The presence of these additional factors has an impact on living circumstances, is associated with arrhythmias and needs to be further explored as prognostic markers. Copyright © 2017 Elsevier B.V. All rights reserved.

Utilizing Three-Dimensional Printing Technology to Assess the Feasibility of High-Fidelity Synthetic Ventricular Septal Defect Models for Simulation in Medical Education.

PubMed

Costello, John P; Olivieri, Laura J; Krieger, Axel; Thabit, Omar; Marshall, M Blair; Yoo, Shi-Joon; Kim, Peter C; Jonas, Richard A; Nath, Dilip S

2014-07-01

The current educational approach for teaching congenital heart disease (CHD) anatomy to students involves instructional tools and techniques that have significant limitations. This study sought to assess the feasibility of utilizing present-day three-dimensional (3D) printing technology to create high-fidelity synthetic heart models with ventricular septal defect (VSD) lesions and applying these models to a novel, simulation-based educational curriculum for premedical and medical students. Archived, de-identified magnetic resonance images of five common VSD subtypes were obtained. These cardiac images were then segmented and built into 3D computer-aided design models using Mimics Innovation Suite software. An Objet500 Connex 3D printer was subsequently utilized to print a high-fidelity heart model for each VSD subtype. Next, a simulation-based educational curriculum using these heart models was developed and implemented in the instruction of 29 premedical and medical students. Assessment of this curriculum was undertaken with Likert-type questionnaires. High-fidelity VSD models were successfully created utilizing magnetic resonance imaging data and 3D printing. Following instruction with these high-fidelity models, all students reported significant improvement in knowledge acquisition (P < .0001), knowledge reporting (P < .0001), and structural conceptualization (P < .0001) of VSDs. It is feasible to use present-day 3D printing technology to create high-fidelity heart models with complex intracardiac defects. Furthermore, this tool forms the foundation for an innovative, simulation-based educational approach to teach students about CHD and creates a novel opportunity to stimulate their interest in this field. © The Author(s) 2014.

Screening and Characterization of Spontaneous Porcine Congenital Heart Defects for Gene Identification and Models of Human Disease

USDA-ARS?s Scientific Manuscript database

Background: Rodent models of human congenital birth defects have been instrumental for gene discovery and investigation of mechanisms of disease. However, these models are limited by their small size making practiced intervention or detailed anatomic evaluation difficult. Swine have similar anato...

Normalization of NAD+ Redox Balance as a Therapy for Heart Failure.

PubMed

Lee, Chi Fung; Chavez, Juan D; Garcia-Menendez, Lorena; Choi, Yongseon; Roe, Nathan D; Chiao, Ying Ann; Edgar, John S; Goo, Young Ah; Goodlett, David R; Bruce, James E; Tian, Rong

2016-09-20

Impairments of mitochondrial function in the heart are linked intricately to the development of heart failure, but there is no therapy for mitochondrial dysfunction. We assessed the reduced/oxidized ratio of nicotinamide adenine dinucleotide (NADH/NAD(+) ratio) and protein acetylation in the failing heart. Proteome and acetylome analyses were followed by docking calculation, mutagenesis, and mitochondrial calcium uptake assays to determine the functional role of specific acetylation sites. The therapeutic effects of normalizing mitochondrial protein acetylation by expanding the NAD(+) pool also were tested. Increased NADH/NAD(+) and protein hyperacetylation, previously observed in genetic models of defective mitochondrial function, also are present in human failing hearts as well as in mouse hearts with pathologic hypertrophy. Elevation of NAD(+) levels by stimulating the NAD(+) salvage pathway suppressed mitochondrial protein hyperacetylation and cardiac hypertrophy, and improved cardiac function in responses to stresses. Acetylome analysis identified a subpopulation of mitochondrial proteins that was sensitive to changes in the NADH/NAD(+) ratio. Hyperacetylation of mitochondrial malate-aspartate shuttle proteins impaired the transport and oxidation of cytosolic NADH in the mitochondria, resulting in altered cytosolic redox state and energy deficiency. Furthermore, acetylation of oligomycin-sensitive conferring protein at lysine-70 in adenosine triphosphate synthase complex promoted its interaction with cyclophilin D, and sensitized the opening of mitochondrial permeability transition pore. Both could be alleviated by normalizing the NAD(+) redox balance either genetically or pharmacologically. We show that mitochondrial protein hyperacetylation due to NAD(+) redox imbalance contributes to the pathologic remodeling of the heart via 2 distinct mechanisms. Our preclinical data demonstrate a clear benefit of normalizing NADH/NAD(+) imbalance in the failing hearts. These findings have a high translational potential as the pharmacologic strategy of increasing NAD(+) precursors are feasible in humans. © 2016 American Heart Association, Inc.

Defective support network: a major obstacle to coping for patients with heart failure: a qualitative study

PubMed Central

Shahrbabaki, Parvin Mangolian; Nouhi, Esmat; Kazemi, Majid; Ahmadi, Fazlollah

2016-01-01

Background Heart failure as a chronic disease poses many challenges for a patient in his or her everyday life. Support in various aspects of life positively affects coping strategies and influences the well-being and health outcomes of heart failure patients. Inadequate support may lead to a worsening of symptoms, increased hospital readmissions, psychological disorders, and a reduced quality of life. Objective This study explored obstacles to coping related to support for heart failure patients as viewed by the patients themselves and their family members and caregivers. Design This qualitative study was conducted using content analysis. The 20 Iranian participants included 11 patients with heart failure, three cardiologists, three nurses, and three family members of heart failure patients selected through purposive sampling. Data were collected through semi-structured interviews and analyzed using the Lundman and Graneheim qualitative content analysis method. Results During data analysis, ‘defective support network’ developed as the main theme along with four other categories of ‘inadequate family performance’, ‘inadequate support by the healthcare team’, ‘distorted societal social support’, and ‘inadequate welfare support’. Conclusion The findings of the current study can assist health authorities and planners in identifying the needs of patients with heart failure so as to focus and plan on facilitating their coping as much as possible by obviating the existing obstacles. PMID:27041539

Heparan Sulfate Biosynthesis Enzyme, Ext1, Contributes to Outflow Tract Development of Mouse Heart via Modulation of FGF Signaling.

PubMed

Zhang, Rui; Cao, Peijuan; Yang, Zhongzhou; Wang, Zhenzhen; Wu, Jiu-Lin; Chen, Yan; Pan, Yi

2015-01-01

Glycosaminoglycans are important regulators of multiple signaling pathways. As a major constituent of the heart extracellular matrix, glycosaminoglycans are implicated in cardiac morphogenesis through interactions with different signaling morphogens. Ext1 is a glycosyltransferase responsible for heparan sulfate synthesis. Here, we evaluate the function of Ext1 in heart development by analyzing Ext1 hypomorphic mutant and conditional knockout mice. Outflow tract alignment is sensitive to the dosage of Ext1. Deletion of Ext1 in the mesoderm induces a cardiac phenotype similar to that of a mutant with conditional deletion of UDP-glucose dehydrogenase, a key enzyme responsible for synthesis of all glycosaminoglycans. The outflow tract defect in conditional Ext1 knockout(Ext1f/f:Mesp1Cre) mice is attributable to the reduced contribution of second heart field and neural crest cells. Ext1 deletion leads to downregulation of FGF signaling in the pharyngeal mesoderm. Exogenous FGF8 ameliorates the defects in the outflow tract and pharyngeal explants. In addition, Ext1 expression in second heart field and neural crest cells is required for outflow tract remodeling. Our results collectively indicate that Ext1 is crucial for outflow tract formation in distinct progenitor cells, and heparan sulfate modulates FGF signaling during early heart development.

Outcome of patients undergoing open heart surgery at the Uganda heart institute, Mulago hospital complex.

PubMed

Aliku, Twalib O; Lubega, Sulaiman; Lwabi, Peter; Oketcho, Michael; Omagino, John O; Mwambu, Tom

2014-12-01

Heart disease is a disabling condition and necessary surgical intervention is often lacking in many developing countries. Training of the superspecialties abroad is largely limited to observation with little or no opportunity for hands on experience. An approach in which open heart surgeries are conducted locally by visiting teams enabling skills transfer to the local team and helps build to build capacity has been adopted at the Uganda Heart Institute (UHI). We reviewed the progress of open heart surgery at the UHI and evaluated the postoperative outcomes and challenges faced in conducting open heart surgery in a developing country. Medical records of patients undergoing open heart surgery at the UHI from October 2007 to June 2012 were reviewed. A total of 124 patients underwent open heart surgery during the study period. The commonest conditions were: venticular septal defects (VSDs) 34.7% (43/124), Atrial septal defects (ASDs) 34.7% (43/124) and tetralogy of fallot (TOF) in 10.5% (13/124). Non governmental organizations (NGOs) funded 96.8% (120/124) of the operations, and in only 4 patients (3.2%) families paid for the surgeries. There was increasing complexity in cases operated upon from predominantly ASDs and VSDs at the beginning to more complex cases like TOFs and TAPVR. The local team independently operated 19 patients (15.3%). Postoperative morbidity was low with arrhythmias, left ventricular dysfunction and re-operations being the commonest seen. Post operative sepsis occurred in only 2 cases (1.6%). The overall mortality rate was 3.2. Open heart surgery though expensive is feasible in a developing country. With increased direct funding from governments and local charities to support open heart surgeries, more cardiac patients access surgical treatment locally.

Alterations in carbohydrate metabolism and its regulation in PPARalpha null mouse hearts

USDA-ARS?s Scientific Manuscript database

Although a shift from fatty acids (FAs) to carbohydrates (CHOs) is considered beneficial for the diseased heart, it is unclear why subjects with FA beta-oxidation defects are prone to cardiac decompensation under stress conditions. The present study investigated potential alterations in the myocardi...

Two brothers with heart defects and limb shortening: case reports and review.

PubMed Central

Reardon, W; Hurst, J; Farag, T I; Hall, C; Baraitser, M

1990-01-01

Two male Arab sibs are reported with congenital heart disease and skeletal malformations. Other published case reports sharing some features in common with these brothers are considered. However, clinical and radiological features in these boys are distinct enough to represent a new cardioskeletal syndrome. Images PMID:2074559

Vitamin D receptor signaling is required for heart development in zebrafish embryo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwon, Hye-Joo, E-mail: hjkwon@pnu.edu.sa; Biology Department, Princess Nourah University, Riyadh 11671

Vitamin D has been found to be associated with cardiovascular diseases. However, the role of vitamin D in heart development during embryonic period is largely unknown. Vitamin D induces its genomic effects through its nuclear receptor, the vitamin D receptor (VDR). The present study investigated the role of VDR on heart development by antisense-mediated knockdown approaches in zebrafish model system. In zebrafish embryos, two distinct VDR genes (vdra and vdrb) have been identified. Knockdown of vdra has little effect on heart development, whereas disrupting vdrb gene causes various cardiac phenotypes, characterized by pericardial edema, slower heart rate and laterality defects.more » Depletion of both vdra and vdrb (vdra/b) produce additive, but not synergistic effects. To determine whether atrioventricular (AV) cardiomyocytes are properly organized in these embryos, the expression of bmp4, which marks the developing AV boundary at 48 h post-fertilization, was examined. Notably, vdra/b-deficient embryos display ectopic expression of bmp4 towards the ventricle or throughout atrial and ventricular chambers. Taken together, these results suggest that VDR signaling plays an essential role in heart development. - Highlights: • VDR signaling is involved in embryonic heart development. • Knockdown of vdrb, but not vdra, causes decreased heart rate in zebrafish embryo. • Loss of vdr results in cardiac laterality defects. • Loss of vdra/b alters atrioventricular boundary formation. • Loss of vdra/b causes abnormal cardiac looping.« less

The E3 ubiquitin ligase Nedd4/Nedd4L is directly regulated by microRNA 1

PubMed Central

Heidersbach, Amy; Kathiriya, Irfan S.; Garay, Bayardo I.; Ivey, Kathryn N.

2017-01-01

miR-1 is a small noncoding RNA molecule that modulates gene expression in heart and skeletal muscle. Loss of Drosophila miR-1 produces defects in somatic muscle and embryonic heart development, which have been partly attributed to miR-1 directly targeting Delta to decrease Notch signaling. Here, we show that overexpression of miR-1 in the fly wing can paradoxically increase Notch activity independently of its effects on Delta. Analyses of potential miR-1 targets revealed that miR-1 directly regulates the 3′UTR of the E3 ubiquitin ligase Nedd4. Analysis of embryonic and adult fly heart revealed that the Nedd4 protein regulates heart development in Drosophila. Larval fly hearts overexpressing miR-1 have profound defects in actin filament organization that are partially rescued by concurrent overexpression of Nedd4. These results indicate that miR-1 and Nedd4 act together in the formation and actin-dependent patterning of the fly heart. Importantly, we have found that the biochemical and genetic relationship between miR-1 and the mammalian ortholog Nedd4-like (Nedd4l) is evolutionarily conserved in the mammalian heart, potentially indicating a role for Nedd4L in mammalian postnatal maturation. Thus, miR-1-mediated regulation of Nedd4/Nedd4L expression may serve to broadly modulate the trafficking or degradation of Nedd4/Nedd4L substrates in the heart. PMID:28246214

ErbB4 in Laminated Brain Structures: A Neurodevelopmental Approach to Schizophrenia

PubMed Central

Perez-Garcia, Carlos G.

2015-01-01

The susceptibility genes for schizophrenia Neuregulin-1 (NRG1) and ErbB4 have critical functions during brain development and in the adult. Alterations in the ErbB4 signaling pathway cause a variety of neurodevelopmental defects including deficiencies in neuronal migration, synaptic plasticity, and myelination. I have used the ErbB4-/- HER4heart KO mice to study the neurodevelopmental insults associated to deficiencies in the NRG1-ErbB4 signaling pathway and their potential implication with brain disorders such as schizophrenia, a chronic psychiatric disease affecting 1% of the population worldwide. ErbB4 deletion results in an array of neurodevelopmental deficits that are consistent with a schizophrenic model. First, similar defects appear in multiple brain structures, from the cortex to the cerebellum. Second, these defects affect multiple aspects of brain development, from deficits in neuronal migration to impairments in excitatory/inhibitory systems, including reductions in brain volume, cortical and cerebellar heterotopias, alterations in number and distribution of specific subpopulations of interneurons, deficiencies in the astrocytic and oligodendrocytic lineages, and additional insults in major brain structures. This suggests that alterations in specific neurodevelopmental genes that play similar functions in multiple neuroanatomical structures might account for some of the symptomatology observed in schizophrenic patients, such as defects in cognition. ErbB4 mutation uncovers flaws in brain development that are compatible with a neurodevelopmental model of schizophrenia, and it establishes a comprehensive model to study the basis of the disorder before symptoms are detected in the adult. PMID:26733804

Tissue Specific Roles for the Ribosome Biogenesis Factor Wdr43 in Zebrafish Development

PubMed Central

Zhao, Chengtian; Andreeva, Viktoria; Gibert, Yann; LaBonty, Melissa; Lattanzi, Victoria; Prabhudesai, Shubhangi; Zhou, Yi; Zon, Leonard; McCann, Kathleen L.; Baserga, Susan; Yelick, Pamela C.

2014-01-01

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome. PMID:24497835

Influence of the medium's dimensionality on defect-mediated turbulence.

PubMed

St-Yves, Ghislain; Davidsen, Jörn

2015-03-01

Spatiotemporal chaos in oscillatory and excitable media is often characterized by the presence of phase singularities called defects. Understanding such defect-mediated turbulence and its dependence on the dimensionality of a given system is an important challenge in nonlinear dynamics. This is especially true in the context of ventricular fibrillation in the heart, where the importance of the thickness of the ventricular wall is contentious. Here, we study defect-mediated turbulence arising in two different regimes in a conceptual model of excitable media and investigate how the statistical character of the turbulence changes if the thickness of the medium is changed from (quasi-) two- dimensional to three dimensional. We find that the thickness of the medium does not have a significant influence in, far from onset, fully developed turbulence while there is a clear transition if the system is close to a spiral instability. We provide clear evidence that the observed transition and change in the mechanism that drives the turbulent behavior is purely a consequence of the dimensionality of the medium. Using filament tracking, we further show that the statistical properties in the three-dimensional medium are different from those in turbulent regimes arising from filament instabilities like the negative line tension instability. Simulations also show that the presence of this unique three-dimensional turbulent dynamics is not model specific.

Complex Genetics and the Etiology of Human Congenital Heart Disease

PubMed Central

Gelb, Bruce D.; Chung, Wendy K.

2014-01-01

Congenital heart disease (CHD) is the most common birth defect. Despite considerable advances in care, CHD remains a major contributor to newborn mortality and is associated with substantial morbidities and premature death. Genetic abnormalities appear to be the primary cause of CHD, but identifying precise defects has proven challenging, principally because CHD is a complex genetic trait. Mainly because of recent advances in genomic technology such as next-generation DNA sequencing, scientists have begun to identify the genetic variants underlying CHD. In this article, the roles of modifier genes, de novo mutations, copy number variants, common variants, and noncoding mutations in the pathogenesis of CHD are reviewed. PMID:24985128

Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function.

PubMed

Sarmah, Swapnalee; Marrs, James A

2016-12-16

Environmental pollution is a serious problem of the modern world that possesses a major threat to public health. Exposure to environmental pollutants during embryonic development is particularly risky. Although many pollutants have been verified as potential toxicants, there are new chemicals in the environment that need assessment. Heart development is an extremely sensitive process, which can be affected by environmentally toxic molecule exposure during embryonic development. Congenital heart defects are the most common life-threatening global health problems, and the etiology is mostly unknown. The zebrafish has emerged as an invaluable model to examine substance toxicity on vertebrate development, particularly on cardiac development. The zebrafish offers numerous advantages for toxicology research not found in other model systems. Many laboratories have used the zebrafish to study the effects of widespread chemicals in the environment on heart development, including pesticides, nanoparticles, and various organic pollutants. Here, we review the uses of the zebrafish in examining effects of exposure to external molecules during embryonic development in causing cardiac defects, including chemicals ubiquitous in the environment and illicit drugs. Known or potential mechanisms of toxicity and how zebrafish research can be used to provide mechanistic understanding of cardiac defects are discussed.

Regional Microstructural and Volumetric Magnetic Resonance Imaging (MRI) Abnormalities in the Corpus Callosum of Neonates With Congenital Heart Defect Undergoing Cardiac Surgery.

PubMed

Hagmann, Cornelia; Singer, Jitka; Latal, Beatrice; Knirsch, Walter; Makki, Malek

2016-03-01

The purpose of the study is to investigate the structural development of the corpus callosum in term neonates with congenital heart defect before and after surgery using diffusion tensor imaging and 3-dimensional T1-weighted magnetic resonance imaging (MRI). We compared parallel and radial diffusions, apparent diffusion coefficient (ADC), fractional anisotropy, and volume of 5 substructures of the corpus callosum: genu, rostral body, body, isthmus, and splenium. Compared to healthy controls, we found a significantly lower volume of the splenium and total corpus callosum and a higher radial diffusion and lower fractional anisotropy in the splenium of patients presurgery; a lower volume in all substructures in the postsurgery group; higher radial diffusion in the rostral body, body, and splenium; and a higher apparent diffusion coefficient in the splenium of postsurgery patients. Similar fractional anisotropy changes in congenital heart defect patients were reported in preterm infants. Our findings in apparent diffusion coefficient in the splenium of these patients (pre and postsurgery) are comparable to findings in preterm neonates with psychomotor delay. Delayed maturation of the isthmus was also reported in preterm infants. © The Author(s) 2015.

Clinical application of three-dimensional reconstruction and rapid prototyping technology of multislice spiral computed tomography angiography for the repair of ventricular septal defect of tetralogy of Fallot.

PubMed

Ma, X J; Tao, L; Chen, X; Li, W; Peng, Z Y; Chen, Y; Jin, J; Zhang, X L; Xiong, Q F; Zhong, Z L; Chen, X F

2015-02-13

Three-dimensional (3D) reconstruction and rapid prototyping technology (RPT) of multislice spiral computed tomography angiography (CTA) was applied to prepare physical models of the heart and ventricular septal defects of tetralogy of Fallot (ToF) patients in order to explore their applications in the diagnosis and treatment of this complex heart disease. CTA data of 35 ToF patients were collected to prepare l:l 3D solid models using digital 3D reconstruction and RPT, and the resultant models were used intraoperatively as reference. The operations of all 35 patients were completed under the guidance of the 3D solid model, without difficulty. Intraoperative findings of the patients were consistent with the morphological and size changes of the 3D solid model, and no significant differences were found between the patches obtained from the 3D solid model and the actual intraoperative measurements (t = 0.83, P = 0.412). 3D reconstruction and RPT of multislice spiral CTA can accurately and intuitively reflect the anatomy of ventricular septal defects in ToF patients, providing the foundation for a solid model of the complex congenital heart.

3D Printing in Surgical Management of Double Outlet Right Ventricle.

PubMed

Yoo, Shi-Joon; van Arsdell, Glen S

2017-01-01

Double outlet right ventricle (DORV) is a heterogeneous group of congenital heart diseases that require individualized surgical approach based on precise understanding of the complex cardiovascular anatomy. Physical 3-dimensional (3D) print models not only allow fast and unequivocal perception of the complex anatomy but also eliminate misunderstanding or miscommunication among imagers and surgeons. Except for those cases showing well-recognized classic surgical anatomy of DORV such as in cases with a typical subaortic or subpulmonary ventricular septal defect, 3D print models are of enormous value in surgical decision and planning. Furthermore, 3D print models can also be used for rehearsal of the intended procedure before the actual surgery on the patient so that the outcome of the procedure is precisely predicted and the procedure can be optimally tailored for the patient's specific anatomy. 3D print models are invaluable resource for hands-on surgical training of congenital heart surgeons.

Dysregulated endocardial TGFβ signaling and mesenchymal transformation result in heart outflow tract septation failure.

PubMed

Ma, Mancheong; Li, Peng; Shen, Hua; Estrada, Kristine D; Xu, Jian; Kumar, S Ram; Sucov, Henry M

2016-01-01

Heart outflow tract septation in mouse embryos carrying mutations in retinoic acid receptor genes fails with complete penetrance. In this mutant background, ectopic TGFβ signaling in the distal outflow tract is responsible for septation failure, but it was uncertain what tissue was responsive to ectopic TGFβ and why this response interfered with septation. By combining RAR gene mutation with tissue-specific Cre drivers and a conditional type II TGFβ receptor (Tgfbr2) allele, we determined that ectopic activation of TGFβ signaling in the endocardium is responsible for septation defects. Ectopic TGFβ signaling results in ectopic mesenchymal transformation of the endocardium and thereby in improperly constituted distal OFT cushions. Our analysis highlights the interactions between myocardium, endocardium, and neural crest cells in outflow tract morphogenesis, and demonstrates the requirement for proper TGFβ signaling in outflow tract cushion organization and septation. Copyright © 2015. Published by Elsevier Inc.

Risks and Benefits of Exercise Training in Adults With Congenital Heart Disease.

PubMed

Chaix, Marie-A; Marcotte, François; Dore, Annie; Mongeon, François-Pierre; Mondésert, Blandine; Mercier, Lise-Andrée; Khairy, Paul

2016-04-01

Exercise capacity in adults with various forms of congenital heart disease is substantially lower than that of the general population. Although the underlying congenital heart defect, and its sequelae, certainly contribute to observed exercise limitations, there is evidence suggesting that deconditioning and a sedentary lifestyle are important implicated factors. The prevalence of acquired cardiovascular comorbidities is on the increase in the aging population with congenital heart disease, such that obesity and a sedentary lifestyle confer increased risk. Health fears and misconceptions are common barriers to regular physical activity in adults with congenital heart disease, despite evidence linking lower functional capacity to poor outcomes, and data supporting the safety and efficacy of exercise in bestowing numerous physical and psychosocial rewards. With few exceptions, adults with congenital heart disease should be counselled to exercise regularly. In this contemporary review, we provide a practical approach to assessing adults with congenital heart disease before exercise training. We examine available evidence supporting the safety and benefits of exercise training. Risks associated with exercise training in adults with congenital heart disease are discussed, particularly with regard to sudden cardiac death. Finally, recommendations for exercise training are provided, with consideration for the type of congenital heart disease, the nature (ie, static vs dynamic) and intensity (ie, low, medium, high) of the physical activity, and associated factors such as systemic ventricular dysfunction and residual defects. Further research is required to determine optimal exercise regimens and to identify effective strategies to implement exercise training as a key determinant of healthy living. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

[Axillary approach for surgical closure of atrial septal defect].

PubMed

Gil-Jaurena, J M; Castillo, R; Zabala, J I; Conejo, L; Cuenca, V; Picazo, B

2013-08-01

Mid-line sternotomy is the routine approach for surgical repair of congenital heart diseases. However, its noticeable scar is a constant reminder of having undergone heart surgery. Several alternative approaches have been developed for simple cardiac conditions to hide the scar. Our series, consisting of 26 patients with axillary closure of atrial septal defect, is presented. The median age was 5.45 years (range 3-13), and median weight was 19.84 Kg. (range 13-37). The defect was closed directly in 13 cases, and with an autologous pericardial patch in the other 13. The number of surgical steps and time taken were the same as in median sternotomy. Functional recovery, intensive care unit stay, and hospital discharge were also standard. The cosmetic result, assessed both by patients and relatives, was excellent. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Anatomy of the ventricular septal defect in outflow tract defects: similarities and differences.

PubMed

Mostefa-Kara, Meriem; Bonnet, Damien; Belli, Emre; Fadel, Elie; Houyel, Lucile

2015-03-01

The study objective was to analyze the anatomy of the ventricular septal defect found in various phenotypes of outflow tract defects. We reviewed 277 heart specimens with isolated outlet ventricular septal defect without subpulmonary stenosis (isolated outlet ventricular septal defect, 19); tetralogy of Fallot (71); tetralogy of Fallot with pulmonary atresia (51); common arterial trunk (54); double outlet right ventricle (65) with subaortic, doubly committed, or subpulmonary ventricular septal defect; and interrupted aortic arch type B (17). Special attention was paid to the rims of the ventricular septal defect viewed from the right ventricular side and the relationships between the tricuspid and aortic valves. The ventricular septal defect was always located in the outlet of the right ventricle, between the 2 limbs of the septal band. There was a fibrous continuity between the tricuspid and aortic valves in 74% of specimens with isolated outlet ventricular septal defect, 66% of specimens with tetralogy of Fallot, 39% of specimens with tetralogy of Fallot with pulmonary atresia, 4.6% of specimens with double outlet right ventricle, 1.8% of specimens with common arterial trunk, and zero of specimens with interrupted aortic arch type B (P < .005). When present, this continuity always involved the anterior tricuspid leaflet. The ventricular septal defect in outflow tract defects is always an outlet ventricular septal defect, cradled between the 2 limbs of the septal band. However, there are some differences regarding the posteroinferior and superior rims of the ventricular septal defect. These differences suggest an anatomic continuum from the isolated outlet ventricular septal defect to the interrupted aortic arch type B rather than distinct physiologic phenotypes, related to various degrees of abnormal rotation of the outflow tract during heart development: minimal in isolated outlet ventricular septal defect; incomplete in tetralogy of Fallot, tetralogy of Fallot with pulmonary atresia, and double outlet right ventricle; absent in common arterial trunk; and excessive in interrupted aortic arch type B. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology

PubMed Central

Roncaglia, Paola; Howe, Douglas G.; Laulederkind, Stanley J.F.; Khodiyar, Varsha K.; Berardini, Tanya Z.; Tweedie, Susan; Foulger, Rebecca E.; Osumi-Sutherland, David; Campbell, Nancy H.; Huntley, Rachael P.; Talmud, Philippa J.; Blake, Judith A.; Breckenridge, Ross; Riley, Paul R.; Lambiase, Pier D.; Elliott, Perry M.; Clapp, Lucie; Tinker, Andrew; Hill, David P.

2018-01-01

Background: A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. Methods and Results: In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. Conclusions: We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. PMID:29440116

Acquired deficiency of tafazzin in the adult heart: Impact on mitochondrial function and response to cardiac injury.

PubMed

Szczepanek, Karol; Allegood, Jeremy; Aluri, Hema; Hu, Ying; Chen, Qun; Lesnefsky, Edward J

2016-04-01

The content and composition of cardiolipin (CL) is critical for preservation of mitochondrial oxidative phosphorylation (OXPHOS) and inner membrane integrity. Tafazzin (Taz) is an enzyme responsible for remodeling of immature CL containing mixed acyl groups into the mature tetralinoleyl form (C18:2)4-CL. We hypothesized that acquired defects in Taz in the mature heart would impact remodeling of CL and augment cardiac injury. The role of acquired Taz deficiency was studied using the inducible Taz knockdown (TazKD) mouse. Taz-specific shRNA is induced by doxycycline (DOX). One day of DOX intake decreased Taz mRNA in the heart to 20% vs. DOX-treated WT. Knockdown was initiated at an adult age and was stable during long term feeding. CL phenotype was assessed by (C18:2)4-CL content and was reduced 40% vs. WT at two months of DOX. TazKD showed increased production of reactive oxygen species and increased susceptibility to permeability transition pore opening at baseline. However, OXPHOS measured using the rate of oxygen consumption was unchanged in the setting of acquired Taz deficiency. Infarct size, measured in isolated buffer-perfused Langendorff hearts following 25min. Stop flow ischemia and 60min. Reperfusion was not altered in TazKD hearts. Thus, impaired Taz-function with onset at adult age does not enhance susceptibility to ischemia-reperfusion injury. Published by Elsevier B.V.

Mechanical Circulatory Support of the Right Ventricle for Adult and Pediatric Patients With Heart Failure.

PubMed

Chopski, Steven G; Murad, Nohra M; Fox, Carson S; Stevens, Randy M; Throckmorton, Amy L

2018-05-10

The clinical implementation of mechanical circulatory assistance for a significantly dysfunctional or failing left ventricle as a bridge-to-transplant or bridge-to-recovery is on the rise. Thousands of patients with left-sided heart failure are readily benefitting from these life-saving technologies, and left ventricular failure often leads to severe right ventricular dysfunction or failure. Right ventricular failure (RVF) has a high rate of mortality caused by the risk of multisystem organ failure and prolonged hospitalization for patients after treatment. The use of a blood pump to support the left ventricle also typically results in an increase in right ventricular preload and may impair right ventricular contractility during left ventricular unloading. Patients with RVF might also suffer from severe pulmonary dysfunction, cardiac defects, congenital heart disease states, or a heterogeneity of cardiophysiologic challenges because of symptomatic congestive heart failure. Thus, the uniqueness and complexity of RVF is emerging as a new domain of significant clinical interest that motivates the development of right ventricular assist devices. In this review, we present the current state-of-the-art for clinically used blood pumps to support adults and pediatric patients with right ventricular dysfunction or failure concomitant with left ventricular failure. New innovative devices specifically for RVF are also highlighted. There continues to be a compelling need for novel treatment options to support patients with significant right heart dysfunction or failure.

Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology.

PubMed

Lovering, Ruth C; Roncaglia, Paola; Howe, Douglas G; Laulederkind, Stanley J F; Khodiyar, Varsha K; Berardini, Tanya Z; Tweedie, Susan; Foulger, Rebecca E; Osumi-Sutherland, David; Campbell, Nancy H; Huntley, Rachael P; Talmud, Philippa J; Blake, Judith A; Breckenridge, Ross; Riley, Paul R; Lambiase, Pier D; Elliott, Perry M; Clapp, Lucie; Tinker, Andrew; Hill, David P

2018-02-01

A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. © 2018 The Authors.

Targets for therapy in sarcomeric cardiomyopathies

PubMed Central

Tardiff, Jil C.; Carrier, Lucie; Bers, Donald M.; Poggesi, Corrado; Ferrantini, Cecilia; Coppini, Raffaele; Maier, Lars S.; Ashrafian, Houman; Huke, Sabine; van der Velden, Jolanda

2015-01-01

To date, no compounds or interventions exist that treat or prevent sarcomeric cardiomyopathies. Established therapies currently improve the outcome, but novel therapies may be able to more fundamentally affect the disease process and course. Investigations of the pathomechanisms are generating molecular insights that can be useful for the design of novel specific drugs suitable for clinical use. As perturbations in the heart are stage-specific, proper timing of drug treatment is essential to prevent initiation and progression of cardiac disease in mutation carrier individuals. In this review, we emphasize potential novel therapies which may prevent, delay, or even reverse hypertrophic cardiomyopathy caused by sarcomeric gene mutations. These include corrections of genetic defects, altered sarcomere function, perturbations in intracellular ion homeostasis, and impaired myocardial energetics. PMID:25634554

Facts about Alcohol and Other Drug Use during Pregnancy. ARC Facts.

ERIC Educational Resources Information Center

Association for Retarded Citizens, Arlington, TX.

The fact sheet provides basic information about how alcohol and drug use during pregnancy can lead to Fetal Alcohol Syndrome (FAS) and Alcohol Related Birth Defects (ARBD), resulting in such problems as mental retardation, sleep disturbances, learning disabilities, muscle problems, heart defects, and small head size. The question and answer format…

The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease

PubMed Central

Ronemus, Michael; Kline, Jennie; Jobanputra, Vaidehi; Williams, Ismee; Anyane-Yeboa, Kwame; Chung, Wendy; Yu, Lan; Wong, Nancy; Awad, Danielle; Yu, Chih-yu; Leotta, Anthony; Kendall, Jude; Yamrom, Boris; Lee, Yoon-ha; Wigler, Michael; Levy, Dan

2013-01-01

Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was used to identify de novo and rare inherited copy number variants (CNVs). Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in 8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4 probands with both. Only 2 % of control families showed a de novo CNV. We also identified a group of ultra-rare inherited CNVs that occurred de novo in our sample, contained a candidate gene for CHD, recurred in our sample or were present in an affected sibling. We confirmed the contribution to CHD of copy number changes in genes such as GATA4 and NODAL and identified several genes in novel recurrent CNVs that may point to novel CHD candidate loci. We also found CNVs previously associated with highly variable pheno-types and reduced penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and del 2q23.1. We found that the presence of extra-cardiac anomalies was not related to the frequency of CNVs, and that there was no significant difference in CNV frequency or specificity between the probands with CNT and HLHS. In agreement with other series, we identified likely causal CNVs in 5.6 % of our total sample, half of which were de novo. PMID:23979609

The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease.

PubMed

Warburton, Dorothy; Ronemus, Michael; Kline, Jennie; Jobanputra, Vaidehi; Williams, Ismee; Anyane-Yeboa, Kwame; Chung, Wendy; Yu, Lan; Wong, Nancy; Awad, Danielle; Yu, Chih-Yu; Leotta, Anthony; Kendall, Jude; Yamrom, Boris; Lee, Yoon-Ha; Wigler, Michael; Levy, Dan

2014-01-01

Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was used to identify de novo and rare inherited copy number variants (CNVs). Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in 8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4 probands with both. Only 2 % of control families showed a de novo CNV. We also identified a group of ultra-rare inherited CNVs that occurred de novo in our sample, contained a candidate gene for CHD, recurred in our sample or were present in an affected sibling. We confirmed the contribution to CHD of copy number changes in genes such as GATA4 and NODAL and identified several genes in novel recurrent CNVs that may point to novel CHD candidate loci. We also found CNVs previously associated with highly variable phenotypes and reduced penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and del 2q23.1. We found that the presence of extra-cardiac anomalies was not related to the frequency of CNVs, and that there was no significant difference in CNV frequency or specificity between the probands with CNT and HLHS. In agreement with other series, we identified likely causal CNVs in 5.6 % of our total sample, half of which were de novo.

Transcriptional coactivators PGC-1α and PGC-lβ control overlapping programs required for perinatal maturation of the heart

PubMed Central

Lai, Ling; Leone, Teresa C.; Zechner, Christoph; Schaeffer, Paul J.; Kelly, Sean M.; Flanagan, Daniel P.; Medeiros, Denis M.; Kovacs, Attila; Kelly, Daniel P.

2008-01-01

Oxidative tissues such as heart undergo a dramatic perinatal mitochondrial biogenesis to meet the high-energy demands after birth. PPARγ coactivator-1 (PGC-1) α and β have been implicated in the transcriptional control of cellular energy metabolism. Mice with combined deficiency of PGC-1α and PGC-1β (PGC-1αβ−/− mice) were generated to investigate the convergence of their functions in vivo. The phenotype of PGC-1β−/− mice was minimal under nonstressed conditions, including normal heart function, similar to that of PGC-1α−/− mice generated previously. In striking contrast to the singly deficient PGC-1 lines, PGC-1αβ−/− mice died shortly after birth with small hearts, bradycardia, intermittent heart block, and a markedly reduced cardiac output. Cardiac-specific ablation of the PGC-1β gene on a PGC-1α-deficient background phenocopied the generalized PGC-1αβ−/− mice. The hearts of the PGC-1αβ−/− mice exhibited signatures of a maturational defect including reduced growth, a late fetal arrest in mitochondrial biogenesis, and persistence of a fetal pattern of gene expression. Brown adipose tissue (BAT) of PGC-1αβ−/− mice also exhibited a severe abnormality in function and mitochondrial density. We conclude that PGC-1α and PGC-1β share roles that collectively are necessary for the postnatal metabolic and functional maturation of heart and BAT. PMID:18628400

Prenatal diagnosis of two fetuses with deletions of 8p23.1, critical region for congenital diaphragmatic hernia and heart defects.

PubMed

Keitges, Elisabeth A; Pasion, Romela; Burnside, Rachel D; Mason, Carla; Gonzalez-Ruiz, Antonio; Dunn, Teresa; Masiello, Meredith; Gebbia, Joseph A; Fernandez, Carlos O; Risheg, Hiba

2013-07-01

Microdeletions of 8p23.1 are mediated by low copy repeats and can cause congenital diaphragmatic hernia (CDH) and cardiac defects. Within this region, point mutations of the GATA4 gene have been shown to cause cardiac defects. However, the cause of CDH in these deletions has been difficult to determine due to the paucity of mutations that result in CDH, the lack of smaller deletions to refine the region and the reduced penetrance of CDH in these large deletions. Mice deficient for one copy of the Gata4 gene have been described with CDH and heart defects suggesting mutations in Gata4 can cause the phenotype in mice. We report on the SNP microarray analysis on two fetuses with deletions of 8p23.1. The first had CDH and a ventricular septal defect (VSD) on ultrasonography and a family history of a maternal VSD. Microarray analysis detected a 127-kb deletion which included the GATA4 and NEIL2 genes which was inherited from the mother. The second fetus had an incomplete atrioventricular canal defect on ultrasonography. Microarray analysis showed a 315-kb deletion that included seven genes, GATA4, NEIL2, FDFT1, CTSB, DEFB136, DEFB135, and DEFB134. These results suggest that haploinsufficiency of the two genes in common within 8p23.1; GATA4 and NEIL2 can cause CDH and cardiac defects in humans. Copyright © 2013 Wiley Periodicals, Inc.

Betaine supplementation reduces congenital defects after prenatal alcohol exposure (Conference Presentation)

NASA Astrophysics Data System (ADS)

Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Sheehan, Megan M.; Ma, Pei; Peterson, Lindsy M.; Linask, Kersti K.; Jenkins, Michael W.; Rollins, Andrew M.; Watanabe, Michiko

2016-03-01

Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. As high as 20-50% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects including outflow and valvuloseptal anomalies that can be life-threatening. Previously we established a model of PAE (modeling a single binge drinking episode) in the avian embryo and used optical coherence tomography (OCT) imaging to assay early-stage cardiac function/structure and late-stage cardiac defects. At early stages, alcohol/ethanol-exposed embryos had smaller cardiac cushions and increased retrograde flow. At late stages, they presented with gross morphological defects in the head and chest wall, and also exhibited smaller or abnormal atrio-ventricular (AV) valves, thinner interventricular septae (IVS), and smaller vessel diameters for the aortic trunk branches. In other animal models, the methyl donor betaine (found naturally in many foods such as wheat bran, quinoa, beets and spinach) ameliorates neurobehavioral deficits associated with PAE but the effects on heart structure are unknown. In our model of PAE, betaine supplementation led to a reduction in gross structural defects and appeared to protect against certain types of cardiac defects such as ventricular septal defects and abnormal AV valvular morphology. Furthermore, vessel diameters, IVS thicknesses and mural AV leaflet volumes were normalized while the septal AV leaflet volume was increased. These findings highlight the importance of betaine and potentially methylation levels in the prevention of PAE-related birth defects which could have significant implications for public health.

Academic Outcomes in Children With Congenital Heart Defects: A Population-Based Cohort Study.

PubMed

Oster, Matthew E; Watkins, Stephanie; Hill, Kevin D; Knight, Jessica H; Meyer, Robert E

2017-02-01

Most studies evaluating neurocognitive outcomes in children with congenital heart defects (CHD) have focused on high-risk patients or used specialized, resource-intensive testing. To determine the association of CHD with academic outcomes and compare outcomes according to the severity of CHD, we linked state educational records with a birth defects registry and birth certificates. We performed a retrospective cohort study using data from the North Carolina Birth Defects Monitoring Program, North Carolina Department of Public Instruction, and North Carolina Department of Health and Human Services vital records. We performed logistic regression, adjusting for maternal education, race/ethnicity, enrollment in public pre-Kindergarten, and gestational age, to determine the association of CHD with not meeting standards on reading and math end-of-grade examinations in third grade in 2006 to 2012. Of 5624 subjects with CHD and 10 832 with no structural birth defects, 2807 (50%) and 6355 (59%) were linked, respectively. Children with CHD had 1.24× the odds of not meeting standards in either reading or math (95% confidence interval, 1.12-1.37), with 44.6% of children with CHD not meeting standards in at least one of these areas compared with 37.5% without CHD. Although children with both critical and noncritical CHD had poorer outcomes, those with critical CHD were significantly more likely to receive exceptional services compared with the noncritical group (adjusted odds ratio, 1.46; 95% confidence interval, 1.15-1.86). Children with all types of CHD have poorer academic outcomes compared with their peers. Evaluation for exceptional services should be considered in children with any type of CHD. © 2017 American Heart Association, Inc.

Bnip3 mediates doxorubicin-induced cardiac myocyte necrosis and mortality through changes in mitochondrial signaling

PubMed Central

Dhingra, Rimpy; Margulets, Victoria; Chowdhury, Subir Roy; Thliveris, James; Jassal, Davinder; Fernyhough, Paul; Dorn, Gerald W.; Kirshenbaum, Lorrie A.

2014-01-01

Doxorubicin (DOX) is widely used for treating human cancers, but can induce heart failure through an undefined mechanism. Herein we describe a previously unidentified signaling pathway that couples DOX-induced mitochondrial respiratory chain defects and necrotic cell death to the BH3-only protein Bcl-2-like 19kDa-interacting protein 3 (Bnip3). Cellular defects, including vacuolization and disrupted mitochondria, were observed in DOX-treated mice hearts. This coincided with mitochondrial localization of Bnip3, increased reactive oxygen species production, loss of mitochondrial membrane potential, mitochondrial permeability transition pore opening, and necrosis. Interestingly, a 3.1-fold decrease in maximal mitochondrial respiration was observed in cardiac mitochondria of mice treated with DOX. In vehicle-treated control cells undergoing normal respiration, the respiratory chain complex IV subunit 1 (COX1) was tightly bound to uncoupling protein 3 (UCP3), but this complex was disrupted in cells treated with DOX. Mitochondrial dysfunction induced by DOX was accompanied by contractile failure and necrotic cell death. Conversely, shRNA directed against Bnip3 or a mutant of Bnip3 defective for mitochondrial targeting abrogated DOX-induced loss of COX1-UCP3 complexes and respiratory chain defects. Finally, Bnip3−/− mice treated with DOX displayed relatively normal mitochondrial morphology, respiration, and mortality rates comparable to those of saline-treated WT mice, supporting the idea that Bnip3 underlies the cardiotoxic effects of DOX. These findings reveal a new signaling pathway in which DOX-induced mitochondrial respiratory chain defects and necrotic cell death are mutually dependent on and obligatorily linked to Bnip3 gene activation. Interventions that antagonize Bnip3 may prove beneficial in preventing mitochondrial injury and heart failure in cancer patients undergoing chemotherapy. PMID:25489073

Micro-computed Tomography Provides High Accuracy Congenital Heart Disease Diagnosis in Neonatal and Fetal Mice

PubMed Central

Kim, Andrew J.; Francis, Richard; Liu, Xiaoqin; Devine, William A.; Ramirez, Ricardo; Anderton, Shane J.; Wong, Li Yin; Faruque, Fahim; Gabriel, George C.; Leatherbury, Linda; Tobita, Kimimasa; Lo, Cecilia W.

2013-01-01

Background Mice are well suited for modeling human congenital heart defects (CHD), given their four-chamber cardiac anatomy. However, mice with CHD invariably die prenatally/neonatally, causing CHD phenotypes to be missed. Therefore, we investigated the efficacy of noninvasive micro-computed tomography (micro-CT) to screen for CHD in stillborn/fetal mice. These studies were carried out using chemically mutagenized mice expected to be enriched for birth defects including CHD. Methods and Results Stillborn/fetal mice obtained from the breeding of N-ethyl-N-nitrosourea (ENU) mutagenized mice were formalin-fixed and stained with iodine, then micro-CT scanned. Those diagnosed with CHD and some CHD-negative pups were necropsied. A subset of these were further analyzed by histopathology to confirm the CHD/no-CHD diagnosis. Micro-CT scanning of 2105 fetal/newborn mice revealed an abundance of ventricular septal defects (VSD) (n=307). Overall, we observed an accuracy of 89.8% for VSD diagnosis. Outflow tract anomalies identified by micro-CT included double outlet right ventricle (n=36), transposition of the great arteries (n=14), and persistent truncus arteriosus (n=3). These were diagnosed with a 97.4% accuracy. Aortic arch anomalies also were readily detected with an overall 99.6% accuracy. This included right aortic arch (n=28) and coarctation/interrupted aortic arch (n=12). Also detected by micro-CT were atrioventricular septal defects (n=22), tricuspid hypoplasia/atresia (n=13), and coronary artery fistulas (n=16). They yielded accuracies of 98.9%, 100%, and 97.8% respectively. Conclusions Contrast enhanced micro-CT imaging in neonatal/fetal mice can reliably detect a wide spectrum of CHD. We conclude micro-CT imaging can be used for routine rapid assessments of structural heart defects in fetal/newborn mice. PMID:23759365

Educational achievement among long-term survivors of congenital heart defects: a Danish population-based follow-up study.

PubMed

Olsen, Morten; Hjortdal, Vibeke E; Mortensen, Laust H; Christensen, Thomas D; Sørensen, Henrik T; Pedersen, Lars

2011-04-01

Congenital heart defect patients may experience neurodevelopmental impairment. We investigated their educational attainments from basic schooling to higher education. Using administrative databases, we identified all Danish patients with a cardiac defect diagnosis born from 1 January, 1977 to 1 January, 1991 and alive at age 13 years. As a comparison cohort, we randomly sampled 10 persons per patient. We obtained information on educational attainment from Denmark's Database for Labour Market Research. The study population was followed until achievement of educational levels, death, emigration, or 1 January, 2006. We estimated the hazard ratio of attaining given educational levels, conditional on completing preceding levels, using discrete-time Cox regression and adjusting for socio-economic factors. Analyses were repeated for a sub-cohort of patients and controls born at term and without extracardiac defects or chromosomal anomalies. We identified 2986 patients. Their probability of completing compulsory basic schooling was approximately 10% lower than that of control individuals (adjusted hazard ratio = 0.79, ranged from 0.75 to 0.82 0.79; 95% confidence interval: 0.75-0.82). Their subsequent probability of completing secondary school was lower than that of the controls, both for all patients (adjusted hazard ratio = 0.74; 95% confidence interval: 0.69-0.80) and for the sub-cohort (adjusted hazard ratio = 0.80; 95% confidence interval: 0.73-0.86). The probability of attaining a higher degree, conditional on completion of youth education, was affected both for all patients (adjusted hazard ratio = 0.88; 95% confidence interval: 0.76-1.01) and for the sub-cohort (adjusted hazard ratio = 0.92; 95% confidence interval: 0.79-1.07). The probability of educational attainment was reduced among long-term congenital heart defect survivors.

[Sex differences in congenital heart disease].

PubMed

Aubry, P; Demian, H

2016-12-01

Gender influences the clinical presentation and the management of some acquired cardiovascular diseases, such as coronary artery disease, resulting in different outcomes. Differences between women and men are also noticed in congenital heart disease. They are mainly related to the prevalence and severity of some congenital heart defects at birth, and in adulthood to the prognosis, incidence of Eisenmenger syndrome and risks of pregnancy. The role of gender on the risk of operative mortality of congenital heart surgery remains debated. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Fungal infections in children in the early postoperative period after cardiac surgery for congenital heart disease: a single-centre experience.

PubMed

Jaworski, Radoslaw; Haponiuk, Ireneusz; Irga-Jaworska, Ninela; Chojnicki, Maciej; Steffens, Mariusz; Paczkowski, Konrad; Zielinski, Jacek

2016-09-01

Postoperative infections are still an important problem in cardiac surgery, especially in the paediatric population, and may influence the final outcome of congenital heart disease treatment. Postoperative infections with fungi are uncommon. The aetiology is poorly understood, and the proper diagnosis and treatment is unclear. In this single-centre study, the frequency of invasive fungal disease in children who underwent surgical management of congenital heart diseases was determined along with the risk factors for infection, treatment options and outcomes. All consecutive paediatric patients (<18 years of age) who underwent cardiac surgery for congenital heart disease between September 2008 and December 2015 in a paediatric cardiac centre in Poland were identified. Those who developed invasive fungal disease in the early postoperative period (30 days) were identified. Of the 1540 cardiosurgical procedures for congenital heart disease, 6 were complicated by fungal infection (0.39%). One patient had a high probability of fungal infection, but the diagnosis was unproved. Nevertheless, the patient was successfully treated with antifungal treatment. Five had proven invasive fungal disease. Of these, 3 were diagnosed with candidaemia. All had undergone cardiopulmonary bypass. Of the remaining 2 patients, 1 was a preterm newborn with complete atrioventricular septal defect who developed rib fungal invasion. The remaining patient had pulmonary atresia with ventricular septal defect and developed Fournier's gangrene after surgery. None of the patients died due to infection in the early postoperative period. However, the child with rib fungal invasion died 39 days after surgery as a result of multiorgan failure. Fungal infections in paediatric patients after cardiac surgery may markedly influence morbidity and mortality. Fungal infection prophylaxis in this specific group of children may reduce morbidity, whereas early empirical treatment followed by a targeted approach may improve outcomes. The 'hit fast, hit hard' treatment strategy may be the best rescue option for children who develop invasive fungal disease after cardiac surgery. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Four-dimensional ultrasonography of the fetal heart with spatiotemporal image correlation.

PubMed

Gonçalves, Luís F; Lee, Wesley; Chaiworapongsa, Tinnakorn; Espinoza, Jimmy; Schoen, Mary Lou; Falkensammer, Peter; Treadwell, Marjorie; Romero, Roberto

2003-12-01

This study was undertaken to describe a new technique for the examination of the fetal heart using four-dimensional ultrasonography with spatiotemporal image correlation (STIC). Volume data sets of the fetal heart were acquired with a new cardiac gating technique (STIC), which uses automated transverse and longitudinal sweeps of the anterior chest wall. These volumes were obtained from 69 fetuses: 35 normal, 16 with congenital anomalies not affecting the cardiovascular system, and 18 with cardiac abnormalities. Dynamic multiplanar slicing and surface rendering of cardiac structures were performed. To illustrate the STIC technique, two representative volumes from a normal fetus were compared with volumes obtained from fetuses with the following congenital heart anomalies: atrioventricular septal defect, tricuspid stenosis, tricuspid atresia, and interrupted inferior vena cava with abnormal venous drainage. Volume datasets obtained with a transverse sweep were utilized to demonstrate the cardiac chambers, moderator band, interatrial and interventricular septae, atrioventricular valves, pulmonary veins, and outflow tracts. With the use of a reference dot to navigate the four-chamber view, intracardiac structures could be simultaneously studied in three orthogonal planes. The same volume dataset was used for surface rendering of the atrioventricular valves. The aortic and ductal arches were best visualized when the original plane of acquisition was sagittal. Volumes could be interactively manipulated to simultaneously visualize both outflow tracts, in addition to the aortic and ductal arches. Novel views of specific structures were generated. For example, the location and extent of a ventricular septal defect was imaged in a sagittal view of the interventricular septum. Furthermore, surface-rendered images of the atrioventricular valves were employed to distinguish between normal and pathologic conditions. Representative video clips were posted on the Journal's Web site to demonstrate the diagnostic capabilities of this new technique. Dynamic multiplanar slicing and surface rendering of the fetal heart are feasible with STIC technology. One good quality volume dataset, obtained from a transverse sweep, can be used to examine the four-chamber view and the outflow tracts. This novel method may assist in the evaluation of fetal cardiac anatomy.

Associations between Maternal Water Consumption and Birth Defects in the National Birth Defects Prevention Study (2000-2005).

PubMed

Alman, Breanna L; Coffman, Evan; Siega-Riz, Anna Maria; Luben, Thomas J

2017-02-15

Water and water-based beverages constitute a major part of daily fluid intake for pregnant women, yet few epidemiologic studies have investigated the role of water consumption on birth outcomes. We used data from the National Birth Defects Prevention Study to conduct a case-control study investigating associations between maternal water consumption during pregnancy and birth defects (BD). We used interview data on water consumption during the first trimester of pregnancy in 14,454 cases (major BDs n ≥ 50) and 5,063 controls. Total water consumption was analyzed as a continuous variable and in quartiles. We evaluated the role of dietary quality and sugar sweetened beverage consumption. Logistic regression models were used to assess effects of water consumption on risk of BDs with adjustment for relevant covariates. Mean daily maternal water consumption among controls was 4.4 eight-ounce glasses. We observed decreases in estimated risk associated with increases in water consumption for several BDs, including neural tube defects (spina bifida), oral clefts (cleft lip), musculoskeletal defects (gastroschisis, limb deficiencies), and congenital heart defects (hypoplastic left heart syndrome, right-sided obstructions, pulmonary valve stenosis). Our results were generally unchanged when an indicator for overall dietary quality was included; however, there was evidence of effect measure modification by heavy consumption of sugar-sweetened beverages for some defects, but not all. These analyses suggest the importance of sufficient water consumption during early pregnancy, above and beyond it being a marker of higher diet quality. Additional analyses are warranted to understand the biological mechanism for this association. Birth Defects Research 109:193-202, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The accuracy of ultrasound in the diagnosis of congenital abnormalities.

PubMed

Munim, Shama; Nadeem, Salva; Khuwaja, Nadya Ali

2006-01-01

To determine the accuracy of ultrasound in the diagnosis of congenital abnormalities at the Aga Khan University Hospital, Karachi. The data of congenital abnormalities was obtained from the obstetrical database and medical records of all cases complicated by congenital abnormalities, delivering from January 2001 to December 2003 and was reviewed. Antenatal ultrasounds had been performed by operators with different level of experience. In addition this data was retrieved from the termination and Congenital anomaly register. A structured data collection form was used to collect information of different variables of interest. Congenital abnormalities, complicated 2.8% (n=170), of all deliveries, including all cases of termination of pregnancy, stillbirth and live births. Out of the total, 11.6% occurred in women above the age of 35 years. Consanguinity was found in 18.2% cases. Prenatal diagnosis was made in just under half of the cases (48.8%). Central nervous system and renal abnormalities were commonly diagnosed. However, facial defects, heart defects or skeletal defects were more commonly missed. Antenatal ultrasound successfully diagnosed foetal abnormalities in 48.8% of cases, and more than 90% Central Nervous system defects and renal abnormalities. In contrast about a quarter of Cardiac defects and none of the facial defects were detected. Based on these findings we recommend that the Sonologist should incorporate four chamber view of the heart and also look at the face carefully.

Congenital heart defects in newborns with apparently isolated single gastrointestinal malformation: A retrospective study.

PubMed

Schierz, Ingrid Anne Mandy; Pinello, Giuseppa; Giuffrè, Mario; La Placa, Simona; Piro, Ettore; Corsello, Giovanni

2016-12-01

Congenital gastrointestinal system malformations/abdominal wall defects (GISM) may appear as isolated defects (single or complex), or in association with multiple malformations. The high incidence of association of GISM and congenital heart defects (CHD) in patients with syndromes and malformative sequences is known, but less expected is the association of apparently isolated single GISM and CHD. The aim of this study was to investigate the frequency of CHD in newborns with isolated GISM, and the possibility to modify the diagnostic-therapeutic approach just before the onset of cardiac symptoms or complications. Anamnestic, clinical, and imaging data of newborns requiring abdominal surgery for GISM, between 2009 and 2014, were compared with a control group of healthy newborns. Distribution of GISM and cardiovascular abnormalities were analyzed, and risk factors for adverse outcomes were identified. Seventy-one newborns with isolated GISM were included in this study. More frequent GISM were intestinal rotation and fixation disorders. CHD were observed in 15.5% of patients, augmenting their risk for morbidity. Risk factors for morbidity related to sepsis were identified in central venous catheter, intestinal stoma, and H2-inhibitor-drugs. Moreover, 28.2% of newborns presented only functional cardiac disorders but an unexpectedly higher mortality. The high incidence of congenital heart disease in infants with apparently isolated GISM confirms the need to perform an echocardiographic study before surgery to improve perioperative management and prevent complications such as sepsis and endocarditis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Xenopus: An Emerging Model for Studying Congenital Heart Disease

PubMed Central

Kaltenbrun, Erin; Tandon, Panna; Amin, Nirav M.; Waldron, Lauren; Showell, Chris; Conlon, Frank L.

2011-01-01

Congenital heart defects affect nearly 1% of all newborns and are a significant cause of infant death. Clinical studies have identified a number of congenital heart syndromes associated with mutations in genes that are involved in the complex process of cardiogenesis. The African clawed frog, Xenopus, has been instrumental in studies of vertebrate heart development and provides a valuable tool to investigate the molecular mechanisms underlying human congenital heart diseases. In this review, we discuss the methodologies that make Xenopus an ideal model system to investigate heart development and disease. We also outline congenital heart conditions linked to cardiac genes that have been well-studied in Xenopus and describe some emerging technologies that will further aid in the study of these complex syndromes. PMID:21538812

Methylene Blue Partially Rescues Heart Defects in a Drosophila Model of Huntington's Disease.

PubMed

Heidari, Raheleh; Monnier, Véronique; Martin, Elodie; Tricoire, Hervé

2015-01-01

Huntington's disease (HD) is a Polyglutamine disease caused by the presence of CAG repeats in the first exon of Huntingtin (Htt), a large protein with multiple functions. In addition to neurodegeneration of specific brain regions, notably the striatum, HD also shows alterations in peripheral tissues, such as the heart, skeletal muscles or peripheral endocrine glands. Mutant Huntingtin (mHtt)-driven mitochondrial impairment may underlie some of the CNS and peripheral tissues dysfunctions, especially in tissues with high energy demand such as the heart. The aim of this study is to characterize two new inducible Drosophila HD heart models and to assay the therapeutic potential of methylene blue in these HD models. We report the construction of inducible Drosophila HD heart models, expressing two Nter fragments of the protein encompassing either exon 1 or the first 171 amino acids and the characterization of heart phenotypes in vivo. We show that both mHtt fragments are able to impair fly cardiac function with different characteristics. Additionally, expression of mHtt, which was limited to adulthood only, leads to mild heart impairment, as opposed to a strong and age-dependent phenotype observed when mHtt expression was driven during both developmental and adult stages. We report that treatment with methylene blue (MB), a protective compound in mitochondria-related diseases, partially protects the fly's heart against mHtt-induced toxicity, but does not rescue neuronal or glial phenotypes in other fly models of HD. This may be linked to its low penetration through the fly's blood-brain barrier. Our data suggest that improvement of mitochondrial function by MB, or related compounds, could be an efficient therapeutic strategy to prevent cardiac failure in HD patients.

Diesel Exhaust-Induced Cardiac Dysfunction Is Mediated by Sympathetic Dominance in Heart Failure-Prone Rats

EPA Science Inventory

Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 ...

Formative research to build mobile technologies that advance transitions of care for adolescents with congenital heart disease

USDA-ARS?s Scientific Manuscript database

Congenital heart diseases (CHDs) are the most common type of birth defects. Improvements in CHD care have led to ~1.4 million survivors reaching adulthood. Thus, successful transition and transfer from pediatric to adult care is crucial. Unfortunately, <30% of adults with CHD successfully transition...

Building mobile technologies to improve transitions of care in adolescents with congenital heart disease

USDA-ARS?s Scientific Manuscript database

Congenital heart diseases (CHDs) are the most common type of birth defects. Improvements in CHD care have led to roughly 1.4 million survivors reaching adulthood. This emerging "survivor" population are often palliated but not cured. Thus successful transition from pediatric to adult care for CHD pa...

Critical congenital heart defects and abnormal levels of routinely collected first- and second-trimester biomarkers.

PubMed

Borelli, Melissa; Baer, Rebecca J; Chambers, Christina D; Smith, Tyler C; Jelliffe-Pawlowski, Laura L

2017-02-01

We examined the association between maternal characteristics, routinely collected first- and second-trimester biomarkers and the risk of having an infant with a critical congenital heart defect (CCHD). Included were women who participated in the California Prenatal Screening Program who had nuchal translucency (NT) measurement and first- and second-trimester serum screening. All pregnancies ended in a live birth of an infant without aneuploidy or a neural tube defect. Poisson regression analyses were used to estimate the relative risk and 95% confidence interval of a CCHD by maternal characteristics, first- and second-trimester serum biomarkers or NT measurements. The sample included 118,194 mother-infant pairs; 284 infants had a CCHD. Women with preexisting diabetes were three-times as likely to have an infant with a CCHD. After adjusting for preexisting diabetes, women with first-trimester human chorionic gonatotropin (hCG) measurement <10th centile were 1.6-times as likely to have an infant with a CCHD (P = 0.011). Women with a NT measurement ≥95th centile were at two- to threefold higher risk of having an infant with a CCHD (P's = 0.004-0.007). Pregnancies with two risk factors for an infant with a CCHD were 5.6-times more likely to have an infant with a CCHD than women with no identified risk factors (P < 0.001). Despite the increased risk, performance testing demonstrated low sensitivity and specificity for screening use of these risk factors. Of the women with an infant with a CCHD, only 21.8% had an identified risk factor. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Left Right Patterning, Evolution and Cardiac Development

PubMed Central

Dykes, Iain M.

2018-01-01

Many aspects of heart development are determined by the left right axis and as a result several congenital diseases have their origins in aberrant left-right patterning. Establishment of this axis occurs early in embryogenesis before formation of the linear heart tube yet impacts upon much later morphogenetic events. In this review I discuss the differing mechanisms by which left-right polarity is achieved in the mouse and chick embryos and comment on the evolution of this system. I then discus three major classes of cardiovascular defect associated with aberrant left-right patterning seen in mouse mutants and human disease. I describe phenotypes associated with the determination of atrial identity and venous connections, looping morphogenesis of the heart tube and finally the asymmetric remodelling of the embryonic branchial arch arterial system to form the leftward looped arch of aorta and associated great arteries. Where appropriate, I consider left right patterning defects from an evolutionary perspective, demonstrating how developmental processes have been modified in species over time and illustrating how comparative embryology can aide in our understanding of congenital heart disease. PMID:29755990

[Heart surgery in Brazilian Indians].

PubMed

Gomes, W J; Carvalho, A C; Vieira Filho, J P; Souza, R B; Palma, J H; Maluf, M A; Branco, J N; Buffolo, E

1997-01-01

Our experience with surgical treatment of heart diseases in Indians living in the Amazon rain forest in primitive stages was reviewed. From 1988 to 1995, 18 patients underwent cardiovascular surgical procedures at the São Paulo Hospital of the Escola Paulista de Medicina. Seven patients had valvar disease, nine congenital heart defects, one submitral aneurysm and one arrhythmia. Thirteen Indians came from tribes of the Amazon rain forest area: three from the Xavante, two from Waiapi, two from Tucano, two from Macuxi, two from Mayoruna, and one of each tribe of Xikrin, Guajajara, Terena, Surui, Galibi, Cinta-Larga and Pataxó. We performed 22 operations, with two hospital deaths. Follow-up was possible in 87.5% of cases, with one late death. The majority of cases were due to congenital heart defects and in this series it was noted the absence of operations to treat coronary artery disease. The incidence of valve disease was higher in accultured or semi-accultured Indians. The surgical treatment of cardiovascular disease has made possible to the surviving indians to return to and be accepted by their fellow tribesmen.

A novel one-shot circular stapler closure for atrial septal defect in a beating-heart porcine model.

PubMed

Tarui, Tatsuya; Tomita, Shigeyuki; Ishikawa, Norihiko; Ohtake, Hiroshi; Watanabe, Go

2015-02-01

In surgical atrial septal defect (ASD) closure, there are no techniques or devices that can close the ASD accurately in a short time under a beating heart. We have developed a simple and automatic ASD closure technique using a circular stapler. This study assessed the feasibility and efficacy of a new circular stapler closure for ASD. Under a continuous beating heart, hand-sewn patch plasty ASD closure was performed in 6 pigs (group A) and circular stapler ASD closure was performed in 6 pigs (group B). The time to close the ASD and the effectiveness of the closure were compared. Closure was significantly faster in group B (10.5 ± 1.0 seconds) than in group A (664 ± 10 seconds; p < 0.05). There was no leakage at the closure site, and sufficient tolerance was confirmed. A circular stapler can be used to treat ASD faster than hand-sewn patch plasty, with sufficient pressure tolerance in a beating heart porcine model. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

High-Frequency Ultrasound for the Study of Early Mouse Embryonic Cardiovascular System.

PubMed

Greco, Adelaide; Coda, Anna Rita Daniela; Albanese, Sandra; Ragucci, Monica; Liuzzi, Raffaele; Auletta, Luigi; Gargiulo, Sara; Lamagna, Francesco; Salvatore, Marco; Mancini, Marcello

2015-12-01

An accurate diagnosis of congenital heart defects during fetal development is critical for interventional planning. Mice can be used to generate animal models with heart defects, and high-frequency ultrasound (HFUS) imaging enables in utero imaging of live mouse embryos. A wide range of physiological measurements is possible using Doppler-HFUS imaging; limitations of any single measurement warrant a multiparameter approach to characterize cardiovascular function. Doppler-HFUS was used to explore the embryonic (heart, aorta) and extraembryonic (umbilical blood flow) circulatory systems to create a database in normal mouse embryos between 9.5 and 16.5 days of gestation. Multivariate analyses were performed to explore correlations between gestational age and embryo echocardiographic parameters. Heart rate and peak velocity in the aorta were positively correlated with gestational time, whereas cardiac cycle length, isovolumetric relaxation time, myocardial performance index, and arterial deceleration time of the umbilical cord were negatively correlated with it. Doppler-HFUS facilitated detailed characterization of the embryonic mouse circulation and represents a useful tool for investigation of the early mouse embryonic cardiovascular system. © The Author(s) 2015.

Rare Copy Number Variants in a Population Based Investigation of Hypoplastic Right Heart Syndrome

PubMed Central

Dimopoulos, Aggeliki; Sicko, Robert J.; Kay, Denise M.; Rigler, Shannon L.; Druschel, Charlotte M.; Caggana, Michele; Browne, Marilyn L.; Fan, Ruzong; Romitti, Paul A.; Brody, Lawrence C.; Mills, James L.

2016-01-01

Background Hypoplastic right heart syndrome (HRHS) is a rare congenital defect characterized by underdevelopment of the right heart structures commonly accompanied by an atrial septal defect. Familial HRHS reports suggest genetic factor involvement. We examined the role of copy number variants (CNVs) in HRHS. Methods We genotyped 32 HRHS cases identified from all New York State live births (1998–2005) using Illumina HumanOmni2.5 microarrays. CNVs were called with PennCNV and prioritized if they were ≥20Kb, contained ≥10 SNPs and had minimal overlap with CNVs from in-house controls, the Database of Genomic Variants, HapMap3 and CHOP database. Results We identified 28 CNVs in 17 cases; several encompassed genes important for right heart development. One case had a 2p16–2p23 duplication spanning LBH, a limb and heart development transcription factor. Lbh mis-expression results in right ventricular hypoplasia and pulmonary valve defects. This duplication also encompassed SOS1, a factor associated with pulmonary valve stenosis in Noonan syndrome. Sos1−/− mice display thin and poorly trabeculated ventricles. In another case, we identified a 1.5Mb deletion associated with Williams Beuren syndrome, a disorder that includes valvular malformations. A third case had a 24Kb deletion upstream of the TGFβ ligand ITGB8. Embryos genetically null for Itgb8, and its intracellular interactant Band 4.1B, display lethal cardiac phenotypes. Conclusions To our knowledge, this is the first study of CNVs in HRHS. We identified several rare CNVs that overlap genes related to right ventricular wall and valve development, suggesting that genetics plays a role in HRHS and providing clues for further investigation. PMID:28009100

[Percutaneous catheter-based implantation of artificial pulmonary valves in patients with congenital heart defects].

PubMed

Wyller, Vegard Bruun; Aaberge, Lars; Thaulow, Erik; Døhlen, Gaute

2011-07-01

Percutaneous catheter-based implantation of artificial heart valves is a new technique that may supplement surgery and which may be used more in the future. We here report our first experience with implantation of artificial pulmonary valves in children with congenital heart defects. Eligible patients were those with symptoms of heart failure combined with stenosis and/or insufficiency in an established artificial right ventricular outflow tract. The valve was inserted through a catheter from a vein in the groin or neck. Symptoms, echocardiography, invasive measurements and angiography were assessed for evaluation of treatment effect. Our treatment results are reported for the period April 2007-September 2009. Ten patients (seven men and three women, median age 17 years) were assessed. The procedure reduced pressure in the right ventricle (p = 0.008) and resolved the pulmonary insufficiency in all patients. The median time in hospital was two days. No patients had complications that were directly associated with the implantation procedure. One patient developed a pseudoaneurysm in the femoral artery, another had a short-lasting fever two days after the procedure and one patient experienced a stent fracture that required surgery 9 months after the implantation. After 6 months all patients had a reduced pressure gradient in the right ventricular outflow tract (p = 0.008), the pulmonary insufficiency had improved (p = 0.006) and they all reported improval of symptoms. These results persisted for at least 24 months for the four patients who were monitored until then. Percutaneous catheter-based implantation of artificial pulmonary valves improves hemodynamics in the right ventricle of selected patients with congenital heart defects. A randomized controlled study should be undertaken to provide a stronger evidence-base for usefulness of this procedure.

Patient-Specific Modeling of Interventricular Hemodynamics in Single Ventricle Physiology

NASA Astrophysics Data System (ADS)

Vedula, Vijay; Feinstein, Jeffrey; Marsden, Alison

2016-11-01

Single ventricle (SV) congenital heart defects, in which babies are born with only functional ventricle, lead to significant morbidity and mortality with over 30% of patients developing heart failure prior to adulthood. Newborns with SV physiology typically undergo three palliative surgeries, in which the SV becomes the systemic pumping chamber. Depending on which ventricle performs the systemic function, patients are classified as having either a single left ventricle (SLV) or a single right ventricle (SRV), with SRV patients at higher risk of failure. As the native right ventricles are not designed to meet systemic demands, they undergo remodeling leading to abnormal hemodynamics. The hemodynamic characteristics of SLVs compared with SRVs is not well established. We present a validated computational framework for performing patient-specific modeling of ventricular flows, and apply it across 6 SV patients (3SLV + 3SRV), comparing hemodynamic conditions between the two subgroups. Simulations are performed with a stabilized finite element method coupled with an immersed boundary method for modeling heart valves. We discuss identification of hemodynamic biomarkers of ventricular remodeling for early risk assessment of failure. This research is supported in part by the Stanford Child Health Research Institute and the Stanford NIH-NCATS-CTSA through Grant UL1 TR001085 and due to U.S. National Institute of Health through NIH NHLBI R01 Grants 5R01HL129727-02 and 5R01HL121754-03.

BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects

PubMed Central

Hilton, Emma; Johnston, Jennifer; Whalen, Sandra; Okamoto, Nobuhiko; Hatsukawa, Yoshikazu; Nishio, Juntaro; Kohara, Hiroshi; Hirano, Yoshiko; Mizuno, Seiji; Torii, Chiharu; Kosaki, Kenjiro; Manouvrier, Sylvie; Boute, Odile; Perveen, Rahat; Law, Caroline; Moore, Anthony; Fitzpatrick, David; Lemke, Johannes; Fellmann, Florence; Debray, François-Guillaume; Dastot-Le-Moal, Florence; Gerard, Marion; Martin, Josiane; Bitoun, Pierre; Goossens, Michel; Verloes, Alain; Schinzel, Albert; Bartholdi, Deborah; Bardakjian, Tanya; Hay, Beverly; Jenny, Kim; Johnston, Kathreen; Lyons, Michael; Belmont, John W; Biesecker, Leslie G; Giurgea, Irina; Black, Graeme

2009-01-01

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked (‘Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects. PMID:19367324

Pharmacological stress, rest perfusion and delayed enhancement cardiac magnetic resonance identifies very early cardiac involvement in systemic sclerosis patients of recent onset.

PubMed

Giacomelli, Roberto; Di Cesare, Ernesto; Cipriani, Paola; Ruscitti, Piero; Di Sibio, Alessandra; Liakouli, Vasiliki; Gennarelli, Antonio; Carubbi, Francesco; Splendiani, Alessandra; Berardicurti, Onorina; Di Benedetto, Paola; Ciccia, Francesco; Guggino, Giuliana; Radchenko, Ganna; Triolo, Giovanni; Masciocchi, Carlo

2017-09-01

To evaluate occult cardiac involvement in asymptomatic systemic sclerosis (SSc) patients by pharmacological stress, rest perfusion and delayed enhancement cardiac magnetic resonance (CMR), for a very early identification of patients at higher risk of cardiac-related mortality. Sixteen consecutive patients with definite SSc, fulfilling the American College of Rheumatology/European League Against Rheumatism 2013 classification criteria in less than 1 year from the onset of Raynaud's phenomenon, underwent pharmacological stress, rest perfusion and delayed enhancement CMR. At enrollment, no patient showed signs and/or symptoms suggestive for cardiac involvement. No patient showed traditional cardiovascular risk factors. Both the 12-lead electrocardiogram examination and echocardiographic evaluation did not show any alterations in our cohort. Stress perfusion defects of left ventricle were detected in six out of 16 (37.5%) patients and these defects did not match with the coronary flow distribution. The results showed the presence of two different patterns of stress perfusion defects: sub-endocardial and/or a midmyocardial. The presence of stress perfusion defects did not correlate with any clinical feature of enrolled patients. Myocardial stress perfusion defects may be detected early by pharmacological stress perfusion CMR, a reliable and sensitive technique for the noninvasive evaluation of SSc heart disease, in patients with SSc of recent onset. These defects seem to be independent from traditional risk factors and associated comorbidities, suggesting they are a specific hallmark of the disease. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Atrial tachyarrhythmia in adult congenital heart disease

PubMed Central

Karbassi, Arsha; Nair, Krishnakumar; Harris, Louise; Wald, Rachel M; Roche, S Lucy

2017-01-01

The adult congenital heart disease (ACHD) population continues to grow and most cardiologists, emergency room physicians and family doctors will intermittently come into contact with these patients. Oftentimes this may be in the setting of a presentation with atrial tachyarrhythmia; one of the commonest late complications of ACHD and problem with potentially serious implications. Providing appropriate initial care and ongoing management of atrial tachyarrhythmia in ACHD patients requires a degree of specialist knowledge and an awareness of certain key issues. In ACHD, atrial tachyarrhythmia is usually related to the abnormal anatomy of the underlying heart defect and often occurs as a result of surgical scar or a consequence of residual hemodynamic or electrical disturbances. Arrhythmias significantly increase mortality and morbidity in ACHD and are the most frequent reason for ACHD hospitalization. Intra-atrial reentrant tachycardia and atrial fibrillation are the most prevalent type of arrhythmia in this patient group. In hemodynamically unstable patients, urgent cardioversion is required. Acute management of the stable patient includes anticoagulation, rate control, and electrical or pharmacological cardioversion. In ACHD, rhythm control is the preferred management strategy and can often be achieved. However, in the long-term, medication side-effects can prove problematic. Electrophysiology studies and catheter ablation are important treatments modalities and in certain cases, surgical or percutaneous treatment of the underlying cardiac defect has a role. ACHD patients, especially those with complex CHD, are at increased risk of thromboembolic events and anticoagulation is usually required. Female ACHD patients of child bearing age may wish to pursue pregnancies. The risk of atrial arrhythmias is increased during pregnancy and management of atrial tachyarrhythmia during pregnancy needs specific consideration. PMID:28706585

Identification of a Recurrent Microdeletion at 17q23.1q23.2 Flanked by Segmental Duplications Associated with Heart Defects and Limb Abnormalities

PubMed Central

Ballif, Blake C.; Theisen, Aaron; Rosenfeld, Jill A.; Traylor, Ryan N.; Gastier-Foster, Julie; Thrush, Devon Lamb; Astbury, Caroline; Bartholomew, Dennis; McBride, Kim L.; Pyatt, Robert E.; Shane, Kate; Smith, Wendy E.; Banks, Valerie; Gallentine, William B.; Brock, Pamela; Rudd, M. Katharine; Adam, Margaret P.; Keene, Julia A.; Phillips, John A.; Pfotenhauer, Jean P.; Gowans, Gordon C.; Stankiewicz, Pawel; Bejjani, Bassem A.; Shaffer, Lisa G.

2010-01-01

Segmental duplications, which comprise ∼5%–10% of the human genome, are known to mediate medically relevant deletions, duplications, and inversions through nonallelic homologous recombination (NAHR) and have been suggested to be hot spots in chromosome evolution and human genomic instability. We report seven individuals with microdeletions at 17q23.1q23.2, identified by microarray-based comparative genomic hybridization (aCGH). Six of the seven deletions are ∼2.2 Mb in size and flanked by large segmental duplications of >98% sequence identity and in the same orientation. One of the deletions is ∼2.8 Mb in size and is flanked on the distal side by a segmental duplication, whereas the proximal breakpoint falls between segmental duplications. These characteristics suggest that NAHR mediated six out of seven of these rearrangements. These individuals have common features, including mild to moderate developmental delay (particularly speech delay), microcephaly, postnatal growth retardation, heart defects, and hand, foot, and limb abnormalities. Although all individuals had at least mild dysmorphic facial features, there was no characteristic constellation of features that would elicit clinical suspicion of a specific disorder. The identification of common clinical features suggests that microdeletions at 17q23.1q23.2 constitute a novel syndrome. Furthermore, the inclusion in the minimal deletion region of TBX2 and TBX4, transcription factors belonging to a family of genes implicated in a variety of developmental pathways including those of heart and limb, suggests that these genes may play an important role in the phenotype of this emerging syndrome. PMID:20206336

The App-Runx1 Region Is Critical for Birth Defects and Electrocardiographic Dysfunctions Observed in a Down Syndrome Mouse Model

PubMed Central

Raveau, Matthieu; Lignon, Jacques M.; Nalesso, Valérie; Duchon, Arnaud; Groner, Yoram; Sharp, Andrew J.; Dembele, Doulaye; Brault, Véronique; Hérault, Yann

2012-01-01

Down syndrome (DS) leads to complex phenotypes and is the main genetic cause of birth defects and heart diseases. The Ts65Dn DS mouse model is trisomic for the distal part of mouse chromosome 16 and displays similar features with post-natal lethality and cardiovascular defects. In order to better understand these defects, we defined electrocardiogram (ECG) with a precordial set-up, and we found conduction defects and modifications in wave shape, amplitudes, and durations in Ts65Dn mice. By using a genetic approach consisting of crossing Ts65Dn mice with Ms5Yah mice monosomic for the App-Runx1 genetic interval, we showed that the Ts65Dn viability and ECG were improved by this reduction of gene copy number. Whole-genome expression studies confirmed gene dosage effect in Ts65Dn, Ms5Yah, and Ts65Dn/Ms5Yah hearts and showed an overall perturbation of pathways connected to post-natal lethality (Coq7, Dyrk1a, F5, Gabpa, Hmgn1, Pde10a, Morc3, Slc5a3, and Vwf) and heart function (Tfb1m, Adam19, Slc8a1/Ncx1, and Rcan1). In addition cardiac connexins (Cx40, Cx43) and sodium channel sub-units (Scn5a, Scn1b, Scn10a) were found down-regulated in Ts65Dn atria with additional down-regulation of Cx40 in Ts65Dn ventricles and were likely contributing to conduction defects. All these data pinpoint new cardiac phenotypes in the Ts65Dn, mimicking aspects of human DS features and pathways altered in the mouse model. In addition they highlight the role of the App-Runx1 interval, including Sod1 and Tiam1, in the induction of post-natal lethality and of the cardiac conduction defects in Ts65Dn. These results might lead to new therapeutic strategies to improve the care of DS people. PMID:22693452

Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Eugene; Corbett, James R.; Moran, Jean M.

Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses tomore » the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.« less

Interventional Cardiology for Congenital Heart Disease

PubMed Central

2018-01-01

Congenital heart interventions are now replacing surgical palliation and correction in an evolving number of congenital heart defects. Right ventricular outflow tract and ductus arteriosus stenting have demonstrated favorable outcomes compared to surgical systemic to pulmonary artery shunting, and it is likely surgical pulmonary valve replacement will become an uncommon procedure within the next decade, mirroring current practices in the treatment of atrial septal defects. Challenges remain, including the lack of device design focused on smaller infants and the inevitable consequences of somatic growth. Increasing parental and physician expectancy has inevitably lead to higher risk interventions on smaller infants and appreciation of the consequences of these interventions on departmental outcome data needs to be considered. Registry data evaluating congenital heart interventions remain less robust than surgical registries, leading to a lack of insight into the longer-term consequences of our interventions. Increasing collaboration with surgical colleagues has not been met with necessary development of dedicated equipment for hybrid interventions aimed at minimizing the longer-term consequences of scar to the heart. Therefore, great challenges remain to ensure children and adults with congenital heart disease continue to benefit from an exponential growth in minimally invasive interventions and technology. This can only be achieved through a concerted collaborative approach from physicians, industry, academia and regulatory bodies supporting great innovators to continue the philosophy of thinking beyond the limits that has been the foundation of our specialty for the past 50 years. PMID:29671282

A de novo 1q22q23.1 Interstitial Microdeletion in a Girl with Intellectual Disability and Multiple Congenital Anomalies Including Congenital Heart Defect.

PubMed

Aleksiūnienė, Beata; Preiksaitiene, Egle; Morkūnienė, Aušra; Ambrozaitytė, Laima; Utkus, Algirdas

2018-01-01

Many studies have shown that molecular karyotyping is an effective diagnostic tool in individuals with developmental delay/intellectual disability. We report on a de novo interstitial 1q22q23.1 microdeletion, 1.6 Mb in size, detected in a patient with short stature, microcephaly, hypoplastic corpus callosum, cleft palate, minor facial anomalies, congenital heart defect, camptodactyly of the 4-5th fingers, and intellectual disability. Chromosomal microarray analysis revealed a 1.6-Mb deletion in the 1q22q23.1 region, arr[GRCh37] 1q22q23.1(155630752_157193893)×1. Real-time PCR analysis confirmed its de novo origin. The deleted region encompasses 50 protein-coding genes, including the morbid genes APOA1BP, ARHGEF2, LAMTOR2, LMNA, NTRK1, PRCC, RIT1, SEMA4A, and YY1AP1. Although the unique phenotype observed in our patient can arise from the haploinsufficiency of the dosage-sensitive LMNA gene, the dosage imbalance of other genes implicated in the rearrangement could also contribute to the phenotype. Further studies are required for the delineation of the phenotype associated with this rare chromosomal alteration and elucidation of the critical genes for manifestation of the specific clinical features. © 2018 S. Karger AG, Basel.

First day of life pulse oximetry screening to detect congenital heart defects.

PubMed

Meberg, Alf; Brügmann-Pieper, Sabine; Due, Reidar; Eskedal, Leif; Fagerli, Ingebjørg; Farstad, Teresa; Frøisland, Dag Helge; Sannes, Catharina Hovland; Johansen, Ole Jakob; Keljalic, Jasmina; Markestad, Trond; Nygaard, Egil Andre; Røsvik, Alet; Silberg, Inger Elisabeth

2008-06-01

To evaluate the efficacy of first day of life pulse oximetry screening to detect congenital heart defects (CHDs). We performed a population-based prospective multicenter study of postductal (foot) arterial oxygen saturation (SpO(2)) in apparently healthy newborns after transfer from the delivery suite to the nursery. SpO(2) < 95% led to further diagnostic evaluations. Of 57,959 live births, 50,008 (86%) were screened. In the screened population, 35 CHDs were [corrected] classified as critical (ductus dependent, cyanotic). CHDs were prospectively registered and diagnosed in 658/57,959 (1.1%) [corrected] Of the infants screened, 324 (0.6%) failed the test. Of these, 43 (13%) had CHDs (27 critical), and 134 (41%) had pulmonary diseases or other disorders. The remaining 147 infants (45%) were healthy with transitional circulation. The median age for babies with CHDs at failing the test was 6 hours (range, 1-21 hours). For identifying critical CHDs, the pulse oximetry screening had a sensitivity rate of 77.1% (95% CI, 59.4-89.0), specificity rate of 99.4% (95% CI, 99.3-99.5), and a false-positive rate of 0.6% (95% CI, 0.5-0.7). Early pulse oximetry screening promotes early detection of critical CHDs and other potentially severe diseases. The sensitivity rate for detecting critical CHDs is high, and the false-positive rate is low.

Toward computer-assisted image-guided congenital heart defect repair: an initial phantom analysis.

PubMed

Kwartowitz, David M; Mefleh, Fuad N; Baker, G Hamilton

2017-10-01

Radiation exposure in interventional cardiology is an important consideration, due to risk of cancer and other morbidity to the patient and clinical staff. Cardiac catheterizations rely heavily on fluoroscopic imaging exposing both patient and clinician to ionizing radiation. An image-guided surgery system capable of facilitating cardiac catheterizations was developed and tested to evaluate dose reduction. Several electromagnetically tracked tools were constructed specifically a 7-Fr catheter with five 5-degree-of-freedom magnetic seeds. Catheter guidance was accomplished using our image guidance system Kit for Navigation by Image-Focused Exploration and fluoroscopy alone. A cardiac phantom was designed and 3D printed to validate the image guidance procedure. In mock procedures, an expert clinician guided and deployed an occluder across the septal defect of the phantom heart. The image guidance method resulted in a dose of 1.26 mSv of radiation dose per procedure, while traditional guidance resulted in a dose of 3.33 mSv. Average overall dose savings for the image-guided method was nearly 2.07 mSv or 62 %. The work showed significant ([Formula: see text]) decrease in radiation dose with use of image guidance methods at the expense of a modest increase in procedure time. This study lays the groundwork for further exploration of image guidance applications in pediatric cardiology.

Using extracorporeal membrane oxygenation support preoperatively and postoperatively as a successful bridge to recovery in a patient with a large infarct-induced ventricular septal defect.

PubMed

Jacob, Samuel; Patel, Mitesh J; Lima, Brian; Felius, Joost; Malyala, Rajasekhar S; Chamogeorgakis, Themistokles; MacHannaford, Juan C; Gonzalez-Stawinski, Gonzalo V; Rafael, Aldo E

2016-07-01

Rupture of the ventricular septum during acute myocardial infarction usually occurs within the first week. The event is usually followed by low cardiac output, heart failure, and multiorgan failure. Despite the many advances in the nonoperative treatment of heart failure and cardiogenic shock, including the intra-aortic balloon pump and a multitude of new inotropic agents and vasodilators, these do not supplant the need for operative intervention in these critically ill patients. This article describes the successful use of extracorporeal membrane oxygenation support as a bridge to recovery postoperatively in a patient with a large infarct-produced ventricular septal defect.

Using extracorporeal membrane oxygenation support preoperatively and postoperatively as a successful bridge to recovery in a patient with a large infarct-induced ventricular septal defect

PubMed Central

Jacob, Samuel; Patel, Mitesh J.; Lima, Brian; Felius, Joost; Malyala, Rajasekhar S.; Chamogeorgakis, Themistokles; MacHannaford, Juan C.; Gonzalez-Stawinski, Gonzalo V.

2016-01-01

Rupture of the ventricular septum during acute myocardial infarction usually occurs within the first week. The event is usually followed by low cardiac output, heart failure, and multiorgan failure. Despite the many advances in the nonoperative treatment of heart failure and cardiogenic shock, including the intra-aortic balloon pump and a multitude of new inotropic agents and vasodilators, these do not supplant the need for operative intervention in these critically ill patients. This article describes the successful use of extracorporeal membrane oxygenation support as a bridge to recovery postoperatively in a patient with a large infarct-produced ventricular septal defect. PMID:27365878

Mothers' lived experiences of support when living with young children with congenital heart defects

PubMed Central

Bruce, Elisabeth; Lilja, Catrine; Sundin, Karin

2014-01-01

Purpose The purpose of this study was to illuminate the meanings of support as disclosed by mothers of children with congenital heart defects (CHD). Design and Method Narrative interviews were conducted with 10 mothers of children with CHD. A phenomenological-hermeneutic method was used for interpretation of the transcribed interviews. Results The comprehensive understanding of mothers' lived experiences of support emerged as the experiences of receiving good support, receiving “poor support,” and absence of support. Practice Implications Mothers receiving person-centered and family-centered care feel more supported and are more likely to adapt to the stresses of parenting a child with CHD. PMID:24124764

Atlas-Based Ventricular Shape Analysis for Understanding Congenital Heart Disease.

PubMed

Farrar, Genevieve; Suinesiaputra, Avan; Gilbert, Kathleen; Perry, James C; Hegde, Sanjeet; Marsden, Alison; Young, Alistair A; Omens, Jeffrey H; McCulloch, Andrew D

2016-12-01

Congenital heart disease is associated with abnormal ventricular shape that can affect wall mechanics and may be predictive of long-term adverse outcomes. Atlas-based parametric shape analysis was used to analyze ventricular geometries of eight adolescent or adult single-ventricle CHD patients with tricuspid atresia and Fontans. These patients were compared with an "atlas" of non-congenital asymptomatic volunteers, resulting in a set of z-scores which quantify deviations from the control population distribution on a patient-by-patient basis. We examined the potential of these scores to: (1) quantify abnormalities of ventricular geometry in single ventricle physiologies relative to the normal population; (2) comprehensively quantify wall motion in CHD patients; and (3) identify possible relationships between ventricular shape and wall motion that may reflect underlying functional defects or remodeling in CHD patients. CHD ventricular geometries at end-diastole and end-systole were individually compared with statistical shape properties of an asymptomatic population from the Cardiac Atlas Project. Shape analysis-derived model properties, and myocardial wall motions between end-diastole and end-systole, were compared with physician observations of clinical functional parameters. Relationships between altered shape and altered function were evaluated via correlations between atlas-based shape and wall motion scores. Atlas-based shape analysis identified a diverse set of specific quantifiable abnormalities in ventricular geometry or myocardial wall motion in all subjects. Moreover, this initial cohort displayed significant relationships between specific shape abnormalities such as increased ventricular sphericity and functional defects in myocardial deformation, such as decreased long-axis wall motion. These findings suggest that atlas-based ventricular shape analysis may be a useful new tool in the management of patients with CHD who are at risk of impaired ventricular wall mechanics and chamber remodeling.

Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons

PubMed Central

Cnattingius, Sven; Villamor, Eduardo; Söderling, Jonas; Pasternak, Björn; Stephansson, Olof; Neovius, Martin

2017-01-01

Objective To estimate the risks of major congenital malformations in the offspring of mothers who are underweight (body mass index (BMI) <18.5), overweight (BMI 25 to <30), or in obesity classes I (BMI 30 to <35), II (35 to <40), or III (≥40) compared with offspring of normal weight mothers (BMI 18.5 to <25) in early pregnancy. Design Population based cohort study. Setting Nationwide Swedish registries. Participants 1 243 957 liveborn singleton infants from 2001 to 2014 in Sweden. Data on maternal and pregnancy characteristics were obtained by individual record linkages. Exposure Maternal BMI at the first prenatal visit. Main outcome measures Offspring with any major congenital malformation, and subgroups of organ specific malformations diagnosed during the first year of life. Risk ratios were estimated using generalised linear models adjusted for maternal factors, sex of offspring, and birth year. Results A total of 43 550 (3.5%) offspring had any major congenital malformation, and the most common subgroup was for congenital heart defects (n=20 074; 1.6%). Compared with offspring of normal weight mothers (risk of malformations 3.4%), the proportions and adjusted risk ratios of any major congenital malformation among the offspring of mothers with higher BMI were: overweight, 3.5% and 1.05 (95% confidence interval 1.02 to 1.07); obesity class I, 3.8% and 1.12 (1.08 to 1.15), obesity class II, 4.2% and 1.23 (1.17 to 1.30), and obesity class III, 4.7% and 1.37 (1.26 to 1.49). The risks of congenital heart defects, malformations of the nervous system, and limb defects also progressively increased with BMI from overweight to obesity class III. The largest organ specific relative risks related to maternal overweight and increasing obesity were observed for malformations of the nervous system. Malformations of the genital and digestive systems were also increased in offspring of obese mothers. Conclusions Risks of any major congenital malformation and several subgroups of organ specific malformations progressively increased with maternal overweight and increasing severity of obesity. For women who are planning pregnancy, efforts should be encouraged to reduce adiposity in those with a BMI above the normal range. PMID:28615173

Association between Prenatal Exposure to Antiretroviral Therapy and Birth Defects: An Analysis of the French Perinatal Cohort Study (ANRS CO1/CO11)

PubMed Central

Sibiude, Jeanne; Mandelbrot, Laurent; Blanche, Stéphane; Le Chenadec, Jérôme; Boullag-Bonnet, Naima; Faye, Albert; Dollfus, Catherine; Tubiana, Roland; Bonnet, Damien; Lelong, Nathalie; Khoshnood, Babak; Warszawski, Josiane

2014-01-01

Background Antiretroviral therapy (ART) has major benefits during pregnancy, both for maternal health and to prevent mother-to-child transmission of HIV. Safety issues, including teratogenic risk, need to be evaluated. We estimated the prevalence of birth defects in children born to HIV-infected women receiving ART during pregnancy, and assessed the independent association of birth defects with each antiretroviral (ARV) drug used. Methods and Findings The French Perinatal Cohort prospectively enrolls HIV-infected women delivering in 90 centers throughout France. Children are followed by pediatricians until 2 y of age according to national guidelines. We included 13,124 live births between 1994 and 2010, among which, 42% (n = 5,388) were exposed to ART in the first trimester of pregnancy. Birth defects were studied using both European Surveillance of Congenital Anomalies (EUROCAT) and Metropolitan Atlanta Congenital Defects Program (MACDP) classifications; associations with ART were evaluated using univariate and multivariate logistic regressions. Correction for multiple comparisons was not performed because the analyses were based on hypotheses emanating from previous findings in the literature and the robustness of the findings of the current study. The prevalence of birth defects was 4.4% (95% CI 4.0%–4.7%), according to the EUROCAT classification. In multivariate analysis adjusting for other ARV drugs, maternal age, geographical origin, intravenous drug use, and type of maternity center, a significant association was found between exposure to zidovudine in the first trimester and congenital heart defects: 2.3% (74/3,267), adjusted odds ratio (AOR) = 2.2 (95% CI 1.3–3.7), p = 0.003, absolute risk difference attributed to zidovudine +1.2% (95% CI +0.5; +1.9%). Didanosine and indinavir were associated with head and neck defects, respectively: 0.5%, AOR = 3.4 (95% CI 1.1–10.4), p = 0.04; 0.9%, AOR = 3.8 (95% CI 1.1–13.8), p = 0.04. We found a significant association between efavirenz and neurological defects (n = 4) using the MACDP classification: AOR = 3.0 (95% CI 1.1–8.5), p = 0.04, absolute risk +0.7% (95% CI +0.07%; +1.3%). But the association was not significant using the less inclusive EUROCAT classification: AOR = 2.1 (95% CI 0.7–5.9), p = 0.16. No association was found between birth defects and lopinavir or ritonavir with a power >85% for an odds ratio of 1.5, nor for nevirapine, tenofovir, stavudine, or abacavir with a power >70%. Limitations of the present study were the absence of data on termination of pregnancy, stillbirths, tobacco and alcohol intake, and concomitant medication. Conclusions We found a specific association between in utero exposure to zidovudine and heart defects; the mechanisms need to be elucidated. The association between efavirenz and neurological defects must be interpreted with caution. For the other drugs not associated with birth defects, the results were reassuring. Finally, whatever the impact that some ARV drugs may have on birth defects, it is surpassed by the major role of ART in the successful prevention of mother-to-child transmission of HIV. Please see later in the article for the Editors' Summary PMID:24781315

Tropomyosin 1: Multiple roles in the developing heart and in the formation of congenital heart defects.

PubMed

England, Jennifer; Granados-Riveron, Javier; Polo-Parada, Luis; Kuriakose, Diji; Moore, Christopher; Brook, J David; Rutland, Catrin S; Setchfield, Kerry; Gell, Christopher; Ghosh, Tushar K; Bu'Lock, Frances; Thornborough, Christopher; Ehler, Elisabeth; Loughna, Siobhan

2017-05-01

Tropomyosin 1 (TPM1) is an essential sarcomeric component, stabilising the thin filament and facilitating actin's interaction with myosin. A number of sarcomeric proteins, such as alpha myosin heavy chain, play crucial roles in cardiac development. Mutations in these genes have been linked to congenital heart defects (CHDs), occurring in approximately 1 in 145 live births. To date, TPM1 has not been associated with isolated CHDs. Analysis of 380 CHD cases revealed three novel mutations in the TPM1 gene; IVS1+2T>C, I130V, S229F and a polyadenylation signal site variant GATAAA/AATAAA. Analysis of IVS1+2T>C revealed aberrant pre-mRNA splicing. In addition, abnormal structural properties were found in hearts transfected with TPM1 carrying I130V and S229F mutations. Phenotypic analysis of TPM1 morpholino-treated embryos revealed roles for TPM1 in cardiac looping, atrial septation and ventricular trabeculae formation and increased apoptosis was seen within the heart. In addition, sarcomere assembly was affected and altered action potentials were exhibited. This study demonstrated that sarcomeric TPM1 plays vital roles in cardiogenesis and is a suitable candidate gene for screening individuals with isolated CHDs. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Great Institutions in Cardiothoracic Surgery: The University of Minnesota.

PubMed

Huddleston, Stephen J; Shumway, Sara

2016-01-01

With the loyal support of the chair of Surgery, Dr. Owen H. Wangensteen, the University of Minnesota cardiac surgery program led the way at the dawn of cardiac surgery when Dr F. John Lewis performed the first open heart surgery in the world using hypothermia while repairing an atrial septal defect on September 2, 1952. Soon after, Dr C. Walt Lillehei performed the first repair of a ventriculoseptal defect in the world using cross-circulation on March 26, 1954. Collaborating with Dr Richard DeWall in 1955, they developed the DeWall-Lillehei bubble oxygentor which was used at the University of Minnesota and many other centers worldwide for years to come, making open heart surgery safe and tractable. Dr Vincent Gott, a resident working in the laboratory of Lillehei, developed a method to treat complete heart block using ventricular pacing with a Grass physiological stimulator, and this led to a collaboration with Earl Bakken, founder of the Medtronic Corporation, to develop a temporary pacemaker. The program was fertile ground for many notable trainees, including Dr Norman Shumway, the "Father of Heart Transplant", and Dr Christiaan Barnard who performed the first heart transplant in the world. The collegial and forward thinking nature of the cardiac surgery program continues in the current training program today. Copyright © 2016 Elsevier Inc. All rights reserved.

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

PubMed Central

Whittaker, Danielle E.; Kasah, Sahrunizam; Donovan, Alex P. A.; Ellegood, Jacob; Riegman, Kimberley L. H.; Volk, Holger A.; McGonnell, Imelda; Lerch, Jason P.

2017-01-01

Mutations in the gene encoding the ATP dependent chromatin‐remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital‐urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio‐temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay. PMID:29168327

Who Should Be Targeted for the Prevention of Birth Defects? A Latent Class Analysis Based on a Large, Population-Based, Cross-Sectional Study in Shaanxi Province, Western China.

PubMed

Zhu, Zhonghai; Cheng, Yue; Yang, Wenfang; Li, Danyang; Yang, Xue; Liu, Danli; Zhang, Min; Yan, Hong; Zeng, Lingxia

2016-01-01

The wide range and complex combinations of factors that cause birth defects impede the development of primary prevention strategies targeted at high-risk subpopulations. Latent class analysis (LCA) was conducted to identify mutually exclusive profiles of factors associated with birth defects among women between 15 and 49 years of age using data from a large, population-based, cross-sectional study conducted in Shaanxi Province, western China, between August and October, 2013. The odds ratios (ORs) and 95% confidence intervals (CIs) of associated factors and the latent profiles of indicators of birth defects and congenital heart defects were computed using a logistic regression model. Five discrete subpopulations of participants were identified as follows: No folic acid supplementation in the periconceptional period (reference class, 21.37%); low maternal education level + unhealthy lifestyle (class 2, 39.75%); low maternal education level + unhealthy lifestyle + disease (class 3, 23.71%); unhealthy maternal lifestyle + advanced age (class 4, 4.71%); and multi-risk factor exposure (class 5, 10.45%). Compared with the reference subgroup, the other subgroups consistently had a significantly increased risk of birth defects (ORs and 95% CIs: class 2, 1.75 and 1.21-2.54; class 3, 3.13 and 2.17-4.52; class 4, 5.02 and 3.20-7.88; and class 5, 12.25 and 8.61-17.42, respectively). For congenital heart defects, the ORs and 95% CIs were all higher, and the magnitude of OR differences ranged from 1.59 to 16.15. A comprehensive intervention strategy targeting maternal exposure to multiple risk factors is expected to show the strongest results in preventing birth defects.

A family of oculofaciocardiodental syndrome (OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS.

PubMed

Kondo, Yukiko; Saitsu, Hirotomo; Miyamoto, Toshinobu; Nishiyama, Kiyomi; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Ryoo, Na-Kyung; Kim, Jeong Hun; Yu, Young Suk; Matsumoto, Naomichi

2012-03-01

Oculofaciocardiodental syndrome (OFCD) is an X-linked dominant disorder associated with male lethality, presenting with congenital cataract, dysmorphic face, dental abnormalities and septal heart defects. Mutations in BCOR (encoding BCL-6-interacting corepressor) cause OFCD. Here, we report on a Korean family with common features of OFCD including bilateral 2nd-3rd toe syndactyly and septal heart defects in three affected females (mother and two daughters). Through the mutation screening and copy number analysis using genomic microarray, we identified a novel heterozygous mutation, c.888delG, in the BCOR gene and two interstitial microduplications at Xp22.2-22.13 and Xp21.3 in all the three affected females. The BCOR mutation may lead to a premature stop codon (p.N297IfsX80). The duplication at Xp22.2-22.13 involved the NHS gene causative for Nance-Horan syndrome, which is an X-linked disorder showing similar clinical features with OFCD in affected males, and in carrier females with milder presentation. Considering the presence of bilateral 2nd-3rd toe syndactyly and septal heart defects, which is unique to OFCD, the mutation in BCOR is likely to be the major determinant for the phenotypes in this family.

Haploinsufficiency of TAB2 Causes Congenital Heart Defects in Humans

PubMed Central

Thienpont, Bernard; Zhang, Litu; Postma, Alex V.; Breckpot, Jeroen; Tranchevent, Léon-Charles; Van Loo, Peter; Møllgård, Kjeld; Tommerup, Niels; Bache, Iben; Tümer, Zeynep; van Engelen, Klaartje; Menten, Björn; Mortier, Geert; Waggoner, Darrel; Gewillig, Marc; Moreau, Yves; Devriendt, Koen; Larsen, Lars Allan

2010-01-01

Congenital heart defects (CHDs) are the most common major developmental anomalies and the most frequent cause for perinatal mortality, but their etiology remains often obscure. We identified a locus for CHDs on 6q24-q25. Genotype-phenotype correlations in 12 patients carrying a chromosomal deletion on 6q delineated a critical 850 kb region on 6q25.1 harboring five genes. Bioinformatics prioritization of candidate genes in this locus for a role in CHDs identified the TGF-β-activated kinase 1/MAP3K7 binding protein 2 gene (TAB2) as the top-ranking candidate gene. A role for this candidate gene in cardiac development was further supported by its conserved expression in the developing human and zebrafish heart. Moreover, a critical, dosage-sensitive role during development was demonstrated by the cardiac defects observed upon titrated knockdown of tab2 expression in zebrafish embryos. To definitively confirm the role of this candidate gene in CHDs, we performed mutation analysis of TAB2 in 402 patients with a CHD, which revealed two evolutionarily conserved missense mutations. Finally, a balanced translocation was identified, cosegregating with familial CHD. Mapping of the breakpoints demonstrated that this translocation disrupts TAB2. Taken together, these data clearly demonstrate a role for TAB2 in human cardiac development. PMID:20493459

Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function

PubMed Central

Sarmah, Swapnalee; Marrs, James A.

2016-01-01

Environmental pollution is a serious problem of the modern world that possesses a major threat to public health. Exposure to environmental pollutants during embryonic development is particularly risky. Although many pollutants have been verified as potential toxicants, there are new chemicals in the environment that need assessment. Heart development is an extremely sensitive process, which can be affected by environmentally toxic molecule exposure during embryonic development. Congenital heart defects are the most common life-threatening global health problems, and the etiology is mostly unknown. The zebrafish has emerged as an invaluable model to examine substance toxicity on vertebrate development, particularly on cardiac development. The zebrafish offers numerous advantages for toxicology research not found in other model systems. Many laboratories have used the zebrafish to study the effects of widespread chemicals in the environment on heart development, including pesticides, nanoparticles, and various organic pollutants. Here, we review the uses of the zebrafish in examining effects of exposure to external molecules during embryonic development in causing cardiac defects, including chemicals ubiquitous in the environment and illicit drugs. Known or potential mechanisms of toxicity and how zebrafish research can be used to provide mechanistic understanding of cardiac defects are discussed. PMID:27999267

MTHFR polymorphisms in Puerto Rican children with isolated congenital heart disease and their mothers

PubMed Central

García-Fragoso, Lourdes; García-García, Inés; Leavitt, Gloria; Renta, Jessicca; Ayala, Miguel A.; Cadilla, Carmen L.

2010-01-01

Congenital heart defects (CHD) are among the most common birth defects. There is evidence suggesting that polymorphisms in folate metabolism could alter susceptibility to CHD. The MTHFR 677TT genotype has been associated with the development of structural congenital heart malformations. The objective of this study was to identify common polymorphisms in the MTHFR gene in children with isolated CHD and their mothers. The DNA analysis for the C677T and A1298C mutations was performed. The study group included 27 mothers, 27 children with CHD, and 220 controls. The prevalence of the TT polymorphism was higher in mothers (22%) than in controls (10%). Compound heterozygosity for both polymorphisms was 3.7 times more common in children with CHD than in the newborn controls. Mothers of children with CHD were more likely to be compound heterozygotes. The higher prevalence of C677T polymorphisms in mothers of children with CHD and of compound heterozygosity for both polymorphisms suggests the possible role of folic acid in the prevention of CHD. Due to the relation of this enzyme to folate metabolism, current folate recommendations for women in childbearing age in Puerto Rico to reduce neural tube defects may need to be extended to the prevention of CHD. PMID:20657745

MTHFR polymorphisms in Puerto Rican children with isolated congenital heart disease and their mothers.

PubMed

García-Fragoso, Lourdes; García-García, Inés; Leavitt, Gloria; Renta, Jessicca; Ayala, Miguel A; Cadilla, Carmen L

2010-03-01

Congenital heart defects (CHD) are among the most common birth defects. There is evidence suggesting that polymorphisms in folate metabolism could alter susceptibility to CHD. The MTHFR 677TT genotype has been associated with the development of structural congenital heart malformations. The objective of this study was to identify common polymorphisms in the MTHFR gene in children with isolated CHD and their mothers. The DNA analysis for the C677T and A1298C mutations was performed. The study group included 27 mothers, 27 children with CHD, and 220 controls. The prevalence of the TT polymorphism was higher in mothers (22%) than in controls (10%). Compound heterozygosity for both polymorphisms was 3.7 times more common in children with CHD than in the newborn controls. Mothers of children with CHD were more likely to be compound heterozygotes. The higher prevalence of C677T polymorphisms in mothers of children with CHD and of compound heterozygosity for both polymorphisms suggests the possible role of folic acid in the prevention of CHD. Due to the relation of this enzyme to folate metabolism, current folate recommendations for women in childbearing age in Puerto Rico to reduce neural tube defects may need to be extended to the prevention of CHD.

Experiences and preferences of care among Swedish immigrants following a prenatal diagnosis of congenital heart defect in the fetus: a qualitative interview study.

PubMed

Carlsson, Tommy; Marttala, Ulla Melander; Mattsson, Elisabet; Ringnér, Anders

2016-06-02

Immigrants experience significant challenges when in contact with healthcare and report less satisfaction with maternity care compared to native Swedes. Research that gives voice to pregnant immigrant women and their partners following a prenatal diagnosis of a fetal anomaly is scarce. Thus, the aim of this study was to explore experiences and preferences of care following a prenatal diagnosis of congenital heart defect among Swedish immigrants. Pregnant immigrants and their partners were consecutively recruited following a prenatal diagnosis of a congenital heart defect in the fetus. Nine respondents were interviewed in five interviews, four with the aid of a professional interpreter. The material was analyzed using manifest qualitative content analysis. The analysis resulted in five categories: 1) "Trustworthy information", 2) "Language barriers", 3) "Psychosocial situation", 4) "Peer support", and 5) "Religious positions". The potential need for interpreter services, visual information, psychosocial support, coordination with welfare officers, and respect for religious positions about termination of pregnancy are all important aspects for health professionals to consider when consulting immigrants faced with a prenatal diagnosis of fetal anomaly in the fetus. Peer support within this context needs to be further explored in future studies.

Associations between exposure to ambient benzene and PM(2.5) during pregnancy and the risk of selected birth defects in offspring.

PubMed

Tanner, Jean Paul; Salemi, Jason L; Stuart, Amy L; Yu, Haofei; Jordan, Melissa M; DuClos, Chris; Cavicchia, Philip; Correia, Jane A; Watkins, Sharon M; Kirby, Russell S

2015-10-01

A growing number of studies have investigated the association between air pollution and the risk of birth defects, but results are inconsistent. The objective of this study was to examine whether maternal exposure to ambient PM2.5 or benzene increases the risk of selected birth defects in Florida. We conducted a retrospective cohort study of singleton infants born in Florida from 2000 to 2009. Isolated and non-isolated birth defect cases of critical congenital heart defects, orofacial clefts, and spina bifida were identified from the Florida Birth Defects Registry. Estimates of maternal exposures to PM2.5 and benzene for all case and non-case pregnancies were derived by aggregation of ambient measurement data, obtained from the US Environmental Protection Agency Air Quality System, during etiologically relevant time windows. Multivariable Poisson regression was used to estimate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) for each quartile of air pollutant exposure. Compared to the first quartile of PM2.5 exposure, higher levels of exposure were associated with an increased risk of non-isolated truncus arteriosus (aPR4th Quartile, 8.80; 95% CI, 1.11-69.50), total anomalous pulmonary venous return (aPR2nd Quartile, 5.00; 95% CI, 1.10-22.84), coarctation of the aorta (aPR4th Quartile, 1.72; 95% CI, 1.15-2.57; aPR3rd Quartile, 1.60; 95% CI, 1.07-2.41), interrupted aortic arch (aPR4th Quartile, 5.50; 95% CI, 1.22-24.82), and isolated and non-isolated any critical congenital heart defect (aPR3rd Quartile, 1.13; 95% CI, 1.02-1.25; aPR4th Quartile, 1.33; 95% CI, 1.07-1.65). Mothers with the highest level of exposure to benzene were more likely to deliver an infant with an isolated cleft palate (aPR4th Quartile, 1.52; 95% CI, 1.13-2.04) or any orofacial cleft (aPR4th Quartile, 1.29; 95% CI, 1.08-1.56). An inverse association was observed between exposure to benzene and non-isolated pulmonary atresia (aPR4th Quartile, 0.19; 95% CI, 0.04-0.84). Our results suggest a few associations between exposure to ambient PM2.5 or benzene and specific birth defects in Florida. However, many related comparisons showed no association. Hence, it remains unclear whether associations are clinically significant or can be causally related to air pollution exposures. Copyright © 2015 Elsevier Inc. All rights reserved.

Comorbid Conditions in Neonates With Congenital Heart Disease.

PubMed

Krishnamurthy, Ganga; Ratner, Veniamin; Bacha, Emile; Aspelund, Gudrun

2016-08-01

The objectives of this review are to discuss the pathophysiology, clinical impact and treatment of major noncardiac anomalies, and prematurity in infants with congenital heart disease. MEDLINE and PubMed. Mortality risk is significantly higher in patients with congenital heart disease and associated anomalies compared with those in whom the heart defect occurs in isolation. Although most noncardiac structural anomalies do not require surgery in the neonatal period, several require surgery for survival. Management of such infants poses multiple challenges. Premature infants with congenital heart disease face challenges imposed by their immature organ systems, which are susceptible to injury or altered function by congenital heart disease and abnormal circulatory physiology independent of congenital heart disease. For optimal outcomes in premature infants or in infants with multiple congenital anomalies, a collaborative interdisciplinary approach is necessary.

Novel mutation of GATA4 gene in Kurdish population of Iran with nonsyndromic congenital heart septals defects.

PubMed

Soheili, Fariborz; Jalili, Zahra; Rahbar, Mahtab; Khatooni, Zahed; Mashayekhi, Amir; Jafari, Hossein

2018-03-01

The mutations in GATA4 gene induce inherited atrial and ventricular septation defects, which is the most frequent forms of congenital heart defects (CHDs) constituting about half of all cases. We have performed High resolution melting (HRM) mutation scanning of GATA4 coding exons of nonsyndrome 100 patients as a case group including 39 atrial septal defects (ASD), 57 ventricular septal defects (VSD) and four patients with both above defects and 50 healthy individuals as a control group. Our samples are categorized according to their HRM graph. The genome sequencing has been done for 15 control samples and 25 samples of patients whose HRM analysis were similar to healthy subjects for each exon. The PolyPhen-2 and MUpro have been used to determine the causative possibility and structural stability prediction of GATA4 sequence variation. The HRM curve analysis exhibit that 21 patients and 3 normal samples have deviated curves for GATA4 coding exons. Sequencing analysis has revealed 12 nonsynonymous mutations while all of them resulted in stability structure of protein 10 of them are pathogenic and 2 of them are benign. Also we found two nucleotide deletions which one of them was novel and one new indel mutation resulting in frame shift mutation, and 4 synonymous variations or polymorphism in 6 of patients and 3 of normal individuals. Six or about 50% of these nonsynonymous mutations have not been previously reported. Our results show that there is a spectrum of GATA4 mutations resulting in septal defects. © 2018 Wiley Periodicals, Inc.

Context-based automated defect classification system using multiple morphological masks

DOEpatents

Gleason, Shaun S.; Hunt, Martin A.; Sari-Sarraf, Hamed

2002-01-01

Automatic detection of defects during the fabrication of semiconductor wafers is largely automated, but the classification of those defects is still performed manually by technicians. This invention includes novel digital image analysis techniques that generate unique feature vector descriptions of semiconductor defects as well as classifiers that use these descriptions to automatically categorize the defects into one of a set of pre-defined classes. Feature extraction techniques based on multiple-focus images, multiple-defect mask images, and segmented semiconductor wafer images are used to create unique feature-based descriptions of the semiconductor defects. These feature-based defect descriptions are subsequently classified by a defect classifier into categories that depend on defect characteristics and defect contextual information, that is, the semiconductor process layer(s) with which the defect comes in contact. At the heart of the system is a knowledge database that stores and distributes historical semiconductor wafer and defect data to guide the feature extraction and classification processes. In summary, this invention takes as its input a set of images containing semiconductor defect information, and generates as its output a classification for the defect that describes not only the defect itself, but also the location of that defect with respect to the semiconductor process layers.

First trimester combined screening biochemistry in detection of congenital heart defects.

PubMed

Alanen, Julia; Korpimaki, Teemu; Kouru, Heikki; Sairanen, Mikko; Leskinen, Markku; Gissler, Mika; Ryynanen, Markku; Nevalainen, Jaana

2018-04-22

To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs). During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down's syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland. Both PAPP-A and fβ-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fβ-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fβ-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively. Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fβ-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans.

Drosophila heart cell movement to the midline occurs through both cell autonomous migration and dorsal closure.

PubMed

Haack, Timm; Schneider, Matthias; Schwendele, Bernd; Renault, Andrew D

2014-12-15

The Drosophila heart is a linear organ formed by the movement of bilaterally specified progenitor cells to the midline and adherence of contralateral heart cells. This movement occurs through the attachment of heart cells to the overlying ectoderm which is undergoing dorsal closure. Therefore heart cells are thought to move to the midline passively. Through live imaging experiments and analysis of mutants that affect the speed of dorsal closure we show that heart cells in Drosophila are autonomously migratory and part of their movement to the midline is independent of the ectoderm. This means that heart formation in flies is more similar to that in vertebrates than previously thought. We also show that defects in dorsal closure can result in failure of the amnioserosa to properly degenerate, which can physically hinder joining of contralateral heart cells leading to a broken heart phenotype. Copyright © 2014 Elsevier Inc. All rights reserved.

Quality of Patient Information Websites About Congenital Heart Defects: Mixed-Methods Study of Perspectives Among Individuals With Experience of a Prenatal Diagnosis.

PubMed

Carlsson, Tommy; Melander Marttala, Ulla; Wadensten, Barbro; Bergman, Gunnar; Axelsson, Ove; Mattsson, Elisabet

2017-09-12

When a heart defect is prenatally diagnosed in the fetus, expectant parents experience a great need for information about various topics. After the diagnosis, the Web is used for supplemental information, and the scarcity of research calls attention to the need to explore patient information websites from the perspectives of the intended consumers. The overarching aim of this study was to explore the quality of Swedish patient information websites about congenital heart defects, from the perspectives of individuals with experience of a prenatal diagnosis of congenital heart defect in the fetus. This was a mixed-methods study of websites identified through systematic searches in the two most used Web-based search engines. Of the total 80 screened hits, 10 hits led to patient information websites about congenital heart defects. A quality assessment tool inspired by a previous study was used to evaluate each website's appearance, details, relevance, suitability, information about treatment choices, and overall quality. Answers were given on a 5-point Likert scale, ranging from 1, representing the lowest score, to 5, representing the highest score. Each website was assessed individually by persons with experience of continued (n=4) and terminated (n=5) pregnancy following a prenatal diagnosis. Assessments were analyzed with Kendall's coefficient of concordance W, Mann-Whitney U test, Friedman's test, and a Wilcoxon-Nemenyi-McDonald-Thompson test. In addition, each assessor submitted written responses to open-ended questions in the quality assessment tool, and two joint focus group discussions were conducted with each group of assessors. The qualitative data were analyzed with inductive manifest content analysis. Assessments represented a low score (median=2.0) for treatment choices and moderate scores (median=3.0) for appearance, details, relevance, suitability, and overall quality. No website had a median of the highest achievable score for any of the questions in the quality assessment tool. Medians of the lowest achievable score were found in questions about treatment choices (n=4 websites), details (n=2 websites), suitability (n=1 website), and overall quality (n=1 website). Websites had significantly different scores for appearance (P=.01), details (P<.001), relevance (P<.001), suitability (P<.001), treatment choices (P=.04), and overall quality (P<.001). The content analysis of the qualitative data generated six categories: (1) advertisements, (2) comprehensiveness, (3) design, (4) illustrations and pictures, (5) language, and (6) trustworthiness. Various issues with the included websites were highlighted, including the use of inappropriate advertisements, biased information, poor illustrations, complex language, and poor trustworthiness. From the perspectives of the intended consumers, patient information websites about congenital heart defects are, to a large extent, inadequate tools for supplemental information following a prenatal diagnosis. Health professionals should initiate discussions with patients about their intentions to use the Web, inform them about the varied quality in the Web-based landscape, and offer recommendations for appropriate Web-based sources. ©Tommy Carlsson, Ulla Melander Marttala, Barbro Wadensten, Gunnar Bergman, Ove Axelsson, Elisabet Mattsson. Originally published in the Interactive Journal of Medical Research (http://www.i-jmr.org/), 12.09.2017.

Quality of Patient Information Websites About Congenital Heart Defects: Mixed-Methods Study of Perspectives Among Individuals With Experience of a Prenatal Diagnosis

PubMed Central

Melander Marttala, Ulla; Wadensten, Barbro; Bergman, Gunnar; Axelsson, Ove; Mattsson, Elisabet

2017-01-01

Background When a heart defect is prenatally diagnosed in the fetus, expectant parents experience a great need for information about various topics. After the diagnosis, the Web is used for supplemental information, and the scarcity of research calls attention to the need to explore patient information websites from the perspectives of the intended consumers. Objective The overarching aim of this study was to explore the quality of Swedish patient information websites about congenital heart defects, from the perspectives of individuals with experience of a prenatal diagnosis of congenital heart defect in the fetus. Methods This was a mixed-methods study of websites identified through systematic searches in the two most used Web-based search engines. Of the total 80 screened hits, 10 hits led to patient information websites about congenital heart defects. A quality assessment tool inspired by a previous study was used to evaluate each website’s appearance, details, relevance, suitability, information about treatment choices, and overall quality. Answers were given on a 5-point Likert scale, ranging from 1, representing the lowest score, to 5, representing the highest score. Each website was assessed individually by persons with experience of continued (n=4) and terminated (n=5) pregnancy following a prenatal diagnosis. Assessments were analyzed with Kendall’s coefficient of concordance W, Mann-Whitney U test, Friedman’s test, and a Wilcoxon-Nemenyi-McDonald-Thompson test. In addition, each assessor submitted written responses to open-ended questions in the quality assessment tool, and two joint focus group discussions were conducted with each group of assessors. The qualitative data were analyzed with inductive manifest content analysis. Results Assessments represented a low score (median=2.0) for treatment choices and moderate scores (median=3.0) for appearance, details, relevance, suitability, and overall quality. No website had a median of the highest achievable score for any of the questions in the quality assessment tool. Medians of the lowest achievable score were found in questions about treatment choices (n=4 websites), details (n=2 websites), suitability (n=1 website), and overall quality (n=1 website). Websites had significantly different scores for appearance (P=.01), details (P<.001), relevance (P<.001), suitability (P<.001), treatment choices (P=.04), and overall quality (P<.001). The content analysis of the qualitative data generated six categories: (1) advertisements, (2) comprehensiveness, (3) design, (4) illustrations and pictures, (5) language, and (6) trustworthiness. Various issues with the included websites were highlighted, including the use of inappropriate advertisements, biased information, poor illustrations, complex language, and poor trustworthiness. Conclusions From the perspectives of the intended consumers, patient information websites about congenital heart defects are, to a large extent, inadequate tools for supplemental information following a prenatal diagnosis. Health professionals should initiate discussions with patients about their intentions to use the Web, inform them about the varied quality in the Web-based landscape, and offer recommendations for appropriate Web-based sources. PMID:28899846

Maternal obesity and tobacco use modify the impact of genetic variants on the occurrence of conotruncal heart defects.

PubMed

Tang, Xinyu; Nick, Todd G; Cleves, Mario A; Erickson, Stephen W; Li, Ming; Li, Jingyun; MacLeod, Stewart L; Hobbs, Charlotte A

2014-01-01

Conotruncal heart defects (CTDs) are among the most severe birth defects worldwide. Studies of CTDs indicate both lifestyle behaviors and genetic variation contribute to the risk of CTDs. Based on a hybrid design using data from 616 case-parental and 1645 control-parental triads recruited for the National Birth Defects Prevention Study between 1997 and 2008, we investigated whether the occurrence of CTDs is associated with interactions between 921 maternal and/or fetal single nucleotide polymorphisms (SNPs) and maternal obesity and tobacco use. The maternal genotypes of the variants in the glutamate-cysteine ligase, catalytic subunit (GCLC) gene and the fetal genotypes of the variants in the glutathione S-transferase alpha 3 (GSTA3) gene were associated with an elevated risk of CTDs among obese mothers. The risk of delivering infants with CTDs among obese mothers carrying AC genotype for a variant in the GCLC gene (rs6458939) was 2.00 times the risk among those carrying CC genotype (95% confidence interval: 1.41, 2.38). The maternal genotypes of several variants in the glutathione-S-transferase (GST) family of genes and the fetal genotypes of the variants in the GCLC gene interacted with tobacco exposures to increase the risk of CTDs. Our study suggests that the genetic basis underlying susceptibility of the developing heart to the adverse effects of maternal obesity and tobacco use involve both maternal and embryonic genetic variants. These results may provide insights into the underlying pathophysiology of CTDs, and ultimately lead to novel prevention strategies.

Increased pulmonary artery pressures during exercise are related to persistent tricuspid regurgitation after atrial septal defect closure.

PubMed

De Meester, Pieter; Van De Bruaene, Alexander; Herijgers, Paul; Voigt, Jens-Uwe; Vanhees, Luc; Budts, Werner

2013-08-01

Although closure of an atrial septal defect type secundum often normalizes right heart dimensions and pressures, mild tricuspid insufficiency might persist. This study aimed at (1) identification of determinants explaining the persistence of tricuspid insufficiency after atrial septal defect closure, and (2) evaluation of functional capacity of patients with persistent mild tricuspid insufficiency. Twenty-five consecutive patients (age 42+17 y) were included from the outpatient clinic of congenital heart disease at the University Hospitals of Leuven. All underwent transthoracic echocardiography, semi-supine bicycle stress echocardiography and cardio-pulmonary exercise testing. Six patients (24%) had mild tricuspid insufficiency (2/4) compared to 19 patients (76%) with no or minimal tricuspid insufficiency ( 1/4) as assessed by semi-quantitative colour Doppler echocardiography. Mann-Whitney U and Fisher's exact tests were performed where applicable. Patients with persistent mild tricuspid insufficiency were significantly older than those with no or minimal tricuspid insufficiency (P = 0.042). At rest, no differences in right heart configuration, mean pulmonary artery pressure or right ventricular function were found. At peak exercise, mean pulmonary artery pressure was significantly higher in patients with mild persistent tricuspid insufficiency (P = 0.026). Peak oxygen uptake was significantly lower in patients with mild persistent tricuspid insufficiency (P = 0.019). Mild tricuspid insufficiency after atrial septal defect repair occurs more frequently in older patients and in patients with higher mean pulmonary artery pressure at peak exercise. In patients with mild tricuspid insufficiency, functional capacity was more reduced. Mild tricuspid insufficiency could be a marker of subclinical persistent pressure load on the right ventricle.

Situs inversus totalis associated with subaortic stenosis, restrictive ventricular septal defect, and tricuspid dysplasia in an adult dog.

PubMed

Piantedosi, Diego; Cortese, Laura; Meomartino, Leonardo; Di Loria, Antonio; Ciaramella, Paolo

2011-11-01

A rare association between situs inversus totalis (SIT), restrictive ventricular septal defect, severe subaortic stenosis, and tricuspid dysplasia was observed in an adult mixed-breed dog. Primary ciliary dyskinesia and Kartagener's syndrome were excluded. After 15 mo the dog died suddenly. The association between SIT and congenital heart diseases is discussed.

Ultra-high frequency ultrasound biomicroscopy and high throughput cardiovascular phenotyping in a large scale mouse mutagenesis screen

NASA Astrophysics Data System (ADS)

Liu, Xiaoqin; Francis, Richard; Tobita, Kimimasa; Kim, Andy; Leatherbury, Linda; Lo, Cecilia W.

2013-02-01

Ultrasound biomicroscopy (UBM) is ideally suited for phenotyping fetal mice for congenital heart disease (CHD), as imaging can be carried out noninvasively to provide both hemodynamic and structural information essential for CHD diagnosis. Using the UBM (Vevo 2100; 40Hz) in conjunction with the clinical ultrasound system (Acuson Sequioa C512; 15Hz), we developed a two-step screening protocol to scan thousands fetuses derived from ENU mutagenized pedigrees. A wide spectrum of CHD was detected by the UBM, which were subsequently confirmed with follow-up necropsy and histopathology examination with episcopic fluorescence image capture. CHD observed included outflow anomalies, left/right heart obstructive lesions, septal/valvular defects and cardiac situs anomalies. Meanwhile, various extracardiac defects were found, such as polydactyly, craniofacial defects, exencephaly, omphalocele-cleft palate, most of which were associated with cardiac defects. Our analyses showed the UBM was better at assessing cardiac structure and blood flow profiles, while conventional ultrasound allowed higher throughput low-resolution screening. Our study showed the integration of conventional clinical ultrasound imaging with the UBM for fetal mouse cardiovascular phenotyping can maximize the detection and recovery of CHD mutants.

Spectrum of heart diseases in children: an echocardiographic study of 1,666 subjects in a pediatric hospital, Yaounde, Cameroon.

PubMed

Chelo, David; Nguefack, Félicitée; Menanga, Alain P; Ngo Um, Suzanne; Gody, Jean C; Tatah, Sandra A; Koki Ndombo, Paul O

2016-02-01

Children's health programs in Sub-Saharan Africa have always been oriented primarily to infectious diseases and malnutrition. We are witnessing in the early 21(st) century an epidemiological transition marked by the decline of old diseases and the identification of new diseases including heart disease. Therefore, it is necessary to describe the spectrum of these diseases in order to better prepare health workers to these new challenges. We conducted a cross-sectional study focused on heart disease diagnosed by echocardiography in children seen from January 2006 to December 2014 in a pediatric hospital of Yaounde. We collected socio-demographic data and the types of heart disease from registers, patients files as well as the electronic database of echocardiographic records. A total of 2,235 patients underwent echocardiographic examination during the study period including 1,666 subjects with heart disease. Congenital cardiopathies were found in 1,230 (73.8%) patients and acquired abnormalities in 429 (25.8%). Seven children (0.4%) had a combination of both types. Congenital heart defects (CHD) were dominated by ventricular septal defect (VSD). Acquired heart disease was mostly rheumatic valvulopathies. Dyspnea on exertion was the most frequent presenting complaint (87.6%). Discovery of a heart murmur was the principal clinical finding on physical examination (81.4%). The median age was 9 months for congenital heart disease and 132 months for acquired heart disease. As infectious diseases recede and the diagnostic facilities are improving, pediatric heart diseases occupy a more important position in the spectrum of pediatric diseases in our context. However, the ability to evoke the diagnosis remains unsatisfactory by the majority of health personnel and therefore needs to be improved. Apart from congenital heart diseases, the impact of acquired heart diseases, rheumatic valvulopathy being the highest ranking, is remarkable in pediatrics. Awareness of health personnel for better management of child tonsillitis is more than ever a necessity. This preventive attitude of rheumatic heart disease is the main attitude available in our disadvantaged economic environment.

A Blood-Resistant Surgical Glue for Minimally Invasive Repair of Vessels and Heart Defects

PubMed Central

Lang, Nora; Pereira, Maria J.; Lee, Yuhan; Friehs, Ingeborg; Vasilyev, Nikolay V.; Feins, Eric N.; Ablasser, Klemens; O'Cearbhaill, Eoin D.; Xu, Chenjie; Fabozzo, Assunta; Padera, Robert; Wasserman, Steve; Freudenthal, Franz; Ferreira, Lino S.; Langer, Robert

2014-01-01

Currently, there are no clinically approved surgical glues that are nontoxic, bind strongly to tissue, and work well within wet and highly dynamic environments within the body. This is especially relevant to minimally invasive surgery that is increasingly performed to reduce postoperative complications, recovery times, and patient discomfort. We describe the engineering of a bioinspired elastic and biocompatible hydrophobic light-activated adhesive (HLAA) that achieves a strong level of adhesion to wet tissue and is not compromised by preexposure to blood. The HLAA provided an on-demand hemostatic seal, within seconds of light application, when applied to high-pressure large blood vessels and cardiac wall defects in pigs. HLAA-coated patches attached to the interventricular septum in a beating porcine heart and resisted supraphysiologic pressures by remaining attached for 24 hours, which is relevant to intracardiac interventions in humans. The HLAA could be used for many cardiovascular and surgical applications, with immediate application in repair of vascular defects and surgical hemostasis. PMID:24401941

Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16

PubMed Central

Cordell, Heather J.; Bentham, Jamie; Topf, Ana; Zelenika, Diana; Heath, Simon; Mamasoula, Chrysovalanto; Cosgrove, Catherine; Blue, Gillian; Granados-Riveron, Javier; Setchfield, Kerry; Thornborough, Chris; Breckpot, Jeroen; Soemedi, Rachel; Martin, Ruairidh; Rahman, Thahira J.; Hall, Darroch; van Engelen, Klaartje; Moorman, Antoon F.M.; Zwinderman, Aelko H; Barnett, Phil; Koopmann, Tamara T.; Adriaens, Michiel E.; Varro, Andras; George, Alfred L.; dos Remedios, Christobal; Bishopric, Nanette H.; Bezzina, Connie R.; O’Sullivan, John; Gewillig, Marc; Bu’Lock, Frances A.; Winlaw, David; Bhattacharya, Shoumo; Devriendt, Koen; Brook, J. David; Mulder, Barbara J.M.; Mital, Seema; Postma, Alex V.; Lathrop, G. Mark; Farrall, Martin; Goodship, Judith A.; Keavney, Bernard D.

2013-01-01

We carried out a genome-wide association study (GWAS) of congenital heart disease (CHD). Our discovery cohort comprised 1,995 CHD cases and 5,159 controls, and included patients from each of the three major clinical CHD categories (septal, obstructive and cyanotic defects). When all CHD phenotypes were considered together, no regions achieved genome-wide significant association. However, a region on chromosome 4p16, adjacent to the MSX1 and STX18 genes, was associated (P=9.5×10−7) with the risk of ostium secundum atrial septal defect (ASD) in the discovery cohort (N=340 cases), and this was replicated in a further 417 ASD cases and 2520 controls (replication P=5.0×10−5; OR in replication cohort 1.40 [95% CI 1.19-1.65]; combined P=2.6×10−10). Genotype accounted for ~9% of the population attributable risk of ASD. PMID:23708191

Mental retardation, congenital heart defect, cleft palate, short stature, and facial anomalies: A new X-linked multiple congenital anomalies/mental retardation syndrome: Clinical description and molecular studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamel, B.C.J.; Mariman, E.C.M.; Beersum, S.E.C. van

1994-07-15

We report on two brothers and their two maternal uncles with severe mental retardation, congenital heart defect, cleft or highly arched palate, short stature and craniofacial anomalies consisting of microcephaly, abnormal ears, bulbous nose, broad nasal bridge, malar hypoplasia, and micro-gnathia. Three of the four patients died at an early age. The mother of the two brothers had an atrial septal defect. She is assumed to be manifesting carrier of a mutant gene, which is expressed in her two sons and two brothers. By multipoint linkage analysis it is found that the most likely location of the responsible gene ismore » the pericentromeric region Xp21.3-q21.3 with DMD and DXS3 as flanking markers. Maximum information is obtained with marker DXS453 (Z = 1.20 at {theta} = 0.0). 24 refs., 12 figs., 1 tab.« less

Amniotic Fluid-Derived Stem Cells for Cardiovascular Tissue Engineering Applications

PubMed Central

Petsche Connell, Jennifer; Camci-Unal, Gulden; Khademhosseini, Ali

2013-01-01

Recent research has demonstrated that a population of stem cells can be isolated from amniotic fluid removed by amniocentesis that are broadly multipotent and nontumorogenic. These amniotic fluid-derived stem cells (AFSC) could potentially provide an autologous cell source for treatment of congenital defects identified during gestation, particularly cardiovascular defects. In this review, the various methods of isolating, sorting, and culturing AFSC are compared, along with techniques for inducing differentiation into cardiac myocytes and endothelial cells. Although research has not demonstrated complete and high-yield cardiac differentiation, AFSC have been shown to effectively differentiate into endothelial cells and can effectively support cardiac tissue. Additionally, several tissue engineering and regenerative therapeutic approaches for the use of these cells in heart patches, injection after myocardial infarction, heart valves, vascularized scaffolds, and blood vessels are summarized. These applications show great promise in the treatment of congenital cardiovascular defects, and further studies of isolation, culture, and differentiation of AFSC will help to develop their use for tissue engineering, regenerative medicine, and cardiovascular therapies. PMID:23350771

Surgical treatment of atrioventricular canal defect.

PubMed

Hardesty, R L; Zuberbuhler, J R; Bahnson, H T

1975-11-01

Fifty-nine patients with congenital anomalies of the atrioventricular canal underwent operation and all survivors were followed up. In 42 patients with partial atrioventricular canal defects, ten had preoperative congestive heart failure. Three, or 7.1%, died of endomyocardial fibroelastosis, high pulmonary vascular resistance, and severe mitral regurgitation. A fourth patient later died of Wolff-Parkinson-White syndrome and fibrilation. Reoperations in five patients were all successful. No patients had persistent atrioventricular blocks, and all patients are asymptomatic. Two of these subjects continue to receive digoxin therapy, and one of them is believed to have substantial mitral insufficiency. Of the 17 patients who had complete atrioventricular canal defects, 13 had a divided common anterior leaflet attached to the septum by chordae tendineae, and four had undivided and unattached anterior leaflets. Two had previously undergone pulmonary banding, and nine were treated for congestive heart failure. Six died after operation. There were no reoperations. No patient presently has required a pacemaker. Two subjects have persistent cardiomegaly.

Clinical Profile of Cardiac Arrhythmias in Children Attending the Out Patient Department of a Tertiary Paediatric Care Centre in Chennai

PubMed Central

Sundararajan, Premkumar; Sangaralingam, Thangavelu

2016-01-01

Introduction The presentation of symptoms of paediatric arrhythmias vary depending on the age and underlying heart disease. Physical examination of children with important arrhythmias may be entirely normal. Aim Aim is to study the characteristics of cardiac arrhythmias in paediatric patients in a tertiary paediatric care centre in Chennai, India. Materials and Methods The participants (n=60) were from birth to 12 years of age. Patients with sinus arrhythmias, sinus tachycardia and sinus bradycardia were excluded. Proportions of various parameters of interest like clinical features, age and sex distribution and underlying heart disease of children presenting with cardiac arrhythmias were arrived. Statistical analysis was performed using SPSS version 16.0. Results Ventricular ectopics were the most common type of arrhythmias observed in the present study followed by Sinus Node Dysfunction (SND). The most common type of SND was sino atrial arrest. Supra ventricular tachycardia was the most frequently sustained tachyarrhythmia in the present study. An increased association of WPW (Wolf Parkinson White Syndrome) with specific congenital cardiac defects was noted. Conclusion Cardiac arrhythmias in children can present at anytime from fetal life to adolescence and their recognition requires high index of suspicion. While majority of children with arrhythmias have structurally normal heart, they are frequently encountered in children with underlying heart disease. Treatment of paediatric arrhythmias should be guided by the severity of the patient, the structure and function of the heart. PMID:28208963

Right atrial isolation associated with atrial septal closure in patients with atrial septal defect and chronic atrial fibrillation.

PubMed

Minzioni, G; Graffigna, A; Pagani, F; Vigano, M

1993-12-01

To restore sinus rhythm in the remaining heart chambers of six adult patients with atrial septal defect and chronic or paroxysmal atrial fibrillation, electrical, right atrial isolation associated with surgical correction of the defect was performed. All but one patient was free from atrial fibrillation without medication 2-25 months after operation. The isolated right atrial appendages showed intrinsic rhythmical activity in five patients and no electrical activity in one. Right atrial isolation is a safe and effective procedure that abolishes atrial fibrillation in patients with arrhythmia after surgical correction of atrial septal defect.

[Percutaneous closure of ductus arteriosus and muscular ventricular defect with amplatzer occluder in a patient with severe pulmonary hypertension].

PubMed

García-Montes, José Antonio; Zabal Cerdeira, Carlos; Calderón-Colmenero, Juan; Espínola, Nilda; Fernández de la Reguera, Guillermo; Buendía Hernández, Alfonso

2005-01-01

Surgical treatment of multiple muscular ventricular septal defects with associated lesions and severe pulmonary hypertension has a high morbility and mortality. Closure of these defects by the Amplatzer muscular VSD occluder is an alternative to surgery, avoiding the need of cardiopulmonary bypass. We present the case of a 38 year-old woman with signs of heart failure in NYHA functional class IV, with two muscular ventricular septal defects, patent ductus arteriosus and severe pulmonary hypertension, that were treated with three Amplatzer muscular VSD occluders, with significant reduction of pulmonary pressure and functional class improvement.

[Pulsatile total cavopulmonary shunt for hypoplastic right heart syndrome with abnormal systemic venous return--a case report].

PubMed

Oiwa, H; Kawauchi, M; Chikada, M; Yagyu, K; Kotsuka, Y; Furuse, A

1995-01-01

A pulsatile total cavopulmonary shunt was successfully performed on a 5-year-old girl with hypoplastic right heart syndrome associated with abnormal systemic venous return; at the same time, modified mitral valve replacement was performed for mitral regurgitation. The right atrium, tricuspid valve and right ventricle were all extremely dimunitive. The diameter of the tricuspid valve was 50% of normal and the volume of the right ventricle was 8.6% of normal. In addition, there were severe subpumonary stenosis, a restrictive ventricular septal defect (VSD) and an atrial septal defect (ASD). The bilateral superior venae cavae (SVCs) and the hepatic vein drained to the left atrium, and the inferior vena cava was infrahepatically interrupted with a hemiazygos connection to the left superior vena cava. At the operation, each SVC was anastomosed end-to-side to each branch of the pulmonary artery (PA). The restrictive ventricular septal defect and stenotic subpulmonary lesion were left. The diameter of the ASD was reduced from 12 mm to 7 mm. The main PA was neither divided nor banded. The pulsatile blood flow from the left heart to the PA was regurated by a native restrictive VSD and stenotic subpulmonary lesion, and that from the right heart via the ASD was limited by reducing the size of the ASD. These described anatomic arrangements produced adequate antegrade pulsatile flow in the PA, which might prevent the development of pulmonary arteriovenous fistulae and, besides permit transfer of drainage of the hepatic vein from the left to the right atrium via the ASD in future.

Stem cell therapy for the systemic right ventricle.

PubMed

Si, Ming-Sing; Ohye, Richard G

2017-11-01

In specific forms of congenital heart defects and pulmonary hypertension, the right ventricle (RV) is exposed to systemic levels of pressure overload. The RV is prone to failure in these patients because of its vulnerability to chronic pressure overload. As patients with a systemic RV reach adulthood, an emerging epidemic of RV failure has become evident. Medical therapies proven for LV failure are ineffective in treating RV failure. Areas covered: In this review, the pathophysiology of the failing RV under pressure overload is discussed, with specific emphasis on the pivotal roles of angiogenesis and oxidative stress. Studies investigating the ability of stem cell therapy to improve angiogenesis and mitigate oxidative stress in the setting of pressure overload are then reviewed. Finally, clinical trials utilizing stem cell therapy to prevent RV failure under pressure overload in congenital heart disease will be discussed. Expert commentary: Although considerable hurdles remain before their mainstream clinical implementation, stem cell therapy possesses revolutionary potential in the treatment of patients with failing systemic RVs who currently have very limited long-term treatment options. Rigorous clinical trials of stem cell therapy for RV failure that target well-defined mechanisms will ensure success adoption of this therapeutic strategy.

Pentalogy of Cantrell: report of a case with consanguineous parents.

PubMed

Pachajoa, Harry; Barragán, Arelis; Potes, Angela; Torres, Javier; Isaza, Carolina

2010-01-01

Pentalogy of Cantrell is a syndrome evidencing five anomalies: a midline, upper abdominal wall abnormality; lower sternal defect; anterior diaphragmatic defect; diaphragmatic pericardial defect, and congenital abnormalities of the heart. Its prevalence is one in every 65,000 live births and a survival rate that is low if the fall the five defects are present or the gravity of the cardiac anomalies. It may be diagnosed during the first trimester obstetric ultrasound. For postnatal care, emission-computed tomography and magnetic resonance imaging is recommended for a clear definition of the extent of the defect and to design a course of corrective surgery. Herein, a case of pentology of Cantrell is reported for a child offspring of consanguineous parents.

Caudal dysgenesis in islet-1 transgenic mice

PubMed Central

Muller, Yunhua Li; Yueh, Yir Gloria; Yaworsky, Paul J.; Salbaum, J. Michael; Kappen, Claudia

2014-01-01

Maternal diabetes during pregnancy is responsible for the occurrence of diabetic embryopathy, a spectrum of birth defects that includes heart abnormalities, neural tube defects, and caudal dysgenesis syndromes. Here, we report that mice transgenic for the homeodomain transcription factor Isl-1 develop profound caudal growth defects that resemble human sacral/caudal agenesis. Isl-1 is normally expressed in the pancreas and is required for pancreas development and endocrine cell differentiation. Aberrant regulation of this pancreatic transcription factor causes increased mesodermal cell death, and the severity of defects is dependent on transgene dosage. Together with the finding that mutation of the pancreatic transcription factor HLXB9 causes sacral agenesis, our results implicate pancreatic transcription factors in the pathogenesis of birth defects associated with diabetes. PMID:12738808

Increasing mortality burden among adults with complex congenital heart disease.

PubMed

Greutmann, Matthias; Tobler, Daniel; Kovacs, Adrienne H; Greutmann-Yantiri, Mehtap; Haile, Sarah R; Held, Leonhard; Ivanov, Joan; Williams, William G; Oechslin, Erwin N; Silversides, Candice K; Colman, Jack M

2015-01-01

Progress in management of congenital heart disease has shifted mortality largely to adulthood. However, adult survivors with complex congenital heart disease are not cured and remain at risk of premature death as young adults. Thus, our aim was to describe the evolution and mortality risk of adult patient cohorts with complex congenital heart disease. Among 12,644 adults with congenital heart disease followed at a single center from 1980 to 2009, 176 had Eisenmenger syndrome, 76 had unrepaired cyanotic defects, 221 had atrial switch operations for transposition of the great arteries, 158 had congenitally corrected transposition of the great arteries, 227 had Fontan palliation, and 789 had repaired tetralogy of Fallot. We depict the 30-year evolution of these 6 patient cohorts, analyze survival probabilities in adulthood, and predict future number of deaths through 2029. Since 1980, there has been a steady increase in numbers of patients followed, except in cohorts with Eisenmenger syndrome and unrepaired cyanotic defects. Between 1980 and 2009, 308 patients in the study cohorts (19%) died. At the end of 2009, 85% of survivors were younger than 50 years. Survival estimates for all cohorts were markedly lower than for the general population, with important differences between cohorts. Over the upcoming two decades, we predict a substantial increase in numbers of deaths among young adults with subaortic right ventricles, Fontan palliation, and repaired tetralogy of Fallot. Anticipatory action is needed to prepare clinical services for increasing numbers of young adults at risk of dying from complex congenital heart disease. © 2014 The Authors. Congenital Heart Disease Published by Wiley Periodicals, Inc.

Bartonella quintana, an Unrecognized Cause of Infective Endocarditis in Children in Ethiopia

PubMed Central

Raucher-Sternfeld, Alona; Tamir, Akiva; Giladi, Michael; Somekh, Eli

2017-01-01

Bartonella quintana endocarditis, a common cause of culture-negative endocarditis in adults, has rarely been reported in children. We describe 5 patients 7–16 years of age from Ethiopia with heart defects and endocarditis; 4 cases were caused by infection with B. quintana and 1 by Bartonella of undetermined species. All 5 patients were afebrile and oligosymptomatic, although 3 had heart failure. C-reactive protein was normal or slightly elevated, and erythrocyte sedimentation rate was high. The diagnosis was confirmed by echocardiographic demonstration of vegetations, the presence of high Bartonella IgG titers, and identification of B. quintana DNA in excised vegetations. Embolic events were diagnosed in 2 patients. Our data suggest that B. quintana is not an uncommon cause of native valve endocarditis in children in Ethiopia with heart defects and that possible B. quintana infection should be suspected and pursued among residents of and immigrants from East Africa, including Ethiopia, with culture-negative endocarditis. PMID:28730981

Percutaneous management of coronary sinus atrial septal defect: two cases representing the spectrum for device closure and a review of the literature.

PubMed

Sandeep, Nefthi; Slack, Michael C

2014-10-01

Coronary sinus atrial septal defects are the rarest defects of the atrial septum comprising <1% of the five different types of atrial septal defects. Despite the widespread adoption of percutaneous device closure of secundum atrial septal defects, the published experience with percutaneous device closure of coronary sinus atrial septal defects is limited to only a few isolated case reports because of uncertainty regarding safety and efficacy. Open-heart surgical repair remains the treatment of choice for coronary sinus atrial septal defects, although this may not be the only treatment option in selected cases. Herein we describe our own experience with two patients with different clinical presentations and our method of successful percutaneous coronary sinus atrial septal defect closure in each. We then present a review of the anatomic spectrum of coronary sinus atrial septal defects along with a review of contemporary surgical and percutaneous device treatment.

[Clinical Experience of Beating Heart Atrial Septostomy Using a Device for Coronary Artery Anastomosis Site Creator].

PubMed

Takahashi, Goro; Sai, Sadahiro; Konishi, Akinobu

2015-09-01

Intra-atrial communication was mandatory for several congenital cardiac diseases, such as pulmonary atresia with intact ventricular septum (PA/IVS), and either sided aortoventricular valve atresia. We assessed whether the new methods of atrial septal defect(ASD)creation was effective. We experienced 4 cases of the surgical atrial septostomy performed under on-pump beating. We used a new device, a circular punch out defect creator. All cases were alive. The mean ASD diameter was enlarged from 4.37 mm to 5.55 mm and the mean ASD shunt flow was significantly decreased from 1.47 m/s to 1.11 m/s. We performed the surgical atrial septostomy using an aortic puncher under beating heart effectively and safely.

On the Prediction of Solar Cell Degradation in Space

NASA Astrophysics Data System (ADS)

Bourgoin, J. C.; Boizot, B.; Khirouni, K.; Khorenko, V.

2014-08-01

We discuss the validity of the procedure which is used to predict End Of Life performances of a solar cell in space. This procedure consists to measure the performances of the cell after it has been irradiated at the EOL fluence during a time ti very short compared to the duration tm of the mission in space, i.e. with a considerably larger flux. We show that this procedure is valid only when the defects created by the irradiation do not anneal (thermally or by carrier injection) with a time constant shorter than tm or larger than ti. This can be a common situation since annealing of irradiation induced defects occurs in all type of cells, at least in specific conditions (temperature, intensity of illumination, flux and nature of irradiating particles). Using modeling, we illustrate the effect of injection or thermal annealing on EOL prediction in the case GaInP, material at the heart of modern high efficiency space solar cells.

Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy

PubMed Central

Cullup, Thomas; Kho, Ay L.; Dionisi-Vici, Carlo; Brandmeier, Birgit; Smith, Frances; Urry, Zoe; Simpson, Michael A.; Yau, Shu; Bertini, Enrico; McClelland, Verity; Al-Owain, Mohammed; Koelker, Stefan; Koerner, Christian; Hoffmann, Georg F.; Wijburg, Frits A.; Hoedt, Amber E. ten; Rogers, Curtis; Manchester, David; Miyata, Rie; Hayashi, Masaharu; Said, Elizabeth; Soler, Doriette; Kroisel, Peter M.; Windpassinger, Christian; Filloux, Francis M.; Al-Kaabi, Salwa; Hertecant, Jozef; Del Campo, Miguel; Buk, Stefan; Bodi, Istvan; Goebel, Hans-Hilmar; Sewry, Caroline A.; Abbs, Stephen; Mohammed, Shehla; Josifova, Dragana; Gautel, Mathias; Jungbluth, Heinz

2012-01-01

Vici syndrome is a recessively inherited multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. To investigate the molecular basis of Vici syndrome, we carried out exome and Sanger sequence analysis in a cohort of 18 patients. We identified recessive mutations in EPG5 (previously KIAA1632), indicating a causative role in Vici syndrome. EPG5 is the human homologue of the metazoan-specific autophagy gene epg-5, encoding a key autophagy regulator (ectopic P-granules autophagy protein 5) implicated in the formation of autolysosomes. Further studies demonstrated a severe block of autophagosomal clearance in muscle and fibroblasts from EPG5 mutant patients, resulting in autophagic cargo accumulation in autophagosomes. These findings indicate Vici syndrome as a paradigm of a human multisystem disorder associated with defective autophagy, and suggest a fundamental role of the autophagy pathway in the anatomical and functional formation of organs such as the brain, the heart and the immune system. PMID:23222957

Gab1 Is Modulated by Chronic Hypoxia in Children with Cyanotic Congenital Heart Defect and Its Overexpression Reduces Apoptosis in Rat Neonatal Cardiomyocytes

PubMed Central

Cherif, Myriam; Nakaoka, Yoshikazu; Angelini, Gianni D.; Ghorbel, Mohamed T.

2015-01-01

Gab1 (Grb2 associated binding protein 1) is a member of the scaffolding/docking proteins (Gab1, Gab2, and Gab3). It is required for fibroblast cell survival and maintaining cardiac function. Very little is known about human Gab1 expression in response to chronic hypoxia. The present study examined the hypothesis that hypoxia regulates Gab1 expression in human paediatric myocardium and cultured rat cardiomyocytes. Here we showed that Gab1 is expressed in myocardial tissue in acyanotic and cyanotic children with congenital heart defects. Gab1 protein was upregulated in cyanotic compared to acyanotic hearts suggesting that Gab1 upregulation is a component of the survival program initiated by hypoxia in cyanotic children. The expression of other Gab1 interacting partners was not affected by hypoxia and Gab1 regulation. Additionally, using an in vitro model, we demonstrated that overexpressing Gab1 in neonatal cardiomyocytes, under hypoxic condition, resulted in the reduction of apoptosis suggesting a role for this protein in cardiomyocyte survival. Altogether, our data provide strong evidence that Gab1 is important for heart cell survival following hypoxic stress. PMID:26090437

Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great Arteries

PubMed Central

Narematsu, Mayu; Kamimura, Tatsuya; Yamagishi, Toshiyuki; Fukui, Mitsuru; Nakajima, Yuji

2015-01-01

Background Transposition of the great arteries is one of the most commonly diagnosed conotruncal heart defects at birth, but its etiology is largely unknown. The anterior heart field (AHF) that resides in the anterior pharyngeal arches contributes to conotruncal development, during which heart progenitors that originated from the left and right AHF migrate to form distinct conotruncal regions. The aim of this study is to identify abnormal AHF development that causes the morphology of transposition of the great arteries. Methods and Results We placed a retinoic acid–soaked bead on the left or the right or on both sides of the AHF of stage 12 to 14 chick embryos and examined the conotruncal heart defect at stage 34. Transposition of the great arteries was diagnosed at high incidence in embryos for which a retinoic acid–soaked bead had been placed in the left AHF at stage 12. Fluorescent dye tracing showed that AHF exposed to retinoic acid failed to contribute to conotruncus development. FGF8 and Isl1 expression were downregulated in retinoic acid–exposed AHF, and differentiation and expansion of cardiomyocytes were suppressed in cultured AHF in medium supplemented with retinoic acid. Conclusions The left AHF at the early looped heart stage, corresponding to Carnegie stages 10 to 11 (28 to 29 days after fertilization) in human embryos, is the region of the impediment that causes the morphology of transposition of the great arteries. PMID:25929268

Interventional Cardiology for Congenital Heart Disease.

PubMed

Kenny, Damien

2018-05-01

Congenital heart interventions are now replacing surgical palliation and correction in an evolving number of congenital heart defects. Right ventricular outflow tract and ductus arteriosus stenting have demonstrated favorable outcomes compared to surgical systemic to pulmonary artery shunting, and it is likely surgical pulmonary valve replacement will become an uncommon procedure within the next decade, mirroring current practices in the treatment of atrial septal defects. Challenges remain, including the lack of device design focused on smaller infants and the inevitable consequences of somatic growth. Increasing parental and physician expectancy has inevitably lead to higher risk interventions on smaller infants and appreciation of the consequences of these interventions on departmental outcome data needs to be considered. Registry data evaluating congenital heart interventions remain less robust than surgical registries, leading to a lack of insight into the longer-term consequences of our interventions. Increasing collaboration with surgical colleagues has not been met with necessary development of dedicated equipment for hybrid interventions aimed at minimizing the longer-term consequences of scar to the heart. Therefore, great challenges remain to ensure children and adults with congenital heart disease continue to benefit from an exponential growth in minimally invasive interventions and technology. This can only be achieved through a concerted collaborative approach from physicians, industry, academia and regulatory bodies supporting great innovators to continue the philosophy of thinking beyond the limits that has been the foundation of our specialty for the past 50 years. Copyright © 2018. The Korean Society of Cardiology.

Effects of Age and Heart Failure on Human Cardiac Stem Cell Function

PubMed Central

Cesselli, Daniela; Beltrami, Antonio P.; D'Aurizio, Federica; Marcon, Patrizia; Bergamin, Natascha; Toffoletto, Barbara; Pandolfi, Maura; Puppato, Elisa; Marino, Laura; Signore, Sergio; Livi, Ugolino; Verardo, Roberto; Piazza, Silvano; Marchionni, Luigi; Fiorini, Claudia; Schneider, Claudio; Hosoda, Toru; Rota, Marcello; Kajstura, Jan; Anversa, Piero; Beltrami, Carlo A.; Leri, Annarosa

2011-01-01

Currently, it is unknown whether defects in stem cell growth and differentiation contribute to myocardial aging and chronic heart failure (CHF), and whether a compartment of functional human cardiac stem cells (hCSCs) persists in the decompensated heart. To determine whether aging and CHF are critical determinants of the loss in growth reserve of the heart, the properties of hCSCs were evaluated in 18 control and 23 explanted hearts. Age and CHF showed a progressive decrease in functionally competent hCSCs. Chronological age was a major predictor of five biomarkers of hCSC senescence: telomeric shortening, attenuated telomerase activity, telomere dysfunction-induced foci, and p21Cip1 and p16INK4a expression. CHF had similar consequences for hCSCs, suggesting that defects in the balance between cardiomyocyte mass and the pool of nonsenescent hCSCs may condition the evolution of the decompensated myopathy. A correlation was found previously between telomere length in circulating bone marrow cells and cardiovascular diseases, but that analysis was restricted to average telomere length in a cell population, neglecting the fact that telomere attrition does not occur uniformly in all cells. The present study provides the first demonstration that dysfunctional telomeres in hCSCs are biomarkers of aging and heart failure. The biomarkers of cellular senescence identified here can be used to define the birth date of hCSCs and to sort young cells with potential therapeutic efficacy. PMID:21703415

Echocardiographic findings in infants with presumed congenital Zika syndrome: Retrospective case series study

PubMed Central

Santos, Cleusa C.; Feitosa, Fabiana G.; Ribeiro, Maria C.; Menge, Paulo; Lira, Izabelle M.

2017-01-01

Objective To report the echocardiographic evaluation of 103 infants with presumed congenital Zika syndrome. Methods An observational retrospective study was performed at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil. 103 infants with presumed congenital Zika syndrome. All infants had microcephaly and head computed tomography findings compatible with congenital Zika syndrome. Zika IgM antibody was detected in cerebrospinal fluid samples of 23 infants. In 80 infants, the test was not performed because it was not available at that time. All infants had negative serology for HIV, syphilis, rubella, cytomegalovirus and toxoplasmosis. A complete transthoracic two-dimensional, M-mode, continuous wave and pulsed wave Doppler and color Doppler echocardiographic (PHILIPS HD11XE or HD15) examination was performed on all infants. Results 14/103 (13.5%) echocardiograms were compatible with congenital heart disease: 5 with an ostium secundum atrial septal defect, 8 had a hemodynamically insignificant small apical muscular ventricular septal defect and one infant with dyspnea had a large membranous ventricular septal defect. The echocardiograms considered normal included 45 infants with a persistent foramen ovale and 16 with a minimum patent ductus arteriosus. Conclusions Preliminarily this study suggests that congenital Zika syndrome may be associated with an increase prevalence of congenital heart disease. However the types of defects noted were septal defects, a proportion of which would not be hemodynamically significant. PMID:28426680

Initial Field Test of a Cloud-Based Cardiac Auscultation System to Determine Murmur Etiology in Rural China.

PubMed

Pyles, Lee; Hemmati, Pouya; Pan, J; Yu, Xiaoju; Liu, Ke; Wang, Jing; Tsakistos, Andreas; Zheleva, Bistra; Shao, Weiguang; Ni, Quan

2017-04-01

A system for collection, distribution, and long distant, asynchronous interpretation of cardiac auscultation has been developed and field-tested in rural China. We initiated a proof-of-concept test as a critical component of design of a system to allow rural physicians with little experience in evaluation of congenital heart disease (CHD) to obtain assistance in diagnosis and management of children with significant heart disease. The project tested the hypothesis that acceptable screening of heart murmurs could be accomplished using a digital stethoscope and internet cloud transmittal to deliver phonocardiograms to an experienced observer. Of the 7993 children who underwent school-based screening in the Menghai District of Yunnan Province, Peoples Republic of China, 149 had a murmur noted by a screener. They had digital heart sounds and phonocardiograms collected with the HeartLink tele auscultation system, and underwent echocardiography by a cardiology resident from the First Affiliated Hospital of Kunming Medical University. The digital phonocardiograms, stored on a cloud server, were later remotely reviewed by a board-certified American pediatric cardiologist. Fourteen of these subjects were found to have CHD confirmed by echocardiogram. Using the HeartLink system, the pediatric cardiologist identified 11 of the 14 subjects with pathological murmurs, and missed three subjects with atrial septal defects, which were incorrectly identified as venous hum or Still's murmur. In addition, ten subjects were recorded as having pathological murmurs, when no CHD was confirmed by echocardiography during the field study. The overall test accuracy was 91% with 78.5% sensitivity and 92.6% specificity. This proof-of-concept study demonstrated the feasibility of differentiating pathologic murmurs due to CHD from normal functional heart murmurs with the HeartLink system. This field study is an initial step to develop a cost-effective CHD screening strategy in low-resource settings with a shortage of trained medical professionals and pediatric heart programs.

The role of spatial organization of Ca2+ release sites in the generation of arrhythmogenic diastolic Ca2+ release in myocytes from failing hearts

PubMed Central

Ho, Hsiang-Ting; Bonilla, Ingrid M.; Terentyeva, Radmila; Schober, Karsten E.; Terentyev, Dmitry; Carnes, Cynthia A.

2018-01-01

In heart failure (HF), dysregulated cardiac ryanodine receptors (RyR2) contribute to the generation of diastolic Ca2+ waves (DCWs), thereby predisposing adrenergically stressed failing hearts to life-threatening arrhythmias. However, the specific cellular, subcellular, and molecular defects that account for cardiac arrhythmia in HF remain to be elucidated. Patch-clamp techniques and confocal Ca2+ imaging were applied to study spatially defined Ca2+ handling in ventricular myocytes isolated from normal (control) and failing canine hearts. Based on their activation time upon electrical stimulation, Ca2+ release sites were categorized as coupled, located in close proximity to the sarcolemmal Ca2+ channels, and uncoupled, the Ca2+ channel-free non-junctional Ca2+ release units. In control myocytes, stimulation of β-adrenergic receptors with isoproterenol (Iso) resulted in a preferential increase in Ca2+ spark rate at uncoupled sites. This site-specific effect of Iso was eliminated by the phosphatase inhibitor okadaic acid, which caused similar facilitation of Ca2+ sparks at coupled and uncoupled sites. Iso-challenged HF myocytes exhibited increased predisposition to DCWs compared to control myocytes. In addition, the overall frequency of Ca2+ sparks was increased in HF cells due to preferential stimulation of coupled sites. Furthermore, coupled sites exhibited accelerated recovery from functional refractoriness in HF myocytes compared to control myocytes. Spatially resolved subcellular Ca2+ mapping revealed that DCWs predominantly originated from coupled sites. Inhibition of CaMK∏ suppressed DCWs and prevented preferential stimulation of coupled sites in Iso-challenged HF myocytes. These results suggest that CaMK∏-(and phosphatase)-dependent dysregulation of junctional Ca2+ release sites contributes to Ca2+-dependent arrhythmogenesis in HF. PMID:28612155

Health-related quality of life in paediatric patients with congenital heart defects: association with the type of heart defect and the surgical technique.

PubMed

Heusch, A; Kahl, H J; Hensel, K O; Calaminus, G

2017-11-01

The aim of the study was to investigate the impact of a number of surgical interventions for a various congenital cardiac defects (CHDs) on self-reported HRQoL. Patients who had received corrective surgery of several congenital heart defects (surgical VSD closure, Fallot, TGA after atrial or arterial switch or Fontan-type circulation for univentricular AV-connection) were interviewed in the office of their home peadiatric cardiologist. HRQoL in children along 7 dimensions was assessed using a standardised questionnaire (PEDQoL); information on the medical case history of each respondent was also collected. HRQoL was assessed in the questionnaire by asking about the frequency (never, rarely, often, always) of specific negative experiences; more frequent experiences indicate a lower quality of life. Frequency expressions were transformed into numerical values (25, 50, 75, 100%), and mean values for HRQoL were calculated for each patient and for each domain. Differences in HRQoL among patients with different types of interventions were analysed using the Mann-Whitney Test or the Kruskal-Wallis Test as appropriate; p values <0.05 were considered to indicate significant differences, while p values <0.1 were considered to indicate notable trends. Patients: 169 patients (60% male, 40% female) were part of the study. The mean age was 11.6 years; 50 patients had surgical VSD closure, 52 surgeries for Tetralogy of Fallot (22 transannular patch, 18 no transannular patch, 12 inaccurate description), 40 had complete transposition of the great arteries (28 atrial switch, 12 arterial switch), 22 had a Fontan-type procedure for univentricular AV-connection. HRQoL differed little among patients with different CHDs for the items "relation to friends," "interactions in the affected families", and "own body image". For other items, notable differences emerged: patients with univentricular hearts rated their physical capacity worse and showed a tendency towards negative ratings in other domains. On the other hand, patients after Fallot or TGA correction tended to rate their HRQoL in several domains as relatively high. Focusing on the mode of surgery for Fallot repair, respectively, TGA correction the only significant difference was found for "physical capacity" in TGA (atrial vs. arterial repair). Mustard patients tended to rate most items worse. Physical capacity was rated worst by patients with a Fontan circulation. Repeated surgery led to lower ratings for all domains except "physical capacity" and "body image". Different surgical techniques for CHD do not affect children's and adolescents' self-reported HRQoL to the extent that one would expect. This observation is in line with observations in groups of children with different chronic diseases. Specialised psychosocial support is necessary in order to maintain this positive self-evaluation and to ensure patients are able to lead autonomous personal and professional lives.

Zebrafish heart failure models: opportunities and challenges.

PubMed

Shi, Xingjuan; Chen, Ru; Zhang, Yu; Yun, Junghwa; Brand-Arzamendi, Koroboshka; Liu, Xiangdong; Wen, Xiao-Yan

2018-05-03

Heart failure is a complex pathophysiological syndrome of pumping functional failure that results from injury, infection or toxin-induced damage on the myocardium, as well as genetic influence. Gene mutations associated with cardiomyopathies can lead to various pathologies of heart failure. In recent years, zebrafish, Danio rerio, has emerged as an excellent model to study human cardiovascular diseases such as congenital heart defects, cardiomyopathy, and preclinical development of drugs targeting these diseases. In this review, we will first summarize zebrafish genetic models of heart failure arose from cardiomyopathy, which is caused by mutations in sarcomere, calcium or mitochondrial-associated genes. Moreover, we outline zebrafish heart failure models triggered by chemical compounds. Elucidation of these models will improve the understanding of the mechanism of pathogenesis and provide potential targets for novel therapies.

[Multi-Target Recognition of Internal and External Defects of Potato by Semi-Transmission Hyperspectral Imaging and Manifold Learning Algorithm].

PubMed

Huang, Tao; Li, Xiao-yu; Jin, Rui; Ku, Jing; Xu, Sen-miao; Xu, Meng-ling; Wu, Zhen-zhong; Kong, De-guo

2015-04-01

The present paper put forward a non-destructive detection method which combines semi-transmission hyperspectral imaging technology with manifold learning dimension reduction algorithm and least squares support vector machine (LSSVM) to recognize internal and external defects in potatoes simultaneously. Three hundred fifteen potatoes were bought in farmers market as research object, and semi-transmission hyperspectral image acquisition system was constructed to acquire the hyperspectral images of normal external defects (bud and green rind) and internal defect (hollow heart) potatoes. In order to conform to the actual production, defect part is randomly put right, side and back to the acquisition probe when the hyperspectral images of external defects potatoes are acquired. The average spectrums (390-1,040 nm) were extracted from the region of interests for spectral preprocessing. Then three kinds of manifold learning algorithm were respectively utilized to reduce the dimension of spectrum data, including supervised locally linear embedding (SLLE), locally linear embedding (LLE) and isometric mapping (ISOMAP), the low-dimensional data gotten by manifold learning algorithms is used as model input, Error Correcting Output Code (ECOC) and LSSVM were combined to develop the multi-target classification model. By comparing and analyzing results of the three models, we concluded that SLLE is the optimal manifold learning dimension reduction algorithm, and the SLLE-LSSVM model is determined to get the best recognition rate for recognizing internal and external defects potatoes. For test set data, the single recognition rate of normal, bud, green rind and hollow heart potato reached 96.83%, 86.96%, 86.96% and 95% respectively, and he hybrid recognition rate was 93.02%. The results indicate that combining the semi-transmission hyperspectral imaging technology with SLLE-LSSVM is a feasible qualitative analytical method which can simultaneously recognize the internal and external defects potatoes and also provide technical reference for rapid on-line non-destructive detecting of the internal and external defects potatoes.