The Congenital Heart Disease Genetic Network Study: Cohort description

Summary Background: Congenital heart disease (CHD) is the most common birth defect; however, the underlying etiology is unrecognized in the majority of cases. GATA-binding protein 4 (GATA4), a cardiac transcription factor gene, has a crucial role in the cardiogenesis process; hence, a number of heterozygote sequence variations were identified as a cause of CHD. G296S heterozygote variant is the most frequently reported GATA4 gene sequence alteration. This study aims to investigate the role of G296S variant of the GATA4 gene in Malaysian CHD subjects. Methods: We have investigated 86 Malaysian CHD subjects with cardiac septation defects for the presence of the GATA4 gene heterozygote variant (G296S) by the new technology of high resolution melting (HRM) analysis. Results: Genotyping of G296S (c.886G>A) by HRM analysis shows that all the sample genotypes were of the wild GG type genotype and the heterozygote mutant GA genotype was totally absent from this study cohort. Conclusions: The results of our study showed that the G296S variant of the GATA4 gene was not associated with the development of CHD in Malaysian subjects. The use of HRM analysis proved a cost-effective, high-throughput, specific and sensitive genotyping technique which eliminates the need for unnecessary sequencing.

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Imaging-Based Wave Intensity Analysis: Applications in Congenital Heart Disease

Volume 1A: Abdominal Aortic Aneurysms; Active and Reactive Soft Matter; Atherosclerosis; BioFluid Mechanics; Education; Biotransport Phenomena; Bone, Joint and Spine Mechanics; Brain Injury; Cardiac Mechanics; Cardiovascular Devices, Fluids and Imaging; Cartilage and Disc Mechanics; Cell and Tissue Engineering; Cerebral Aneurysms; Computational Biofluid Dynamics; Device Design, Human Dynamics, and Rehabilitation; Drug Delivery and Disease Treatment; Engineered Cellular Environments ◽

10.1115/sbc2013-14453 ◽

2013 ◽

Author(s):

Giovanni Biglino ◽

Hopewell N. Ntsinjana ◽

Kim H. Parker ◽

Silvia Schievano ◽

Andrew M. Taylor

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Congenital Heart ◽

Arterial Switch Operation ◽

Small Population ◽

Wave Intensity ◽

Study Cohort ◽

Intensity Analysis ◽

Wave Intensity Analysis ◽

Congenital Aortic Stenosis

Wave intensity analysis is a hemodynamic index evaluating the working condition of the heart in relation to the rest of the vasculature [1]. As such it carries valuable mechanistic information on ventriculo-arterial (VA) coupling. Its applications have ranged from studies of cardiac assist devices to fetal studies. Our group has proposed a way to derive wave intensity from phase-contrast magnetic resonance (PCMR) data [2]. We now suggest that this technique has a duple potential: (a) comparing patients against healthy subjects to investigate VA coupling and mechanistic changes related to surgery or devices, and (b) providing measures and indices to assess hemodynamic scenarios adding valuable mechanistic considerations. We aim to show both applications in the complex field of congenital heart disease. In the first instance, we will use this methodology to assess changes in wave speed and VA coupling in patients with transposition of the great arteries (TGA) repaired with arterial switch operation and palliated with atrial switch. In the second case, we will assess the potential of wave intensity-derived parameters for detecting diastolic dysfunction, and we selected a small population of patients with congenital aortic stenosis as a first suitable study cohort.

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Network Assisted Analysis of De Novo Variants Using Protein-Protein Interaction Information Identified 46 Candidate Genes for Congenital Heart Disease

10.1101/2021.11.30.21267069 ◽

2021 ◽

Author(s):

Yuhan Xie ◽

Wei Jiang ◽

Weilai Dong ◽

Hongyu Li ◽

Sheng Chih Jin ◽

...

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Candidate Genes ◽

Protein Interaction ◽

Congenital Heart ◽

De Novo ◽

Study Cohort ◽

Risk Genes ◽

Protein Protein Interaction ◽

Ppi Networks

De novo variants (DNVs) with deleterious effects have proved informative in identifying risk genes for early-onset diseases such as congenital heart disease (CHD). A number of statistical methods have been proposed for family-based studies or case/control studies to identify risk genes by screening genes with more DNVs than expected by chance in Whole Exome Sequencing (WES) studies. However, the statistical power is still limited for cohorts with thousands of subjects. Under the hypothesis that connected genes in protein-protein interaction (PPI) networks are more likely to share similar disease association status, we develop a Markov Random Field model that can leverage information from publicly available PPI databases to increase power in identifying risk genes. We identified 46 candidate genes with at least 1 DNV in the CHD study cohort, including 18 known human CHD genes and 35 highly expressed genes in mouse developing heart. Our results may shed new insight on the shared protein functionality among risk genes for CHD.

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The Congenital Heart Disease Genetic Network Study

Circulation Research ◽

10.1161/circresaha.111.300297 ◽

2013 ◽

Vol 112 (4) ◽

pp. 698-706 ◽

Cited By ~ 76

Author(s):

◽

Bruce Gelb ◽

Martina Brueckner ◽

Wendy Chung ◽

Elizabeth Goldmuntz ◽

...

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Congenital Heart ◽

Genetic Network

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Prevalence, Type, and Molecular Spectrum of NF1 Mutations in Patients with Neurofibromatosis Type 1 and Congenital Heart Disease

Genes ◽

10.3390/genes10090675 ◽

2019 ◽

Vol 10 (9) ◽

pp. 675 ◽

Cited By ~ 1

Author(s):

Pinna ◽

Daniele ◽

Calcagni ◽

Mariniello ◽

Criscione ◽

...

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Neurofibromatosis Type 1 ◽

Odds Ratio ◽

Congenital Heart ◽

Pulmonary Valve ◽

Neurofibromatosis Type ◽

Study Cohort ◽

Pulmonary Valve Stenosis

The aim of this study was to assess the prevalence and type of congenital heart disease (CHD) and the associated mutation spectrum in a large series of patients with neurofibromatosis type 1 (NF1), and correlate the mutation type with the presence and subgroups of cardiac defects. The study cohort included 493 individuals with molecularly confirmed diagnosis of NF1 for whom cardiac evaluation data were available. CHD was reported in 62/493 (12.6%) patients. Among these patients, 23/62 (37.1%) had pulmonary valve stenosis/dysplasia, 20/62 (32.3%) had mitral valve anomalies, and 10/62 (16.1%) had septal defects. Other defects occurred as rare events. In this NF1 subcohort, three subjects carried a whole-gene deletion, while 59 were heterozygous for an intragenic mutation. A significantly increased prevalence of non-truncating intragenic mutations was either observed in individuals with CHD (22/59, 37.3%) or with pulmonary valve stenosis (13/20, 65.0%), when compared to individuals without CHD (89/420, 21.2%) (p = 0.038) or pulmonary valve stenosis (98/459, 21.4%) (p = 0.002). Similarly, patients with non-truncating NF1 mutations displayed two- and six-fold higher risk of developing CHD (odds ratio = 1.9713, 95% confidence interval (CI): 1.1162–3.4814, p = 0.0193) and pulmonary valve stenosis (odds ratio = 6.8411, 95% CI: 2.6574–17.6114, p = 0.0001), respectively. Noteworthy, all but one patient (19/20, 95.0%) with pulmonary valve stenosis, and 18/35 (51.4%) patients with other CHDs displayed Noonan syndrome (NS)-like features. Present data confirm the significant frequency of CHD in patients with NF1, and provide further evidence for a higher than expected prevalence of NF1 in-frame variants and NS-like characteristics in NF1 patients with CHD, particularly with pulmonary valve stenosis.

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Cryopreserved Saphenous Vein Compared With PTFE Graft for Use as Modified Blalock-Taussig or Central Shunt in Cyanotic Congenital Heart Disease

World Journal for Pediatric and Congenital Heart Surgery ◽

10.1177/2150135118776616 ◽

2018 ◽

Vol 9 (5) ◽

pp. 509-512 ◽

Cited By ~ 1

Author(s):

Resham Kaur ◽

Dilli Bhurtel ◽

Mark R. Bielefeld ◽

J. Mark Morales ◽

Lucian A. Durham

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Saphenous Vein ◽

Incomplete Data ◽

Congenital Heart ◽

Study Cohort ◽

Ptfe Graft ◽

Safe Alternative ◽

Cardiac Condition ◽

Shunt Group

Many infants with congenital heart disease undergo palliative shunt procedures. In our center, cryopreserved saphenous vein and polytetrafluoroethylene (PTFE) are used as grafts to construct these shunts. In this retrospective review, we compare morbidity, mortality, and freedom from reoperation associated with the use of these graft materials. We conducted a retrospective study of 136 consecutive patients who were palliated with shunts between 2006 and 2015. A total of 136 patients were identified, 9 had incomplete data; thus, 127 patients were included: 69 saphenous and 58 PTFE. The cohorts were matched with respect to birth weight, gestational age, age and weight at time of surgery, and underlying cardiac condition. There were 15 (12%) deaths in the study cohort with no intraoperative mortality. Thrombosis was seen in 5.2% (2/38) of the saphenous modified Blalock-Taussig shunt (mBTS) group and 20.6% (14/68) of those with PTFE mBTS. There was no thrombosis in the central shunt group. Freedom from reoperation was 83% in the saphenous vein group and 81% in the PTFE group. There was no difference in overall morbidity or mortality, although thrombosis was significantly less in the saphenous vein group. Cryopreserved saphenous vein is a safe alternative, either as a mBTS or as a central shunt.

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MLPA � first-tier Screening Assay in Newborns with Nonsyndromic Congenital Heart Disease

Revista de Chimie ◽

10.37358/rc.20.2.7912 ◽

2020 ◽

Vol 71 (2) ◽

pp. 175-178

Author(s):

Elena Moldovan ◽

Valeriu Moldovan ◽

Claudia Banescu ◽

Lucian Puscasiu ◽

Manuela Cucerea

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Copy Number ◽

Congenital Heart ◽

Correct Diagnosis ◽

Neonatal Morbidity ◽

Copy Number Variations ◽

Molecular Testing ◽

Study Cohort ◽

Screening Assay

Congenital heart disease(CHD) is the most frequent malformative pathology seen in newborns, with an incidence of 10/1000 births, and is considered a major cause of neonatal morbidity and mortality. About one third of congenital heart disease cases are of genetic origin, particular copy number variations being described as possible nonsyndromic and syndromic congenital heart disease causes. Here, we set out to find whether the MLPA technique could be used as a first-tier screening assay in newborns with apparently nonsyndromic CHDs, and thus to genetically confirm the CHD diagnosis. The study cohort included 60 newborns diagnosed with apparently nonsyndromic congenital heart disease, recruited for a period of 18 months. MLPA analysis was performed using the SALSA MLPA P311 and P250 kits. 10 newborns (16.67%) showed known genetically relevant copy number variations, namely three patients with 22q11.21 deletion, that were diagnosed with DiGeorge syndrome, and seven patients with a probable single exon 8p23.1 duplication that will be subjected to further molecular testing, in order to correctly assess their diagnosis. We can conclude that the screening of patients with apparently nonsyndromic congenital heart disease may lead to their early and correct diagnosis, and thus them benefitting from the detection of clinically relevant copy number variations using the MLPA technique.

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Factors associated with a lower chance of having gaps in care in adult congenital heart disease

Cardiology in the Young ◽

10.1017/s1047951121000524 ◽

2021 ◽

pp. 1-6

Author(s):

Jong Mi Ko ◽

Lisa R. Yanek ◽

Ari M. Cedars

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Congenital Heart ◽

Adult Congenital Heart Disease ◽

Multivariable Logistic Regression Analysis ◽

Study Cohort ◽

Factors Associated ◽

Paediatric Care ◽

Significant Difference ◽

Care Gaps

Abstract Background: To promote good health in patients with congenital heart disease (CHD), prevention of gaps in care is essential, as adverse prognosis is associated with care gaps. A well-organised, formal transition programme may help prevent loss to follow up after leaving paediatric care. To inform the development of a transition programme, we investigated factors associated with care gaps in adults with CHD. Methods: Between 15 October 2018 and 15 November 2019 data on patient characteristics and patient experiences with transition-related education, difficulties, and gaps in care were collected and assessed in 87 adults with CHD. Two groups (with gaps in care versus without gaps) were compared to identify informative differences using chi-squared, Fisher’s exact tests, or Wilcoxon rank-sum tests. To assess the relationship between care gaps and identified variables, factors with significant difference (p < 0.05) in bivariate analyses were employed as covariates in multivariable logistic regression analysis. Results: About half of the study cohort reported having gaps in care. In a multivariate model, patients having thorough discussion about the importance of receiving adult care in paediatric care were 70% less likely to experience gaps (odds ratio 0.303, 95% CI 0.14, 0.66). Forty-seven percent of patient-perceived barriers to transitioning originated from negative feelings associated with transfer. Conclusion: Gaps in care are highly prevalent in adults with CHD. For a transition programme to be most effective, curriculum development may need to consider the differential impact of various factors and target areas to mitigate the psychological stress associated with transfer.

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Perioperative Morbidity and Mortality after Noncardiac Surgery in Young Adults with Congenital or Early Acquired Heart Disease: A Retrospective Cohort Analysis of the National Surgical Quality Improvement Program Database

The American Surgeon ◽

10.1177/000313481408000411 ◽

2014 ◽

Vol 80 (4) ◽

pp. 321-326 ◽

Cited By ~ 15

Author(s):

Bryan G. Maxwell ◽

Jim K. Wong ◽

Robert L. Lobato

Keyword(s):

Congenital Heart Disease ◽

Cardiac Surgery ◽

Heart Disease ◽

Congenital Heart ◽

Noncardiac Surgery ◽

Study Cohort ◽

Improvement Program ◽

Surgical Quality ◽

Perioperative Morbidity ◽

History Of

An increasing number of patients with congenital heart disease survive to adulthood. Expert opinion suggests that noncardiac surgery is a high-risk event, but few data describe perioperative outcomes in this population. Using the National Surgical Quality Improvement Program database, we identified a cohort of patients aged 18 to 39 years with prior heart surgery who underwent noncardiac surgery between 2005 and 2010. A comparison cohort with no prior cardiovascular surgery was matched on age, sex, race/ethnicity, operation year, American Society of Anesthesiologists physical status, and Current Procedural Terminology code. A study cohort consisting of 1191 patients was compared with a cohort of 5127 patients. Baseline dyspnea, inpatient status at the time of surgery, and a prior operation within 30 days were more common in the study cohort. Postoperative outcomes were less favorable in the study cohort. Observed rates of death, peri-operative cardiac arrest, myocardial infarction, stroke, respiratory complications, renal failure, sepsis, venous thromboembolism, perioperative transfusion, and reoperation were significantly higher in the study cohort ( P < 0.01 for all). Mean postoperative length of stay was greater in the study cohort (5.8 vs 3.6 days, P < 0.01). Compared with a matched control cohort, young adult patients with a history of prior cardiac surgery experienced significantly greater perioperative morbidity and mortality after noncardiac surgery. A history of prior cardiac surgery represents a marker of substantial perioperative risk in this young population that is not accounted for by the matched variables. These results suggest that adult patients with congenital heart disease are at risk for adverse outcomes and support the need for further registry-based investigations.

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Clevidipine for Perioperative Blood Pressure Control in Infants and Children Undergoing Cardiac Surgery for Congenital Heart Disease

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-16.1.55 ◽

2011 ◽

Vol 16 (1) ◽

pp. 55-60

Author(s):

Joseph D. Tobias ◽

William S. Schechter ◽

Alistair Phillips ◽

Samuel Weinstein ◽

Robert Michler ◽

...

Keyword(s):

Blood Pressure ◽

Congenital Heart Disease ◽

Cardiac Surgery ◽

Heart Disease ◽

Continuous Infusion ◽

Congenital Heart ◽

Infants And Children ◽

Effective Control ◽

Study Cohort ◽

In Infants And Children

ABSTRACT OBJECTIVE To determine the efficacy and adverse effect profile of clevidipine when used for perioperative blood pressure (BP) control during surgery for congenital heart disease (CHD). METHODS We retrospectively reviewed our experience with the perioperative use of clevidipine in pediatric-aged patients undergoing surgery for CHD. RESULTS The study cohort included 14 patients ranging from 11 months to 15 years (7.4 ± 4.6 years) and weighing from 5 to 41 kg (21.8 ± 11.1 kg). Clevidipine was administered as a continuous infusion for control of either postoperative BP or intraoperative mean arterial pressure (MAP) during cooling and cardiopulmonary bypass (CPB). It was administered as a bolus for BP control during emergence from anesthesia following cardiac surgery. The continuous infusion was started at 1 mcg/kg/min and increased in increments of 0.5 to 1 mcg/kg/min as needed. For postoperative BP control, dosing requirements varied from 1 to 7 mcg/kg/min (mean = 2.0 ± 1.2 mcg/kg/min). The target BP was achieved within 5 minutes in all patients. Two patients were treated with intravenous or oral propranolol for an increase in heart rate (HR) while receiving clevidipine. Despite doses up to 10 mcg/kg/min, effective control of MAP could not be achieved during CPB and cooling (core body temperature 28°C to 32°C). Bolus doses of clevidipine (10 to 15 mcg/kg) controlled BP during emergence from anesthesia with a decrease of the MAP from 97 ± 6 mm Hg to 71 ± 5 mm Hg (p<0.01). CONCLUSIONS Clevidipine is effective for perioperative BP control in infants and children with CHD; however, it does not appear effective in controlling MAP during cooling and CPB.

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