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This is a text on the radiologic diagnosis of congenital heart disease and its clinical manifestations. The main thrust of the book is the logical approach which allows an understanding of the complex theory of congenital heart disease. The atlas gives a concise overview of the entire field of congenital heart disease. Emphasis is placed on the understanding of the pathophysiology and its clinical and radiological consequences. Surgical treatment is included since it provides a different viewpoint of the anatomy.
Sparks, Susan E
Glycosylation is an essential process by which sugars are attached to proteins and lipids. Complete lack of glycosylation is not compatible with life. Because of the widespread function of glycosylation, inherited disorders of glycosylation are multisystemic. Since the identification of the first defect on N-linked glycosylation in the 1980s, there are over 40 different congenital protein hypoglycosylation diseases. This review will include defects of N-linked glycosylation, O-linked glycosylation and disorders of combined N- and O-linked glycosylation. PMID:23776380
Higgins, C.B.; Silverman, N.H.; Kersting-Somerhoff, B.A.
The book covers the tomographic anatomy of the normal and congenitally malformed heart and tomographic imaging of the normal heat. It then compares echocardiographic evaluation and the use of MR imaging in the diagnosis and evaluation of individual congenital cardiac malformations.
Putotto, Carolina; Unolt, Marta; Caiaro, Angela; Marino, Dario; Massaccesi, Valerio; Marino, Bruno; Digilio, Maria Cristina
Are there gender differences in prevalence, surgical results and long-term survival of patients with congenital heart disease? Available literature data allow us to state what follows. At birth there is a mild but significant prevalence of congenital heart disease in females. The most severe congenital heart diseases are less frequent in girls, but when they are present in females, they are linked to a higher surgical mortality rate, due perhaps to lower weight at birth and to the prevalence of extracardiac malformations and/or of associated genetic syndromes. On the other hand, in adults, surgery for congenital heart disease is at higher risk in males, and so the long-term survival rate is higher in females. Particular psychological attitudes, a higher incidence of pulmonary hypertension, as well as specific problems linked to the reproductive function characterize congenital heart disease in adult women. The knowledge and analysis of these data are essential for a correct management of congenital heart disease in neonates, children and adults.
Lindley, Kathryn J; Conner, Shayna N; Cahill, Alison G
With the success of modern surgical techniques for congenital heart disease, the population of women of childbearing age with congenital heart disease is growing. Because of the significant hemodynamic load of pregnancy, labor, and delivery, women with congenital heart disease require preconceptual risk assessment and expert multidisciplinary care throughout pregnancy. The aim of this review is to discuss the management of cardiovascular, obstetric, and fetal care issues that are commonly encountered during pregnancy in women with congenital heart disease.
The story of congenital heart disease is one of the major successes of medicine in the last 50 years. Heart conditions previously associated with early death are now successfully treated. Many of these women are now in their child-bearing years wishing to have children of their own. All of these women should be offered comprehensive pre-conception counselling by a dedicated multi-disciplinary team. Each woman will present a unique set of cardiac and obstetric challenges that require an individualised assessment of risk and a carefully documented care plan. In this chapter, I describe the most common forms of congenital heart disease and the specific issues that should be assessed before conception. I present a systematic approach to risk stratification and care planning. These lesions range from mild disease with little implications for pregnancy to those with a sizable risk of maternal mortality or complications. I will also discuss fetal risk factors.
Fletcher, B.D.; Jacobstein, M.D.
Focusing primarily on MR imaging of the heart, this book covers other diagnostic imaging modalities as well. The authors review new technologies and diagnostic procedures pertinent to congenital heat disease and present each congenital heat abnormality as a separate entity.
Richards, Ashleigh A; Garg, Vidu
Cardiovascular malformations are the most common type of birth defect and result in significant mortality worldwide. The etiology for the majority of these anomalies remains unknown but genetic factors are being recognized as playing an increasingly important role. Advances in our molecular understanding of normal heart development have led to the identification of numerous genes necessary for cardiac morphogenesis. This work has aided the discovery of an increasing number of monogenic causes of human cardiovascular malformations. More recently, studies have identified single nucleotide polymorphisms and submicroscopic copy number abnormalities as having a role in the pathogenesis of congenital heart disease. This review discusses these discoveries and summarizes our increasing understanding of the genetic basis of congenital heart disease. PMID:21532774
Martínez Quintana, E; Agredo Muñoz, J; Rodríguez González, F; Nieto Lago, V
Congenital heart diseases are a frequent cause of cardiology consultation. New diagnostic and therapeutic techniques have allowed greater survival and quality of life of patients who wish to participate in sports. What they can do is not always easy to determine. Guidelines are helpful at the time of deciding, although finally is the doctor the one that must determine in each case the situation of the patient and the type of exercise they can do depending on the severity and type of cardiopathy.
van der Bom, Teun; Zomer, A Carla; Zwinderman, Aeilko H; Meijboom, Folkert J; Bouma, Berto J; Mulder, Barbara J M
Congenital heart disease is the most common congenital disorder in newborns. Advances in cardiovascular medicine and surgery have enabled most patients to reach adulthood. Unfortunately, prolonged survival has been achieved at a cost, as many patients suffer late complications, of which heart failure and arrhythmias are the most prominent. Accordingly, these patients need frequent follow-up by physicians with specific knowledge in the field of congenital heart disease. However, planning of care for this population is difficult, because the number of patients currently living with congenital heart disease is difficult to measure. Birth prevalence estimates vary widely according to different studies, and survival rates have not been well recorded. Consequently, the prevalence of congenital heart disease is unclear, with estimates exceeding the number of patients currently seen in cardiology clinics. New developments continue to influence the size of the population of patients with congenital heart disease. Prenatal screening has led to increased rates of termination of pregnancy. Improved management of complications has changed the time and mode of death caused by congenital heart disease. Several genetic and environmental factors have been shown to be involved in the etiology of congenital heart disease, although this knowledge has not yet led to the implementation of preventative measures. In this Review, we give an overview of the etiology, birth prevalence, current prevalence, mortality, and complications of congenital heart disease.
Lara, Diego A; Lopez, Keila N
Public health research is an integral part of the study of congenital heart disease. While this type of research has become more popular, particularly over the past decade, it has a history that stretches back to almost the beginnings of pediatric cardiology as a field. This review aims to introduce the concepts and methodologies of public health and how they relate to congenital heart disease, describe some of the challenges of traditional research methods in congenital heart disease, describe the history of public health research, and demonstrate the relevance of public health research, particularly databases, to pediatric cardiology fellows.
With the rapid increase in knowledge on the genetic origin of diseases within the gastrointestinal tract the number of congenital diseases, which already manifest during childhood have drastically increased. Due to the large application of molecular genetics the number is steadily increasing. To make the access to these rare diseases fast and efficient the data base of the National Library of Medicine (Online Mendelian Inheritance of Man - OMIN) is a very helpful online tool, with which all these disease entities can be found easily (http://www.ncbi.nlm.nih.gov/omim). Detailed tables are given to find most of the congenitally inherited disease, which affect the gastrointestinal tract. A variety of congenital diarrheas with disturbances of digestion, hydrolysis, absorption and secretion is described in detail: lactose intolerance, sucrose intolerance, glucose-galactose malabsorption, fructose malabsorption, trehalase and enterokinase deficiency, congenital chloride and sodium diarrhea, congenital hypomagnesaemia, primary bile acid malabsorption, acrodermatitis enteropathica and Menke's syndrome. Also described in detail are diseases with structural anomalies of the intestine like microvillous inclusion disease, congenital tufting enteropathy and IPEX syndrome. The diagnosis in the disturbances of carbohydrate hydrolysis or absorption can be established by H2-breath tests after appropriate sugar challenge. Treatment consists of elimination of the responsible sugar from the diet. The diagnosis of the congenital secretory diarrheas is established by investigation of electrolytes in blood and stool. Substitution of high doses of the responsible mineral can improve the clinical outcome. In acrodermatitis enteropathica low serum zinc level together with the typical skin lesions guide to the diagnosis. High doses of oral zinc aspartate can cure the symptoms of the disease. The diagnosis of structural congenital lesions of the intestine can be established by histology and
Mulvihill, John J.
Reviews observations on domestic animals that have led to the identification of environmental teratogens, and have provided insight into the pathogenesis of congenital defects and genetic diseases in man." (Author/AL)
... right ventricle, D-transposition of the great arteries , Ebstein anomaly, hypoplastic left heart syndrome , interrupted aortic arch, ... Testing Registry: Congenital heart disease Genetic Testing Registry: Ebstein's anomaly Genetic Testing Registry: Hypoplastic left heart syndrome ...
Oliver Ruiz, José María; Mateos García, Marta; Bret Zurita, Montserrat
Improvements in the diagnosis and surgical treatment of congenital heart disease during infancy and childhood have resulted in an outstanding increase in the prevalence of these entities during adulthood. Congenital heart disease in the adult represents a new diagnostic challenge to the consultant cardiologist, unfamiliar with the anatomical and functional complexities of cardiac malformations. Assessment of adult congenital heart disease with imaging techniques can be as accurate as in children. However, these techniques cannot substitute for a detailed clinical assessment. Physical examination, electrocardiography and chest x-rays remain the three main pillars of bedside diagnosis. Transthoracic echocardiography is undoubtedly the imaging technique which provides most information, and in many situations no additional studies are needed. Nevertheless, ultrasound imaging properties in adults are not as favorable as in children, and prior surgical procedures further impair image quality. Despite recent advances in ultrasound technologies such as harmonic or contrast imaging, other diagnostic procedures are sometimes required. Fortunately, transesophageal echocardiography and magnetic resonance imaging are easily performed in the adult, and do not require anaesthetic support, in contrast to pediatric patients. These techniques, together with nuclear cardiology and cardiac catheterization, complete the second tier of diagnostic techniques for congenital heart disease. To avoid unnecessary repetition of diagnostic procedures, the attending cardiologist should choose the sequence of diagnostic techniques carefully; although the information this yields is often redundant, it is also frequently complementary. This article aims to compare the diagnostic utility of different imaging techniques in adult patients with congenital heart disease, both with and without prior surgical repair.
Minamata disease is alkylmercury poisoning causing Hunter-Russell syndrome due to ingestion of seafood polluted by industrial waste. Two epidemics occurred in Minamata (1956) and Niigata (1965), Japan. Many infants with "cerebral palsy" in villages where adult cases occurred were established as having congenital Minamata disease. Developing brains were affected by alkylmercury through transplacental exposure and even by breastfeeding. This report reviews the history, clinical features, pathology, epidemiology, metal analysis, experiments, and sociolegal aspects of congenital Minamata disease. Many victims are still alive and their present conditions are reviewed.
Ware, Stephanie M.; Jefferies, John Lynn
There has been remarkable progress in understanding the genetic basis of cardiovascular malformations. Chromosome microarray analysis has provided a new tool to understand the genetic basis of syndromic cardiovascular malformations resulting from microdeletion or microduplication of genetic material, allowing the delineation of new syndromes. Improvements in sequencing technology have led to increasingly comprehensive testing for aortopathy, cardiomyopathy, single gene syndromic disorders, and Mendelian-inherited congenital heart disease. Understanding the genetic etiology for these disorders has improved their clinical recognition and management and led to new guidelines for treatment and family-based diagnosis and surveillance. These new discoveries have also expanded our understanding of the contribution of genetic variation, susceptibility alleles, and epigenetics to isolated congenital heart disease. This review summarizes the current understanding of the genetic basis of syndromic and non-syndromic congenital heart disease and highlights new diagnostic and management recommendations. PMID:22822471
Pinto Júnior, Valdester Cavalcante; Branco, Klébia Magalhães P. Castello; Cavalcante, Rodrigo Cardoso; Carvalho Junior, Waldemiro; Lima, José Rubens Costa; de Freitas, Sílvia Maria; Fraga, Maria Nazaré de Oliveira; de Souza, Nayana Maria Gomes
Introduction Congenital heart disease is an abnormality in the structure or cardiocirculatory function, occurring from birth, even if diagnosed later. It can result in intrauterine death in childhood or in adulthood. Accounted for 6% of infant deaths in Brazil in 2007. Objective To estimate underreporting in the prevalence of congenital heart disease in Brazil and its subtypes. Methods The calculations of prevalence were performed by applying coefficients, giving them function rates for calculations of health problems. The study makes an approach between the literature and the governmental registries. It was adopted an estimate of 9: 1000 births and prevalence rates for subtypes applied to births of 2010. Estimates of births with congenital heart disease were compared with the reports to the Ministry of Health and were studied by descriptive methods with the use of rates and coefficients represented in tables. Results The incidence in Brazil is 25,757 new cases/year, distributed in: North 2,758; Northeast 7,570; Southeast 10,112; South 3,329; and Midwest 1,987. In 2010, were reported to System of Live Birth Information of Ministry of Health 1,377 cases of babies with congenital heart disease, representing 5.3% of the estimated for Brazil. In the same period, the most common subtypes were: ventricular septal defect (7,498); atrial septal defect (4,693); persistent ductus arteriosus (2,490); pulmonary stenosis (1,431); tetralogy of Fallot (973); coarctation of the aorta (973); transposition of the great arteries (887); and aortic stenosis 630. The prevalence of congenital heart disease, for the year of 2009, was 675,495 children and adolescents and 552,092 adults. Conclusion In Brazil, there is underreporting in the prevalence of congenital heart disease, signaling the need for adjustments in the methodology of registration. PMID:26107454
Krieger, Eric V; Leary, Peter J; Opotowsky, Alexander R
Patients with adult congenital heart disease have an increased risk of developing pulmonary hypertension. There are several mechanisms of pulmonary hypertension in patients with adult congenital heart disease, and understanding them requires a systematic approach to define the patient's hemodynamics and physiology. This article reviews the updated classification of pulmonary hypertension in patients with adult congenital heart disease with a focus on pathophysiology, diagnostics, and the evaluation of pulmonary hypertension in special adult congenital heart disease populations.
DeBowes, R M; Gaughan, E M
Equine congenital dental deformities are not limited merely to those presented here; however, the examples discussed offer the reader an appreciation for the range of severity and complexity that may be found in affected horses. The veterinarian is obligated to provide the best possible care for the patient and to relieve animal suffering. The lack of definitive evidence for heritability of many of these defects can place the veterinarian in an untenable position, particularly when presented with literature that proclaims or suggests without evidence that a particular condition is inherited. In such cases, the veterinarian is encouraged to counsel owners, citing substantiated medical information, and to recommend that owners make the decision to eliminate the affected animals' ability to reproduce.
Bouma, Berto J; Mulder, Barbara J M
Congenital heart disease is the most frequently occurring congenital disorder affecting ≈0.8% of live births. Thanks to great efforts and technical improvements, including the development of cardiopulmonary bypass in the 1950s, large-scale repair in these patients became possible, with subsequent dramatic reduction in morbidity and mortality. The ongoing search for progress and the growing understanding of the cardiovascular system and its pathophysiology refined all aspects of care for these patients. As a consequence, survival further increased over the past decades, and a new group of patients, those who survived congenital heart disease into adulthood, emerged. However, a large range of complications raised at the horizon as arrhythmias, endocarditis, pulmonary hypertension, and heart failure, and the need for additional treatment became clear. Technical solutions were sought in perfection and creation of new surgical techniques by developing catheter-based interventions, with elimination of open heart surgery and new electronic devices enabling, for example, multisite pacing and implantation of internal cardiac defibrillators to prevent sudden death. Over time, many pharmaceutical studies were conducted, changing clinical treatment slowly toward evidence-based care, although results were often limited by low numbers and clinical heterogeneity. More attention has been given to secondary issues like sports participation, pregnancy, work, and social-related difficulties. The relevance of these issues was already recognized in the 1970s when the need for specialized centers with multidisciplinary teams was proclaimed. Finally, research has become incorporated in care. Results of intervention studies and registries increased the knowledge on epidemiology of adults with congenital heart disease and their complications during life, and at the end, several guidelines became easily accessible, guiding physicians to deliver care appropriately. Over the past decades
Hoffman, Julien Ie
Although the incidence of congenital heart disease (CHD) is similar worldwide, the burden of supporting these patients falls more heavily on countries with high fertility rates. In a country with a fertility rate of about eight per woman, the population has to support four times as many children with CHD as in a country with a fertility rate of two. Countries with the highest fertility rates tend to have the lowest incomes per capita, thus accentuating the disparity. Countries with high fertility rates have more children with congenital heart disease per wage earner. Improving local health services and controlling infectious diseases (diarrhoeal illness, rheumatic fever, measles, rotoviral infection) are important but are mere 'band-aids' compared to improving education, empowering women and reducing birth rates.
Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas; Holstein-Rathlou, Niels-Henrik; Søndergaard, Lars
Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether patients with CCHD are protected against atherosclerosis. Results have shown that the coronary arteries of patients with CCHD are free from plaques and stenosis. Decreased carotid intima-media thickness and low total plasma cholesterol may indicate a reduced risk of later development of atherosclerosis. However, the evidence is still sparse and questionable, and a reasonable explanation for the decreased risk of developing atherosclerosis in patients with CCHD is still missing.This review provides an overview of what is known about the prevalence and potential causes of the reduced risk of atherosclerosis in patients with CCHD.
Beghetti, Maurice; Tissot, Cecile
Pulmonary hypertension complicates the course of many children and adults with congenital heart diseases (CHDs). The increase in pulmonary pressure associated with CHD is secondary to either increased pulmonary blood flow or increased postcapillary pressures. Pulmonary arterial hypertension is in the vast majority associated with congenital cardiac shunts. Despite major advances in the understanding of the regulation of the pulmonary vascular bed and the pulmonary endothelial lesions leading to pulmonary vascular disease, despite the advances in surgical repair and the discovery of potential therapies in the pre- and postoperative period, pulmonary hypertension still carries a significant mortality and morbidity in patients with CHD. The recent introduction of targeted therapies in other forms of pulmonary arterial hypertension has led to a renewed interest in pulmonary hypertension associated with CHD and this particularly for the most advanced form, the so-called Eisenmenger syndrome (ES). This review summarizes the current knowledge on pulmonary hypertension associated with CHD, focusing on the pathophysiology and treatment of ES.
Bhatt, Ami B; DeFaria Yeh, Doreen
Most women with known congenital heart disease can have successful pregnancy, labor, and delivery. Preconception assessment is essential in understanding anatomy, repairs, and current physiology, all of which can influence risk in pregnancy. With that foundation, a multidisciplinary cardio-obstetric team can predict and prepare for complications that may occur with superimposed hemodynamic changes of pregnancy. Individuals with Eisenmenger syndrome, pulmonary hypertension, cyanosis, significant left heart obstruction, ventricular dysfunction, or prior major cardiac event are among the highest risk for complications.
The spectrum of congenital heart disease (CHD) seen in the adult varies widely. Malformations range from mild anomalies requiring no intervention to extremely complex pathologies characterized by the presence of multiple coexistent defects. Echocardiography represents the primary noninvasive imaging modality in the assessment of these lesions. The transesophageal approach expands the applications of echocardiography by allowing the acquisition of anatomic and functional information that may not be obtainable by transthoracic imaging. PMID:28074821
Robbers-Visser, Daniëlle; Luijnenburg, Saskia E; van den Berg, Jochem; Moelker, Adriaan; Helbing, Willem A
In patients with coronary arterial disease, stress imaging is able to demonstrate abnormalities in the motion of the ventricular walls, and abnormalities in coronary arterial perfusion not apparent at rest. It can also provide information on prognostic factors. In patients with congenitally malformed hearts, stress imaging is used to determine contractile reserve, abnormalities of mural motion, and global systolic function, but also to assess diastolic and vascular function. In most of these patients, stress is usually induced using pharmacological agents, mainly dobutamine given in varying doses. The clinical usefulness of abnormal responses to the stress induced in such patients has to be addressed in follow-up studies. The abnormal stress might serve as surrogate endpoints, predicting primary endpoints at an early stage, which are useful for stratification of risk in this population of growing patients. We review here the stress imaging studies performed to date in patients with congenitally malformed hearts, with a special emphasis on echocardiography and cardiac magnetic resonance imaging.
Mazor Dray, Efrat; Marelli, Ariane J
This article reviews the changing epidemiology of congenital heart disease summarizing its impact on the demographics of the congenital heart disease population and the progress made in order to improve outcomes in this patient population. Birth prevalence of congenital heart disease can be modified by many factors. As a result of decreasing mortality and increasing survival in all forms of congenital heart disease, the median age of patients has increased and adults now compose two-thirds of patients with congenital heart disease. Disease burden and resulting health services utilization increase significantly across the lifespan. Bridging the gap between policy and quality of care can be improved by referral to specialized adult congenital heart disease centers and planning delivery of specialized services that are commensurate with population needs, program accreditation criteria and certified training of designated workforce.
Scansen, Brian A; Schneider, Matthias; Bonagura, John D
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.
Muntean, Iolanda; Togănel, Rodica; Benedek, Theodora
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.
A genetic background is discussed in many disorders of the gastrointestinal tract with a disposition in addition to environmental factors. The pathophysiology of most hereditary diseases is unknown although the mode of inheritance is established. Biochemical analysis may show molecular defects or inborn lack of enzymes, cytogenetic studies may reveal chromosomal abnormalities. The knowledge of genetic factors in gastrointestinal disorders may contribute to the early detection of persons afflicted but not yet symptomatic, in some rare syndromes genetic counseling may become mandatory. Finally, there are many congenital malformations which may not cause symptoms for many years so that doubts may arise whether they are developmental anomalies or acquired conditions.
Wood, John C
Cardiac MRI (CMR) is replacing diagnostic cardiac catheterization as the modality of choice for anatomic and functional characterization of congenital heart disease (CHD) when echocardiographic imaging is insufficient. In this manuscript, we discuss the principles of anatomic imaging of CHD, placing emphasis on the appropriate choice and modification of pulse sequences necessary to evaluate infants and small children. Clinical examples are provided to illustrate the relative strengths and shortcomings of different CMR imaging techniques. Although cardiovascular function and flow techniques are not described, their role in evaluating the severity of anatomic defects is emphasized. Anatomic characterization represents the first component of a carefully-planned, integrated CMR assessment of CHD.
Graziani, Francesca; Delogu, Angelica Bibiana
The clinical approach to adults with congenital heart diseases (ACHDs) is unique in cardiovascular medicine because these patients encompass a broad range of presentations. Each patient, despite having similar diagnosis, will be anatomically and physiologically unlike others within ACHD population, in relation to the type of repair, age at repair, associated defects, with specific long-term risk factors and complications. Furthermore, as many patients will not complain of symptoms, clinical evaluation and diagnostic testing must also be based on the underlying main diagnostic category, with complete standardized lesion-specific clinical protocols, investigating all known risk factors specific for each congenital heart disease and performed as part of screening for significant long-term complications. The first part of this review will focus on clinical history, physical examination, and the most important diagnostic testing in ACHD population. The second part of the article will focus on some clinical issues we have to face in our daily practice, such as heart failure, cyanosis, and pulmonary hypertension. Furthermore, as survival rates of ACHD population continue to improve and patients with this condition live longer, we will briefly report on a new clinical concern regarding the impact of acquired morbidities like coronary artery disease that appear to be of greater importance in defining outcome in older patients with ACHD.
De Feo, Stefania; Iacovoni, Attilio; Faggiano, Pompilio
Heart diseases are the leading cause of maternal morbidity and mortality. The number of patients with congenital heart diseases reaching childbearing age, as well as the proportion of women with acquired conditions, such as ischemic heart disease, becoming pregnant is constantly increasing. All women with known heart disease should have pre-pregnancy counseling, to assess maternal and fetal risk. Women at moderate or high risk should be under the care of a specialist prenatal team with experience in managing women with heart disease during pregnancy. Conditions that are considered at particularly high risk (mortality >10%) include Marfan syndrome with dilated aortic root, severe left ventricular dysfunction, severe left heart obstructive lesions, and pulmonary hypertension. Peripartum cardiomyopathy is a rare and potentially fatal disease related to pregnancy and the postnatal period that presents with symptoms of congestion and/or hypoperfusion and may rapidly progress to acute and life-threatening heart failure. However, the majority of women with heart disease can tolerate pregnancy; therefore an adequate multidisciplinary approach with the gynecologist, anesthesiologist and cardiologist should be advocated in order to reduce maternal and fetal risks associated with pregnancy.
Kimberlin, D.W.; Jester, P.M.; Sánchez, P.J.; Ahmed, A.; Arav-Boger, R.; Michaels, M.G.; Ashouri, N.; Englund, J.A.; Estrada, B.; Jacobs, R.F.; Romero, J.R.; Sood, S.K.; Whitworth, M.S.; Abzug, M.J.; Caserta, M.T.; Fowler, S.; Lujan-Zilbermann, J.; Storch, G.A.; DeBiasi, R.L.; Han, J.-Y.; Palmer, A.; Weiner, L.B.; Bocchini, J.A.; Dennehy, P.H.; Finn, A.; Griffiths, P.D.; Luck, S.; Gutierrez, K.; Halasa, N.; Homans, J.; Shane, A.L.; Sharland, M.; Simonsen, K.; Vanchiere, J.A.; Woods, C.R.; Sabo, D.L.; Aban, I.; Kuo, H.; James, S.H.; Prichard, M.N.; Griffin, J.; Giles, D.; Acosta, E.P.; Whitley, R.J.
BACKGROUND The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time. METHODS We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear (“best-ear” hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline. RESULTS A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P = 0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P = 0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P = 0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P = 0.004) and on the receptive-communication scale (P = 0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P = 0.64). CONCLUSIONS Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared
Cho, Young Kuk; Ma, Jae Sook
Despite developments in surgical techniques and other interventions, right ventricular (RV) failure remains an important clinical problem in several congenital heart diseases (CHD). RV function is one of the most important predictors of mortality and morbidity in patients with CHD. RV failure is a progressive disorder that begins with myocardial injury or stress, neurohormonal activation, cytokine activation, altered gene expression, and ventricular remodeling. Pressure-overload RV failure caused by RV outflow tract obstruction after total correction of tetralogy of Fallot, pulmonary stenosis, atrial switch operation for transposition of the great arteries, congenitally corrected transposition of the great arteries, and systemic RV failure after the Fontan operation. Volume-overload RV failure may be caused by atrial septal defect, pulmonary regurgitation, or tricuspid regurgitation. Although the measurement of RV function is difficult because of many reasons, the right ventricle can be evaluated using both imaging and functional modalities. In clinical practice, echocardiography is the primary mode for the evaluation of RV structure and function. Cardiac magnetic resonance imaging is increasingly used for evaluating RV structure and function. A comprehensive evaluation of RV function may lead to early and optimal management of RV failure in patients with CHD.
Sun, RongRong; Liu, Min; Lu, Lei; Zheng, Yi; Zhang, Peiying
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.
Herreman, G; Sauvaget, F; Généreau, T; Galezowski, N
Congenital heart block is rare; it is acquired in utero, definitive and, more often than not, complete. It can be diagnosed by the appearance of fetal bradycardia around the 23rd week of gestation, during ultrasonographic monitoring of pregnancy. Heart block is usually associated with the presence of anti-Ro and/or anti-La antibodies in the mother's serum. These maternal immunological abnormalities can be isolated or associated with an autoimmune disease, usually systemic lupus erythematosus, but also Sjögren's syndrome, or more rarely still, an as yet unclassified connective tissue disease. Anti-Ro and anti-La antibodies cross the placental barrier and react with a fetal heart, leading to acute fetal myocarditis by the 17th week of gestation. When severe, it is lethal, otherwise it can result in degeneration and endocardial fibroelastosis, disrupting conduction and leading to congenital heart block. The ideal treatment would be prevention with corticosteroids. When the mother is Ro or La antibody-positive before pregnancy, elimination of these circulating antibodies can be attempted by treatment with 0.5 mg/kg body wt/d of prednisolone for 3 months. If the treatment is successful, corticotherapy can be prescribed early in the pregnancy to try to protect the fetus. However, there is not always a relationship between maternal anti-Ro antibodies and fetal heart block. If the Ro/La antibody-positive woman is already pregnant, but before her 17th week, it is possible to prescribe dexamethasone, which crosses the placenta and remains active, sometimes in association with plasmapheresis.
Burchill, Luke J
Heart failure (HF) in adult congenital heart disease (ACHD) is vastly different to that observed in acquired heart disease. Unlike acquired HF in which pharmacological strategies are the cornerstone for protecting and improving ventricular function, ACHD-related HF relies heavily upon structural and other interventions to achieve these aims. patients with ACHD constitute a small percentage of the total adult heart transplant population (∼3%), although the number of ACHD heart transplant recipients is growing rapidly with a 40% increase over the last two decades. The worldwide experience to date has confirmed heart transplantation as an effective life-extending treatment option in carefully selected patients with ACHD with end-stage cardiac disease. Opportunities for improving outcomes in patients with ACHD-related HF include (i) earlier recognition and referral to centres with combined expertise in ACHD and HF, (ii) increased awareness of arrhythmia and sudden cardiac death risk in this population, (iii) greater collaboration between HF and ACHD specialists at the time of heart transplant assessment, (iv) expert surgical planning to reduce ischaemic time and bleeding risk at the time of transplant, (v) tailored immunosuppression in the post-transplant period and (vi) development and validation of ACHD-specific risk scores to predict mortality and guide patient selection. The purpose of this article is to review current approaches to diagnosing and treating advanced HF in patients with ACHD including indications, contraindications and clinical outcomes after heart transplantation.
Yang, X F; Zhang, Y F; Zhao, C F; Liu, M M; Si, J P; Fang, Y F; Xing, W W; Wang, F L
Congenital heart disease in children is a type of birth defect. Previous studies have suggested that the transcription factor, TBX20, is involved in the occurrence and development of congenital heart disease in children; however, the specific regulatory mechanisms are yet to be evaluated. Hence, this study aimed to evaluate the relationship between the TBX20 polymorphism and the occurrence and development of congenital heart disease. The TBX20 gene sequence was obtained from the NCBI database and the polymorphic locus candidate was predicted. Thereafter, the specific gene primers were designed for the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) of DNA extracted from the blood of 80 patients with congenital heart disease and 80 controls. The results of the PCR were subjected to correlation analysis to identify the differences between the amplicons and to determine the relationship between the TBX20 gene polymorphism and congenital heart disease. One of the single nucleotide polymorphic locus was found to be rs3999950: c.774T>C (Ala265Ala). The TC genotype frequency in the patients was higher than that in the controls, similar to that for the C locus. The odds ratio of the TC genotypes was above 1, indicating that the presence of the TC genotype increases the incidence of congenital heart diseases. Thus, rs3999950 may be associated with congenital heart disease, and TBX20 may predispose children to the defect.
Lin, Kimberly Y; D'Alessandro, Lisa C A; Goldmuntz, Elizabeth
On March 16, 2012, the Ethics of the Heart 2012: Ethical and Policy Challenges in Pediatric and Adult Congenital Heart Disease Conference took place in Philadelphia, Pennsylvania. The first session focused on the ethics surrounding genetic testing in patients with congenital heart disease. Summarized here is the introductory presentation given by Dr Elizabeth Goldmuntz entitled "The Role of Genetic Testing in Congenital Heart Disease," followed by a case presentation given by Dr Lisa D'Alessandro. The case and the panel discussion that ensued highlight several ethical principles and challenges in this unique patient population.
Woolf, Adrian S; Stuart, Helen M; Newman, William G
Lower urinary tract and/or kidney malformations are collectively the most common cause of end-stage renal disease in children, and they are also likely to account for a major subset of young adults requiring renal replacement therapy. Advances have been made regarding the discovery of the genetic causes of human kidney malformations. Indeed, testing for mutations of key nephrogenesis genes is now feasible for patients seen in nephrology clinics. Unfortunately, less is known about defined genetic bases of human lower urinary tract anomalies. The focus of this review is the genetic bases of congenital structural and functional disorders of the urinary bladder. Three are highlighted. First, prune belly syndrome, where mutations of CHRM3, encoding an acetylcholine receptor, HNF1B, encoding a transcription factor, and ACTA2, encoding a cytoskeletal protein, have been reported. Second, the urofacial syndrome, where mutations of LRIG2 and HPSE2, encoding proteins localised in nerves invading the fetal bladder, have been defined. Finally, we review emerging evidence that bladder exstrophy may have genetic bases, including variants in the TP63 promoter. These genetic discoveries provide a new perspective on a group of otherwise poorly understood diseases.
Moss, A. J.
A number of practical office and bedside clues to cardiac disease in infants and children have been passed on through the years. They relate to the history, to the inspection and palpation components of the physical examination, and to knowledge of the specific cardiac defects that are likely to be associated with certain clinical syndromes. With the possible exception of coarctation of the aorta, the clues are not diagnostically specific. In many instances, however, they serve to narrow a broad array of diagnostic possibilities to 2 or 3 and, with the aid of other clues and auscultation, they can often be distinguished from one another. When a primary care physician is confronted with a child who has an incidental murmur that is "probably" innocent but could be organic, useful clues favoring an organic murmur are a history of congenital heart disease in a first-degree relative; a history of maternal rubella syndrome, alcohol use, or teratogenic drug use during pregnancy; a history of inappropriate sweating; a history of syncope, chest pain, or squatting; maternal diabetes mellitus; premature birth; birth at a high altitude; cyanosis; abnormal pulsations; recurrent bronchiolitis or pneumonia; chronic unexplained hoarseness; asymmetric facies with crying; and a physical appearance suggestive of a clinical syndrome. PMID:1574882
Allan, Catherine K
Prevalence of congenital heart disease in the adult population has increased out of proportion to that of the pediatric population as survival has improved, and adult congenital heart disease patients make up a growing percentage of pediatric and adult cardiac intensive care unit admissions. These patients often develop complex multiorgan system disease as a result of long-standing altered cardiac physiology, and many require reoperation during adulthood. Practitioners who care for these patients in the cardiac intensive care unit must have a strong working knowledge of the pathophysiology of complex congenital heart disease, and a full team of specialists must be available to assist in the care of these patients. This chapter will review some of the common multiorgan system effects of long-standing congenital heart disease (eg, renal and hepatic dysfunction, coagulation abnormalities, arrhythmias) as well as some of the unique cardiopulmonary physiology of this patient population.
... critical congenital heart disease (CCHD) in newborns. 2 Physiology of Pulse Oximetry Oxygen breathed in through the ... Previous Article Next Article Jump to Article Introduction Physiology of Pulse Oximetry The Ductus Arteriosus in CCHD ...
Simpson, J M; Cook, A; Fagg, N L; MacLachlan, N A; Sharland, G K
Two familial cases of spondylothoracic dysostosis are reported. Both cases had severe congenital heart disease in addition to the skeletal malformations which are characteristic of the condition. Images PMID:7473656
Burlet, A; Drukker, A; Guignard, J P
We performed renal function tests in 18 young patients, 1.8-14.6 years of age, with cyanotic congenital heart disease (CCHD). Glomerular filtration rate was normal (116 +/- 4.5 ml/min/1.73 m2), and renal plasma flow was decreased (410 +/- 25 ml/min/1.73 m2) with a rise in the filtration fraction (29 +/- 1.1%). The suggested pathophysiologic explanation of these findings is that the blood hyperviscosity seen in patients with CCHD causes an overall increase in renal vascular resistance with a rise in intraglomerular blood pressure. Despite a sluggish flow of blood in the glomerular capillary bed, the effective filtration pressure was adjusted to conserve the glomerular filtration rate. In addition to these renal hemodynamic parameters, we also studied renal acidification and tubular sodium and water handling during a forced water diuresis. Our data indicate that children with CCHD have a mild to moderate normal ion gap metabolic acidosis due to a low proximal tubular threshold for bicarbonate. Proximal tubular sodium and water reabsorption under these conditions were somewhat increased, though not significantly, probably due to intrarenal hydrostatic forces, in particular the rise in the oncotic pressure in the postglomerular capillaries in patients with high hematocrit values. The distal tubular functions such as sodium handling and acidification were not affected.
Houyel, Lucile; To-Dumortier, Ngoc-Tram; Lepers, Yannick; Petit, Jérôme; Roussin, Régine; Ly, Mohamed; Lebret, Emmanuel; Fadel, Elie; Hörer, Jürgen; Hascoët, Sébastien
With the advances in congenital cardiac surgery and postoperative care, an increasing number of children with complex congenital heart disease now reach adulthood. There are already more adults than children living with a congenital heart defect, including patients with complex congenital heart defects. Among these adults with congenital heart disease, a significant number will develop ventricular dysfunction over time. Heart failure accounts for 26-42% of deaths in adults with congenital heart defects. Heart transplantation, or heart-lung transplantation in Eisenmenger syndrome, then becomes the ultimate therapeutic possibility for these patients. This population is deemed to be at high risk of mortality after heart transplantation, although their long-term survival is similar to that of patients transplanted for other reasons. Indeed, heart transplantation in adults with congenital heart disease is often challenging, because of several potential problems: complex cardiac and vascular anatomy, multiple previous palliative and corrective surgeries, and effects on other organs (kidney, liver, lungs) of long-standing cardiac dysfunction or cyanosis, with frequent elevation of pulmonary vascular resistance. In this review, we focus on the specific problems relating to heart and heart-lung transplantation in this population, revisit the indications/contraindications, and update the long-term outcomes.
Mabrut, Jean-Yves; Partensky, Christian; Jaeck, Daniel; Oussoultzoglou, Elie; Baulieux, Jacques; Boillot, Olivier; Lerut, Jan; de Ville de Goyet, Jean; Hubert, Catherine; Otte, Jean-Bernard; Audet, Maxime; Ducerf, Christian; Gigot, Jean-François
Objective: To report clinical presentation, perioperative outcome, and long-term results of surgical management of congenital intrahepatic bile duct (IHBD) dilatations (including Caroli disease) in a multi-institutional setting. Summary Background Data: Congenital IHBD dilatations are a rare congenital disorder predisposing to intrahepatic stones, cholangitis, and cholangiocarcinoma. The management remains difficult and controversial for bilobar forms of the disease or when concurrent congenital hepatic fibrosis is associated. Methods: From 1976 to 2004, 33 patients (range 11 to 79 years) were retrospectively enrolled. Disease extent into the liver was unilobar in 26 patients and bilobar in 7 patients (21%). Cholangiocarcinoma, congenital hepatic fibrosis, and intrahepatic stones were present in 2, 10, and 20 patients, respectively. Transplantations or liver resections were performed in 5 and 27 patients, respectively, whereas 1 asymptomatic patient was managed conservatively. Results: Postoperative mortality was nil. Postoperative complications occurred in 16 of 32 operated patients (50%) and additional procedures for residual stones were required in 5 patients. During a median follow-up of 80 months (1 patient being lost for follow-up) no patient developed metachronous carcinoma. Six patients (30%) developed recurrent intrahepatic stones but satisfactory late outcome was achieved in 27 patients (87%). Conclusions: Partial or total liver resection achieves satisfactory late outcome in congenital IHBD dilatations, when the affection is treated at an early stage and when the extent of liver resection is tailored to intrahepatic disease extent and takes into consideration the presence and severity of underlying chronic liver and renal diseases. PMID:17667502
Trevisan, Patrícia; Rosa, Rafael Fabiano M.; Koshiyama, Dayane Bohn; Zen, Tatiana Diehl; Paskulin, Giorgio Adriano; Zen, Paulo Ricardo G.
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
Calderón-Colmenero, Juan; Cervantes-Salazar, Jorge Luis; Curi-Curi, Pedro José; Ramírez-Marroquín, Samuel
Congenital cardiopathies are the most frequent congenital malformations. Reports of its prevalence around the world range from 2.1 to 12.3 for every 1000 newborns. Prevalence in our country remains unknown, but it probably occupies sixth place for mortality in infants less than a year old, and third place for mortality in those aged between 1 and 4 years. Based on birthrate, it is calculated that 10 to 12 000 infants in our country have some cardiac malformation. To understand the magnitude of the problem, it is important to identify the global number of newborns with some congenital cardiopathy each year and the type of malformation that they have, in order to determine the necessary resources and to plan their distribution. The main objective of regionalization is the justification of the resources with an emphasis in the specialized medical services to provide the best results for the patients. Hence, reason, based on the resources of each state, as well as their natality and infant mortality rates related to congenital cardiovascular pathology, we should proceed to regionalize the attention, and to simultaneously create a trustworthy database of the congenital cardiopathies. This should have many benefits, such as increase the number of total attended cases, improve the quality of attention, use appropriately the existent resources, and -surely- decrease the infant mortality.
Kaltenbrun, Erin; Tandon, Panna; Amin, Nirav M.; Waldron, Lauren; Showell, Chris; Conlon, Frank L.
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
Book, Wendy M; Shaddy, Robert E
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.
Serra-Juhé, Clara; Cuscó, Ivon; Homs, Aïda; Flores, Raquel; Torán, Núria; Pérez-Jurado, Luis A
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.
Ashraf, Mohd; Chowdhary, J; Khajuria, K; Reyaz, A M
A retrospective analysis of case-records data of 53,653 patients (0-18 years) over a two and half year period was conducted to ascertain the spectrum of congenital heart diseases. Two hundred and twenty one patients were found having congenital heart diseases; a prevalence of 4.1/1000. Ventricular septal defect (VSD) was the most frequent lesion seen in 69 (31.2%), followed by patent ductus arteriosus (PDA) in 36 (16.3%) children. Tetralogy of Fallot (TOF) was the most frequent cyanotic heart disease seen in 17 (7.8%) patients.
Fanning, Rebecca; O'Donnell, Brian; Lynch, Brian; Stephens, Michael; O'Donovan, Frances
We report on the perioperative management of anesthesia and analgesia in a child with sickle cell disease and a congenital myopathy, presenting for corrective orthopedic surgery. The case illustrates two valuable points of interest: the many benefits of regional anesthesia in complex medical cases and the successful use of tourniquets in children with sickle cell disease.
Chou, Hsin-Hsu; Chiou, Meng-Jiun; Liang, Fu-Wen; Chen, Lea-Hua; Lu, Tsung-Hsueh; Li, Chung-Yi
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
Congenital diarrhoeal disorders are a heterogeneous group of inherited malabsorptive or secretory diseases typically appearing in the first weeks of life, which may be triggered by the introduction of distinct nutrients. However, they may also be unrecognised for a while and triggered by exogenous factors later on. In principle, they can be clinically classified as osmotic, secretory or inflammatory diarrhoea. In recent years the disease-causing molecular defects of these congenital disorders have been identified. According to the underlying pathophysiology they can be classified into four main groups: 1) Defects of digestion, absorption and transport of nutrients or electrolytes 2) Defects of absorptive enterocyte differentiation or polarisation 3) Defects of the enteroendocrine cells 4) Defects of the immune system affecting the intestine. Here, we describe the clinical presentation of congenital intestinal diarrhoeal diseases, the diagnostic work-up and specific treatment aspects.
Panesar, Dilveer Kaur; Burch, Michael
Diastolic function is an important component of left ventricular (LV) function which is often overlooked. It can cause symptoms of heart failure in patients even in the presence of normal systolic function. The parameters used to assess diastolic function often measure flow and are affected by the loading conditions of the heart. The interpretation of diastolic function in the context of congenital heart disease requires some understanding of the effects of the lesions themselves on these parameters. Individual congenital lesions will be discussed in this paper. Recently, load-independent techniques have led to more accurate measurements of ventricular compliance and remodeling in heart disease. The combination of inflow velocities and tissue Doppler measurements can be used to estimate diastolic function and LV filling pressures. This review focuses on diastolic function and assessment in congenital heart disease. PMID:28261582
Velarde, César Náquira
American Trypanosomosis is an important parasitic infection in Peru. Human cases, reservoirs and vectors have been showed in two known geographic areas in the endemic zones: southwestern and northern and northeastern regions of the country; however vectors belonging to the three genera of triatominae: Triatoma, Panstrongylus and Rhodnius have been collected in almost all the territory. The serological surveys in blood banks in the southwestern region is 2-6% and human cases found out of the endemic areas show the possibility of congenital cases. The study of the prevalence is starting. This preliminary study performed on 3000 pregnant of Arequipa shows serological positives in 22 (0.7%) and only a newborn positive at IgM. This result indicates a probable low rate of congenital transmission and necessary to perform more studies.
Pennati, Giancarlo; Corsini, Chiara; Hsia, Tain-Yen; Migliavacca, Francesco
Mathematical modeling is a powerful tool to investigate hemodynamics of the circulatory system. With improving imaging techniques and detailed clinical investigations, it is now possible to construct patient-specific models of reconstructive surgeries for the treatment of congenital heart diseases. These models can help clinicians to better understand the hemodynamic behavior of different surgical options for a treated patient. This review outlines recent advances in mathematical modeling in congenital heart diseases, the discoveries and limitations these models present, and future directions that are on the horizon.
Canobbio, M M
The number of children with congenital heart disease surviving beyond adolescence is rapidly increasing. Consequently, pediatric health providers not only have to address medical issues associated with the cardiac condition but must begin to develop programs that assist adolescents and their families in dealing with special health care needs for the young patient to successfully move into the adult world. Transitional health-related issues facing the adolescent with congenital heart disease including medical follow-up, insurability, employability, sexuality, and reproduction are described. Discussion about advising and counseling both patient and parents is included.
Egbe, Alexander; Lee, Simon; Ho, Deborah; Uppu, Santosh; Srivastava, Shubhika
Background: There is a known association between congenital heart disease (CHD) and other congenital anomalies (CA). These associations have been altered by changes in prenatal factors in recent time. We reviewed the largest database of inpatient hospitalization information and analyzed the current association between common CHD diagnoses and other congenital anomalies. Materials and Methods: Case-control study design. We reviewed the Nationwide Inpatient Sample (NIS) database from 1998 to 2008 and identified all live births with CHD diagnosis (case) and live births without CHD diagnosis (control). We compared prevalence of associated congenital anomalies between the case and control groups. Results: Our cohort consisted of 97,154 and 12,078,482 subjects in the case and control groups, respectively. In the CHD population, prevalence of non-syndromic congenital anomaly (NSCA), genetic syndrome (GS), and overall extra-cardiac congenital anomaly (CA) were 11.4, 2.2, and 13.6%, respectively. In the control group, prevalence of NSCA, GS, and CA were 6.7, 0.3, and 7.0%, respectively. NSCA (odds ratio (OR): 1.88, confidence interval (CI): 1.73-1.94), GS (OR 2.52, CI 2.44-2.61), and overall CA (OR: 2.01, CI: 1.97-2.14) were strongly associated with CHD. Prevalence of GS and multiple organ-system CA decreased significantly over the study period. Conclusions: This is the largest and most comprehensive population-based study evaluating association between CHD and extra-cardiac malformation (ECM) in newborns. There was significant decrease in prevalence of GS and multiple CA over the study period. PMID:24987252
Mavroudis, Constantine; Deal, Barbara J
Certain congenital heart anomalies make patients more susceptible to arrhythmia development throughout their lives. This poses the question whether prophylactic arrhythmia surgery should be incorporated into reparative open heart procedures for congenital heart disease. There is currently no consensus on what constitutes a standard prophylactic procedure, owing to the questions that remain regarding lesions to be performed; energy sources to use; proximity of energy source or incisions to coronary arteries, sinoatrial node, atrioventricular node; circumstances for right atrial, left atrial, or biatrial appendectomy; and whether to perform a right, left, or biatrial maze procedure. These considerations are important because prophylactic arrhythmia procedures are performed without knowing if the patient will actually develop an arrhythmia in his or her lifetime. By reviewing and summarizing the literature, congenital heart disease patients who are at risk for developing atrial arrhythmias can be identified and lesion sets can be suggested in an effort to standardize experimental protocols for prophylactic arrhythmia surgery.
Janoušek, Jan; Kubuš, Peter
Cardiac resynchronization therapy (CRT) is an established treatment option for adult patients suffering heart failure due to idiopathic or ischemic cardiomyopathy associated with electromechanical dyssynchrony. There is limited evidence suggesting similar efficacy of CRT in patients with congenital heart disease (CHD). Due to the heterogeneity of structural and functional substrates, CRT implantation techniques are different with a thoracotomy or hybrid approach prevailing. Efficacy of CRT in CHD seems to depend on the anatomy of the systemic ventricle with best results achieved in systemic left ventricular patients upgraded to CRT from conventional pacing. Indications for CRT in patients with CHD were recently summarized in the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS) Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease and are presented in the text.
Deal, Barbara J.
Certain congenital heart anomalies make patients more susceptible to arrhythmia development throughout their lives. This poses the question whether prophylactic arrhythmia surgery should be incorporated into reparative open heart procedures for congenital heart disease. There is currently no consensus on what constitutes a standard prophylactic procedure, owing to the questions that remain regarding lesions to be performed; energy sources to use; proximity of energy source or incisions to coronary arteries, sinoatrial node, atrioventricular node; circumstances for right atrial, left atrial, or biatrial appendectomy; and whether to perform a right, left, or biatrial maze procedure. These considerations are important because prophylactic arrhythmia procedures are performed without knowing if the patient will actually develop an arrhythmia in his or her lifetime. By reviewing and summarizing the literature, congenital heart disease patients who are at risk for developing atrial arrhythmias can be identified and lesion sets can be suggested in an effort to standardize experimental protocols for prophylactic arrhythmia surgery. PMID:27709096
Mari, Mariana Alievi; Cascudo, Marcelo Matos; Alchieri, João Carlos
Objective: To evaluate the child development and evaluate a possible association with the commitment by biopsychosocial factors of children with and without congenital heart disease. Methods: Observational study of case-control with three groups: Group 1 - children with congenital heart disease without surgical correction; Group 2 - children with congenital heart disease who underwent surgery; and Group 3 - healthy children. Children were assessed by socio-demographic and clinical questionnaire and the Denver II Screening Test. Results: One hundred and twenty eight children were evaluated, 29 in Group 1, 43 in Group 2 and 56 in Group 3. Of the total, 51.56% are girls and ages ranged from two months to six years (median 24.5 months). Regarding the Denver II, the children with heart disease had more "suspicious" and "suspect/abnormal" ratings and in the group of healthy children 53.6% were considered with "normal" development (P≤0.0001). The biopsychosocial variables that were related to a possible developmental delay were gender (P=0.042), child's age (P=0.001) and income per capita (P=0.019). Conclusion: The results suggest that children with congenital heart disease are likely to have a developmental delay with significant difference between children who have undergone surgery and those awaiting surgery under clinical follow-up. PMID:27074272
The recognition of morphological stigmata other than cardiac, which are now known to be associated with congenital heart disease, coupled with a familial occurrence, may permit diagnosis of specific cardiac lesions at a very early age. Eleven such morphological associations have been reviewed. ImagesFig. 1Fig. 2Fig. 4 PMID:4400598
The study addresses parental coping patterns of children with congenital heart disease in the state of Hawaii. Attention was given to geography and ethnicity as well as parental and child characteristics as factors impacting on the coping pattern. Telephone interviews with parents (N=32) obtained data concerning parent characteristics, their…
Greutmann, Matthias; Pieper, Petronella G
Congenital heart defects are the most common birth defects. Major advances in open-heart surgery have led to rapidly evolving cohorts of adult survivors and the majority of affected women now survive to childbearing age. The risk of cardiovascular complications during pregnancy and peripartum depends on the type of the underlying defect, the extent and severity of residual haemodynamic lesions and comorbidities. Careful individualized, multi-disciplinary pre-pregnancy risk assessment and counselling, including assessment of risks in the offspring and estimation on long-term outcomes of the underlying heart defect, will enable informed decision making. Depending on the estimated risks, a careful follow-up plan during pregnancy as well as a detailed plan for delivery and postpartum care can reduce the risks and should be made by the multi-disciplinary team.
Eubanks, Jason David; Belding, Jon; Schnaser, Erik; Rowan, Andrew; Moffitt, Gable; Weaver, John; Reich, Michael S; Bechtel, Chris; Xie, Ke; Gande, Abhiram; Hohl, Justin; Braly, Brett; Hilibrand, Alan; Kang, James D
Symptomatic adjacent segment disease (ASD) after anterior cervical fusion (ACF) is reported in 25% of patients at 10 years postoperatively. Debate continues as to whether this degeneration is due to the natural history of the disk or the changed biomechanics after ACF. This study explored whether congenital stenosis predisposes patients to an increased incidence of ASD after ACF. A retrospective review of 635 patients with myelopathy or radiculopathy was performed; 364 patients had complete records for review. Patients underwent 1- to 5-level ACF (94 one-level, 145 two-level, 79 three-level, 45 four-level, and 1 five-level). Radiographs were evaluated for bony congenital stenosis using validated parameters, and ASD was measured according to Hilibrand's criteria and correlated with symptomatic ASD. Congenital stenosis was found in 21.7% of patients and radiographic ASD in 33.5%, with a significant association between these parameters. However, symptomatic ASD occurred in 11.8% of patients; no association between congenital stenosis and symptomatic ASD or myelopathy and ASD was found. Clinical results demonstrated excellent or good Robinson scores in 86.2% of patients and Odom scores in 87% of patients. Despite mostly excellent to good outcomes, symptomatic ASD is common after ACF. Although congenital stenosis appears to increase the incidence of radiographic ASD, it does not appear to predict symptomatic ASD.
Report from The International Society for Nomenclature of Paediatric and Congenital Heart Disease: cardiovascular catheterisation for congenital and paediatric cardiac disease (Part 1 - Procedural nomenclature).
Bergersen, Lisa; Everett, Allen Dale; Giroud, Jorge Manuel; Martin, Gerard R; Franklin, Rodney Cyril George; Béland, Marie Josée; Krogmann, Otto Nils; Aiello, Vera Demarchi; Colan, Steven D; Elliott, Martin J; Gaynor, J William; Kurosawa, Hiromi; Maruszewski, Bohdan; Stellin, Giovanni; Tchervenkov, Christo I; Walters, Henry Lane; Weinberg, Paul; Jacobs, Jeffrey Phillip
Interventional cardiology for paediatric and congenital cardiac disease is a relatively young and rapidly evolving field. As the profession begins to establish multi-institutional databases, a universal system of nomenclature is necessary for the field of interventional cardiology for paediatric and congenital cardiac disease. The purpose of this paper is to present the results of the efforts of The International Society for Nomenclature of Paediatric and Congenital Heart Disease to establish a system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease, focusing both on procedural nomenclature and on the nomenclature of complications associated with interventional cardiology. This system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease is a component of The International Paediatric and Congenital Cardiac Code. This manuscript is the first part of a two-part series. Part 1 will cover the procedural nomenclature associated with interventional cardiology as treatment for paediatric and congenital cardiac disease. This procedural nomenclature of The International Paediatric and Congenital Cardiac Code will be used in the IMPACT Registry™ (IMproving Pediatric and Adult Congenital Treatment) of the National Cardiovascular Data Registry® of The American College of Cardiology. Part 2 will cover the nomenclature of complications associated with interventional cardiology as treatment for paediatric and congenital cardiac disease.
Homsy, Jason; Zaidi, Samir; Shen, Yufeng; Ware, James S; Samocha, Kaitlin E; Karczewski, Konrad J; DePalma, Steven R; McKean, David; Wakimoto, Hiroko; Gorham, Josh; Jin, Sheng Chih; Deanfield, John; Giardini, Alessandro; Porter, George A; Kim, Richard; Bilguvar, Kaya; López-Giráldez, Francesc; Tikhonova, Irina; Mane, Shrikant; Romano-Adesman, Angela; Qi, Hongjian; Vardarajan, Badri; Ma, Lijiang; Daly, Mark; Roberts, Amy E; Russell, Mark W; Mital, Seema; Newburger, Jane W; Gaynor, J William; Breitbart, Roger E; Iossifov, Ivan; Ronemus, Michael; Sanders, Stephan J; Kaltman, Jonathan R; Seidman, Jonathan G; Brueckner, Martina; Gelb, Bruce D; Goldmuntz, Elizabeth; Lifton, Richard P; Seidman, Christine E; Chung, Wendy K
Congenital heart disease (CHD) patients have an increased prevalence of extracardiac congenital anomalies (CAs) and risk of neurodevelopmental disabilities (NDDs). Exome sequencing of 1213 CHD parent-offspring trios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed in the developing heart and brain. These mutations accounted for 20% of patients with CHD, NDD, and CA but only 2% of patients with isolated CHD. Mutations altered genes involved in morphogenesis, chromatin modification, and transcriptional regulation, including multiple mutations in RBFOX2, a regulator of mRNA splicing. Genes mutated in other cohorts examined for NDD were enriched in CHD cases, particularly those with coexisting NDD. These findings reveal shared genetic contributions to CHD, NDD, and CA and provide opportunities for improved prognostic assessment and early therapeutic intervention in CHD patients.
Calderón-Colmenero, Juan; Sandoval Zárate, Julio; Beltrán Gámez, Miguel
Pulmonary arterial hypertension is a common complication of congenital heart disease (CHD). Congenital cardiopathies are the most frequent congenital malformations. The prevalence in our country remains unknown, based on birthrate, it is calculated that 12,000 to 16,000 infants in our country have some cardiac malformation. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodeling and endothelial dysfunction secondary to an imbalance in vasoactive mediators which promotes vasoconstriction, inflammation, thrombosis, cell proliferation, impaired apotosis and fibrosis. The progressive rise in pulmonary vascular resistance and increased pressures in the right heart provocated reversal of the shunt may arise with the development of Eisenmenger' syndrome the most advanced form de Pulmonary arterial hypertension associated with congenital heart disease. The prevalence of Pulmonary arterial hypertension associated with CHD has fallen in developed countries in recent years that is not yet achieved in developing countries therefore diagnosed late as lack of hospital infrastructure and human resources for the care of patients with CHD. With the development of targeted medical treatments for pulmonary arterial hypertension, the concept of a combined medical and interventional/surgical approach for patients with Pulmonary arterial hypertension associated with CHD is a reality. We need to know the pathophysiological factors involved as well as a careful evaluation to determine the best therapeutic strategy.
Bolger, Aidan P; Gatzoulis, Michael A
Injury to the myocardium disrupts geometric integrity and results in changes to intracardiac pressure, wall stress and tension, and the pattern of blood flow through the heart. Significant disruption to pump function results in heart failure which is defined in terms of symptoms: breathlessness and fatigue, signs of salt and water retention, and neurohormonal activation. This syndrome most commonly occurs in the context of injury due to ischaemic heart disease and dilated cardiomyopathy but because patients with congenital heart disease (CHD) are born with sometimes gross distortions of cardiac anatomy they too are subject to the forces that drive heart failure. This paper explores the available data relating to the clinical and neurohormonal manifestations of heart failure in patients with congenital heart disease and describes how, by additionally exploring events at a cellular level, we may be able to arrive at a definition of heart failure relevant to this population.
Hartofilakidis, G; Babis, G C; Georgiades, G; Kourlaba, G
We studied the effect of trochanteric osteotomy in 192 total hip replacements in 140 patients with congenital hip disease. There was bony union in 158 hips (82%), fibrous union in 29 (15%) and nonunion in five (3%). The rate of union had a statistically significant relationship with the position of reattachment of the trochanter, which depended greatly on the pre-operative diagnosis. The pre-operative Trendelenburg gait substantially improved in all three disease types (dysplasia, low and high dislocation) and all four categories of reattachment position. A persistent Trendelenburg gait post-operatively was noticed mostly in patients with defective union (fibrous or nonunion). Acetabular and femoral loosening had a statistically significant relationship with defective union and the position of reattachment of the trochanter. These results suggest that the complications of trochanteric osteotomy in total hip replacement for patients with congenital hip disease are less important than the benefits of this surgical approach.
Subirana, M Teresa; Oliver, José M; Sáez, José M; Zunzunegui, José L
This article contains a review of some of the most important publications on congenital heart disease and pediatric cardiology that appeared in 2010 and up until September 2011. Of particular interest were studies on demographic changes reported in this patient population and on the need to manage the patients' transition from the pediatric to the adult cardiology department. This transition has given rise to the appearance of new areas of interest: for example, pregnancy in women with congenital heart disease, and the effect of genetic factors on the etiology and transmission of particular anomalies. In addition, this review considers some publications on fetal cardiology from the perspective of early diagnosis and, if possible, treatment. There follows a discussion on new contributions to Eisenmenger's syndrome and arrhythmias, as well as on imaging techniques, interventional catheterization and heart transplantation. Finally, there is an overview of the new version of clinical practice guidelines on the management of adult patients with congenital heart disease and of recently published guidelines on pregnancy in women with heart disease, both produced by the European Society of Cardiology.
Fuenmayor, Gabriela; Redondo, Ana Carolina Costa; Shiraishi, Karen Saori; Souza, Rogerio; Elias, Patrícia Figueiredo; Jatene, Ieda Biscegli
Dyslipidemia is one of the main risk factors associated with cardiovascular diseases. Few data on the impacts of congenital heart diseases are available with regard to the prevalence of dyslipidemia in children. Our study evaluated the lipid profile in children with congenital heart disease at a referral center. From January 2011 to July 2012, 52 pediatric patients had their lipid, metabolic and clinical profiles traced. The mean age was 10.4 ± 2.8 years and male/female rate of 1.38:1. Our population had 53.8% patients with high levels of total cholesterol and 13.4% (CI 95 %, from 6.6 to 25.2%) of them also presenting LDL levels ≥ 130 mg/dL, which characterizes dyslipidemia. The group of dyslipidemic patients presented only two obese individuals. Our data show that the presence of congenital heart disease does not lead to higher risk associated with the prevalence of dyslipidemia. Therefore, the screening of this specific population should follow the regular pediatric guidelines, which are also independent of the nutritional status of the children tested. PMID:24061754
Del Fabbro, M; Francetti, L; Pizzoni, L; Weinstein, R L
An alteration of the immune system function is one of the main factors involved in the development of periodontal disease. Polymorpho-nuclear neutrophil leukocytes (PMN) play a crucial role in the cell-mediated immune response against bacterial challenge. The mechanism of neutralization of pathogen microorganisms by PMNs involves many different steps: adhesion to capillary endothelium in the inflamed region, trans-endothelial migration, chemotaxis, phagocytosis and, ultimately, bacterial killing by oxidative and non-oxidative mechanisms. A defect in one of these steps leads to altered neutrophil function and, consequently, to a higher host susceptibility to periodontal tissue infection. The main intrinsic neutrophil diseases such as neutropenia, leukocyte adhesion deficiency (LAD-1), Chediak-Higashi syndrome, Papillon-Lefèvre syndrome, chronic granulomatous disease (CGD), are often related to severe and early-onset forms of periodontitis, as described by many evidences in the literature. Therefore PMN dysfunctions, both intrinsic and extrinsic, represent an important risk factor for periodontal disease. Studies on the basic molecular mechanisms of such dysfunctions, also in terms of genetic polymorphisms, recently allowed to identify some specific markers related to a higher susceptibility to the development of disease. Many researches have yet to be performed aiming to gain insight on the dynamics of PMN activation and interaction with other cells, in order to improve and modulate neutrophil function and to develop specific approaches for care and prevention of periodontal diseases.
Ho, J J
An analysis was done of available data from the Department of Statistics Malaysia, on the type of congenital abnormality contributing to death, to determine whether progress in health care over recent years was associated with any decline in mortality from congenital abnormality. A significant decline in death due to congenital abnormality was observed between 1991 and 1996. This was attributable to a decline in deaths due to congenital heart disease occurring because of improvements in cardiac surgical services for infants. In 1997 death due to congenital heart disease increased significantly. This could be attributed to improvements in the diagnosis of congenital heart disease in the neonate.
El-Alameey, Inas R.; Ahmed, Hanaa H.; Tawfik, Sawsan M.; Hassaballa, Fawzia; Gawad, Ayman M. Abdel; Eltahlawy, Eman
BACKGROUND: Gastrointestinal symptoms are a common feature in infants with congenital heart disease. AIM: This study was designed to evaluate age-dependent serum levels of antigliadin antibodies among malnourished Egyptian infants with congenital heart disease (CHD) and gastrointestinal symptoms. SUBJECTS AND METHODS: This case-control study conducted on 60 infants with established congenital heart disease. They were subdivided into cyanotic and acyanotic groups, and each group includes 30 patients compared with thirty apparently healthy infants of matched age, sex, and social class. Serum antigliadin antibodies levels were measured using ELISA. RESULTS: The mean age of introduction of cereals in the diet and appearance of gastrointestinal symptoms were six months. On comparison with controls, patients showed highly significant higher serum levels of antigliadin antibodies (P < 0.000). On analysing risk factors using odds ratio, the age at onset of GIT symptoms, diarrhoea, abdominal pain, and distension had been found to be significantly associated with high serum antigliadin antibodies among malnourished CHD infants with a prediction of 95%. CONCLUSION: Serum IgA, IgM, and IgG class antibodies to gliadin play a significant role in the pathogenesis of malnutrition in infants with CHD. Gluten containing foods should never be introduced before the end of the six months. PMID:28293318
Zhang, Jian; Yuan, Yan; Li, Peiling; Wang, Tuanjie; Gao, Jun; Yao, Jinhua; Li, Shujun
Objective: To study the pathogen distribution, antimicrobial susceptibility and risk factors of postoperative nosocomial infections among children with congenital heart disease. Methods: Three hundreds children with congenital heart disease admitted to our hospital to receive surgeries from February 2010 to February 2013 were selected. Results: A total of 120 children were tested as positive by sputum culture, with the infection rate of 40.0%. The top five most common pathogenic microorganisms included Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus, Pseudomonas aeruginosa, and Candida albicans. S. epidermidis, S. aureus and Enterococcus were highly resistant to penicillin, azithromycin and erythromycin, moderately susceptible to levofloxacin and cefazolin, and completely susceptible to vancomycin. Multivariate Logistic regression analysis showed that hospitalization stay length, combined use of antibiotics, systemic use of hormones, mechanical ventilation and catheter indwelling were the independent risk factors of postoperative nosocomial infections (P<0.05). Conclusion: Nosocomial infection, which was the most frequent postoperative complication of pediatric congenital heart disease, was predominantly induced by Gram-positive bacteria that were highly susceptible to cephalosporins and vancomycin. Particular attention should be paid to decrease relevant risk factors to improve the prognosis. PMID:24948978
Masi, G; Brovedani, P
A most significant life event in the first years of life is a disease, especially if it is of early onset, severe, life threatening, with an uncertain prognosis, and with the necessity of frequent diagnostic and therapeutic interventions. Psychological implications are a significant parts of the illness, not a marginal component; they can affect prognosis and outcome. The authors describe the different psychological implications of an experience of chronic disease in children and adolescents and their families (parents and siblings). Congenital disease (for example congenital heart failure) has a peculiar significance: since it is diagnosed early, it influences mother-infant interactions from the beginning, in a crucial moment of the infant's psychological development; diagnostic and therapeutical interventions are early and frequent; congenital defects determine the strongest guilt feelings in the parents. Some specific psychological aspects can be described: the weakening of the Bodily self, the inhibition of thinking, the theories the child and the family formulates on the disease, the death feelings. Emotional features in children and adolescents with congenital cardiopathy are described: inhibition of emotions, marked anxiety, depressive reaction, with loneliness, low self-esteem and inadequacy, emotional lability, with oscillation between omnipotence and inadequacy; impulsiveness; weakness of self identity; especially in bodily Self. Some psychopathological aspects in children and adolescents with heart transplant and their families are also described. Intellectual level of patients with congenital heart disease is in the normal range, although significantly lower than normal controls. There is a positive correlation between worsening of intellectual functioning and clinical severity of the heart disease; this clinical severity is related both to restrictions in normal daily life activities, and blood oxygen saturation. It is hard to tease apart the role of
Stewart, Garrick C; Mayer, John E
Heart transplantation has become an increasingly common and effective therapy for adults with end-stage congenital heart disease (CHD) because of advances in patient selection and surgical technique. Indications for transplantation in CHD are similar to other forms of heart failure. Pretransplant assessment of CHD patients emphasizes evaluation of cardiac anatomy, pulmonary vascular disease, allosensitization, hepatic dysfunction, and neuropsychiatric status. CHD patients experience longer waitlist times and higher waitlist mortality than other transplant candidates. Adult CHD patients undergoing transplantation carry an early hazard for mortality compared with non-CHD recipients, but by 10 years posttransplant, CHD patients have a slight actuarial survival advantage.
Seckeler, Michael D; Thomas, Ian D; Andrews, Jennifer; Joiner, Keith; Klewer, Scott E
Adults living with congenital heart disease (CHD) now outnumber children with the disease. Thanks to medical advances over the past 75 years, many of these fatal childhood heart problems have changed to chronic medical conditions. As the population of adults with CHD increases, they will require increasingly complex medical, surgical and catheter-based therapies. In addition, social burdens including education, employment and insurability, which increase the societal costs of adult CHD, are now being recognized for adults living with CHD. This review summarizes the available literature on the economics of adult CHD.
Wijnmaalen, Adrianus P; Zeppenfeld, Katja
Radiofrequency catheter ablation (RFCA) is an important treatment modality to prevent ventricular tachycardia (VT) recurrence in patients with repaired congenital heart disease. Identification and ablation of anatomic isthmuses has improved acute ablation outcome with excellent VT-free survival in those with preserved biventricular function. Reports on RFCA for VT in patients with infiltrative disease are sparse and cardiac sarcoidosis seems to be the most prevalent cause for ventricular arrhythmia. Patients with active and ongoing inflammation are at high risk for VT recurrence. RFCA reduces the number of VT but often multiple procedures are required and long-term VT-free survival is unfavorable in those with left ventricular dysfunction.
Chagas disease is a chronic infection that kills approximately 12,000 people a year. Mass migration of chronically infected and asymptomatic persons has caused globalization of Chagas disease and has made nonvectorial infection, including vertical and blood-borne transmission, more of a threat to human communities than vectorial infection. To control transmission, it is essential to test all pregnant women living in endemic countries and all pregnant women having migrated from, or having lived in, endemic countries. All children born to seropositive mothers should be tested not only within the first month of life but also at ~6 months and ~12 months of age. The diagnosis is made by identification of the parasite in blood before the age of 6 months and by identification of the parasite in blood and/or positive serology after 10 months of age. Follow up for a year is essential as a significant proportion of cases are initially negative and are only detected at a later stage. If the condition is diagnosed and treated early, the clinical response is excellent and the majority of cases are cured. PMID:24949443
Franklin, Rodney C G; Jacobs, Jeffrey Phillip; Krogmann, Otto N; Béland, Marie J; Aiello, Vera D; Colan, Steven D; Elliott, Martin J; William Gaynor, J; Kurosawa, Hiromi; Maruszewski, Bohdan; Stellin, Giovanni; Tchervenkov, Christo I; Walters Iii, Henry L; Weinberg, Paul; Anderson, Robert H
Clinicians working in the field of congenital and paediatric cardiology have long felt the need for a common diagnostic and therapeutic nomenclature and coding system with which to classify patients of all ages with congenital and acquired cardiac disease. A cohesive and comprehensive system of nomenclature, suitable for setting a global standard for multicentric analysis of outcomes and stratification of risk, has only recently emerged, namely, The International Paediatric and Congenital Cardiac Code. This review, will give an historical perspective on the development of systems of nomenclature in general, and specifically with respect to the diagnosis and treatment of patients with paediatric and congenital cardiac disease. Finally, current and future efforts to merge such systems into the paperless environment of the electronic health or patient record on a global scale are briefly explored. On October 6, 2000, The International Nomenclature Committee for Pediatric and Congenital Heart Disease was established. In January, 2005, the International Nomenclature Committee was constituted in Canada as The International Society for Nomenclature of Paediatric and Congenital Heart Disease. This International Society now has three working groups. The Nomenclature Working Group developed The International Paediatric and Congenital Cardiac Code and will continue to maintain, expand, update, and preserve this International Code. It will also provide ready access to the International Code for the global paediatric and congenital cardiology and cardiac surgery communities, related disciplines, the healthcare industry, and governmental agencies, both electronically and in published form. The Definitions Working Group will write definitions for the terms in the International Paediatric and Congenital Cardiac Code, building on the previously published definitions from the Nomenclature Working Group. The Archiving Working Group, also known as The Congenital Heart Archiving
Brickner, M Elizabeth
The population of adults with CHD continues to expand,and thus the number of women with CHD who contemplate pregnancy or become pregnant is also growing. Mothers with low-risk defects can be managed by general cardiologist,whereas those with more complex defects should be managed by or with the assistance of ACHD cardiologists. It is important to acknowledge that all patients with CHD may have unique anatomy or physiology, despite their classification as having a simple, moderate, or complex defect. As such, clinicians evaluating these patients should have adequate knowledge and expertise when assessing patient's risk for pregnancy,when performing imaging or hemodynamic studies, and when managing these patients during pregnancy. The American Board of Medical Specialties has recently recognized ACHD as a subspecialty of cardiovascular disease to treat the specialized needs of these patients in adulthood. ACHD experts can provide expertise in the management of specific defects or lesions, imaging techniques, prepregnancy risk assessment,and can manage these patients or comanage them with other medical providers during their pregnancy. Because many of these ACHD patients are lost to follow-up in adulthood, pregnancy represents a time when these patients seek medical care(and for some, represents a time of vulnerability and increased risk). This represents an opportunity to establish or reestablish care with ACHD specialists and to reestablish continuing long-term care for their CHD. Pregnancy also provides an opportunity to create partnerships between primary care physicians,adult cardiologists, and ACHD specialists to provide optimal care for these women throughout their lives.
Adisa, Olufolake A.; Oster, Matthew E.; McConnell, Michael; Mahle, William T.
Sickle cell disease is a risk factor for cerebrovascular accidents in the pediatric population. This risk is compounded by hypoxemia. Cyanotic congenital heart disease can expose patients to prolonged hypoxemia. To our knowledge, the long-term outcome of patients who have combined sickle cell and cyanotic congenital heart disease has not been reported. We retrospectively reviewed patient records at our institution and identified 5 patients (3 girls and 2 boys) who had both conditions. Their outcomes were uniformly poor: 4 died (age range, 12 mo–17 yr); 3 had documented cerebrovascular accidents; and 3 developed ventricular dysfunction. The surviving patient had developmental delays. On the basis of this series, we suggest mitigating hypoxemia, and thus the risk of stroke, in patients who have sickle cell disease and cyanotic congenital heart disease. Potential therapies include chronic blood transfusions, hydroxyurea, earlier surgical correction to reduce the duration of hypoxemia, and heart or bone marrow transplantation. PMID:28100970
Cotts, Timothy; Khairy, Paul; Opotowsky, Alexander R.; John, Anitha S.; Valente, Anne Marie; Zaidi, Ali N.; Cook, Stephen C.; Aboulhosn, Jamil; Ting, Jennifer Grando; Gurvitz, Michelle; Landzberg, Michael J.; Verstappen, Amy; Kay, Joseph; Earing, Michael; Franklin, Wayne; Kogon, Brian; Broberg, Craig S.
Background Adult congenital heart disease (ACHD) clinicians are hampered by the paucity of data to inform clinical decision-making. The objective of this study was to identify priorities for clinical research in ACHD. Methods A list of 45 research questions was developed by the Alliance for Adult Research in Congenital Cardiology (AARCC), compiled into a survey, and administered to ACHD providers. Patient input was sought via the Adult Congenital Heart Association at community meetings and online forums. The 25 top questions were sent to ACHD providers worldwide via an online survey. Each question was ranked based on perceived priority and weighted based on time spent in ACHD care. The top 10 topics identified are presented and discussed. Results The final online survey yielded 139 responses. Top priority questions related to tetralogy of Fallot (timing of pulmonary valve replacement and criteria for primary prevention ICDs), patients with systemic right ventricles (determining the optimal echocardiographic techniques for measuring right ventricular function, and indications for tricuspid valve replacement and primary prevention ICDs), and single ventricle/Fontan patients (role of pulmonary vasodilators, optimal anticoagulation, medical therapy for preservation of ventricular function, treatment for protein losing enteropathy). In addition, establishing criteria to refer ACHD patients for cardiac transplantation was deemed a priority. Conclusions The ACHD field is in need of prospective research to address fundamental clinical questions. It is hoped that this methodical consultation process will inform researchers and funding organizations about clinical research topics deemed to be of high priority. PMID:24411207
Andersen, Troels Askhøj; Troelsen, Karin de Linde Lind; Larsen, Lars Allan
Congenital heart disease (CHD) affects nearly 1 % of the population. It is a complex disease, which may be caused by multiple genetic and environmental factors. Studies in human genetics have led to the identification of more than 50 human genes, involved in isolated CHD or genetic syndromes, where CHD is part of the phenotype. Furthermore, mapping of genomic copy number variants and exome sequencing of CHD patients have led to the identification of a large number of candidate disease genes. Experiments in animal models, particularly in mice, have been used to verify human disease genes and to gain further insight into the molecular pathology behind CHD. The picture emerging from these studies suggest that genetic lesions associated with CHD affect a broad range of cellular signaling components, from ligands and receptors, across down-stream effector molecules to transcription factors and co-factors, including chromatin modifiers.
Belaval, Vinay; Gadabanahalli, Karthik; Raj, Vimal; Shah, Sejal
Acyanotic heart disease constitutes a significant majority of patient who may present with non-cardiac symptoms. Either they are detected incidentally or present with respiratory complaints. Equipped with knowledge of anatomy by echocardiography and radiographic methods described in previous part of this presentation, diagnosis may be confidently attempted. On plain radiography acyanotic congenital heart diseases have variable appearance depending upon severity of disease. Cardiac size, chamber enlargement and pulmonary vascular pattern are key elements. Typically left to right shunts with large volume flow are associated with pulmonary plethora. Plain radiography has an important role in detecting manifestation of pulmonary arterial hypertension. Severe stenosis of pulmonary valve is associated with pulmonary oligemia. Small intra-cardiac shunts and anomalies of coronary arteries generally present with normal cardiac size and pulmonary arterial pattern. Disease spectrum presented in this illustration demands thorough scrutiny of pulmonary, osseous and abdominal abnormalities. This section illustrates some commonly encountered spectrum of acyanotic cardiac disease. PMID:27504381
Bhat, Venkatraman; Belaval, Vinay; Gadabanahalli, Karthik; Raj, Vimal; Shah, Sejal
Acyanotic heart disease constitutes a significant majority of patient who may present with non-cardiac symptoms. Either they are detected incidentally or present with respiratory complaints. Equipped with knowledge of anatomy by echocardiography and radiographic methods described in previous part of this presentation, diagnosis may be confidently attempted. On plain radiography acyanotic congenital heart diseases have variable appearance depending upon severity of disease. Cardiac size, chamber enlargement and pulmonary vascular pattern are key elements. Typically left to right shunts with large volume flow are associated with pulmonary plethora. Plain radiography has an important role in detecting manifestation of pulmonary arterial hypertension. Severe stenosis of pulmonary valve is associated with pulmonary oligemia. Small intra-cardiac shunts and anomalies of coronary arteries generally present with normal cardiac size and pulmonary arterial pattern. Disease spectrum presented in this illustration demands thorough scrutiny of pulmonary, osseous and abdominal abnormalities. This section illustrates some commonly encountered spectrum of acyanotic cardiac disease.
Mazwi, Mjaye L; Henner, Natalia; Kirsch, Roxanne
Patients with critical congenital heart disease are exposed to significant lifetime morbidity and mortality. Prenatal diagnosis can provide opportunities for anticipatory co-management of patients between palliative subspecialists and the cardiac care team. The benefits of palliative care include support for longitudinal decision-making and avoidance of interventions not consistent with family goals. Effectively counseling families requires an up-to-date understanding of outcomes and knowledge of provider biases. Patient-proxy reported quality of life (QOL) is highly variable in this population and healthcare providers need to be aware of limitations in their own subjective assessment of QOL.
Sanapo, Laura; Moon-Grady, Anita J; Donofrio, Mary T
Advances in fetal echocardiography have improved prenatal diagnosis of congenital heart disease (CHD) and allowed better delivery and perinatal management. Some newborns with CHD require urgent intervention after delivery. In these cases, delivery close to a pediatric cardiac center may be considered, and the presence of a specialized cardiac team in the delivery room or urgent transport of the infant should be planned in advance. Delivery planning, monitoring in labor, rapid intervention at birth if needed, and avoidance of iatrogenic preterm delivery have the potential to improve outcomes for infants with prenatally diagnosed CHD.
Greil, Gerald; Tandon, Animesh (Aashoo); Silva Vieira, Miguel; Hussain, Tarique
Three-dimensional (3D) whole heart techniques form a cornerstone in cardiovascular magnetic resonance imaging of congenital heart disease (CHD). It offers significant advantages over other CHD imaging modalities and techniques: no ionizing radiation; ability to be run free-breathing; ECG-gated dual-phase imaging for accurate measurements and tissue properties estimation; and higher signal-to-noise ratio and isotropic voxel resolution for multiplanar reformatting assessment. However, there are limitations, such as potentially long acquisition times with image quality degradation. Recent advances in and current applications of 3D whole heart imaging in CHD are detailed, as well as future directions. PMID:28289674
Kennea, N; Norbury, R; Anderson, G; Tekay, A
Prenatal ultrasound has led to confidence in the antenatal diagnosis of intestinal obstruction allowing counseling and birth planning. We describe a male infant of a diabetic mother who had an antenatal diagnosis of distal bowel obstruction. This baby was subsequently found not to have bowel obstruction, but a congenital enteropathy - microvillous inclusion disease. The antenatal scans had demonstrated polyhydramnios as well as multiple fluid-filled dilated loops of bowel in the fetal abdomen. To our knowledge, similar prenatal ultrasound findings have not been previously described in this condition. The baby was delivered in a pediatric surgical center and postnatally there was no evidence of bowel obstruction either clinically or on abdominal X-ray. This baby initially fed well, but became collapsed and acidotic on his third day, having lost 26% of his birth weight due to excessive stool loss. The diagnosis of microvillous inclusion disease was made by electron microscopy of a small bowel biopsy. Congenital microvillous inclusion disease is a very rare inherited enteropathy with high mortality and morbidity. This condition, and other enteropathies, should be considered in cases in which antenatally diagnosed bowel obstruction is not confirmed after birth.
Coffield, Daniel J.; Spagnuolo, Anna Maria; Shillor, Meir; Mema, Ensela; Pell, Bruce; Pruzinsky, Amanda; Zetye, Alexandra
This work presents a new mathematical model for the domestic transmission of Chagas disease, a parasitic disease affecting humans and other mammals throughout Central and South America. The model takes into account congenital transmission in both humans and domestic mammals as well as oral transmission in domestic mammals. The model has time-dependent coefficients to account for seasonality and consists of four nonlinear differential equations, one of which has a delay, for the populations of vectors, infected vectors, infected humans, and infected mammals in the domestic setting. Computer simulations show that congenital transmission has a modest effect on infection while oral transmission in domestic mammals substantially contributes to the spread of the disease. In particular, oral transmission provides an alternative to vector biting as an infection route for the domestic mammals, who are key to the infection cycle. This may lead to high infection rates in domestic mammals even when the vectors have a low preference for biting them, and ultimately results in high infection levels in humans. PMID:23840647
Marsden, Alison L.; Feinstein, Jeffrey A.
Purpose of review Recent methodological advances in computational simulations are enabling increasingly realistic simulations of hemodynamics and physiology, driving increased clinical utility. We review recent developments in the use of computational simulations in pediatric and congenital heart disease, describe the clinical impact in modeling in single ventricle patients, and provide an overview of emerging areas. Recent Findings Multiscale modeling combining patient specific hemodynamics with reduced order (i.e. mathematically and computationally simplified) circulatory models has become the defacto standard for modeling local hemodynamics and “global” circulatory physiology. We review recent advances that have enabled faster solutions, discuss new methods, (e.g. fluid structure interaction and uncertainty quantification), which lend realism both computationally and clinically to results, highlight novel computationally-derived surgical methods for single ventricle patients, and discuss areas in which modeling has begun to exert its influence including Kawasaki disease, fetal circulation, tetralogy of Fallot, (and pulmonary tree), and circulatory support. Summary Computational modeling is emerging as a crucial tool for clinical decision-making and evaluation of novel surgical methods and interventions in pediatric cardiology and beyond. Continued development of modeling methods, with an eye towards clinical needs, will enable clinical adoption in a wide range of pediatric and congenital heart diseases. PMID:26262579
Orwat, Stefan; Diller, Gerhard-Paul; Baumgartner, Helmut
Major advances in noninvasive imaging of adult congenital heart disease have been accomplished. These tools play now a key role in comprehensive diagnostic work-up, decision for intervention, evaluation for the suitability of specific therapeutic options, monitoring of interventions and regular follow-up. Besides echocardiography, magnetic resonance (CMR) and computed tomography (CT) have gained particular importance. The choice of imaging modality has thus become a critical issue. This review summarizes strengths and limitations of the different imaging modalities and how they may be used in a complementary fashion. Echocardiography obviously remains the workhorse of imaging routinely used in all patients. However, in complex disease and after surgery echocardiography alone frequently remains insufficient. CMR is particularly useful in this setting and allows reproducible and accurate quantification of ventricular function and comprehensive assessment of cardiac anatomy, aorta, pulmonary arteries and venous return including complex flow measurements. CT is preferred when CMR is contraindicated, when superior spatial resolution is required or when "metallic" artefacts limit CMR imaging. In conclusion, the use of currently available imaging modalities in adult congenital heart disease needs to be complementary. Echocardiography remains the basis tool, CMR and CT should be added considering specific open questions and the ability to answer them, availability and economic issues.
Muscular Dystrophy; Congenital Muscular Dystrophy; Fukutin-related Protein Gene; Limb Girdle; FKRP Gene; Childhood Onset LGMD; Adult Onset LGMD; POMT1; POMT2; POMGnT1; LARGE; Alpha Dystroglycan; Dystroglycanopathy; Centronuclear; Multiminicore; Multicore; Minicore; Congenital Fiber Type Disproportion; Myotubular; Nemaline; Congenital Myopathy; Neuromuscular; Rigid Spine; Phenotype-Genotype Correlation; Cough Assisted Device; Neuromuscular Disease; Respiratory Exacerbation; Invasive Ventilation; Chest Physiotherapy; Congenital Myopathies; Genetic Mutations; Hypertrophic Cardiomyopathy; Wheelchair Use; Cataract; Opthalmoplegia; Ullrich Congenital Muscular Dystrophy; Intermediate Collagen VI Myopathy; Laminin Alpha 2 Related Congenital Muscular Dystrophy; MDC1A; Merosin Deficient Congenital Muscular Dystrophy; Congenital Muscular Dystrophy Undiagnosed; Congenital Muscular Dystrophy Merosin Positive; Walker Warburg Syndrome; Muscle Eye Brain Disease; Fukuyama; Integrin Alpha 7 Deficiency; Integrin Alpha 9 Deficiency; Laminopathy; Lamin AC; SEPN1 Related Myopathies; Bethlem Myopathy; Dystroglycanopathies; LGMD2K; LGMD2I; LGMD2L; LGMD2N; Actin Aggregation Myopathy; Cap Disease; Central Core Disease; Centronuclear Myopathy; Core Rod Myopathy; Hyaline Body Myopathy; Multiminicore Myopathy; Myotubular Myopathy; Nemaline Myopathy; Tubular Aggregate Myopathy; Zebra Body Disease Myopathy; Congenital Myopathy Other; Reducing Body Myopathy; Sarcotubular Myopathy; Spheroid Body Myopathy
San Agustin, Jovenal T; Klena, Nikolai; Granath, Kristi; Panigrahy, Ashok; Stewart, Eileen; Devine, William; Strittmatter, Lara; Jonassen, Julie A; Liu, Xiaoqin; Lo, Cecilia W; Pazour, Gregory J
Structural birth defects in the kidney and urinary tract are observed in 0.5% of live births and are a major cause of end-stage renal disease, but their genetic aetiology is not well understood. Here we analyse 135 lines of mice identified in large-scale mouse mutagenesis screen and show that 29% of mutations causing congenital heart disease (CHD) also cause renal anomalies. The renal anomalies included duplex and multiplex kidneys, renal agenesis, hydronephrosis and cystic kidney disease. To assess the clinical relevance of these findings, we examined patients with CHD and observed a 30% co-occurrence of renal anomalies of a similar spectrum. Together, these findings demonstrate a common shared genetic aetiology for CHD and renal anomalies, indicating that CHD patients are at increased risk for complications from renal anomalies. This collection of mutant mouse models provides a resource for further studies to elucidate the developmental link between renal anomalies and CHD.
San Agustin, Jovenal T.; Klena, Nikolai; Granath, Kristi; Panigrahy, Ashok; Stewart, Eileen; Devine, William; Strittmatter, Lara; Jonassen, Julie A.; Liu, Xiaoqin; Lo, Cecilia W.; Pazour, Gregory J.
Structural birth defects in the kidney and urinary tract are observed in 0.5% of live births and are a major cause of end-stage renal disease, but their genetic aetiology is not well understood. Here we analyse 135 lines of mice identified in large-scale mouse mutagenesis screen and show that 29% of mutations causing congenital heart disease (CHD) also cause renal anomalies. The renal anomalies included duplex and multiplex kidneys, renal agenesis, hydronephrosis and cystic kidney disease. To assess the clinical relevance of these findings, we examined patients with CHD and observed a 30% co-occurrence of renal anomalies of a similar spectrum. Together, these findings demonstrate a common shared genetic aetiology for CHD and renal anomalies, indicating that CHD patients are at increased risk for complications from renal anomalies. This collection of mutant mouse models provides a resource for further studies to elucidate the developmental link between renal anomalies and CHD. PMID:27002738
Bouzo-López, Raquel; González-Represas, Alicia
For many years, the treatment of congenital heart diseases has been a field in which, based on the seriousness of these conditions, treatment options were viewed with the greatest deference. This has conditioned, in many cases, the interventions to be undertaken in each. In this sense, exercise was thought to have a negative impact and thus the practise of almost any physical activity was limited. Although there has recently been a change in the paradigm with respect to exercise, this idea continues to hold sway. For many cardiopathies, the information obtained through a stress test is essential in order to implement and supervise an exercise program. The aim of this study is to analyze the parameters within the stress test which allow for an adequate stratification of the risk to subjects with congenital heart diseases who undertake exercise, as well as their values in accordance with the type of pathology, the gravity of such, and the age of the patients. Furthermore, these parameters will be analyzed for both their survival markers and the protocols that can best be adjusted for patients with these characteristic.
Hartofilakidis, George; Lampropoulou-Adamidou, Kalliopi
Orthopaedic surgeons specialising in adult hip reconstruction surgery often face the problem of osteoarthritis secondary to congenital hip disease (CHD). To achieve better communication among physicians, better treatment planning and evaluation of the results of various treatment options, an agreed terminology is needed to describe the entire pathology. Furthermore, a generally accepted classification of the deformities is necessary. Herein, the authors propose the use of the term “congenital hip disease” and its classification as dysplasia, low dislocation and high dislocation. Knowledge of the CHD natural history facilitates comprehension of the potential development and progression of the disease, which differs among the aforementioned types. This can lead to better understanding of the anatomical abnormalities found in the different CHD types and thus facilitate preoperative planning and choice of the most appropriate management for adult patients. The basic principles for improved results of total hip replacement in patients with CHD, especially those with low and high dislocation, are: Wide exposure, restoration of the normal centre of rotation and the use of special techniques and implants for the reconstruction of the acetabulum and femur. Application of these principles during total hip replacement in young female patients born with severe deformities of the hip joint has led to radical improvement of their quality of life. PMID:28032030
Belaval, Vinay; Gadabanahalli, Karthik; Raj, Vimal; Shah, Sejal
From the stand point of radiographic analysis most of the complex cyanotic congenital heart diseases (CHD), can be divided into those associated with decreased or increased pulmonary vascularity. Combination of a specific cardiac configuration and status of lung vasculature in a clinical context allows plain film diagnosis to be predicted in some CHD. Correlation of the position of the cardiac apex in relation to the visceral situs is an important information that can be obtained from the plain film. This information helps in gathering information about the atrio-ventricular, ventricular arterial concordance or discordance. Categorization of the cyanotic heart disease based on vascularity is presented below. Thorough understanding of cardiac anatomy by different imaging methods is essential in understanding and interpreting complex cardiac disease. Basic anatomical details and background for interpretation are provided in the previous parts of this presentation. PMID:27630924
Roberts, Jillian; Massie, Kendra; Mortimer, Tamara; Maxwell, Lani
Congenital heart disease is one of the most common pediatric chronic illnesses that can have an impact on the lives of affected children and their families. Despite the growing number of school-age children who live with congenital heart disease, few researchers have investigated the lives and well-being of these children and their families. The…
Flores-Chávez, María; Faez, Yamile; Olalla, José M; Cruz, Israel; Gárate, Teresa; Rodríguez, Mercedes; Blanc, Pilar; Cañavate, Carmen
The early diagnosis of congenital Chagas' disease is very important if infected newborns, whether symptomatic or not, are to receive adequate treatment. This paper describes the complications arising in the diagnosis of a newborn with fatal congenital Chagas' disease in Spain, a non-endemic area where visceral leishmaniasis is present. PMID:18992159
Minnesota State Dept. of Health, Minneapolis. Services for Children with Handicaps.
These guidelines were written to help families coordinate the health care that may be needed by a child with congenital heart disease. The booklet begins with general information about congenital heart disease. It then discusses the goals of health care, the health care team, the importance of periodic health care, and record keeping procedures.…
The aim of this review of hereditary and congenital ocular disease in cats is to present an overview of the most common disorders seen in this species, the pathogenesis of the problems and wherever possible, how they are treated. Several defects are common in breeds such as the Persian, Himalayan and Burmese cats and affect the anterior segment of the eye. Examples are agenesis of the eyelids, dermoids, entropion and corneal sequestrum. Other problems such as cataracts, lens luxation and retinal dysplasia, cause problems of the intraocular structures, but are less common in cats compared to dogs. Finally, various parts of the retina and in some diseases other parts of the eye, are specifically affected by hereditary diseases. Examples of these are lysosomal storage disease, Chediak-Higashi syndrome and progressive rod cone degeneration and rod cone dysplasia. Research of the latter two hereditary diseases, both described in the Abyssinian breed of cat, have made affected individuals important animal models for research into comparable diseases of humans.
Chaix, Marie-A; Marcotte, François; Dore, Annie; Mongeon, François-Pierre; Mondésert, Blandine; Mercier, Lise-Andrée; Khairy, Paul
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.
Yamamoto, Keiko; Namba, Noriyuki; Kubota, Takuo; Usui, Takeshi; Takahashi, Kunihiko; Kitaoka, Taichi; Fujiwara, Makoto; Hori, Yumiko; Kogaki, Shigetoyo; Oue, Takaharu; Morii, Eiichi; Ozono, Keiichi
Abstract. Coincidental cyanotic congenital heart disease and pheochromocytoma is uncommon, although some cases have been reported. We describe a girl aged 15 yr and 11 mo with pheochromocytoma and tricuspid atresia treated by performing the Fontan surgery. The patient did not have any specific symptoms of syndrome related to pheochromoytoma or a family history of pheochromocytoma. During cardiac catheterization, her blood pressure increased markedly, and an α-blocker was administered. Catecholamine hypersecretion was observed in the blood and urine, and abdominal computed tomography revealed a tumor in the right adrenal gland. Scintigraphy showed marked accumulation of 123I-metaiodobenzylguanidine in the tumor, which led to a diagnosis of pheochromocytoma. We did not detect any germline mutations in the RET, VHL, SDHB, SDHD, TMEM127, or MAX genes. This patient had experienced mild systemic hypoxia since birth, which may have contributed to the development of pheochromocytoma. PMID:27212797
Vecoli, Cecilia; Pulignani, Silvia; Foffa, Ilenia; Andreassi, Maria Grazia
Congenital heart diseases (CHDs) are recognized as the most common type of birth malformations. Although recent advances in pre- and neonatal diagnosis as well as in surgical procedures have reduced the morbidity and mortality for many CHD, the etiology for CHD remains undefined. In non-syndromic and isolated (without a familial history or a Mendelian inheritance) forms of CHDs, a multifactorial pathogenesis with interplay between inherited and non-inherited causes is recognized. In this paper, we discuss the current knowledge of the potential molecular mechanisms, mediating abnormal cardiac development in non-syndromic and isolated CHD, including mutations in cardiac transcription factors, the role of somatic mutations and epigenetic alterations as well as the influence of gene-environment interactions. In the near future, the advent of high-throughput genomic technologies with the integration of system biology will expand our understanding of isolated, non-syndromic CHDs for their prevention, early diagnosis and therapy. PMID:25435801
Lu, Chun-Wei; Wu, Mei-Hwan; Wang, Jou-Kou; Lin, Min-Tai; Chen, Chun-An; Chiu, Shenn-Nan; Chiu, Hsin-Hui
With advances that have been made over the recent decades in transcatheter and surgical interventions, most patients with congenital heart disease (CHD) can survive into adulthood. Overall, probably half of these surviving patients are female. When these female CHD patients reach childbearing age, however, pregnancy management will be a major issue. In order to meet the demands of fetal growth, the maternal cardiovascular system starts a series of adaptations beginning in early pregnancy. These adaptations include: decreased systemic and pulmonary vascular resistances, decreased blood pressure, expansion of the blood volume, increased heart rate and increased cardiac output. For women with CHD, this hemodynamic alteration may increase the risks of adverse cardiovascular events as well as the fetal and neonatal complications. Therefore, proper risk stratification and effective counseling for women with CHD who are planning their pregnancies is an important undertaking. PMID:27122914
Pediatric cardiac care in India is still in its infancy. We have no data on congenital heart disease (CHD) prevalence at birth or on proportional mortality from CHD. The resources are not only limited but also are at times improperly utilized. There are very few specialized pediatric cardiology training programs, those that are, are concentrated in certain regions of India and are often imparted through combined adult and pediatric programs. The existing number of trained personnel for pediatric cardiology and pediatric cardiac surgery is inadequate. Above all there is no national policy for pediatric heart care. Increasing awareness of the problem amongst the pediatricians through CMEs, seminars, symposia is likely to be most helpful in early diagnosis and timely referral of cases. Training programs exclusively dedicated to pediatric cardiology and pediatric cardiac surgery need to be established in centres with good standards of pediatric cardiac care.
Serino, G; Giacomazzi, F
Pulmonary Hypertension (PH) is definited by a mean pulmonary artery pressure (PAPm) >25 mmHg at rest. The Dana Point 2008 Revised Classification System represents the most recent classification system update with respect of various etiologies of PH. About 10 % of adolescents or adults with uncorrected congenital heart disease (CHD) with left-to-right shunt and high pulmonary blood flow develop Pulmonary Arterial Hypertension (PAH) . Progressive vascular remodeling and increase in pulmonary vascular resistance (PVR) may ultimately lead to reversal of the shunt (pulmonary to systemic) causing cyanosis and determining the so-called Eisenmenger Syndrome (ES). Recent advances in the early diagnosis and medical targeted treatment of adult patients with CHD-PAH and ES can improve PAP, PVR and exercise tolerance, together with NYHA Class and survival, and may potentially reverse the vascular remodeling process in selected patients.
Kafka, Henryk; Johnson, Mark R; Gatzoulis, Michael A
The successful pediatric management of congenital heart disease has resulted in increasing numbers of these patients in the reproductive age group and increasing clinical challenges for their physicians. These challenges can be met successfully, with improved results for mother and child, through a concerted comprehensive team approach that relies on a thorough understanding of the patient's underlying cardiac pathology and its anticipated interaction with the pregnancy, and ongoing close evaluation and communication with a team of trained and experienced specialist, including (but not limited to) cardiologist, obstetricians, anesthetists, pediatricians, clinical nurse specialists, and clinical geneticists. Such teams are not always available locally and it will be necessary to refer medium- and high-risk patients to a specialized tertiary care center.
The number of adults with congenital heart disease is increasing due to the great achievements in the field of paediatric cardiology, congenital heart surgery and intensive care medicine over the last decades. Mortality has shifted away from the infant and childhood period towards adulthood. As congenital heart disease patients get older, a high prevalence of cardiovascular risk factors is encountered similar to the general population. Consequently, the contribution of acquired morbidities, especially acquired heart conditions to patient outcome, is becoming increasingly important. Therefore, to continue the success story of the last decades in the treatment of congenital heart disease and to further improve the outcome of these patients, more attention has to be given to the prevention, detection and adequate therapy of acquired heart conditions. The aim of this review is to give an overview about acquired heart conditions that may be encountered in adults with congenital heart disease.
Osteen, Kathryn A; Beal, Claudia C
The purpose of this article was to examine reproductive health issues for women with congenital structural abnormalities of the heart. Because of surgical advances and innovations in healthcare, infants with congenital heart disease often live now into adulthood. Women with congenital heart disease have reported the desire to have children but expressed concern about fertility and the health consequences of pregnancy. Although many women with congenital heart disease are able to give birth without adverse outcomes, life-threatening complications can occur. Best practices for the care of women with congenital heart disease are grounded in an understanding of how cardiac defects may affect pregnancy and in communicating the implications of cardiac defects for reproductive health to support informed decision making.
Li, Xing; Martinez-Fernandez, Almudena; Hartjes, Katherine A; Kocher, Jean-Pierre A; Olson, Timothy M; Terzic, Andre; Nelson, Timothy J
Mammalian heart development is built on highly conserved molecular mechanisms with polygenetic perturbations resulting in a spectrum of congenital heart diseases (CHD). However, knowledge of cardiogenic ontogeny that regulates proper cardiogenesis remains largely based on candidate-gene approaches. Mapping the dynamic transcriptional landscape of cardiogenesis from a genomic perspective is essential to integrate the knowledge of heart development into translational applications that accelerate disease discovery efforts toward mechanistic-based treatment strategies. Herein, we designed a time-course transcriptome analysis to investigate the genome-wide dynamic expression landscape of innate murine cardiogenesis ranging from embryonic stem cells to adult cardiac structures. This comprehensive analysis generated temporal and spatial expression profiles, revealed stage-specific gene functions, and mapped the dynamic transcriptome of cardiogenesis to curated pathways. Reconciling known genetic underpinnings of CHD, we deconstructed a disease-centric dynamic interactome encoded within this cardiogenic atlas to identify stage-specific developmental disturbances clustered on regulation of epithelial-to-mesenchymal transition (EMT), BMP signaling, NF-AT signaling, TGFb-dependent EMT, and Notch signaling. Collectively, this cardiogenic transcriptional landscape defines the time-dependent expression of cardiac ontogeny and prioritizes regulatory networks at the interface between health and disease.
Li, Xing; Martinez-Fernandez, Almudena; Hartjes, Katherine A.; Kocher, Jean-Pierre A.; Olson, Timothy M.; Terzic, Andre
Mammalian heart development is built on highly conserved molecular mechanisms with polygenetic perturbations resulting in a spectrum of congenital heart diseases (CHD). However, knowledge of cardiogenic ontogeny that regulates proper cardiogenesis remains largely based on candidate-gene approaches. Mapping the dynamic transcriptional landscape of cardiogenesis from a genomic perspective is essential to integrate the knowledge of heart development into translational applications that accelerate disease discovery efforts toward mechanistic-based treatment strategies. Herein, we designed a time-course transcriptome analysis to investigate the genome-wide dynamic expression landscape of innate murine cardiogenesis ranging from embryonic stem cells to adult cardiac structures. This comprehensive analysis generated temporal and spatial expression profiles, revealed stage-specific gene functions, and mapped the dynamic transcriptome of cardiogenesis to curated pathways. Reconciling known genetic underpinnings of CHD, we deconstructed a disease-centric dynamic interactome encoded within this cardiogenic atlas to identify stage-specific developmental disturbances clustered on regulation of epithelial-to-mesenchymal transition (EMT), BMP signaling, NF-AT signaling, TGFb-dependent EMT, and Notch signaling. Collectively, this cardiogenic transcriptional landscape defines the time-dependent expression of cardiac ontogeny and prioritizes regulatory networks at the interface between health and disease. PMID:24803680
Ahmad, Waheed; Miteff, Ferdi; Collins, Nicholas
Headache in adult patients with congenital heart disease may be a manifestation of the underlying cardiac condition or more common alternative causes of headache. In patients with pre-existing congenital heart disease, consideration of potentially uncommon aetiologies of headache is important. We report an uncommon case of headache in a patient with complex congenital heart disease characterised by Ebstein's anomaly with previous surgical repair complicated by idiopathic intracranial hypertension. This case illustrates the importance of understanding the implications of headache with reference to the underlying cardiac disease as well as specific issues related to a relatively young cohort of patients.
Ross, Danielle S; Dollard, Sheila C; Victor, Marcia; Sumartojo, Esther; Cannon, Michael J
Perhaps no single cause of birth defects and developmental disabilities in the United States currently provides greater opportunity for improved outcomes in more children than congenital cytomegalovirus (CMV). --Cannon and Davis. BMC Public Health 2005;5:70 Each year in the United States, thousands of children and their families are affected by congenital cytomegalovirus (CMV) infection. More children may be affected by congenital CMV than by other, better known childhood conditions, such as Down syndrome, fetal alcohol syndrome, and spina bifida. The Centers for Disease Control and Prevention (CDC) has formed a Workgroup on Congenital CMV, led by the National Center on Birth Defects and Developmental Disabilities and the National Center on Infectious Diseases. This report provides background on congenital CMV infection and describes the goals and activities of the workgroup for reducing the burden of sequelae of congenital CMV infection.
Ríos-Méndez, Raúl Enrique; Lozano Chinga, Michell Marola
Clinical congenital anophthalmia is described as the uni- or bilateral absence of the eyeball that might occur in isolation or as part of a syndrome. It has a very low prevalence and its etiology is heterogeneous. Complex congenital cardiac malformations are also rare. The association of congenital anophthalmia and congenital heart disease is rarer still, and the etiology of those associations is not well understood yet. We report the case of a patient who had the very rare association of bilateral anophthalmia, multiple cardiac malformations and severe pulmonary hypertension.
Zomer, A Carla; Vaartjes, Ilonca; Uiterwaal, Cuno S P; van der Velde, Enno T; Sieswerda, Gert-Jan T; Wajon, Elly M C; Plomp, Koos; van Bergen, Paul F M; Verheugt, Carianne L; Krivka, Eva; de Vries, Cees J; Lok, Dirk J A; Grobbee, Diederick E; Mulder, Barbara J M
We aimed to evaluate how the presence and severity of congenital heart disease (CHD) influence social life and lifestyle in adult patients. A random sample (n = 1,496) from the CONgenital CORvitia (n = 11,047), the Dutch national registry of adult patients with CHD, completed a questionnaire on educational attainment, employment and marital statuses, and lifestyle (response 76%). The Utrecht Health Project provided a large reference group (n = 6,810) of unaffected subjects. Logistic regression models were used for subgroup analyses and to adjust for age, gender, and socioeconomic status where appropriate. Of all patients 51.5% were men (median age 39 years, interquartile range 29 to 51) with mild (46%), moderate (44%), and severe (10%) CHD. Young (<40-year-old) patients with CHD were more likely to have achieved a lower education (adjusted odds ratios [ORs] 1.6 for men and 1.9 for women, p <0.05 for the 2 comparisons), significantly more often unemployed (adjusted ORs 5.9 and 2.0 for men and women, respectively), and less likely to be in a relationship compared to the reference group (adjusted ORs 8.5 for men and 4.5 for women). These poorer outcomes were seen in all severity groups. Overall, the CHD population smoked less (adjusted OR 0.5, p <0.05), had more sports participation (adjusted OR 1.2, p <0.05), and had less obesity (adjusted OR 0.7, p <0.05) than the reference group. In conclusion, there was a substantial social disadvantage in adult patients with CHD, which was seen in all severity groups and primarily in young men. In contrast, adults with CHD had healthier lifestyles compared to the reference group.
... Disease Featured Resource Find an Endocrinologist Search Congenital Hypothyroidism March 2012 Download PDFs English Espanol Editors Rosalind S. ... Pediatric Endocrine Society MedlinePlus (NIH) What is congenital hypothyroidism? Newborn babies who are unable to make enough ...
Loomba, Rohit S; Aggarwal, Saurabh; Pelech, Andrew N
A larger number of individuals born with congenital heart disease is living into adolescence and young adulthood. With this comes the responsibility to counsel these patients regarding their sexual and reproductive health. This study utilizes representative data from the National Health and Nutrition Examination Survey to compare sexual measures including percentage of that sexually active, age of first sexual activity, number of sexual partners, condom use, and history of sexually transmitted diseases in those with and without congenital heart disease. A total of 1086 patients (1057 without congenital heart disease and 29 with congenital heart disease) were included in this study. Likelihood of being sexually active, age of first sexual intercourse, and condom use did not differ significantly between the two groups after multivariate analysis. Incidence of sexually transmitted disease did not differ between the two groups after multivariate analysis except for genital warts. There are no major differences in sexual measures between those with and without congenital heart disease. The absence of significant differences in sexual measures in those with congenital heart disease compared with the general population places this group of individuals at increased health risk known to occur with pregnancy.
Ladouceur, Magalie; Iserin, Laurence; Cohen, Sarah; Legendre, Antoine; Boudjemline, Younes; Bonnet, Damien
Increasing survival rates of patients with congenital heart disease have resulted in a new and growing patient population of adults with operated congenital heart disease. Medical professionals face the specific medical needs of these patients but must also deal with their daily life issues. Adult patients with congenital heart disease report difficulties in several areas of daily life, such as sport, employment, insurability and travel or driving. Moreover, they must have a healthy lifestyle to prevent cardiovascular complications. All these issues can be addressed in a specific educational program. In this review, we discuss the different daily life issues of adults with congenital heart disease and the preventive measures that can be proposed to improve their quality of life.
Chiavarino, Claudia; Bianchino, Claudia; Brach-Prever, Silvia; Riggi, Chiara; Palumbo, Luigi; Bara, Bruno G; Bosco, Francesca M
This article provides the first assessment of theory of mind, that is, the ability to reason about mental states, in adult patients with congenital heart disease. Patients with congenital heart disease and matched healthy controls were administered classical theory of mind tasks and a semi-structured interview which provides a multidimensional evaluation of theory of mind (Theory of Mind Assessment Scale). The patients with congenital heart disease performed worse than the controls on the Theory of Mind Assessment Scale, whereas they did as well as the control group on the classical theory-of-mind tasks. These findings provide the first evidence that adults with congenital heart disease may display specific impairments in theory of mind.
... Research Home / Your Heart / Health Information / Birth Control Birth Control for Women with Congenital Heart Disease Of the ... woman and/or the baby. For these women, birth control is more than just a method to conveniently ...
Strickland, Matthew J; Riehle-Colarusso, Tiffany J; Jacobs, Jeffrey P; Reller, Mark D; Mahle, William T; Botto, Lorenzo D; Tolbert, Paige E; Jacobs, Marshall L; Lacour-Gayet, Francois G; Tchervenkov, Christo I; Mavroudis, Constantine; Correa, Adolfo
Background Administrative databases are often used for congenital heart disease research and evaluation, with little validation of the accuracy of the diagnostic codes. Methods Metropolitan Atlanta Congenital Defects Program surveillance records were reviewed and classified using a version of the International Pediatric and Congenital Cardiac Code. Using this clinical nomenclature as the referent, we report the sensitivity and false positive fraction (1 – positive predictive value) of the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for tetralogy of Fallot, transposition of the great arteries, and hypoplastic left heart syndrome. Results We identified 4918 infants and foetuses with congenital heart disease from the surveillance records. Using only the International Classification of Diseases diagnosis codes, there were 280 records with tetralogy, 317 records with transposition, and 192 records with hypoplastic left heart syndrome. Based on the International Pediatric and Congenital Cardiac Code, 330 records were classified as tetralogy, 163 records as transposition, and 179 records as hypoplastic left heart syndrome. The sensitivity of International Classification of Diseases diagnosis codes was 83% for tetralogy, 100% for transposition, and 95% for hypoplastic left heart syndrome. The false positive fraction was 2% for tetralogy, 49% for transposition, and 11% for hypoplastic left heart syndrome. Conclusions Analyses based on International Classification of Diseases diagnosis codes may have substantial misclassification of congenital heart disease. Isolating the major defect is difficult, and certain codes do not differentiate between variants that are clinically and developmentally different. PMID:19063779
Meijboom, Folkert; Mulder, Barbara
The prevalence of congenital heart disease among adults in Europe, or in any country in Europe, is not known. This is due to a lack of agreement on the incidence of congenital heart disease, with estimations varying from four per 1000 births to 50 per 1000 births, and it is not known how many patients with congenital heart disease have died. Based on several studies that estimated and calculated the number of adult patients with congenital heart disease, the number of patients should be much higher than the number of patients that are actually seen in specialized centres throughout Europe. This implies that either a large proportion of adult patients with congenital heart disease do not receive appropriate medical care, or that the calculations and estimations are grossly wrong. A combination of the two is also possible. A substantial expansion of the number and size of specialized centres for adult congenital heart disease is advocated, but since setting up (and running) a service for this disease is a costly affair, and because uncertainty remains about the actual number of patients needing specialized care, this has been difficult to realize in most European countries in the past few years.
Chaix, Marie A; Andelfinger, Gregor; Khairy, Paul
Congenital heart disease (CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient follow-up. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel. PMID:26981213
Guo, Changlong; Wang, Qidi; Wang, Yuting; Yang, Liping; Luo, Haiyan; Cao, Xiao Fang; An, Lisha; Qiu, Yue; Du, Meng; Ma, Xu; Li, Hui; Lu, Cailing
Genetic variation in specific transcription factors during heart formation may lead to congenital heart disease (CHD) or even miscarriage. The aim of the present study was to identify CHD‑associated genes using next generation sequencing (NGS). The whole exome DNA sequence was obtained from a stillborn fetus diagnosed with tricuspid atresia and complete transposition of the great arteries using high‑throughput sequencing methods. Subsequently, genetic variants of CHD‑associated genes were selected and verified in 215 non‑syndromic CHD patients and 249 healthy control subjects using polymerase chain reaction combined with Sanger sequencing. Genetic variants of previously reported CHD‑inducing genes, such as cysteine rich with EGF like domains 1 and cbp/p300‑interacting transactivator with Glu/Asp rich carboxy‑terminal domain 2, were discovered through the NGS analysis. In addition, a novel non‑synonymous mutation of the iroquois homeobox 1 (IRX1) gene (p.Gln240Glu) was identified. A total of three non‑synonymous mutations (p.Gln240Glu, p.Ser298Asn and p.Ala381Glu) of the IRX1 gene were verified in 215 non‑syndromic CHD patients, but not in 249 healthy volunteers. The results demonstrated that NGS is a powerful tool to study the etiology of CHD. In addition, the results suggest that genetic variants of the IRX1 gene may contribute to the pathogenesis of CHD.
Trevisan, Patrícia; Zen, Tatiana Diehl; Rosa, Rafael Fabiano Machado; da Silva, Juliane Nascimento; Koshiyama, Dayane Bohn; Paskulin, Giorgio Adriano; Zen, Paulo Ricardo Gazzola
Background Chromosomal abnormalities (CAs) are an important cause of congenital heart disease (CHD). Objective Determine the frequency, types and clinical characteristics of CAs identified in a sample of prospective and consecutive patients with CHD. Method Our sample consisted of patients with CHD evaluated during their first hospitalization in a cardiac intensive care unit of a pediatric referral hospital in Southern Brazil. All patients underwent clinical and cytogenetic assessment through high-resolution karyotype. CHDs were classified according to Botto et al. Chi-square, Fisher exact test and odds ratio were used in the statistical analysis (p < 0.05). Results Our sample consisted of 298 patients, 53.4% males, with age ranging from 1 day to 14 years. CAs were observed in 50 patients (16.8%), and 49 of them were syndromic. As for the CAs, 44 (88%) were numeric (40 patients with +21, 2 with +18, 1 with triple X and one with 45,X) and 6 (12%) structural [2 patients with der(14,21), +21, 1 with i(21q), 1 with dup(17p), 1 with del(6p) and 1 with add(18p)]. The group of CHDs more often associated with CAs was atrioventricular septal defect. Conclusions CAs detected through karyotyping are frequent in patients with CHD. Thus, professionals, especially those working in Pediatric Cardiology Services, must be aware of the implications that performing the karyotype can bring to the diagnosis, treatment and prognosis and for genetic counseling of patients and families. PMID:24145389
Barbosa, M M; Rocha, C M G; Katina, T; Caldas, M; Codorniz, A; Medeiros, C
To establish the prevalence of congenital heart diseases (CHDs) in cleft patients, the type of cleft and the presence of a syndrome were coded in 220 patients. A Doppler echocardiogram with color-flow mapping (DE) was obtained in all patients. Mean age was 112.0 +/- 101.2 months (range, 1-576 months), and 56.8% (125) were males. Cleft lip and palate occurred in 144 patients (65.5%), cleft lip in 40 (18.2%), and cleft palate in 36 (16.4%). Cleft palates were more frequent among females. Twenty-four CHDs were diagnosed in 21 of 220 patients (9.5%): 7 mitral valve prolapses, 6 atrial septal defects, 4 patent ductus arteriosus, 3 ventricular septal defects, 2 cases of tetralogy of Fallot, 1 pulmonary stenosis, and 1 bicuspid aortic valve. The presence of CHD did not correlate with the type of cleft. Syndromes occurred in 28 patients (12.7%), and this association was higher among patients with a cleft palate.
Jegatheeswaran, Anusha; Oliveira, Carol; Batsos, Constantine; Moon-Grady, Anita J; Silverman, Norman H; Hornberger, Lisa K; Coyte, Peter; Friedberg, Mark K
Little information is available about the transportation costs incurred from the missed prenatal diagnosis of congenital heart disease (CHD). The objectives of the present study were to analyze the costs of emergency transportation related to the postnatal diagnosis of major CHD and to perform a cost/benefit analysis of additional training for ultrasound technicians to study the implications of improved prenatal detection rates. The 1-year costs incurred for emergency transportation of pre- and postnatally diagnosed infants with CHD in Northern California and North Western Nevada were calculated and compared. The prenatal detection rate in our cohort (n = 147) was 30.6%. Infants postnatally diagnosed were 16.5 times more likely (p <0.001) to require emergency transport. The associated emergency transportation costs were US$542,143 in total for all patients with CHD. The mean cost per patient was $389.00 versus $5,143.51 for prenatally and postnatally diagnosed infants, respectively (p <0.001). Assuming an improvement in detection rates after 1-day training for ultrasound technicians, the investment in training cost can be recouped in 1 year if the detection rate increased by 2.4% to 33%. Savings of $6,543,476 would occur within 5 years if the detection rate increased to 50%. In conclusion, CHD diagnosed postnatally results in greater costs related to emergency transportation of ill infants. Improving the prenatal detection rates through improved ultrasound technician training could result in considerable cost savings.
Feilij, H; Muller, L; Gonzalez Cappa, S M
A microhematocrit concentration method (MH) for immediate diagnosis of Chagas' disease during the acute stage or in congenital cases was standardized. Parasitemia as low as 1,000 parasites per ml was detected, after centrifugation of six 50-microliters capillary tubes, by 10-min microscopic observation of each buffy coat spread between slide and cover glass. Operator's time was reduced by at least one-third when compared with a fresh blood observation (FB). In 12 of the 15 patients studied, diagnosis was performed in 4.9 +/- 3.08 min with MH, whereas 27.0 +/- 12.1 min were necessary when FB was used. In the three remaining patients whose FB results were negative, MH became positive after 13, 16, and 40 min. In our experience, FB proved to be more sensitive than previously reported. Suckling mouse inoculation also proved to be sensitive but, as in xenodiagnosis and in hemoculture, the delay in getting the final result was a limiting factor. PMID:6413530
Hopkins, William E
Underappreciated is the fact that the right ventricle is often the primary determinant of long-term morbidity and mortality in patients with congenital heart disease. Right ventricular performance in these patients depends on a unique set of physiologic and pathophysiologic factors that are rarely considered in acquired heart disease. This article explores this unique physiology and pathophysiology in the hope that it will enhance understanding of a wide variety of congenital cardiac anomalies.
Kathiria, Nazima N; Higgins, Charles B; Ordovas, Karen G
Many novel cardiac MR sequences can be used for assessment of adult patients with congenital heart disease. Although most of these techniques are still primarily used in the research arena, there are many potential applications in clinical practice. Advanced cardiac MR assessment of myocardial tissue characterization, flow hemodynamics, and myocardial strain are promising tools for diagnostic and prognostic assessment late after repair of congenital heart diseases.
Bessolo, Rodney J.; Vincent, William R.
The differential diagnosis of congenital heart disease which presents cyanosis or respiratory distress, or both, in the first two weeks of life, is difficult. Close correlation of clinical features, electrocardiogram and chest roentgenogram is most helpful. The diagnosis of congenital heart disease should lead to immediate cardiac catheterization, angiocardiography and appropriate therapy. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7.Figure 8.Figure 9.Figure 10.Figure 11.Figure 12. PMID:5773478
McLaren, M J; Lachman, A S; Barlow, J B
A survey conducted by cardiologists in Soweto, Johannesburg, provided an opportunity of assessing the frequency of congenital heart disease in black schoolchildren. Among 12,050 schoolchildren aged 2 to 18 years, 48 had a congenital heart defect, yielding a prevalence of 3.9 per 1000. Only in 2- to 6-year-old children did the prevalence exceed that of rheumatic heart disease. The distribution of the types of defects was largely similar to that reported in other surveys with a predominance (52%) of ventricular septal defects. Two unusual findings were the unexplained absence of persistent ductus arteriosus in these children, and the detection of 5 children with situs inversus (1 in 2410). In all but one child, the congenital heart defect was first discovered during the survey. Despite the limitations of a prevalence study, it can be concluded that congenital heart disease is at least as common in this South African black community as in Caucasians. PMID:465225
Fifer, William P.; Andrews, Howard
We evaluated differences in growth between fetuses with and without congenital heart disease (CHD) and tested associations between growth and early childhood neurodevelopment (ND). In this prospective cohort study, fetuses with hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and tetralogy of Fallot (TOF) and controls had biparietal diameter (BPD), head (HC) and abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) recorded serially during pregnancy at 18and controls were assessed using–26 weeks GA (F1), at 27–33 weeks GA (F2), and at 34–40 weeks GA (F3). CHD subjects underwent Bayley Scales of Infant Development-III ND testing at 18 months. Differences between CHD fetuses and controls were assessed using t tests and generalized linear modeling. Correlations between biometry and ND informed regression modeling. We enrolled 41 controls and 68 fetuses with CHD (N = 24 HLHS, N = 21 TGA, N = 23 TOF), 46 of whom had ND scores available. At 18–26 weeks, CHD fetuses were smaller than controls in all biometric parameters. Differences in growth rates were observed for HC, BPD, and AC, but not for FL or EFW. Cognitive score correlated with HC/AC at F2 (r = −0.33, P = 0.04) and mean HC/AC across gestation (r = −0.35, P = 0.03). Language correlated with FL/BPD at F2 (r = 0.34, P = 0.04). In stepwise linear regression, mean HC/AC predicted Cognition (B = −102, P = 0.026, R2 = 0.13) and FL/BPD at F2 predicted Language score (B = 127, P = 0.03, R2 = 0.12). Differences in growth between CHD fetuses and controls can be measured early in pregnancy. In CHD fetuses, larger abdominal relative to head circumference is associated with better 18-month neurodevelopment. PMID:25753684
Quartermain, Michael D.; Pasquali, Sara K.; Hill, Kevin D.; Goldberg, David J.; Huhta, James C.; Jacobs, Jeffrey P.; Jacobs, Marshall L.; Kim, Sunghee; Ungerleider, Ross M.
Background Prenatal diagnosis allows for improved peri-operative outcomes of fetuses with certain forms of congenital heart disease (CHD). Variability in prenatal diagnosis has been demonstrated in other countries, leading to efforts to improve fetal imaging protocols and access to care, but has not been examined across the United States. Objective To evaluate national variation in prenatal detection across geographic region and defect type in neonates and infants with CHD undergoing heart surgery. Methods Cardiovascular operations performed in patients ≤ 6 months of age within the United States and included in the STS-CHS Surgical Database (2006–2012) were eligible for inclusion. Centers with >15% missing prenatal diagnosis data were excluded from the study. Prenatal diagnosis rates were compared across geographic location of residence and defect type using the Chi-square test. Results Overall, the study included 31,374 patients from 91 STS-CHS participating centers across the United States. Prenatal detection occurred in 34% and increased every year from 26% (2006) to 42% (2012). There was significant geographic variation in rates of prenatal diagnosis across states (range 11.8 – 53.4%, p < 0.0001). Significant variability by defect type was also observed with higher rates for lesions identifiable on 4-chamber view versus those requiring outflow tract visualization (57% versus 32%, p < 0.0001). Conclusions Rates of prenatal CHD detection in the United States remain low for patients undergoing surgical intervention, with significant variability between states and across defect type. Further studies are needed to identify reasons for this variation and the potential impact on patient outcomes. PMID:26216324
Mulkey, Sarah B.; Swearingen, Christopher J.; Melguizo, Maria S.; Reeves, Rachel N.; Rowell, Jacob A.; Gibson, Neal; Holland, Greg; Bhutta, Adnan T.; Kaiser, Jeffrey R.
Children with early surgery for congenital heart disease (CHD) are known to have impaired neurodevelopment; their performance on school-age achievement tests and their need for special education remains largely unexplored. The study aimed to determine predictors of academic achievement at school-age and placement in special education services among early CHD surgery survivors. Children with CHD surgery at <1 year of age from 1/1/1998─12/31/2003 at the Arkansas Children’s Hospital were identified. Out-of-state births and infants with known genetic and/or neurologic conditions were excluded. Infants were matched to an Arkansas Department of Education database containing standardized assessments at early school-age and special education codes. Predictors for achieving proficiency in literacy and mathematics and the receipt of special education were determined. 256 children who attended Arkansas public schools and had surgery as infants were included; 77.7% had either school-age achievement-test scores or special education codes of mental retardation or multiple disabilities. Scores on achievement tests for these children were 7–13% lower than Arkansas students (p<0.01). They had an 8-fold increase in the receipt of special education due to multiple disabilities (OR 10.66, 95% CI 4.23─22.35) or mental retardation (OR 4.96, 95% CI 2.6─8.64). Surgery after the neonatal period was associated with reduced literacy proficiency and cardiopulmonary bypass during the first surgery was associated with reduced mathematics proficiency. Children who had early CHD surgery were less proficient on standardized school assessments and many received special education. This is concerning since achievement- test scores at school-age are “real-world” predictors of long-term outcomes. PMID:24000004
The surgical treatment of patients with extracardiac structural anomalies and congenital heart disease often carries major risk and remains a challenging field. An appropriate, solid treatment plan should be developed during the early phase with interactive intelligence sharing between a pediatric surgery team and congenital heart surgery team. As the top of the chain of command, the role of a neonatologist is important. This article reviews the history of surgery for congenital heart disease and the progress of the Japan Congenital Cardiovascular Surgery Database. Finally, as an example of a combination of diseases, the clinical course and intelligence sharing during treatment of a patient with biliary atresia requiring living-donor liver transplantation and hypoplastic left heart syndrome is reported. The National Quality Forum provided structural measures, process measures, and outcome measures for congenital heart surgery. Structural measures provided by the National Quality Forum included participation in a preoperative multidisciplinary conference. To improve the outcome of surgical treatment of patients with congenital heart disease and extracardiac structural anomalies, the importance of a preoperative multidisciplinary conference involving not only pediatric surgeons, pediatric cardiologists, and pediatric cardiac surgeons but also neonatologists, anesthesiologists, and nurses cannot be overemphasized.
Passantino, Annamaria; Pugliese, Michela; Quartarone, Valeria; Russo, Natalia; Bussadori, Roberto; Guercio, Bartolomeo
Aim: The veterinarian should be able to assess congenital and inherited malformations such as heart defects because they may be object of legal disputes. In this study, the authors report some cases of congenital heart defects in pets (dogs and cats) to clarify whether or not they may be considered a redhibitory defect. Materials and Methods: A total of 28 medical records of pets referred with suspected congenital heart disease were examined. All patients aged between 3 and 24 months underwent clinical examination, chest X-ray examination, electrocardiogram, and echocardiography and angiocardiography when necessary. Results: Congenital heart diseases or associated cardiac malformations were confirmed. Considering the above congenital diseases as redhibitory defect and the rights of the owners from a strictly legal viewpoint, 9 owners demanded an estimatory action and 11 a redhibitory action; 1 owner decided to demand the reimbursement of veterinary expenses because the animal died; 7 owners took no legal action but requested surgical intervention. Conclusions: Until more appropriate and detailed legislation on the buying and selling of pet animals is put in place; the authors propose to include in the contract a temporal extension of the guarantee relating to congenital heart disease, which can often become evident later. PMID:28246457
Wald, Rachel M; Sermer, Mathew; Colman, Jack M
Young women with heart disease are increasingly being seen in obstetrical referral centres owing, in large part, to the dramatic improvements in survival of young adults with congenital heart disease in recent years. Although pregnancies in most women with heart disease result in favourable outcomes, there are important exceptions that must be recognized. These exceptions pose significant mortality risk to the mother and/or the fetus. The present article outlines cardiovascular adaptations to pregnancy, general outcomes and management considerations for practitioners caring for pregnant young women with congenital heart disease. A lesion-specific review is published in a complementary article. PMID:22468131
Coran, D L; Rodgers, W B; Keane, J F; Hall, J E; Emans, J B
The strong association between congenital heart disease and spinal deformity is well established, but data on the risks and outcome of spinal fusion surgery in patients with congenital heart disease are scarce. The purpose of this study was to identify predictors of perioperative risk and outcome in a large series of children and adolescents with congenital heart disease who underwent spinal fusion for scoliosis or kyphosis. In the authors' retrospective analysis of 74 consecutive patients with congenital heart disease undergoing spinal fusion, there were two deaths (2.7%) and 18 significant complications (24.3%) in the perioperative period. Preoperative cyanosis (arterial oxygen saturation < 90% at rest) with uncorrected or incompletely corrected congenital heart disease was associated with both deaths. Complications occurred in nine of 18 (50%) patients with cyanosis and in 11 of 56 (20%) patients without cyanosis. As judged by multivariate analysis the best predictors of perioperative outcome were the overall physical status of the patient as represented by the American Society of Anesthesiologists' preoperative score and a higher rate of intraoperative blood loss. Seventeen of 43 patients (40%) with an American Society of Anesthesiologists score of 3 or higher experienced complications including two perioperative deaths. Successful spinal fusion and correction were achieved in 97% of patients. Children and adolescents with congenital heart disease can undergo elective spinal fusion with risks that relate to overall cardiac status. Careful assessment of preoperative status by pediatric cardiologists and cardiac anesthesiologists familiar with surgical treatment of patients with congenital heart disease will assist the orthopaedic surgeon in providing the most realistic estimate of risk.
Gazit, Avihu Z; Canter, Charles E
Congenital heart disease is one of the major diagnoses in pediatric heart transplantation recipients of all age groups. Assessment of pulmonary vascular resistance in these patients prior to transplantation is crucial to determine their candidacy, however, it is frequently inaccurate because of their abnormal anatomy and physiology. This problem places them at significant risk for pulmonary hypertension and right ventricular failure post transplantation. The pathophysiology of pulmonary vascular disease in children with congenital heart disease depends on their pulmonary blood flow patterns, systemic ventricle function, as well as semilunar valves and atrioventricular valves structure and function. In our review we analyze the pathophysiology of pulmonary vascular disease in children with congenital heart disease and end-stage heart failure, and outline the state of the art pre-transplantation medical and surgical management to achieve reverse remodeling of the pulmonary vasculature by using pulmonary vasodilators and mechanical circulatory support. PMID:22548028
Rostol'tsev, K V; Burenkov, R A; Kuz'micheva, I A
Clinico-anatomic observation of autosomal-recessive renal cystic disease and congenital hepatic fibrosis at two fetuses from the same family was done. Mutation of His3124Tyr in 58 exon of PKHD1 gene in heterozygous state was found out. The same pathomorphological changes in the epithelium of cystic renal tubules and bile ducts of the liver were noted. We suggest that the autopsy research of fetuses with congenital abnormalities, detected after prenatal ultrasonic screening, has high diagnostic importance.
den Hollander, Anneke I; Roepman, Ronald; Koenekoop, Robert K; Cremers, Frans P M
Leber congenital amaurosis (LCA) is the most severe retinal dystrophy causing blindness or severe visual impairment before the age of 1 year. Linkage analysis, homozygosity mapping and candidate gene analysis facilitated the identification of 14 genes mutated in patients with LCA and juvenile retinal degeneration, which together explain approximately 70% of the cases. Several of these genes have also been implicated in other non-syndromic or syndromic retinal diseases, such as retinitis pigmentosa and Joubert syndrome, respectively. CEP290 (15%), GUCY2D (12%), and CRB1 (10%) are the most frequently mutated LCA genes; one intronic CEP290 mutation (p.Cys998X) is found in approximately 20% of all LCA patients from north-western Europe, although this frequency is lower in other populations. Despite the large degree of genetic and allelic heterogeneity, it is possible to identify the causative mutations in approximately 55% of LCA patients by employing a microarray-based, allele-specific primer extension analysis of all known DNA variants. The LCA genes encode proteins with a wide variety of retinal functions, such as photoreceptor morphogenesis (CRB1, CRX), phototransduction (AIPL1, GUCY2D), vitamin A cycling (LRAT, RDH12, RPE65), guanine synthesis (IMPDH1), and outer segment phagocytosis (MERTK). Recently, several defects were identified that are likely to affect intra-photoreceptor ciliary transport processes (CEP290, LCA5, RPGRIP1, TULP1). As the eye represents an accessible and immune-privileged organ, it appears to be uniquely suitable for human gene replacement therapy. Rodent (Crb1, Lrat, Mertk, Rpe65, Rpgrip1), avian (Gucy2D) and canine (Rpe65) models for LCA and profound visual impairment have been successfully corrected employing adeno-associated virus or lentivirus-based gene therapy. Moreover, phase 1 clinical trials have been carried out in humans with RPE65 deficiencies. Apart from ethical considerations inherently linked to treating children, major
Dewan, Pooja; Gomber, Sunil; Das, Saurabhi
Congenital tuberculosis is difficult to diagnose unless there is a high index of suspicion. A 2-month-old infant boy presented with a history of fever since birth and failure to thrive. Chest radiograph demonstrated right upper lobe collapse/consolidation and an ultrasonogram of the abdomen showed multiple hypo-echoic hepatic and splenic lesions, and multiple retroperitoneal nodes. Fine needle aspiration of a cervical lymph node detected acid-fast bacilli (AFB). The mother's chest radiograph demonstrated features of pulmonary tuberculosis. Placental histology detected AFB. The combined clinical and laboratory features in both mother and infant supports the diagnosis of congenital tuberculosis.
Bertoletti, Juliana; Marx, Giovana Caroline; Hattge, Sérgio Pedro; Pellanda, Lucia Campos
Advances in cardiac surgery techniques and early diagnosis have enabled the increased survival of individuals with congenital heart disease. The investigation of the quality of life in children and adolescents with congenital heart disease provides complementary information to clinical data that can assist in decision making on the part of health professionals. Although many studies have been conducted to investigate the quality of life of children and adolescents with congenital heart disease, the results prove to be contradictory; while some studies show that congenital heart disease can impact the quality of life, others describe a better perception of quality of life among children and adolescents who suffer from the disease when compared with healthy control subjects. The purpose of this study is to review the literature on the assessment of health related quality of life in children and adolescents with congenital heart disease, in order to systematize the existing knowledge on this topic today. It is observed that research seeks to investigate aspects of personality in cardiac patients, their coping strategies used and perceived social support, aiming at better understanding the association of these variables with the level of quality of life in this population. PMID:24676375
Zhuang, Jian; Chen, Guanchun; Mai, Jinzhuang; Guo, Xiaoling; Ou, Yanqiu; Chen, Jimei; Gong, Wei; Gao, Xiangmin; Wu, Yong; Nie, Zhiqiang
There are 16.5 million newborns in China annually. However, the incidence of congenital heart disease (CHD) has not been evaluated. In 2004, we launched an active province-wide hospital-based CHD registry in the Guangdong Province of southern China. In this study, we examined the incidence of CHD and its subtypes from 2004 to 2012 and compared our findings to the literature. Our results indicate there is an increasing trend of CHD incidence. The increase in incidence occurred mainly for single lesion and the most common subtypes (e.g., ventricular or atrial septal defect, patent ductus arteriosus). There were no increases found for multiple lesions or more complex subtypes. The proportion of CHD cases that were detected early (e.g., 1 week) increased over time. The incidence of CHD stabilized in 2010–2012 with the average cumulative incidences of 9.7, 9.9, and 11.1 per 1,000 live births at 1 week, 1 month, and 1 year, respectively. The incidences of CHD subtypes were comparable with recent international results. The data did not support previous reports that Asian children have a higher incidence of pulmonary outflow obstructions and lower incidence of transposition of the great arteries. However, there was a lower incidence of left ventricular outflow tract obstructions observed in our series. The increase in CHD incidence observed over time was due to improved detection and diagnosis. The true incidence of CHD in China was approximately 11.1 per 1,000 live births, which is higher than previously reported. PMID:27409588
Tchervenkov, Christo I; Jacobs, Jeffrey Phillip; Bernier, Pierre-Luc; Stellin, Giovanni; Kurosawa, Hiromi; Mavroudis, Constantine; Jonas, Richard A; Cicek, Sertac M; Al-Halees, Zohair; Elliott, Martin J; Jatene, Marcelo B; Kinsley, Robin H; Kreutzer, Christian; Leon-Wyss, Juan; Liu, Jinfen; Maruszewski, Bohdan; Nunn, Graham R; Ramirez-Marroquin, Samuel; Sandoval, Nestor; Sano, Shunji; Sarris, George E; Sharma, Rajesh; Shoeb, Ayman; Spray, Thomas L; Ungerleider, Ross M; Yangni-Angate, Hervé; Ziemer, Gerhard
The diagnosis and treatment for paediatric and congenital cardiac disease has undergone remarkable progress over the last 60 years. Unfortunately, this progress has been largely limited to the developed world. Yet every year approximately 90% of the more than 1,000,000 children who are born with congenital cardiac disease across the world receive either suboptimal care or are totally denied care.While in the developed world the focus has changed from an effort to decrease post-operative mortality to now improving quality of life and decreasing morbidity, which is the focus of this Supplement, the rest of the world still needs to develop basic access to congenital cardiac care. The World Society for Pediatric and Congenital Heart Surgery [http://www.wspchs.org/] was established in 2006. The Vision of the World Society is that every child born anywhere in the world with a congenital heart defect should have access to appropriate medical and surgical care. The Mission of the World Society is to promote the highest quality comprehensive care to all patients with pediatric and/or congenital heart disease, from the fetus to the adult, regardless of the patient's economic means, with emphasis on excellence in education, research and community service.We present in this article an overview of the epidemiology of congenital cardiac disease, the current and future challenges to improve care in the developed and developing world, the impact of the globalization of cardiac surgery, and the role that the World Society should play. The World Society for Pediatric and Congenital Heart Surgery is in a unique position to influence and truly improve the global care of children and adults with congenital cardiac disease throughout the world [http://www.wspchs.org/].
Silversides, Candice K; Salehian, Omid; Oechslin, Erwin; Schwerzmann, Markus; Vonder Muhll, Isabelle; Khairy, Paul; Horlick, Eric; Landzberg, Mike; Meijboom, Folkert; Warnes, Carole; Therrien, Judith
With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. They have distinctive forms of heart failure and their cardiac disease can be associated with pulmonary hypertension, thromboemboli, complex arrhythmias and sudden death. Medical aspects that need to be considered relate to the long-term and multisystemic effects of single ventricle physiology, cyanosis, systemic right ventricles, complex intracardiac baffles and failing subpulmonary right ventricles. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. Part III of the guidelines includes recommendations for the care of patients with complete transposition of the great arteries, congenitally corrected transposition of the great arteries, Fontan operations and single ventricles, Eisenmenger's syndrome, and cyanotic heart disease. Topics addressed include genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy risk and follow-up requirements. The complete document consists of four manuscripts, which are published online in the present issue of The Canadian Journal of Cardiology. The complete document and references can also be found at www.ccs.ca or www.cachnet.org.
Swischuk, L.E.; Sapire, D.W.
The book retains its previous format with chapters on embryology, plain film interpretation, classification of pulmonary vascular patterns, cardiac malpositions and vascular anomalies, and illustrative cases. The book is organized with an abundance of illustrative figures, diagrams, and image reproductions. These include plain chest radiographs, angiograms, echocardiograms, and MR images. The authors present the pathophysiology and imaging of congenital heart lesions.
Jensen, A S; Idorn, L; Nørager, B; Vejlstrup, N; Sondergaard, L
Adults with congenital heart disease are a growing population. One of the major challenges in the care of these patients is to prevent thromboembolic episodes. Despite relative young age and no typical cardiovascular risk factors, this cohort has a high prevalence of thrombotic events. It is difficult to use treatment algorithms from the general adult population with acquired heart disease in this heterogeneous population due to special conditions such as myocardial scarring after previous surgery, atypical atrial flutter, prothrombotic conditions and the presence of interatrial shunts. Furthermore, there is a lack of scientific evidence regarding how to prevent thromboembolic events with anticoagulation in adults with congenital heart disease. The aim of this paper is to review the current literature pertaining to anticoagulation in adults with congenital heart disease and hence enable recommendations for which patients are likely to benefit from which anticoagulation treatments, when they should be considered and how these would be carried out.
Torniainen, Suvi; Savilahti, Erkki; Järvelä, Irma
Congenital lactase deficiency belongs to the Finnish Disease Heritage and is a recessively inherited diarrheal disease of the newborn, in which the activity of the lactase enzyme of the epithelial cells of the small intestine is very low ever since the birth. For the newborn infant, ingestion of lactose causes symptoms so severe that breastfeeding is not possible. Untreated disease leads to dehydration that usually requires hospitalization. Congenital lactase deficiency is caused by mutations in the gene coding for the lactase enzyme (LCT). Seven mutations in a total of 43 patients have been found in Finland so far.
Baggen, Vivan J M; Eindhoven, Jannet A; van den Bosch, Annemien E; Witsenburg, Maarten; Cuypers, Judith A A E; Langstraat, Jannette S; Boersma, Eric; Roos-Hesselink, Jolien W
Context Matrix metalloproteinases (MMPs) are associated with diastolic dysfunction and heart failure in acquired heart disease. Objective To investigate the role of MMPs as novel biomarkers in clinically stable adults with congenital heart disease. Methods We measured serum MMP-2, -3, -9 and tissue inhibitor of matrix metalloproteinase-1 in 425 patients and analysed the association with cardiac function and exercise capacity. Results MMP-2 was significantly associated with exercise capacity, ventilatory efficiency and left ventricular deceleration time, independently of age, sex, body surface area and NT-proBNP. Conclusion MMP-2 may provide new information in the clinical evaluation of adults with congenital heart disease.
Peterson, Cora; Ailes, Elizabeth; Riehle-Colarusso, Tiffany; Oster, Matthew E.; Olney, Richard S.; Cassell, Cynthia H.; Fixler, David E.; Carmichael, Suzan L.; Shaw, Gary M.; Gilboa, Suzanne M.
IMPORTANCE Critical congenital heart disease (CCHD) was added to the Recommended Uniform Screening Panel for Newborns in the United States in 2011. Many states have recently adopted or are considering requirements for universal CCHD screening through pulse oximetry in birth hospitals. Limited previous research is directly applicable to the question of how many US infants with CCHD might be identified through screening. OBJECTIVES To estimate the proportion of US infants with late detection of CCHD (>3 days after birth) based on existing clinical practice and to investigate factors associated with late detection. DESIGN, SETTING, AND PARTICIPANTS Descriptive and multivariable analysis. Data were obtained from a multisite population-based study of birth defects in the United States, the National Birth Defects Prevention Study (NBDPS). We included all live-born infants with estimated dates of delivery from January 1, 1998, through December 31, 2007, and nonsyndromic, clinically verified CCHD conditions potentially detectable through screening via pulse oximetry. MAIN OUTCOMES AND MEASURES The main outcome measure was the proportion of infants with late detection of CCHD through echocardiography or at autopsy under the assumption that universal screening at birth hospitals might reduce the number of such late diagnoses. Secondary outcome measures included prevalence ratios for associations between selected demographic and clinical factors and late detection of CCHD. RESULTS Of 3746 live-born infants with nonsyndromic CCHD, late detection occurred in 1106 (29.5% [95%CI, 28.1%–31.0%]), including 6 (0.2%) (0.1% –0.4%) first receiving a diagnosis at autopsy more than 3 days after birth. Late detection varied by CCHD type from 9 of 120 infants (7.5%[95%CI, 3.5%–13.8%]) with pulmonary atresia to 497 of 801 (62.0% [58.7%–65.4%]) with coarctation of the aorta. In multivariable analysis, late detection varied significantly by CCHD type and study site, and infants with
Zühlke, Liesl; Mirabel, Mariana; Marijon, Eloi
Africa has one of the highest prevalence of heart diseases in children and young adults, including congenital heart disease (CHD) and rheumatic heart disease (RHD). We present here an extensive review of recent data from the African continent highlighting key studies and information regarding progress in CHD and RHD since 2005. Main findings include evidence that the CHD burden is underestimated mainly due to the poor outcome of African children with CHD. The interest in primary prevention for RHD has been recently re-emphasised, and new data are available regarding echocardiographic screening for subclinical RHD and initiation of secondary prevention. There is an urgent need for comprehensive service frameworks to improve access and level of care and services for patients, educational programmes to reinforce the importance of prevention and early diagnosis and a relevant research agenda focusing on the African context.
Alabdulgader, A A A
To provide an overview of the epidemiology of congenital heart disease, the results of epidemiological studies done in 4 regions of Saudi Arabia (August 1988-February 2000) and 2604 individuals with congenital heart disease were evaluated. Ventricular septal defect was the commonest lesion (33.9%) followed by atrial septal defect (18.1%). Overall, sex distribution was similar; for 3 conditions, more males than females were affected. Of 2269 (59%) presenting in the first year of life, 566 (24.9%) had neonatal congenital heart disease. Down syndrome was the commonest cause. Distribution of specific lesions and sex distribution was similar to findings from other parts of the world; however, the overall detection rate at 1 year of age was lower.
Baltaxe, H.A.; Mooring, P.; Kugler, J.; Pinsky, W.; Chu, W.K.
Twenty patients under the age of 2 years with suspected congenital heart disease received alternately Renografin 76 and metrizamide for angiocardiography. The dose was 2.0 ml/kg per injection for both contrast media into the left ventricle. Metrizamide induced slightly lesser change in heart rate, peak systolic pressure, and peak end-diastolic pressures. Serum osmolality, hematocrit, and serum electrolytes were affected equally by the contrast media. Metrizamide was well tolerated by the neonates with congenital heart disease and its radiopacity was adequate for diagnostic purposes. At the doses administered, metrizamide does not seem to have any great advantage over Renografin 76 for angiocardiography in infants with severe congenital heart disease.
van der Bom, Teun; Luijendijk, Paul; Bouma, Berto J; Koolbergen, Dave R; de Groot, Joris R; Mulder, Barbara J M; Mulder, Barbara B J
Adults with congenital heart disease form a new and relatively young population, since surgical treatment of heart defects became available three to four decades ago. Owing to improved survival this population is steadily growing in number and age. Little is known regarding long-term survival; however, late complications occur frequently. During adulthood, almost half of the patients have one or more complication, such as endocarditis, stroke, systemic or pulmonary hypertension, aortic aneurysm or dissection and arrhythmias. Heart failure and sudden cardiac death are the main causes of death. Treatment of adults with congenital heart disease is aimed at the reduction of symptoms, but also at minimizing the risk and severity of late complications. In this article the most recent advances in the treatment of congenital heart disease will be discussed. The main focus of the article will be on pharmacological, interventional and surgical interventions that reduce the risk of heart failure, arrhythmias, vascular complications, pulmonary hypertension and endocarditis.
Korenburg, J.R. ); Bradley, C.; Disteche, C.M. )
Down syndrome (DS) is a major cause of congenital heart and gut disease and mental retardation. DS individuals also have characteristic facies, hands, and dermatoglyphics, in addition to abnormalities of the immune system, and increased risk of leukemia, and an Alzheimer-like dementia. Although their molecular basis is unknown, recent work on patients with DS and partial duplications of chromosome 21 has suggested small chromosomal regions located in band q22 that are likely to contain the genes for some of these features. The authors now extend these analyses to define molecular markers for the congenital heart disease, the duodenal stenosis, and an 'overlap' region for the facial and some of the skeletal features. They report the clinical, cytogenetic, and molecular analysis of two patients. These studies provide the molecular basis for the construction of a DS phenotypic map and focus the search for genes responsible for the physical features, congenital heart disease, and duodenal stenosis of DS.
Cervantes-Salazar, Jorge; Curi-Curi, Pedro; Ramírez-Marroquín, Samuel; Calderón-Colmenero, Juan; Munoz-Castellanos, Luis
Based on the sequentiality principle, this review proposes a practical method that allows the systematization of the anatomic diagnosis of congenital heart disease. We emphasize the need to use sequential connection between the different cardiac segments: atria, ventricles and great arteries. Five ordered steps are defined, which include determination of atrial situs and of the connection features between the ventricles and the great arteries. Related lesions and some additional special features are a second stage in the sequential analysis of congenital heart disease, which is also important for the integral diagnosis.
Asp, Ann; Bratt, Ewa-Lena; Bramhagen, Ann-Cathrine
More than 90% of children born with congenital heart disease survive into adulthood due to successes of cardiac surgery and medical management. Interviews with 16 young adults with congenital heart disease to explore their experiences of transfer from pediatric to adult care were performed. The analysis identified five themes; Feeling secure during the transfer process, Experiencing trust in the care, Expecting to be involved, Assuming responsibility for one's health is a process and Lack of knowledge leads to uncertainty. In conclusion; a structured and gradual transfer process was necessary to enable the informants to shoulder the responsibility for self-care.
Frascaroli, G; Fucà, A; Buda, S; Gargiulo, G; Pace, C
The incidence of congenital heart diseases accounts for 8-10 over 1000 liveborn. In Italy about 4000-4500 babies each year are born with congenital heart diseases; 50% of those babies (2000-2200) need cardiac surgery shortly after birth or within the first few months of life. Of the remaining 50%, half undergoes cardiac surgery later on in life and half does not necessitate any surgery; 30% of all cardiac operations consist of palliative procedures and the remaining 70% consist of one-stage corrective procedures. Improvements achieved both in surgical and anesthesiologic techniques, and in cardiopulmonary bypass and myocardial protection, have led to better results in pediatric cardiac surgery, with excellent long term survival rate, even for the more complex variants of congenital heart malformations. Therefore anesthesiologists are now more often required to deal with patients affected by congenital heart defects, for other than cardiac problems. Accurate investigation of patient's clinical history is strongly suggested. Moreover knowledge and familiarity with the modifications of the physiology, occurring in congenital heart disease patients, are mandatory for the choice of the more appropriate anesthesiologic strategy for each patient, in order to optimise the risk-benefits ratio and achieve a less traumatic impact on the cardio-circulatory and respiratory equilibrium. With the aim of achieving better results, interaction between anesthesiologist, cardiologist, pediatrician, surgeon and sometime neonatologist and cardiac surgeon, is strongly recommended in the evaluation of risks, and in decision making of strategies and timing of treatment.
Report from The International Society for Nomenclature of Paediatric and Congenital Heart Disease: cardiovascular catheterisation for congenital and paediatric cardiac disease (Part 2 - Nomenclature of complications associated with interventional cardiology).
Bergersen, Lisa; Giroud, Jorge Manuel; Jacobs, Jeffrey Phillip; Franklin, Rodney Cyril George; Béland, Marie Josée; Krogmann, Otto Nils; Aiello, Vera Demarchi; Colan, Steven D; Elliott, Martin J; Gaynor, J William; Kurosawa, Hiromi; Maruszewski, Bohdan; Stellin, Giovanni; Tchervenkov, Christo I; Walters, Henry Lane; Weinberg, Paul; Everett, Allen Dale
Interventional cardiology for paediatric and congenital cardiac disease is a relatively young and rapidly evolving field. As the profession begins to establish multi-institutional databases, a universal system of nomenclature is necessary for the field of interventional cardiology for paediatric and congenital cardiac disease. The purpose of this paper is to present the results of the efforts of The International Society for Nomenclature of Paediatric and Congenital Heart Disease to establish a system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease, focusing both on procedural nomenclature and the nomenclature of complications associated with interventional cardiology. This system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease is a component of The International Paediatric and Congenital Cardiac Code. This manuscript is the second part of the two-part series. Part 1 covered the procedural nomenclature associated with interventional cardiology as treatment for paediatric and congenital cardiac disease. Part 2 will cover the nomenclature of complications associated with interventional cardiology as treatment for paediatric and congenital cardiac disease.
The aim of the author is to discuss special issues of rare diseases, with emphasis on circumstances present in Hungary, including those leading to the foundation of the non-governmental organization, the Hungarian Federation of People with Rare and Congenital Diseases. The author briefly reviews the most important findings of current international surveys which have been performed with or without the involvement of member associations of the Hungarian Federation of People with Rare and Congenital Diseases. At the level of medical and social services in Hungary, it is still "incidental" to get to the appropriate expert or centre providing the diagnosis or treatment. It is difficult to find the still very few existing services due to the lack of suitable "pathways" and referrals. There are long delays in obtaining the first appointment, resulting in vulnerability and inequality along the regions. The overall consequence is the insufficiency or lack of access to medical and social services. There are also difficulties related to the supply of orphan medication and the long duration of hospitalization. At the level of patient organizations financial scarcity and uncertainty are typical, combined with inappropriate infrastructural background and human resources. The poor quality of organization of patient bodies along with insufficient cooperation among them are characteristic as well. The author concludes that a National Plan or Strategy is needed to improve the current fragmentation of services which would enable patients and health, social and educational professionals to provide and use the best care in the practice. This would ensure all patients with rare diseases to be diagnosed within a possible shortest time allowing access to the care and support needed in time resulting in a decrease in burden of families and society.
Trujillo-Honeysberg, Mónica; Diazgranados-Cuenca, Lucy
Although tuberculosis is highly prevalent worldwide, congenital tuberculosis is one of the least common manifestations of the disease. The diagnosis is usually difficult because of the non-specific clinical presentation and the lack of awareness of maternal disease prior to pregnancy and delivery. We present the case of a preterm neonate with congenital tuberculosis, born to a previously healthy mother who had developed severe disseminated tuberculosis during her pregnancy. Once the diagnosis was confirmed in the mother, the congenital infection was confirmed by isolation of Mycobacterium tuberculosis in gastric aspirates, and positive polymerase chain reaction in a cerebrospinal fluid examination. Treatment for tuberculosis with a four-drug regimen resulted in an adequate clinical response in both the mother and infant. PMID:26508944
Salam, Alex P; Rojek, Amanda; Dunning, Jake; Horby, Peter W
Zika virus (ZIKV) infection in pregnancy is associated with adverse fetal outcomes, such as microcephaly and other congenital malformations. No therapeutic options are available to pregnant women with ZIKV infection to prevent these effects. Drug trials in pregnancy raise several scientific, ethical, and logistical challenges, which are compounded further in ZIKV because of limited knowledge of the disease pathophysiology and a product development pipeline in its infancy. We evaluate the major challenges in choosing therapeutics to prevent congenital ZIKV disease and conducting clinical trials of these treatments, with a focus on preventing congenital central nervous system malformations. These challenges must be characterized and planned for now so that clinical trials can progress expediently and effectively in the future.
Motasaddi Zarandy, Masoud; Mahmoudi, Mohammad Jafar; Malekzadeh, Iran; Nasirmohtaram, Sevil
Introduction: Hearing impairment is the most frequent sensorial congenital defect in newborns and has increased to 2–4 cases per 1,000 live births. Sensory-neural hearing loss (SNHL) accounts for more than 90% of all hearing loss. This disorder is associated with other congenital disorders such as renal, skeletal, ocular, and cardiac disorders. Given that congenital heart diseases are life-threatening, we decided to study the frequency of congenital heart diseases in children with congenital sensory-neural deafness. Materials and Methods: All children who had undergone cochlear implantation surgery due to SNHL and who had attended our hospital for speech therapy during 2008–2011 were evaluated by Doppler echocardiography. Results: Thirty-one children (15 boys and 16 girls) with a mean age of 55.70 months were examined, and underwent electrocardiography (ECG) and echocardiography. None of the children had any signs of heart problems in their medical records. Most of their heart examinations were normal, one patient had expiratory wheeze, four (12%) had mid-systolic click, and four (12%) had an intensified S1 sound. In echocardiography, 15 children (46%) had mitral valve prolapse (MVP) and two (6%) had minimal mitral regurgitation (MR). Mean ejection fraction (EF) was 69% and the mean fractional shortening (FS) was 38%. Conclusion: This study indicates the need for echocardiography and heart examinations in children with SNHL. PMID:27280096
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
Moola, Fiona; Faulkner, Guy E. J.; Kirsh, Joel A.; Kilburn, Jennifer
This study explored perceptions toward physical activity and sport in the lives of youth with congenital heart disease. Thirteen cardiac participants were interviewed in the presence of their parents, and a process of inductive analysis was conducted. Sport was not considered a valued pursuit despite the belief that it is essential for the…
Johnson, Beena; Francis, Johnson
Major physical illnesses usually have an impact on the psychological well-being of any individual. An illness of early onset, with necessity of frequent diagnostic and therapeutic interventions can adversely affect the emotional balance and behavioural adaptation of children and adolescents. This is applicable for congenital heart disease,…
Wallgren, C G; Kretzschmar, G; Zetterqvist, P
Twenty-three patients have been studied by exercise testing during right heart catheterization. Cardiac output was measured by the earpiece densitometric technique before, during and after the exercise period. It is concluded that the earpiece densitometric technique in conjunction with exercise testing offers an attractive alternative for the study of pressure and flow characteristics in children with congenital heart disease.
Schleich, Jean-Marc; Schnell, Frédéric; Brouant, Benoît; Phan, Gerald; Lafay, Vincent; Bonnemains, Laurent; Bédossa, Marc
The number of recreational scuba divers is steadily increasing. In its latest recommendations, the French Federation of Undersea Studies and Sports listed congenital heart disease as a formal and final contraindication to scuba diving. On the other hand, with the progress made in their management, the prognosis and quality of life of patients with congenital heart diseases have improved considerably, enabling them to engage in physical and sports endeavours, which are known to confer general health and psychological benefits. As a consequence, the ability of these patients to dive has become a regular and recurrent issue. We review the various types of scuba diving, the physical performance required for its practice, its effects on cardiovascular function and the elements that need to be considered before recommending whether it can be practiced safely at various levels of difficulty. Because of the diversity and broad heterogeneity of congenital heart diseases, a detailed evaluation of each patient's performance based on clinical criteria common to all congenital heart diseases is recommended.
Cardiac disease is the most common congenital defect in children, affecting between 3 and 10 in every 1000 live births. While significant advances in medical and surgical management have resulted in increasing numbers of survivors, it is also recognized that there is a growing population of children living with neurological impairment and lowered…
The purpose of this study was to explore the transition process in congenital heart disease (CHD) care through the perceived needs and concerns of adolescents (pretransition) and the experiential insight from adults (post-transition), in order to inform future transition initiatives and information ...
McGrath, K A; Truesdell, S C
Employability is an important issue for adolescents and young adults with congenital heart disease. This article provides an overview of specific federal laws that protect these individuals and information about state vocational rehabilitation programs. Guidelines are provided to help health care providers counsel their patients more effectively.
Aykanat, Alper; Yavuz, Taner; Özalkaya, Elif; Topçuoğlu, Sevilay; Ovalı, Fahri; Karatekin, Güner
Prostaglandin E1 is crucial for keeping the patent ductus arteriosus in critical congenital heart disease for the survival and palliation of particularly prematurely born babies until a cardiosurgical intervention is available. In this study, the side effects of prostaglandin E1 in newborns with critical congenital heart disease and clinical outcomes were evaluated. Thirty-five newborns diagnosed with critical congenital heart disease were treated with prostaglandin E1 between January 2012 and September 2014 at our hospital. Patient charts were examined for prostaglandin E1 side effects (metabolic, gastric outlet obstruction, apnea), clinical status, and prognosis. Acquired data were analyzed in the SPSS 20.0 program. Patients with birth weight under 2500 g needed more days of prostaglandin E1 infusion than ones with birthweight over 2500 g (P = 0.016). The ratio of patients with birth weight under 2500 g who received prostaglandin E1 longer than 7 days was higher than the patients with birth weight over 2500 g (P = 0.02). Eighteen side effects were encountered in 11 of 35 patients (31%). Of these side effects, 1 patient had 4, 4 patients had 2, and 6 patients had only 1 side effect. Discontinuation of the therapy was never needed. Prostaglandin E1 is an accepted therapy modality for survival and outcome in critical congenital heart disease in particularly low-birth-weight babies until a surgical intervention is available. Side effects are not less encountered but are almost always manageable, and discontinuation is not needed.
Long, Suzanne H.; Eldridge, Bev J.; Galea, Mary P.; Harris, Susan R.
Infants with congenital heart disease (CHD) that is severe enough to require early surgery are at risk for cognitive and motor delays, as well as musculoskeletal impairments, and are best managed by an interdisciplinary team during their hospital stay and after discharge. The purpose of this article is to review some of the risk factors associated…
Ozmen, Ayten; Terlemez, Semiha; Tunaoglu, Fatma Sedef; Soysal, Sebnem; Pektas, Ayhan; Cilsal, Erman; Koca, Ulker; Kula, Serdar; Deniz Oguz, Ayse
Background: The rate of congenital heart disease is 0.8% in all live births. The majority of this, however, is acyanotic congenital heart disease. The survival rate of children with cardiac disease has increased with the developments provided in recent years and their lifetime is extended. Objectives: This study aims to evaluate neurodevelopment of children with uncomplicated acyanotic congenital heart disease in preschool period and determine the factors affecting their neurodevelopmental process. Patients and Methods: 132 children with acyanotic congenital heart disease aged 6 - 72 months were involved in the study. Mental development and intelligence levels of patients under 2 years old were assessed by using Bayley Development Scale-III, and Stanford Binet Intelligence test was employed for patients over 2 years old. Denver Developmental Screening Test II was applied to all patients for their personal-social, fine motor, gross motor and language development. Results: The average age of patients (67 girls, 65 boys) included in the study was 35.2 ± 19.6 months. It was determined that there were subnormal mental level in 13 (10%) patients and at least one specific developmental disorder in 33 (25%) patients. Bayley Mental Development Scale score of patients who had received incubator care in perinatal period was found significantly low (88 ± 4.2) compared to those with no incubator care (93.17 ± 8.5) (P = 0.028). Low educational level of father was established to be linked with low mental development scores at the age of 2 and following that age (P < 0.05). Iron deficiency anemia was discovered to be related to low psychometric test scores at every age (P < 0.05). Conclusions: Neurodevelopmental problems in children with acyanotic congenital heart disease were found higher compared to those in society. Mental development and intelligence levels of patients were determined to be closely associated with receiving incubator care, father’s educational level and
The size of the national population of patients with grown-up congenital heart disease (GUCH) is uncertain, but since 80–85% of patients born with congenital heart disease now survive to adulthood (age 16 years), an annual increase of 2500 can be anticipated according to birth rate. Organisation of medical care is haphazard with only three of 18 cardiac surgical centres operating on over 30 cases per annum and only two established specialised units fully equipped and staffed. Not all grown-ups with congenital heart disease require the same level of expertise; 20–25% are complex, rare, etc, and require life long expert supervision and/or intervention; a further 35–40% require access to expert consultation. The rest, about 40%, have simple or cured diseases and need little or no specialist expertise. The size of the population needing expertise is small in comparison to coronary and hypertensive disease, aging, and increasing in complexity. It requires expert cardiac surgery and specialised medical cardiology, intensive care, electrophysiology, imaging and interventions, "at risk" pregnancy services, connection to transplant services familiar with their basic problem, clinical nurse specialist advisors, and trained nurses. An integrated national service is described with 4–6 specialist units established within adult cardiology, ideally in relation or proximity to university hospital/departments in appropriate geographic location, based in association with established paediatric cardiac surgical centres with designated inpatient and outpatient facilities for grown-up patients with congenital heart disease. Specialist units should accept responsibility for educating the profession, training the specialists, cooperative research, receiving patients "out of region", sharing particular skills between each other, and they must liaise with other services and trusts in the health service, particularly specified outpatient clinics in district and regional centres. Not
Jacobs, Jeffrey P; Wernovsky, Gil; Elliott, Martin J
This review discusses the historical aspects, current state of the art, and potential future advances in the areas of nomenclature and databases for the analysis of outcomes of treatments for patients with congenitally malformed hearts. We will consider the current state of analysis of outcomes, lay out some principles which might make it possible to achieve life-long monitoring and follow-up using our databases, and describe the next steps those involved in the care of these patients need to take in order to achieve these objectives. In order to perform meaningful multi-institutional analyses, we suggest that any database must incorporate the following six essential elements: use of a common language and nomenclature, use of an established uniform core dataset for collection of information, incorporation of a mechanism of evaluating case complexity, availability of a mechanism to assure and verify the completeness and accuracy of the data collected, collaboration between medical and surgical subspecialties, and standardised protocols for life-long follow-up. During the 1990s, both The European Association for Cardio-Thoracic Surgery and The Society of Thoracic Surgeons created databases to assess the outcomes of congenital cardiac surgery. Beginning in 1998, these two organizations collaborated to create the International Congenital Heart Surgery Nomenclature and Database Project. By 2000, a common nomenclature, along with a common core minimal dataset, were adopted by The European Association for Cardio-Thoracic Surgery and The Society of Thoracic Surgeons, and published in the Annals of Thoracic Surgery. In 2000, The International Nomenclature Committee for Pediatric and Congenital Heart Disease was established. This committee eventually evolved into the International Society for Nomenclature of Paediatric and Congenital Heart Disease. The working component of this international nomenclature society has been The International Working Group for Mapping and Coding
Martins da Silva, Viviane; de Oliveira Lopes, Marcos Venícios; Leite de Araujo, Thelma
The purpose of this study was to evaluate the correlation between anthropometric measures of children with congenital heart disease with percentiles that represent their growth indicators. Anthropometric evaluations of 135 hospitalized children with congenital heart disease were performed in a hospital specialized in cardiac diseases in Fortaleza, CE, Brazil. For the growth evaluation, percentiles of height by age, weight by height and weight by age were calculated. Children's average age was 4.74 months (+ 3.78) and 66.7% of the children were male. The medians of the three percentiles presented values below percentile 10, indicating a high proportion of values considered of risk. The subscapular thickness presented positive correlation with the three percentiles. The values of percentiles studied indicated growth delay.
Iwańczak, Barbara; Kosmowska-Miśków, Agnieszka; Jamer, Tatiana; Patkowski, Dariusz
A case of a 4.5-year-old girl from a twin pregnancy, who was diagnosed after birth with the congenital esophageal atresia (type 3), and at the age of 4 with the potential coeliac disease. Congenital esophageal atresia was successfully treated surgically in infancy with the thoracoscopic method. The potential coeliac disease was detected in the child with a correct histopathological examination of intestinal villi and showing no enteropathy symptoms based on the presence of antibodies against tissue transglutaminase and against endomysial antibodies of smooth muscles in serum and the presence of HLA DQ2.5. In the treatment of the potential coeliac disease the girl followed a gluten-free diet.
Fassl, Jens; Tobler, Daniel; Zumofen, Daniel; Steiner, Luzius A.; Goettel, Nicolai
We report the case of a 39-year-old male with complex cyanotic congenital heart disease undergoing emergency craniotomy for a cerebral abscess. Maintenance of intraoperative hemodynamic stability and adequate tissue oxygenation during anesthesia may be challenging in patients with cyanotic congenital heart disease. In this case, we decided to perform the surgery as an awake craniotomy after interdisciplinary consensus. We discuss general aspects of anesthetic management during awake craniotomy and specific concerns in the perioperative care of patients with congenital heart disease. PMID:27928498
Pasquali, Sara K; Jacobs, Jeffrey P; Farber, Gregory K; Bertoch, David; Blume, Elizabeth D; Burns, Kristin M; Campbell, Robert; Chang, Anthony C; Chung, Wendy K; Riehle-Colarusso, Tiffany; Curtis, Lesley H; Forrest, Christopher B; Gaynor, William J; Gaies, Michael G; Go, Alan S; Henchey, Paul; Martin, Gerard R; Pearson, Gail; Pemberton, Victoria L; Schwartz, Steven M; Vincent, Robert; Kaltman, Jonathan R
The National Heart, Lung, and Blood Institute convened a working group in January 2015 to explore issues related to an integrated data network for congenital heart disease research. The overall goal was to develop a common vision for how the rapidly increasing volumes of data captured across numerous sources can be managed, integrated, and analyzed to improve care and outcomes. This report summarizes the current landscape of congenital heart disease data, data integration methodologies used across other fields, key considerations for data integration models in congenital heart disease, and the short- and long-term vision and recommendations made by the working group.
von Rhein, Michael; Buchmann, Andreas; Hagmann, Cornelia; Huber, Reto; Klaver, Peter; Knirsch, Walter; Latal, Beatrice
Patients with complex congenital heart disease are at risk for neurodevelopmental impairments. Evidence suggests that brain maturation can be delayed and pre- and postoperative brain injury may occur, and there is limited information on the long-term effect of congenital heart disease on brain development and function in adolescent patients. At a mean age of 13.8 years, 39 adolescent survivors of childhood cardiopulmonary bypass surgery with no structural brain lesions evident through conventional cerebral magnetic resonance imaging and 32 healthy control subjects underwent extensive neurodevelopmental assessment and cerebral magnetic resonance imaging. Cerebral scans were analysed quantitatively using surface-based and voxel-based morphometry. Compared with control subjects, patients had lower total brain (P = 0.003), white matter (P = 0.004) and cortical grey matter (P = 0.005) volumes, whereas cerebrospinal fluid volumes were not different. Regional brain volume reduction ranged from 5.3% (cortical grey matter) to 11% (corpus callosum). Adolescents with cyanotic heart disease showed more brain volume loss than those with acyanotic heart disease, particularly in the white matter, thalami, hippocampi and corpus callosum (all P-values < 0.05). Brain volume reduction correlated significantly with cognitive, motor and executive functions (grey matter: P < 0.05, white matter: P < 0.01). Our findings suggest that there are long-lasting cerebral changes in adolescent survivors of cardiopulmonary bypass surgery for congenital heart disease and that these changes are associated with functional outcome.
Causes of pulmonary arterial hypertension (PAH) are similar in adults and children. The main difference is that PAH secondary to congenital heart diseases, is the predominant cause in pediatric patients. Persistent pulmonary hypertension of the newborn shows completely different clinical course and pathophysiological mechanisms. It is usually seen in full term babies with a high morbidity and mortality rate. Improved prognosis has been reported with inhaled nitric oxide (NO) and extracorporeal membrane oxygenation therapy in babies hospitalized in well equipped and experienced newborn centers. Primary pulmonary hypertension and familial pulmonary hypertension are rare in pediatric age group because the diagnosis is initially made in adolescence. The incidence of PAH secondary to congenital heart disease is estimated as 1.6 - 12.5 case/million/year. Eisenmenger syndrome is diagnosed in 1% of patients with PAH. Patients with left to right shunts are the main group who develop pulmonary vascular disease if not treated in the early infancy. Some cyanotic congenital heart diseases are also the causes of PAH. The best treatment of patients at risk for the development of pulmonary vascular disease is prevention by early surgical elimination of defects or repairing the anatomy. Treatment options with vasodilating agents like NO, prostaglandin analogs, phosphodiesterase -5 inhibitors and endothelin receptor antagonists are used to improve survival and quality of life. Heart lung or bilateral lung transplantation is the only surgical option for many of these patients. Results of national and international registries will bring valuable epidemiological and prognostic perspectives to pediatric PAH.
Harada, M; Akagi, H; Tsuda, T; Kizaki, T; Ohno, H
A total of 151 umbilical cords during the period from 1950 to 1969 were collected from the residents of the Minamata area (including 25 patients with congenital Minamata disease) for methylmercury (MeHg) analysis. When the MeHg discharge from the Chisso Company's Minamata factory into the Minamata Bay is compared with the incidence of congenital Minamata disease, the abrupt increase of the former in 1952 [Nishimura H. Chem. Today 1998;323:60-66] was found to precede that of the latter by approximately 2 years, thereby indicating that MeHg is the cause of the disaster. This was confirmed by the elevated levels of MeHg in the umbilical cords from residents of the Minamata area [from 0.35 +/- 0.30 (S.D.) ppm in 1952 to 0.96 +/- 0.75 ppm in 1955], the MeHg levels (1.60 +/- 1.00 ppm) in the cords from patients with congenital Minamata disease showing the highest values [P < 0.01 vs. acquired Minamata disease (0.72 +/- 0.65 ppm), mental retardation (0.74 +/- 0.64 ppm), other diseases (0.22 +/- 0.15 ppm), and no symptoms (0.28 +/- 0.20 ppm), respectively]. Thus, in order to fill a gap, which extends over a long period of time, in studies on environmental Hg pollution, umbilical cord samples were considered to be a useful tool.
Valenzuela, David M; Ordovas, Karen G
Improved surgical and medical therapy have prolonged survival in patients with congenital heart disease (CHD) such that general medical conditions like coronary artery disease (CAD) are now the main determinants of mortality. A summary of the association of CAD with CHD, as well as a discussion of the radiologic evaluation of the coronary arteries in adults with CHD is described herein. Cross sectional imaging to evaluate CAD in adults with CHD should follow the same appropriateness criteria as gender and aged matched patients without CHD. Coronary CT imaging may be particularly valuable in evaluating the coronary arteries in this patient population as invasive coronary angiography may prove challenging secondary to complicated or unconventional anatomy of the coronary arteries. Further, typical methods for evaluating CAD such as stress or echocardiography may be impractical in adults with CHD. Finally, delineating the anatomic relationship of the coronary arteries and their relationship with the sternum, chest wall, conduits, grafts, and valves is highly recommended in patients with CHD prior to reintervention to avoid iatrogenic complications.
Hasserius, Johan; Hedbys, Josefine
Purpose. Congenital heart disease (CHD) is reported to be associated with Hirschsprung disease (HD). The aim was to evaluate any differences between children with HD with and without CHD, respectively, with regard to patient characteristics, medical care, and patient reported bowel function. Method. This is a retrospective chart study and a cross-sectional long-term follow-up of patients older than 4 years old, including all children with HD operated on with transanal endorectal pull-through (TERPT) at a tertiary center of pediatric surgery. Information about patient characteristics, diagnostics, surgery, and medical care was compiled. At long-term follow-up, bowel function was assessed by Bowel Function Score. Results. Included were 53 HD-patients, 13 with CHD and 40 without CHD. Children with CHD more commonly presented with failure to thrive; 4 (23%) compared to those without CHD (0%) (p < 0.01). In the long-term follow-up, including 32 patients (6 with CHD), constipation was more commonly reported by children with CHD 5 (83%) than by children without CHD 4 (27%) (p = 0.01). No differences were shown in the other parameters such as fecal control and incontinence. Conclusion. HD-patients with CHD more commonly presented with failure to thrive and more frequently reported constipation than HD-patients without CHD. The findings indicate that HD-patients with CHD might need special consideration in their initial care and long-term follow-up. PMID:28373976
Demirpençe, Savaş; Demirpençe, Banu İnce; Meşe, Timur; Arslanoğlu, Sertaç; Tavlı, Vedide; Çalkavur, Şebnem; Olukman, Özgür; Firuzan, Ali Rıza
Aim: In this study, we aimed to evaluate the postnatal problems of infants of mothers with pregestational and gestational diabetes and the clinical properties of infants who were found to have congenital cardiac disease. Material and Methods: We retrospectively examined the records of 337 newborns who were followed up with a diagnosis of infant of diabetic mother between January 2010 and January 2012 in our Neonatology Unit. The demographic data of the diabetic mothers and their babies, the postnatal problems of the babies of diabetic mothers and congenital heart diseases found on transthoracic echocardiography were examined. Results: The patients were classified as group A, B and C in accordance with the recommendations of The American Congress of Obstetricians and Gynecologists (ACOG) according to the type of diabetes. The most common postnatal problems included hyperbilirubinemia, respiratory distress, hypoglycemia and hypocalcemia. The rate of congenital heart disease was found be 17.3% in group A, 50% in group B and 9% in group C. No correlation was found between congenital heart disease and gender, multiple pregnancy, diabetes type, diet treatment, use of oral antidiabetic drugs and drug usage. A positive significant correlation was found between congenital heart disease and genetic disease, murmur, cyanosis and presence of gestational hypertension. It was shown that use of insulin, genetic disease and presence of gestational diabetes increased the risk of congenital heart disease. Conclusions: In our study, the overall incidence of congenital heart disease was found to be 24% in infants of diabetic mothers. It should be kept in mind that it is important to investigate the infants of mothers with pregestational and gestational diabetes in terms of the risk of congenital heart disease. PMID:26078681
Subirana, M Teresa; Barón-Esquivias, Gonzalo; Manito, Nicolás; Oliver, José M; Ripoll, Tomás; Lambert, Jose Luis; Zunzunegui, José L; Bover, Ramon; García-Pinilla, José Manuel
This article presents the most relevant developments in 2013 in 3 key areas of cardiology: congenital heart disease, clinical cardiology, and heart failure and transplant. Within the area of congenital heart disease, we reviewed contributions related to sudden death in adult congenital heart disease, the importance of specific echocardiographic parameters in assessing the systemic right ventricle, problems in patients with repaired tetralogy of Fallot and indication for pulmonary valve replacement, and confirmation of the role of specific factors in the selection of candidates for Fontan surgery. The most recent publications in clinical cardiology include a study by a European working group on correct diagnostic work-up in cardiomyopathies, studies on the cost-effectiveness of percutaneous aortic valve implantation, a consensus document on the management of type B aortic dissection, and guidelines on aortic valve and ascending aortic disease. The most noteworthy developments in heart failure and transplantation include new American guidelines on heart failure, therapeutic advances in acute heart failure (serelaxin), the management of comorbidities such as iron deficiency, risk assessment using new biomarkers, and advances in ventricular assist devices.
Tan, Sainan; Wen, Qiaolian; Wang, Jing; Zhu, Xiaomei; Wang, Xi; Li, Congmin; Ma, Xu; Pan, Hong
CITED2 was identified as a cardiac transcription factor which is essential to the heart development. Cited2-deficient mice showed cardiac malformations, adrenal agenesis and neural crest defects. To explore the potential impact of mutations in CITED2 on congenital heart disease (CHD) in humans, we screened the coding region of CITED2 in a total of 700 Chinese people with congenital heart disease and 250 healthy individuals as controls. We found five potential disease-causing mutations, p.P140S, p.S183L, p.S196G, p.Ser161delAGC and p. Ser192_Gly193delAGCGGC. Two mammalian two-hybrid assays showed that the last four mutations significantly affected the interaction between p300CH1 and CITED2 or HIF1A. Further studies showed that four CITED2 mutations recovered the promoter activity of VEGF by decreasing its competitiveness with HIF1A for binding to p300CH1 and three mutations decreased the consociation of TFAP2C and CITED2 in the transactivation of PITX2C. Both VEGF and PITX2C play very important roles in cardiac development. In conclusion, we demonstrated that CITED2 has a potential causative impact on congenital heart disease. PMID:24848765
Broberg, Craig S; Burchill, Luke J
Pioneers in congenital heart surgery observed that exercise capacity did not return to normal levels despite successful surgical repair, leading some to cite a "myocardial factor" playing a role. They conjectured that residual alterations in myocardial function would be significant for patients' long-term outlook. In fulfillment of their early observations, today's adult congenital heart disease (ACHD) population shows well-recognized features of heart failure, even among patients without clear residual anatomic or hemodynamic abnormalities, demonstrating the vital role of the myocardium in their morbidity and mortality. Whereas the 'myocardial factor' was an elusive concept in the early history of congenital heart care, we now have imaging techniques to detect and quantify one such factor--myocardial fibrosis. Understanding the importance of myocardial fibrosis as a final common pathway in a variety of congenital lesions provides a framework for both the study and treatment of clinical heart failure in this context. While typical heart failure pharmacology should reduce or attenuate fibrogenesis, efforts to show meaningful improvements with standard pharmacotherapy in ACHD repeatedly fall short. This paper considers the importance of myocardial fibrosis and function, the current body of evidence for myocardial fibrosis in ACHD, and its implications for research and treatment.
Broberg, Craig S.; Burchill, Luke J.
Pioneers in congenital heart surgery observed that exercise capacity did not return to normal levels despite successful surgical repair, leading some to cite a “myocardial factor” playing a role. They conjectured that residual alterations in myocardial function would be significant for patients’ long-term outlook. In fulfillment of their early observations, today’s adult congenital heart disease (ACHD) population shows well-recognized features of heart failure, even among patients without clear residual anatomic or hemodynamic abnormalities, demonstrating the vital role of the myocardium in their morbidity and mortality. Whereas the ‘myocardial factor’ was an elusive concept in the early history of congenital heart care, we now have imaging techniques to detect and quantify one such factor – myocardial fibrosis. Understanding the importance of myocardial fibrosis as a final common pathway in a variety of congenital lesions provides a framework for both the study and treatment of clinical heart failure in this context. While typical heart failure pharmacology should reduce or attenuate fibrogenesis, efforts to show meaningful improvements with standard pharmacotherapy in ACHD repeatedly fall short. This paper considers the importance of myocardial fibrosis and function, the current body of evidence for myocardial fibrosis in ACHD, and its implications for research and treatment. PMID:25897907
Cardiovascular magnetic resonance (CMR) has expanded its role in the diagnosis and management of congenital heart disease (CHD) and acquired heart disease in pediatric patients. Ongoing technological advancements in both data acquisition and data presentation have enabled CMR to be integrated into clinical practice with increasing understanding of the advantages and limitations of the technique by pediatric cardiologists and congenital heart surgeons. Importantly, the combination of exquisite 3D anatomy with physiological data enables CMR to provide a unique perspective for the management of many patients with CHD. Imaging small children with CHD is challenging, and in this article we will review the technical adjustments, imaging protocols and application of CMR in the pediatric population. PMID:21936913
Hayes, Madeline; Gao, Xiaochong; Yu, Lisa X; Paria, Nandina; Henkelman, R. Mark; Wise, Carol A.; Ciruna, Brian
Scoliosis is a complex genetic disorder of the musculoskeletal system, characterized by three-dimensional rotation of the spine. Curvatures caused by malformed vertebrae (congenital scoliosis (CS)) are apparent at birth. Spinal curvatures with no underlying vertebral abnormality (idiopathic scoliosis (IS)) most commonly manifest during adolescence. The genetic and biological mechanisms responsible for IS remain poorly understood due largely to limited experimental models. Here we describe zygotic ptk7 (Zptk7) mutant zebrafish, deficient in a critical regulator of Wnt signalling, as the first genetically defined developmental model of IS. We identify a novel sequence variant within a single IS patient that disrupts PTK7 function, consistent with a role for dysregulated Wnt activity in disease pathogenesis. Furthermore, we demonstrate that embryonic loss-of-gene function in maternal-zygotic ptk7 mutants (MZptk7) leads to vertebral anomalies associated with CS. Our data suggest novel molecular origins of, and genetic links between, congenital and idiopathic forms of disease. PMID:25182715
Brouwer, Charlotte; Hazekamp, Mark G
Advances in surgical repair techniques for various types of congenital heart disease have improved survival into adulthood over the past decades, thus exposing these patients to a high risk of atrial and ventricular arrhythmias later in life. These arrhythmias arise from complex arrhythmogenic substrates. Substrate formation may depend on both pathological myocardial remodelling and variable anatomical boundaries, determined by the type and timing of prior corrective surgery. Accordingly, arrhythmogenic substrates after repair have changed as a result of evolving surgical techniques. Radiofrequency catheter ablation offers an important therapeutic option but remains challenging due to the variable anatomy, surgically created obstacles and the complex arrhythmogenic substrates. Recent technical developments including electroanatomical mapping and image integration for delineating the anatomy facilitate complex catheter ablation procedures. The purpose of this review is to provide an update on the changing anatomical arrhythmogenic substrates and their potential impact on catheter ablation in patients with repaired congenital heart disease and tachyarrhythmias. PMID:27617095
Díaz-Caraballo, Eva; González-García, Ana E; Reñones, Margarita; Sánchez-Recalde, Angel; García-Río, Francisco; Oliver-Ruiz, José M
The BREATHE-5 study demonstrated that bosentan, an oral endothelin receptor antagonist, provides clinical benefits in patients with Eisenmenger's syndrome. As a result, the European Medicines Agency (EMEA) approved its use for this indication. However, follow-up in that study was limited to 16 weeks and patients with complex congenital heart disease were excluded. We assessed the effect of long-term bosentan treatment in 10 patients with complex congenital heart disease and Eisenmenger's syndrome. In the mean clinical follow-up period of 25 months, all patients reached the target dose without developing side effects and without experiencing a change in arterial oxygen consumption at either rest or maximal exercise. Moreover, there were significant changes in clinical parameters: NYHA functional class improved from 3.3+/-0.7 to 2.5+/-0.9 (P=.002) and the 6-minute walk distance increased from 266+/-161 m to 347+/-133 m (P=.015).
Hayes, Madeline; Gao, Xiaochong; Yu, Lisa X; Paria, Nandina; Henkelman, R Mark; Wise, Carol A; Ciruna, Brian
Scoliosis is a complex genetic disorder of the musculoskeletal system, characterized by three-dimensional rotation of the spine. Curvatures caused by malformed vertebrae (congenital scoliosis (CS)) are apparent at birth. Spinal curvatures with no underlying vertebral abnormality (idiopathic scoliosis (IS)) most commonly manifest during adolescence. The genetic and biological mechanisms responsible for IS remain poorly understood due largely to limited experimental models. Here we describe zygotic ptk7 (Zptk7) mutant zebrafish, deficient in a critical regulator of Wnt signalling, as the first genetically defined developmental model of IS. We identify a novel sequence variant within a single IS patient that disrupts PTK7 function, consistent with a role for dysregulated Wnt activity in disease pathogenesis. Furthermore, we demonstrate that embryonic loss-of-gene function in maternal-zygotic ptk7 mutants (MZptk7) leads to vertebral anomalies associated with CS. Our data suggest novel molecular origins of, and genetic links between, congenital and idiopathic forms of disease.
... Congenital and inherited cataracts. In: Tasman W, Jaeger EA, eds. Duane's Ophthalmology . 16th ed. Philadelphia, PA: Lippincott ... Cataracts and systemic disease. In: Tasman W, Jaeger EA, eds. Duane's Ophthalmology . 16th ed. Philadelphia, PA: Lippincott ...
Rodriguez, Fred H; Marelli, Ariane J
The impact of lifelong exposure to myocardial dysfunction in populations with congenital heart disease (CHD) is becoming increasingly recognized. Most children born with CHD now reach adulthood and the long-term sequelae of treatment are contributing to substantial comorbidity. The combination of structural changes present at birth with changes resulting from cardiac surgery can result in heart failure. This article reports on the current state of knowledge on the epidemiology of heart failure in this patient population.
Boss, Renee D; Holmes, Kathryn W; Althaus, Janyne; Rushton, Cynda H; McNee, Hunter; McNee, Theresa
A prenatal diagnosis of ductal-dependent, complex congenital heart disease was made in a fetus with trisomy 18. The parents requested that the genetic diagnosis be excluded from all medical and surgical decision-making and that all life-prolonging therapies be made available to their infant. There was conflict among the medical team about what threshold of neonatal benefit could outweigh maternal and neonatal treatment burdens. A prenatal ethics consultation was requested.
Lepetsos, Panagiotis; Anastasopoulos, Panagiotis P.; Galanakos, Spyridon P.
Total hip replacement (THR) is the treatment of choice for the patient suffering from end-stage hip osteoarthritis. In the presence of deformities due to congenital hip disease (CHD), THR is, in most of the cases, a difficult task, since the technique of performing such an operation is demanding and the results could vary. We present our experience and preferred strategies focusing on challenges and surgical techniques associated with reconstructing the dysplastic hip. PMID:28090526
Luyckx, Koen; Goossens, Eva; Van Damme, Carolien; Moons, Philip
Identity formation is a core developmental task in adolescence and functions as a key resource for transitioning to adulthood. This study investigated how adolescents with congenital cardiac disease form their identity and how it relates to demographic and medical parameters, quality of life, perceived health, depressive symptoms, and loneliness. A total of 429 adolescents aged 14-18 years with congenital cardiac disease and 403 matched controls completed questionnaires on identity and all outcome variables. There were five meaningful identity statuses, similar to those obtained in the control sample, which were found in the patient sample. Of them, two statuses--achievement and foreclosure--were characterised by a strong sense of identity; one status--diffused diffusion--especially was characterised by a weak sense of identity combined with high scores on worry about the future. These identity statuses were differentially related to outcome variables, with individuals in diffused diffusion especially scoring highest on depressive symptoms, problems in school, treatment anxiety, and communication problems with clinicians, and lowest on quality of life. Having a strong sense of personal identity was found to protect against such maladaptive outcomes. In sum, most adolescents with congenital cardiac disease moved through their identity formation process in a similar manner to other adolescents. Adolescents with a diffused identity were particularly at risk of experiencing maladjustment and problems in treatment adherence. Hence, developing intervention strategies to provide continuity of care on the road to adulthood involves paying attention to core developmental tasks, such as identity formation in adolescents with congenital cardiac disease.
Karachalios, T; Hartofilakidis, G
This paper reviews the current knowledge relating to the management of adult patients with congenital hip disease. Orthopaedic surgeons who treat these patients with a total hip replacement should be familiar with the arguments concerning its terminology, be able to recognise the different anatomical abnormalities and to undertake thorough pre-operative planning in order to replace the hip using an appropriate surgical technique and the correct implants and be able to anticipate the clinical outcome and the complications.
Tikkanen, J; Heinonen, O P
To test the effect of maternal habits and home exposures during early pregnancy on the occurrence of congenital heart disease in the offspring, 406 cases and 756 controls were studied. The cases included all cardiovascular malformations detected in Finland during 1982-1983, while the healthy controls were randomly selected from all babies born during the same period. Case and control mothers were interviewed after delivery using a structured and pre-tested questionnaire. Maternal overall drug consumption during the first trimester was as prevalent among case mothers (13.3%) as controls (14.6%). Neither was the risk of congenital heart disease associated with maternal use of contraceptive pills, salicylates, diazepam, or sweetening agents separately. Maternal exposures to disinfectants, dyes, lacquers, paints, pesticides, or glues at home were equally prevalent in case and control groups. Several earlier miscarriages was a predictor of an infant born with congenital heart disease (OR = 2.7, CI95 = 1.4-5.3). Maternal ultrasound examination was performed during the first 16 weeks of pregnancy more often among the case group (28.3%) than among the control group (22.0%). However, the association between ultrasound examination and the risk of congenital heart disease in the offspring was not statistically significant (OR = 1.2, 95% confidence interval 0.9-1.7) when adjusted for confounding factors such as the threat of miscarriage in logistic regression analysis. It is concluded that maternal ultrasound examination, intake of some common drugs, and exposure to a number of environmental factors at home during early pregnancy are probably not harmful for the developing fetal heart.
Wijesekera, N. T. Padley, S. P.; Kazmi, F.; Davies, C. L.; McCall, J. M.
Uterine arteriovenous malformation (AVM) is a rare cause of vaginal bleeding and miscarriage. We report two cases of uterine AVMs in patients with a history of complex congenital heart disease, an association that has not been previously described. Both patients were treated by selective uterine artery embolization, a minimally invasive therapy that has revolutionized the management of uterine AVMs, thus offering an alternative to conventional hysterectomy.
Sato, Y.; Ogino, H.; Hara, M.; Satake, M.; Oshima, H.; Banno, T.; Mizuno, K.; Mishima, A.; Shibamoto, Y.
Our objective was to evaluate the usefulness of embolizing collateral vessels using mechanically detachable coils (MDCs) in children aged 3 years or younger with congenital heart disease. The subjects were 8 children with congenital heart disease featuring collateral vessels (age 18 days-3 years): 3 with a single ventricle, 2 with the tetralogy of Fallot, 2 with pulmonary atresia, and 1 with a ventricular septal defect. The embolized vessels were the major aortopulmonary collateral artery (MAPCA) in 5 patients, the persistent left superior vena cava in 2, and the coronary arteriovenous fistula in 1. A 4 or a 5 F catheter was used as the guiding device, and embolization was performed using MDCs and other conventional coils introduced through the microcatheter. One patient had growth of new MAPCAs after embolization, and these MAPCAs were also embolized with MDCs. Thus, a total of 9 embolization procedures were performed in 8 patients. Complete occlusion of the collateral vessels was achieved in 8 of 9 procedures (89%). Seven of 8 patients (88%) had uneventful courses after embolization, and MDC procedures appeared to play important roles in avoiding coil migration and achievement of safe coil embolization. One patient who underwent MAPCA embolization showed no improvement in heart function and died 2 months and 19 days later. Embolization of collateral vessels using MDCs in young children with congenital heart disease can be an effective procedure and a valuable adjunct to surgical management.
Sojka, Stephen; Amin, Nirav M; Gibbs, Devin; Christine, Kathleen S; Charpentier, Marta S; Conlon, Frank L
The identification and characterization of the cellular and molecular pathways involved in the differentiation and morphogenesis of specific cell types of the developing heart are crucial to understanding the process of cardiac development and the pathology associated with human congenital heart disease. Here, we show that the cardiac transcription factor CASTOR (CASZ1) directly interacts with congenital heart disease 5 protein (CHD5), which is also known as tryptophan-rich basic protein (WRB), a gene located on chromosome 21 in the proposed region responsible for congenital heart disease in individuals with Down's syndrome. We demonstrate that loss of CHD5 in Xenopus leads to compromised myocardial integrity, improper deposition of basement membrane, and a resultant failure of hearts to undergo cell movements associated with cardiac formation. We further report that CHD5 is essential for CASZ1 function and that the CHD5-CASZ1 interaction is necessary for cardiac morphogenesis. Collectively, these results establish a role for CHD5 and CASZ1 in the early stages of vertebrate cardiac development.
Schulkey, Claire E; Regmi, Suk D; Magnan, Rachel A; Danzo, Megan T; Luther, Herman; Hutchinson, Alayna K; Panzer, Adam A; Grady, Mary M; Wilson, David B; Jay, Patrick Y
Maternal age is a risk factor for congenital heart disease even in the absence of any chromosomal abnormality in the newborn. Whether the basis of this risk resides with the mother or oocyte is unknown. The impact of maternal age on congenital heart disease can be modelled in mouse pups that harbour a mutation of the cardiac transcription factor gene Nkx2-5 (ref. 8). Here, reciprocal ovarian transplants between young and old mothers establish a maternal basis for the age-associated risk in mice. A high-fat diet does not accelerate the effect of maternal ageing, so hyperglycaemia and obesity do not simply explain the mechanism. The age-associated risk varies with the mother's strain background, making it a quantitative genetic trait. Most remarkably, voluntary exercise, whether begun by mothers at a young age or later in life, can mitigate the risk when they are older. Thus, even when the offspring carry a causal mutation, an intervention aimed at the mother can meaningfully reduce their risk of congenital heart disease.
Wray, J.; Sensky, T.
AIM—Research into intellectual impairment among children with congenital heart disease has focused mainly on older children. This study was designed to determine whether previous findings are applicable to preschool children. METHODS—Three groups of children under 31/2 years old were assessed immediately before treatment and 12 months later: a group with congenital heart disease awaiting surgery, another awaiting bone marrow transplantation, and a healthy comparison group. RESULTS—Although the means of the three groups were within the normal range, preoperatively the cardiac and transplant groups showed deficits compared with the healthy controls. Postoperatively, continuing developmental deficits were significant only in the children with cyanotic lesions. CONCLUSIONS—Conclusions about intellectual development in older children with congenital heart disease do not apply to preschool children. Before corrective surgery, chronic illness itself appears to be the predominant influence on development. Postoperatively, cyanotic and acyanotic lesions are associated with different short term outcomes. PMID:10331998
Fredriksen, Per Morten; Mengshoel, Anne Marit; Frydenlund, Aina; Sørbye, Øystein; Thaulow, Erik
The objective of the study was to assess behavioural and emotional problems, as well as physical capacity, in children and adolescents with congenital cardiac disease. From the database of Paediatric Heart Section, Children's Clinic, Rikshospitalet University Hospital, Oslo, Norway, we identified 430 patients whose parents received questionnaires using the Child Behaviour Check-List. The response rate was 75.8%. In addition, the parents received a questionnaire focusing on special issues with regard to physical activity. Parents of children and adolescents with congenital cardiac diseases reported significantly more behavioural problems than did a reference population and boys were scored higher compared to girls. Analysis showed a significant impact of physical capacity on the score representing total problems, as well as scores for externalising and internalising behaviour. Compared to a reference population, parents of children and adolescents with congenital cardiac disease score their children higher on most scales when rated using the Child Behaviour Check-List. The type of diagnosis did not affect the scores reflecting the total problem. The main factor of impact on behavioural problems was, as evaluated by the parents, the physical capacity of the children.
Ou, Phalla; Celermajer, David S; Calcagni, Giulio; Brunelle, Francis; Bonnet, Damien; Sidi, Daniel
New generation multislice CT technology has changed the approach to non‐invasive assessment of congenital heart disease, in both paediatric and adult patients. This is mainly because of rapid advances in spatial and temporal resolution and in post‐processing capability. At Hôpital Necker‐Enfants Malades, CT with multiplanar and three‐dimensional reconstruction has become a routine examination in the evaluation of congenital heart disease planning surgery, complex interventional catheterisations and for follow‐up. It has proved to be an invaluable diagnostic and decision‐aiding methodology in these situations, as a complement to echocardiography and, increasingly, as a substitute for diagnostic angiography (which is usually associated with higher‐dose radiation and longer sedation times, as well as occasional morbidity). This review illustrates the current status of 64‐slice CT in congenital heart diseases, including assessment of the aorta, the coronary arteries, the pulmonary arteries, the systemic and pulmonary veins, and other intra‐ and extracardiac malformations. PMID:16952967
Parruti, Giustino; Polilli, Ennio; Ursini, Tamara; Tontodonati, Monica
Immunoglobulins are one major component of adaptive immunity to external and resident microorganisms, evolving very early in phylogenesis. They help eukaryotes in controlling infections, mainly through their neutralizing activity, which quenches both the cytopathic and inflammatory potential of invading microorganisms. Cytomegalovirus (CMV)-related disease is generally blunted in seropositive subjects with conserved specific humoral responses. CMV-seropositive pregnant women, in accordance with such evidence, suffer little or no fetal damage when reexposed to CMV. Several seminal experiences and early experimental models confirmed that repeated infusions of immunoglobulins, either with hyperimmune or standard preparations, may help to reduce maternal-fetal CMV transmission, as well as to quench fetal disease upon transmission. This review focused on experimental evidence supporting the potential role of immunoglobulins as a tool to control fetal CMV-related disease in pregnant women.
Cordiner, David S; Evans, Clair A; Brundler, Marie-Anne; McPhillips, Maeve; Murio, Enric; Darling, Mark; Taheri, Sepideh
This case outlines the potential complexity of autosomal recessive polycystic kidney disease (ARPKD). It highlights the challenges involved in managing this condition, some of the complications faced and areas of uncertainty in the decision making process. With a paucity of published paediatric cases on this subject, this should add to the pool of information currently available. PMID:22605879
Jabłoński, Janusz; Jankowski, Zbigniew; Sitkiewicz, Anna; Lewandowska, Małgorzata; Andrzejewska, Ewa
Congenital cystic adenomatoid malformation (CCAM) is a rare pulmonary abnormality that results from aberrant fetal lung development. It about 4-26% of cases it can be associated with other congenital abnormalities. We describe a case of congenital cystic adenomatoid malformation 2 associated with polycystic kidney disease. The association of these two congenital malformations is exceptional. Only four similar cases have been reported in the literature. A 2-year-old girl was referred to the Department of Paediatric Surgery and Oncology Medical University of Lodz with pneumonia and left pneumothorax. For three weeks prior to referral the patient was treated with antibiotics. Chest x-ray revealed hyperinflation of left upper lobe with mediastinal shift to right. Computer tomographic scan of the lung revealed multiple cyst in the left upper lobe, left-site pneumothorax and mediastinal shift to the right. The patient underwent thoracotomy. Intraoperatively, multiple cysts in the left upper lobe were found and left upper lobectomy was performed. Histologic study was compatible with type 2 congenital cystic adenomatoid malformation. Ultrasound examination showed multilocular cysts in both kidneys. The dimensions of the cysts were: MWR4. 54x45x45 mm and 25x21x24 mm on the left and right sides, respectively. Significant increase in cyst size on the left side was observed. Ten months after first hospitalization resection of the cystic lower pole of the left kidney was performed. The presence of even a single renal cyst in a child with CCAM is an indication for further follow up examinations.
Moulton, Matthew J.; Letsou, Anthea
ABSTRACT Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence), include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes. PMID:26935104
optimism and reduced occurrence of nonfatal MI [present risk], angina pectoris (relative risk 0.45, 95% confidence interval = 0.29 - 0.68), and...individuals, including post surgical sternal wound infection, angina , MI, referal for angioplasty, and necessity for repeat bypass surgery (N=247, b=-.09...Demographic Factors (age, gender) Risk Factors (hypertension, IDDM, PVD) Cardiac Disease Severity (ejection fraction, angina , dyspenea
Zhu, Jun-Yi; Fu, Yulong; Nettleton, Margaret; Richman, Adam; Han, Zhe
Genomic sequencing has implicated large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system is needed to validate gene associations with pathology. We developed a Drosophila-based functional system to screen candidate disease genes identified from Congenital Heart Disease (CHD) patients. 134 genes were tested in the Drosophila heart using RNAi-based gene silencing. Quantitative analyses of multiple cardiac phenotypes demonstrated essential structural, functional, and developmental roles for more than 70 genes, including a subgroup encoding histone H3K4 modifying proteins. We also demonstrated the use of Drosophila to evaluate cardiac phenotypes resulting from specific, patient-derived alleles of candidate disease genes. We describe the first high throughput in vivo validation system to screen candidate disease genes identified from patients. This approach has the potential to facilitate development of precision medicine approaches for CHD and other diseases associated with genetic factors.
Brassard, Patrice; Ferland, Annie; Marquis, Karine; Maltais, François; Jobin, Jean; Poirier, Paul
Several chronic diseases are known to negatively affect the ability of an individual to perform exercise. However, the altered exercise capacity observed in these patients is not solely associated with the heart and lungs dysfunction. Exercise has also been shown to play an important role in the management of several pathologies encountered in the fields of cardiology and pneumology. Studies conducted in our institution regarding the influence of diabetes, chronic heart failure, congenital heart disease and chronic pulmonary obstructive disease on the acute and chronic exercise responses, along with the beneficial effects of exercise training in these populations, are reviewed. PMID:17932595
Kümpers, Philipp; Denecke, Agnieszka; Westhoff-Bleck, Mechthild; Schieffer, Bernhard; Bauersachs, Johann; Kielstein, Jan T.; Tutarel, Oktay
Background Chronic heart failure is an important cause for morbidity and mortality in adults with congenital heart disease (ACHD). While NT-proBNP is an established biomarker for heart failure of non-congenital origin, its application in ACHD has limitations. The angiogenic factors Angiopoietin-1 and -2 (Ang-1, Ang-2), vascular endothelial growth factor (VEGF), and soluble receptor tyrosine kinase of the Tie family (sTie2) correlate with disease severity in heart failure of non-congenital origin. Their role in ACHD has not been studied. Methods In 91 patients Ang-2 and NT-proBNP were measured and related to New York Heart Association class, systemic ventricular function and parameters of cardiopulmonary exercise testing. Ang-1, VEGF, and sTie2 were also measured. Results Ang-2 correlates with NYHA class and ventricular dysfunction comparable to NT-proBNP. Further, Ang-2 showed a good correlation with parameters of cardiopulmonary exercise testing. Both, Ang-2 and NT-proBNP identified patients with severely limited cardiopulmonary exercise capacity. Additionally, Ang-2 is elevated in patients with a single ventricle physiology in contrast to NT-proBNP. VEGF, Ang-1, and sTie2 were not correlated with any clinical parameter. Conclusion The performance of Ang-2 as a biomarker for heart failure in ACHD is comparable to NT-proBNP. Its significant elevation in patients with single ventricle physiology indicates potential in this patient group and warrants further studies. PMID:23826161
Carellos, E V M; Caiaffa, W T; Andrade, G M Q; Abreu, M N S; Januário, J N
This study aimed to investigate the distribution of congenital toxoplasmosis in the state of Minas Gerais, Southeastern Brazil and describe the demographic and socioeconomic profile of the municipalities associated with the disease. An ecological study was conducted using socioeconomic indicators of a database (MGSSRI) created by Fundação João Pinheiro (a government technical support agency of Minas Gerais), in order to show the development of the municipalities in the state. The prevalence of toxoplasmosis was the outcome and the items of the MGSSRI were the explanatory variables. Of 146,307 newborns screened (November 2006 to May 2007), 190 had congenital toxoplasmosis, yielding a prevalence of 1·3/1000, ranging from 0 to 76·9/1000 in the municipalities. The multivariate model indicated a higher occurrence of toxoplasmosis in municipalities with smaller populations and worse indexes of tax performance. Congenital toxoplasmosis appears to be a neglected disease in the state of Minas Gerais, given the high prevalence found and its concentration in municipalities with worse socioeconomic indexes.
Almenar, Luis; Zunzunegui, José Luis; Barón, Gonzalo; Carrasco, José Ignacio; Gómez-Doblas, Juan José; Comín, Josep; Barrios, Vivencio; Subirana, M Teresa; Díaz-Molina, Beatriz
In the year 2012, 3 scientific sections-heart failure and transplant, congenital heart disease, and clinical cardiology-are presented together in the same article. The most relevant development in the area of heart failure and transplantation is the 2012 publication of the European guidelines for heart failure. These describe new possibilities for some drugs (eplerenone and ivabradine); expand the criteria for resynchronization, ventricular assist, and peritoneal dialysis; and cover possibilities of percutaneous repair of the mitral valve (MitraClip(®)). The survival of children with hypoplastic left heart syndrome in congenital heart diseases has improved significantly. Instructions for percutaneous techniques and devices have been revised and modified for the treatment of atrial septal defects, ostium secundum, and ventricular septal defects. Hybrid procedures for addressing structural congenital heart defects have become more widespread. In the area of clinical cardiology studies have demonstrated that percutaneous prosthesis implantation has lower mortality than surgical implantation. Use of the CHA2DS2-VASc criteria and of new anticoagulants (dabigatran, rivaroxaban and apixaban) is also recommended. In addition, the development of new sequencing techniques has enabled the analysis of multiple genes.
Avolio, Elisa; Caputo, Massimo; Madeddu, Paolo
This review article reports on the new field of stem cell therapy and tissue engineering and its potential on the management of congenital heart disease. To date, stem cell therapy has mainly focused on treatment of ischemic heart disease and heart failure, with initial indication of safety and mild-to-moderate efficacy. Preclinical studies and initial clinical trials suggest that the approach could be uniquely suited for the correction of congenital defects of the heart. The basic concept is to create living material made by cellularized grafts that, once implanted into the heart, grows and remodels in parallel with the recipient organ. This would make a substantial improvement in current clinical management, which often requires repeated surgical corrections for failure of implanted grafts. Different types of stem cells have been considered and the identification of specific cardiac stem cells within the heterogeneous population of mesenchymal and stromal cells offers opportunities for de novo cardiomyogenesis. In addition, endothelial cells and vascular progenitors, including cells with pericyte characteristics, may be necessary to generate efficiently perfused grafts. The implementation of current surgical grafts by stem cell engineering could address the unmet clinical needs of patients with congenital heart defects. PMID:26176009
Donofrio, Mary T; Massaro, An N
Advances in cardiac surgical techniques and perioperative intensive care have led to improved survival in babies with congenital heart disease (CHD). While it is true that the majority of children with CHD today will survive, many will have impaired neurodevelopmental outcome across a wide spectrum of domains. While continuing to improve short-term morbidity and mortality is an important goal, recent and ongoing research has focused on defining the impact of CHD on brain development, minimizing postnatal brain injury, and improving long-term outcomes. This paper will review the impact that CHD has on the developing brain of the fetus and infant. Neurologic abnormalities detectable prior to surgery will be described. Potential etiologies of these findings will be discussed, including altered fetal intrauterine growth, cerebral blood flow and brain development, associated congenital brain abnormalities, and risk for postnatal brain injury. Finally, reported neurodevelopmental outcomes after surgical repair of CHD will be reviewed.
Donofrio, Mary T.; Massaro, An N.
Advances in cardiac surgical techniques and perioperative intensive care have led to improved survival in babies with congenital heart disease (CHD). While it is true that the majority of children with CHD today will survive, many will have impaired neurodevelopmental outcome across a wide spectrum of domains. While continuing to improve short-term morbidity and mortality is an important goal, recent and ongoing research has focused on defining the impact of CHD on brain development, minimizing postnatal brain injury, and improving long-term outcomes. This paper will review the impact that CHD has on the developing brain of the fetus and infant. Neurologic abnormalities detectable prior to surgery will be described. Potential etiologies of these findings will be discussed, including altered fetal intrauterine growth, cerebral blood flow and brain development, associated congenital brain abnormalities, and risk for postnatal brain injury. Finally, reported neurodevelopmental outcomes after surgical repair of CHD will be reviewed. PMID:20862365
Birks, Yvonne; Sloper, Patricia; Lewin, Robert; Parsons, Jonathan
Abstract Objective To determine the health‐related experiences of children with congenital heart disease. Design Qualitative, semi‐structured interviews. Participants A purposive sample (N = 35) of children and young people, aged between 8 and 19 years, with a variety of congenital heart conditions recruited from one treatment care centre in the north of England. Results The main themes identified included: physical limitations of their condition; restrictions; attitudes of others; choices about information; coping with life and privacy. Conclusions This study suggests that while many of this sample of children said that they coped well with their condition some children did experience significant impact on their quality of life in several domains. Children and young people identified a need for improved strategies to help them communicate about their condition with peers, schoolteachers and health‐care professionals to allow a better understanding of what they are able to achieve. PMID:17324192
Homsy, Jason; Zaidi, Samir; Shen, Yufeng; Ware, James S.; Samocha, Kaitlin E.; Karczewski, Konrad J.; DePalma, Steven R.; McKean, David; Wakimoto, Hiroko; Gorham, Josh; Jin, Sheng Chih; Deanfield, John; Giardini, Alessandro; Porter, George A.; Kim, Richard; Bilguvar, Kaya; Lopez, Francesc; Tikhonova, Irina; Mane, Shrikant; Romano-Adesman, Angela; Qi, Hongjian; Vardarajan, Badri; Ma, Lijiang; Daly, Mark; Roberts, Amy E.; Russell, Mark W.; Mital, Seema; Newburger, Jane W.; Gaynor, J. William; Breitbart, Roger E.; Iossifov, Ivan; Ronemus, Michael; Sanders, Stephan J.; Kaltman, Jonathan R.; Seidman, Jonathan G.; Brueckner, Martina; Gelb, Bruce D.; Goldmuntz, Elizabeth; Lifton, Richard P.; Seidman, Christine E.; Chung, Wendy K.
Congenital heart disease (CHD) patients have increased prevalence of extra-cardiac congenital anomalies (CA) and risk of neurodevelopmental disabilities (NDD). Exome sequencing of 1,213 CHD parent-offspring trios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed in developing heart and brain. These mutations accounted for 20% of patients with CHD, NDD and CA but only 2% with isolated CHD. Mutations altered genes involved in morphogenesis, chromatin modification, and transcriptional regulation, including multiple mutations in RBFOX2, an mRNA splice regulator. Genes mutated in other cohorts ascertained for NDD were enriched in CHD cases, particularly those with coexisting NDD. These findings reveal shared genetic contributions to CHD, NDD, and CA and provide opportunities for improved prognostic assessment and early therapeutic intervention in CHD patients. PMID:26785492
Yamamoto, Tomohiro; Schindler, Ehrenfried
Congenital heart disease (CHD) is the most common form of congenital abnormality and occurs in over 1% of newborns. Approximately 30% of children with CHD have other extra-cardiac anomalies, which significantly increases mortality in CHD patients. It is expected that the number of CHD patients who consult non-specialized hospitals for non-cardiac surgery after palliative or corrective operations will increase because of the extraordinary progression of treatments, such as surgical procedures, interventional procedures, and intensive care medicine, as well as diagnosis. The aim of this article is to enable anaesthesiologists who are not usually engaged in the anaesthesia management of CHD patients to provide perioperative management for CHD patients safely and with confidence by having basic and advanced knowledge about CHD patients and their pathophysiological characteristics.
Blue, Gillian M; Kirk, Edwin P; Giannoulatou, Eleni; Sholler, Gary F; Dunwoodie, Sally L; Harvey, Richard P; Winlaw, David S
Our understanding of the genetics of congenital heart disease (CHD) is rapidly expanding; however, many questions, particularly those relating to sporadic forms of disease, remain unanswered. Massively parallel sequencing technology has made significant contributions to the field, both from a diagnostic perspective for patients and, importantly, also from the perspective of disease mechanism. The importance of de novo variation in sporadic disease is a recent highlight, and the genetic link between heart and brain development has been established. Furthermore, evidence of an underlying burden of genetic variation contributing to sporadic and familial forms of CHD has been identified. Although we are still unable to identify the cause of CHD for most patients, recent findings have provided us with a much clearer understanding of the types of variants and their individual contributions and collectively mark an important milestone in our understanding of both familial and sporadic forms of disease.
Deng, Lisa X; Khan, Abigail May; Drajpuch, David; Fuller, Stephanie; Ludmir, Jonathan; Mascio, Christopher E; Partington, Sara L; Qadeer, Ayesha; Tobin, Lynda; Kovacs, Adrienne H; Kim, Yuli Y
Post-traumatic stress disorder (PTSD) is associated with adverse outcomes and increased mortality in cardiac patients. No studies have examined PTSD in the adult congenital heart disease (ACHD) population. The objectives of this study were to assess the prevalence of self-reported symptoms of PTSD in patients with ACHD and explore potential associated factors. Patients were enrolled from an outpatient ACHD clinic and completed several validated measures including the Impact of Event Scale-Revised, PTSD Checklist-Civilian Version, and the Hospital Anxiety and Depression Scale. Clinical data were abstracted through medical data review. A total of 134 participants (mean age 34.6 ± 10.6; 46% men) were enrolled. Of the 127 participants who completed the Impact of Event Scale-Revised, 14 (11%) met criteria for elevated PTSD symptoms specifically related to their congenital heart disease or treatment. Of the 134 patients who completed PTSD Checklist-Civilian Version, 27 (21%) met criteria for global PTSD symptoms. In univariate analyses, patients with congenital heart disease-specific PTSD had their most recent cardiac surgery at an earlier year (p = 0.008), were less likely to have attended college (p = 0.04), had higher rates of stroke or transient ischemic attack (p = 0.03), and reported greater depressive symptoms on the Hospital Anxiety and Depression Scale (7 vs 2, p <0.001). In multivariable analysis, the 2 factors most strongly associated with PTSD were depressive symptoms (p <0.001) and year of most recent cardiac surgery (p <0.03). In conclusion, PTSD is present in 11% to 21% of subjects seen at a tertiary referral center for ACHD. The high prevalence of PTSD in this complex group of patients has important implications for the medical and psychosocial management of this growing population.
Chistyakov, I S; Medvedev, A P; Pichugin, V V
The purpose of this study was to evaluate the effectiveness of combined surgical and medical treatment of infective endocarditis in patients with congenital valvular heart disease when included in a regimen of the drug Reamberin. In this regard, the analysis of the effectiveness of a combination regimen of 74 patients with valvular congenital heart diseases complicated with infective endocarditis. Given the indications for surgical correction operative technique features and possible technical difficulties in carrying out such operations, due to the inflammatory changes and tissue destruction, and ways to overcome them. For the correction of metabolic disorders in the postoperative period, 47 patients (main group) was appointed Reamberin: once, intravenous drip 400 ml/day during the first 5 days after surgery. 27 patients (control group) was conducted infusion therapy depending on the severity of the condition according to the classical scheme. In addition to standard clinical and laboratory examination, to assess the effectiveness of Reamberin was investigated catalase activity of CPK in blood serum in the dynamics of observation (1, 3 and 5 days after surgery). It is revealed that surgical approach, used in complex treatment of patients with valvular congenital heart diseases, including reorganization of the cavities of the heart, increasing the frequency of joints and the use of reinforcing strips of synthetic material that prevents the cutting of sutures through the inflamed tissue has achieved good short-and long-term results. Infective endocarditis and destruction of the valvular annulus fibrosus the use of a frame of strips of polytetrafluoroethylene allows you to restore its integrity and to implant a mechanical prosthesis. The inclusion in the regimen of patients with infective endocarditis complicated by cardiac insufficiency in the early postoperative period the drug Reamberin improves the efficiency of treatment by a more rapid restoration of the normal
Bulut, Ozgul; Gul, Doruk; Sevuk, Sibel; Mungan, Ilke; Buyukkayhan, Derya
Chylothorax is defined as the accumulation of lymphatic fluid or chyle in the pleural space. Chylothorax treatment is composed of conservative; pleural drainage, termination of enteral feeding, total parenteral nutrition and supplementation with medium- chain triglycerides and surgical therapies; ductus thoracicus ligation, pleuroperitoneal shunts or pleuredesis. Nowadays, for cases among which conservative therapies fail, treatment with octreotide has been reported to be beneficial with promising results. A neonate who developed chylothorax after surgery performed for congenital heart disease was treated successfully with octreotide. PMID:28058372
Çelik, Muhittin; Aldudak, Bedri; Akar, Melek; Akdeniz, Osman; Tüzün, Heybet; Çelebi, Vefik
Aim: In this study, it was aimed to determine the problems of the neonates who were diagnosed with congenital heart disease requiring early intervention in our hospital. Material and Methods: The files of the newborn babies with congenital heart disease requiring early intervention who were admitted to the neonatal intensive care unit of our hospital between January 2011 and January 2013 were evaluated retrospectively. In all cases, echocardiography and ‘’Score for Neonatal Acute Physiology-II” (SNAP-II) scoring were performed within the first day of admission. The data were interpreted using Number Cruncher Statistical System 2007 software. The statistical significance was set at p<0.05. Results: A total of 83 babies were included in the study. Forty six of the patients were male (55%), and 37 (45%) were female. Sixty eight percent of the patients were referred from the neighboring provinces and 32% were transferred from the centers within the city. The age range was between 0 and 28 (5.6±6.4 day) days. The SNAP-II scores upon admission ranged between 0 and 90 (mean: 20±20.3). None of the patients was diagnosed prenatally. The most common diagnoses included transposition of the great arteries (33.7%) and pulmonary atresia (19.3%). Nineteen (22%) patients were lost in the neonatal intensive care unit. There was a significant relationship between the mortality and the SNAP-II scores (p=0.0001) and use of vasopressors (p=0.004). The diagnosis, gender, use of alprostadil and age were not related to mortality. Three patients were discharged following planning of elective surgery and 60 patients were referred to a tertiary center by air ambulance. Conclusions: The results of our study indicated that prenatal diagnosis could not be made in neonates with congenital heart disease requiring intervention in our region. The mortality rates of these patients were related to the severity of the clinical status at presentation rather than to the age, gender and type of
Mylotte, Darren; Martucci, Giuseppe; Piazza, Nicolo; McElhinney, Doff
In the context of congenital heart disease (CHD), the complex biochemical and physiologic response to the pressure- or volume-loaded ventricle can be induced by stenotic and shunt/regurgitant lesions, respectively. A range of transcatheter therapies have recently emerged to expand the therapeutic potential of the more traditional surgical and medical interventions for heart failure in patients with CHD. Together, these complementary interventions aim to treat the growing patient population with adult CHD (ACHD). In this article, the most commonly used transcatheter interventions for heart failure in patients with ACHD are reviewed.
Kovacs, Adrienne H; Utens, Elisabeth M
Most infants born with congenital heart disease (CHD) are now expected to reach adulthood. However, adults with CHD of moderate or great complexity remain at elevated risk of heart failure, arrhythmias, additional surgeries and interventional procedures, and premature mortality. This creates a need for lifelong specialized cardiac care and leads to 2 sets of potential challenges: (1) the transition from pediatric to adult care and (2) the psychosocial implications of coping with a chronic and often life-shortening medical condition. Many adolescents struggle with the transition to adult care, and mood and anxiety disorders are not uncommon in the adult setting.
Evans, William; Castillo, William; Rollins, Robert; Luna, Carlos; Kip, Katrinka; Ludwick, Joseph; Madan, Nitin; Ciccolo, Michael; Galindo, Alvaro; Rothman, Abraham; Mayman, Gary; Cass, Kathleen; Thomas, Vincent; Restrepo, Humberto; Acherman, Ruben
This study compares the current, prenatal detection rate for critical congenital heart disease in Southern Nevada with the previously reported rate, after developing and expanding a comprehensive, community-wide fetal cardiology program. For the current-period analysis, we inquired our database and electronic health records for patients born in Clark County, Nevada, with critical congenital heart disease between May 2012 and April 2014, and we compared the results with the previous period between May 2003 and April 2006. The major components of the community-wide program include fetal congenital heart disease screening via general obstetric ultrasound studies performed in obstetrician's offices, radiology imaging centers, or maternal-fetal medicine specialty practices; subsequent referral for comprehensive fetal echocardiography performed in maternal-fetal medicine offices under the on-site supervision by fetal cardiologists; and recurring community educational programs teaching the 5-axial plane, fetal echocardiographic screening protocol to general obstetric sonographers and instructing perinatal sonographers in advanced imaging topics. For the current period, the prenatal detection rate for critical congenital heart disease in Southern Nevada was 71 versus 36% for the previous period (p < 0.001). The temporal improvement in prenatal detection of critical congenital heart disease may be related to our expanded decentralized, community-wide fetal cardiology program, and our experiences may be applicable to other metropolitan areas.
Arruda, Bailey L.; Arruda, Paulo H.; Magstadt, Drew R.; Schwartz, Kent J.; Dohlman, Tyler; Schleining, Jennifer A.; Patterson, Abby R.; Visek, Callie A.; Victoria, Joseph G.
Congenital tremors is a sporadic disease of neonatal pigs characterized by action-related repetitive myoclonus. A majority of outbreaks of congenital tremors have been attributed to an unidentified virus. The objectives of this project were to 1) detect potential pathogen(s) in samples from piglets with congenital tremors and 2) develop an infection model to reproduce disease. Using next-generation sequencing, a divergent lineage pestivirus was detected in piglets with congenital tremors. The virus was originally most closely related to a bat pestivirus but is now more closely related to a recently published novel porcine pestivirus provisionally named atypical porcine pestivirus. A quantitative real-time PCR detected the virus in samples from neonatal piglets with congenital tremors from two separate farms, but not in samples from unaffected piglets from the same farm. To fulfill the second objective, pregnant sows were inoculated with either serum containing the pestivirus or PBS (control) by intravenous and intranasal routes simultaneously with direct inoculation of fetal amniotic vesicles by ultrasound-guided surgical technique. Inoculations were performed at either 45 or 62 days of gestation. All sows inoculated with the novel pestivirus farrowed piglets affected with congenital tremors while PBS-inoculated control piglets were unaffected. Tremor severity for each piglet was scored from videos taken 0, 1 and 2 days post-farrowing. Tremor severity remained relatively constant from 0 to 2 days post-farrowing for a majority of piglets. The prevalence of congenital tremors in pestivirus-inoculated litters ranged from 57% (4 out of 7 affected piglets) to 100% (10 out of 10 affected piglets). The virus was consistently detected by PCR in tissues from piglets with congenital tremors but was not detected in control piglets. Samples positive by PCR in greater than 90% of piglets sampled included brainstem (37 out of 41), mesenteric lymph node (37 out of 41
Arruda, Bailey L; Arruda, Paulo H; Magstadt, Drew R; Schwartz, Kent J; Dohlman, Tyler; Schleining, Jennifer A; Patterson, Abby R; Visek, Callie A; Victoria, Joseph G
Congenital tremors is a sporadic disease of neonatal pigs characterized by action-related repetitive myoclonus. A majority of outbreaks of congenital tremors have been attributed to an unidentified virus. The objectives of this project were to 1) detect potential pathogen(s) in samples from piglets with congenital tremors and 2) develop an infection model to reproduce disease. Using next-generation sequencing, a divergent lineage pestivirus was detected in piglets with congenital tremors. The virus was originally most closely related to a bat pestivirus but is now more closely related to a recently published novel porcine pestivirus provisionally named atypical porcine pestivirus. A quantitative real-time PCR detected the virus in samples from neonatal piglets with congenital tremors from two separate farms, but not in samples from unaffected piglets from the same farm. To fulfill the second objective, pregnant sows were inoculated with either serum containing the pestivirus or PBS (control) by intravenous and intranasal routes simultaneously with direct inoculation of fetal amniotic vesicles by ultrasound-guided surgical technique. Inoculations were performed at either 45 or 62 days of gestation. All sows inoculated with the novel pestivirus farrowed piglets affected with congenital tremors while PBS-inoculated control piglets were unaffected. Tremor severity for each piglet was scored from videos taken 0, 1 and 2 days post-farrowing. Tremor severity remained relatively constant from 0 to 2 days post-farrowing for a majority of piglets. The prevalence of congenital tremors in pestivirus-inoculated litters ranged from 57% (4 out of 7 affected piglets) to 100% (10 out of 10 affected piglets). The virus was consistently detected by PCR in tissues from piglets with congenital tremors but was not detected in control piglets. Samples positive by PCR in greater than 90% of piglets sampled included brainstem (37 out of 41), mesenteric lymph node (37 out of 41
Roberts, Neil A.; Hilton, Emma N.; Woolf, Adrian S.
We present a scientific investigation into the pathogenesis of a urinary bladder disease. The disease in question is called urofacial syndrome (UFS), a congenital condition inherited in an autosomal recessive manner. UFS features incomplete urinary bladder emptying and vesicoureteric reflux, with a high risk of recurrent urosepsis and end-stage renal disease. The story starts from a human genomic perspective, then proceeds through experiments that seek to determine the roles of the implicated molecules in embryonic frogs and newborn mice. A future aim would be to use such biological knowledge to intelligently choose novel therapies for UFS. We focus on heparanase proteins and the peripheral nervous system, molecules and tissues that appear to be key players in the pathogenesis of UFS and therefore must also be critical for functional differentiation of healthy bladders. These considerations allow the envisioning of novel biological treatments, although the potential difficulties of targeting the developing bladder in vivo should not be underestimated. PMID:26315301
Attenhofer Jost, C H
The incidence of patients with degenerative valvular but also of patients with congenital heart disease surviving until adulthood or even old age will increase in the next decades. Auscultation with the stethoscope remains an important diagnostic means in the detection and treatment of heart disease. Heart murmurs (especially systolic heart murmurs) are extremely common. There are helpful clues to differentiate heart murmurs. It can occasionally be relatively simple to differentiate a systolic murmur due to valvular heart disease from an innocent, ejection murmur; however, there are important limitations of auscultation. Overall, auscultation and clinical examination alone do not suffice to correctly diagnose and treat patients with heart failure or a murmur Clinically significant aortic stenosis, aortic regurgitation and mitral regurgitation as well as hypertrophic cardiomyopathy are not uncommonly missed or misinterpreted. An echocardiographic exam is mandatory in all patients with more than a soft systolic murmur, any diastolic murmur, cardiac symptoms and/or ECG changes.
Gatzoulis, M; Hechter, S; Siu, S; Webb, G
Objective—To examine the evolving role of specialised outpatient services for adult patients with congenital heart disease. Design—A retrospective analysis of all patients attending the Toronto Congenital Cardiac Centre for Adults over three corresponding three month periods in 1987, 1992, and 1997. Setting—A tertiary referral centre. Main outcome measures—Patient demographics, residence, medical and surgical history, type and source of referral, and investigations performed. Results—In all, 570 patients were seen at the clinic during these three periods. There was a 44% and a 269% increase in workload between 1987 to 1992 and 1992 to 1997, respectively. There was a steady fall in mean age of patients seen at the clinic with time (38.5, 33.6, and 31.7 years in 1987, 1992, and 1997, respectively, p < 0.001). New referrals from community cardiologists and family physicians increased more in relative terms than did referrals from the Hospital for Sick Children, Toronto (6.7%, 15%, and 37.5%, p = 0.02). There was a steady increase in patients with previous reparative surgery (48.9%, 59.2%, and 69.2%, p < 0.002). The proportion of patients with previous reoperations also increased (2.3%, 10%, and 9.2%, p < 0.01). Echocardiography remained the predominant method of diagnosis. The diagnostic mix did not change with time. Conclusions—Over the past 10 years there has been a large increase in adults with congenital heart disease requiring and seeking specialised care in a tertiary health centre, with a concomitant evolution of referral patterns. These data may be helpful in planning of similar paediatric and adult cardiac services for this expanding population. Keywords: congenital heart disease; ambulatory clinics PMID:10220546
Torres-Cosme, José Luis; Rolón-Porras, Constanza; Aguinaga-Ríos, Mónica; Acosta-Granado, Pedro Manuel; Reyes-Muñoz, Enrique; Murguía-Peniche, Teresa
Background and Objectives Temporal trends in mortality from congenital heart disease (CHD) vary among regions. It is therefore necessary to study this problem in each country. In Mexico, congenital anomalies were responsible for 24% of infant mortality in 2013 and CHD represented 55% of total deaths from congenital anomalies among children under 1 year of age. The objectives of this study were to analyze the trends in infant mortality from CHD in Mexico (1998 to 2013), its specific causes, age at death and associated socio-demographic factors. Methods Population-based study which calculated the compounded annual growth rate of death rom CHD between 1998 and 2013. Specific causes, age at which death from CHD occurred and risk factors associated with mortality were analyzed for the year 2013. Results Infant mortality from CHD increased 24.8% from 1998 to 2013 (114.4 to 146.4/ 100,000 live births). A total of 3,593 CHD deaths occurred in 2013; the main causes were CHD with left-to-right shunt (n = 487; 19.8/100,000 live births) and cyanotic heart disease (n = 410; 16.7/100,000). A total of 1,049 (29.2%) deaths from CHD occurred during the first week of life. Risk factors associated with mortality from CHD were, in order of magnitude: non-institutional birth, rural area, birth in a public hospital and male sex. Conclusions Mortality from CHD has increased in Mexico. The main causes were CHD with left-to-right shunt, which are not necessarily fatal if treated promptly. Populations vulnerable to death from CHD were identified. Approximately one-third of the CHD occurred during the first week of life. It is important to promote early diagnosis, especially for non-institutional births. PMID:26937635
Stammers, A H; Rauch, E D; Willett, L D; Newberry, J W; Duncan, K F
Severe coagulation defects often develop in neonates undergoing cardiac surgery, both as a result of the surgical intervention, and as pre-existing defects in the hemostatic mechanisms. The following case report describes a newborn patient with complex congenital heart disease and respiratory failure whose pre-operative coagulopathy was aggressively managed prior to surgical correction. A 5-day-old, 2.5 kg child presented with interrupted aortic arch, ventricular septal defect, atrial septal defect, and patent ductus arteriosus. On admission, he was in respiratory arrest suffering from profound acidemia. In addition, the child was hypothermic (30.1 degrees C), septic (Streptococcus viridans), and coagulopathic (disseminated intravascular coagulation-DIC). The patient was immediately intubated and initial coagulation assessment revealed the following: prothrombin time (PT) 48.9 s (international normalized ratio (INR) 15.7), activated partial thromboplastin time (aPTT) >106 s, platelet count 30,000 mm(3), fibrinogen 15 mg dL(-1) and antithrombin III (AT-III) 10%. Before cardiac surgery could be performed, the patient's DIC was corrected with the administration of cryoprecipitate (15 ml), fresh frozen plasma (300 ml), and platelets (195 ml). In spite of the large transfusion of fresh frozen plasma, the AT-III activity, measured as a percentage, remained depressed at 33. Initial thromboelastographic (TEG) determination revealed an index of +2.02, and following 100 IU administration of an AT-III concentrate, declined to -2.32. Sequential TEG profiles were performed over several days, with the results used to guide both transfusion and medical therapy. The congenital heart defect correction was subsequently performed with satisfactory initial results, but the patient developed a fungal infection and expired on the 16th post-operative day. The present case describes techniques of coagulation management for a newborn with both a severe hemostatic defect and congenital
Central Core Disease; Centronuclear Myopathy; Congenital Fiber Type Disproportion; Multiminicore Disease; Myotubular Myopathy; Nemaline Myopathy; Rigid Spine Muscular Dystrophy; Undefined Congenital Myopathy
Farooqi, Kanwal M; Saeed, Omar; Zaidi, Ali; Sanz, Javier; Nielsen, James C; Hsu, Daphne T; Jorde, Ulrich P
As the population of adults with congenital heart disease continues to grow, so does the number of these patients with heart failure. Ventricular assist devices are underutilized in adults with congenital heart disease due to their complex anatomic arrangements and physiology. Advanced imaging techniques that may increase the utilization of mechanical circulatory support in this population must be explored. Three-dimensional printing offers individualized structural models that would enable pre-surgical planning of cannula and device placement in adults with congenital cardiac disease and heart failure who are candidates for such therapies. We present a review of relevant cardiac anomalies, cases in which such models could be utilized, and some background on the cost and procedure associated with this process.
... heart disease. Google+ Hangout on the first large-scale gene sequencing analysis of congenital heart disease 05/ ... in the journal Nature, about the first large-scale sequencing analysis of congenital heart disease. This NHLBI- ...
... heart disease. Google+ Hangout on the first large-scale gene sequencing analysis of congenital heart disease 05/ ... in the journal Nature, about the first large-scale sequencing analysis of congenital heart disease. This NHLBI- ...
Animasahun, B A; Ekure, E N; Njokanma, O F
A double-chambered right ventricle (DCRV) is a rare congenital heart disease and an uncommon cause of congestive cardiac failure. An anomalous muscle band divides the right ventricle into two cavities, causing variable degrees of obstruction. Echocardiography is considered a useful method for the diagnosis of this pathology, especially in children. An eight-year-old patient with a small ventricular septal defect (VSD) and double-chambered right ventricle presented with a history of palpitations, easy fatigability and recurrent fever. On presentation, she had features of congestive cardiac failure. A complete diagnosis was initially missed with transthoracic two-dimensional (2-D) echocardiography but later obtained based on transthoracic 2-D echocardiography with Doppler facility. This was confirmed with cardiac catheterisation. The patient was referred for surgical correction, which was successful. Due to the rarity of this condition and the consequences of missing the diagnosis, we present this case in order to highlight the rarity of this congenital heart disease in childhood.
Baquero-Artigao, F; del Castillo Martín, F; Fuentes Corripio, I; Goncé Mellgren, A; Fortuny Guasch, C; de la Calle Fernández-Miranda, M; González-Tomé, M I; Couceiro Gianzo, J A; Neth, O; Ramos Amador, J T
Congenital toxoplasmosis is the result of transplacental fetal infection by Toxoplasma gondii after the primary maternal infection. The severity of the disease depends on the gestational age at transmission. First trimester infections are more severe, but less frequent, than third trimester infections. Acute maternal infection is diagnosed by seroconversion or by the detection of IgM antibodies and a low IgG avidity test. In these cases, spiramycin should be initiated to prevent transmission to the fetus. For identification of fetal infection, polymerase chain reaction (PCR) testing of amniotic fluid after 18 weeks gestation should be performed. If fetal infection is confirmed, the mothers should be treated with pyrimethamine, sulfadiazine and folinic acid. Most infants infected in utero are born with no obvious signs of toxoplasmosis, but up to 80% developed learning and visual disabilities later in life. Neonatal diagnosis with IgM/IgA antibodies or blood/cerebrospinal fluid PCR may be difficult because false-negative results frequently occur. In these cases diagnosis is possible by demonstrating a rise in IgG titers during follow-up or by the detection of antibodies beyond one year of age. Early treatment with pyrimethamine and sulfadiazine may improve the ophthalmologic and neurological outcome. Congenital toxoplasmosis is a preventable disease. Pre-pregnancy screening and appropriate counseling regarding prevention measures in seronegative women may prevent fetal infection.
Cevik, Ayhan; Olgunturk, Rana; Kula, Serdar; Saylan, Berna; Pektas, Ayhan; Oguz, Deniz; Tunaoglu, Sedef
Objective. The objective of this study was to determine the frequency of pulmonary arterial hypertension (PAH) in congenital heart disease (CHD) with an isolated, large left-to-right shunt and to indicate the factors in the development of PAH. Methods. The pressure measurements in the cardiac chambers and the calculations based on the Fick's principle were compared among 3 separate groups of patients, respectively, with PAH, with hyperkinetic pulmonary hypertension (HPH), and with neither PAH nor HPH. Results. PAH was diagnosed in 30 (12.3%) patients, HPH in 35 (14.4%), while 177 (73.1%) were free of either. The highest risk for the development of PAH was found in the presence of perimembranous ventricular septal defect. A statistically significant difference was seen among these groups as to their left atrial pressure (p = 0.005) and the mean pulmonary arterial pressure (PAPmean; p < 0.001). While a correlation was present between RpI on one hand and age on the other (p = 0.014), a multiple linear regression could not evidence any correlation among age (p = 0.321), gender (p = 0.929). Conclusion. Our findings do not allow establishing a correlation between the duration of the high pulmonary flow and pulmonary vascular resistance increase or PAH development in isolated left-to-right shunts with congenital heart diseases. PMID:23862073
Chen, Jodi; Zimmerman, Robert A.; Jarvik, Gail P.; Nord, Alex S.; Clancy, Robert R.; Wernovsky, Gil; Montenegro, Lisa M.; Hartman, Diane M.; Nicolson, Susan C.; Spray, Thomas L.; Gaynor, J. William; Ichord, Rebecca
Background The prevalence of perioperative stroke in infants undergoing operations for congenital heart disease has not been well described. The objectives of this study were to determine the prevalence of stroke as assessed by postoperative brain magnetic resonance imaging (MRI), characterize the neuroanatomic features of focal ischemic injury, and identify risk factors for its development. Methods Brain MRI was performed in 122 infants 3 to 14 days after cardiac operation with cardiopulmonary bypass, with or without deep hypothermic circulatory arrest. Preoperative, intraoperative, and postoperative data were collected. Risk factors were tested by logistic regression for univariate and multivariate associations with stroke. Results Stroke was identified in 12 of 122 patients (10%). Strokes were preoperative in 6 patients and possibly intraoperative or postoperative in the other 6 patients, and were clinically silent except in 1 patient who had clinical seizures. Arterial-occlusive and watershed infarcts were identified with equal distribution in both hemispheres. Multivariate analysis identified lower birth weight, preoperative intubation, lower intraoperative hematocrit, and higher blood pressure at admission to the cardiac intensive care unit postoperatively as significant factors associated with stroke. Prematurity, younger age at operation, duration of cardiopulmonary bypass, and use of deep hypothermic circulatory arrest were not significantly associated with stroke. Conclusions The prevalence of stroke in infants undergoing operations for congenital heart disease was 10%, half of which occurred preoperatively. Most were clinically silent and undetected without neuroimaging. Mechanisms included thromboembolism and hypoperfusion, with patient-specific, procedure-specific, and postoperative contributions to increased risk. PMID:19699905
Glass, Hannah C; Bowman, Chelsea; Chau, Vann; Moosa, Alisha; Hersh, Adam L; Campbell, Andrew; Poskitt, Kenneth; Azakie, Anthony; Barkovich, A James; Miller, Steven P; McQuillen, Patrick S
More than 60% of newborns with severe congenital cardiac disease develop perioperative brain injuries. Known risk factors include: pre-operative hypoxemia, cardiopulmonary bypass characteristics, and post-operative hypotension. Infection is an established risk factor for white matter injury in premature newborns. In this study, we examined term infants with congenital cardiac disease requiring surgical repair to determine whether infection is associated with white matter injury. Acquired infection was specified by site - bloodstream, pneumonia, or surgical site infection - according to strict definitions. Infection was present in 23 of 127 infants. Pre- and post-operative imaging was evaluated for acquired injury by a paediatric neuroradiologist. Overall, there was no difference in newly acquired post-operative white matter injury in infants with infection (30%), compared to those without (31%). When stratified by anatomy, infants with transposition of the great arteries, and bloodstream infection had an estimated doubling of risk of white matter injury that was not significant, whereas those with single ventricle anatomy had no apparent added risk. When considering only infants without stroke, the estimated association was higher, and became significant after adjusting for duration of inotrope therapy. In this study, nosocomial infection was not associated with white matter injury. Nonetheless, when controlling for risk factors, there was an association between bloodstream infection and white matter injury in selected sub-populations. Infection prevention may have the potential to mitigate long-term neurologic impairment as a consequence of white matter injury, which underscores the importance of attention to infection control for these patients.
Moons, P; Barrea, C; De Wolf, D; Gewillig, M; Massin, M; Mertens, L; Ovaert, C; Suys, B; Sluysmans, T
Sports camps for children with cardiac anomalies have existed for many years. However, no formal evaluation of the benefits of attending such camps has been undertaken heretofore. We assessed potential changes in the self-perceived health of children with congenital heart disease who attended a special sports camp. Thirty-one children with cardiac anomalies attended a 3-day multisports camp. Sixteen children, all of whom were 10 years or older, literate, and Dutch- or French-speaking, completed the Child Health Questionnaire (CHQ-CF87) before and after attending the camp. The scores of the children were compared with those of healthy peers by calculating mean standardized differences. After attendance at the sports camp, the children achieved significant improvements in the self-perception of their physical functioning, role functioning due to emotional problems, role functioning due to behavioral problems, mental health, and general behavior. The children's self-esteem and general behavior after the camp were significantly better than that of their healthy counterparts. We conclude that children with congenital heart disease who participate in activities at special sports camps may reap benefits in terms of their subjective health status. Although further research is needed, we recommend the participation in sport activities by children with heart defects, and more specifically their participation in sports camps.
Meier, L M; Meineri, M; Qua Hiansen, J; Horlick, E M
Advances in catheter-based interventions in structural and congenital heart disease have mandated an increased demand for three-dimensional (3D) visualisation of complex cardiac anatomy. Despite progress in 3D imaging modalities, the pre- and periprocedural visualisation of spatial anatomy is relegated to two-dimensional flat screen representations. 3D printing is an evolving technology based on the concept of additive manufacturing, where computerised digital surface renders are converted into physical models. Printed models replicate complex structures in tangible forms that cardiovascular physicians and surgeons can use for education, preprocedural planning and device testing. In this review we discuss the different steps of the 3D printing process, which include image acquisition, segmentation, printing methods and materials. We also examine the expanded applications of 3D printing in the catheter-based treatment of adult patients with structural and congenital heart disease while highlighting the current limitations of this technology in terms of segmentation, model accuracy and dynamic capabilities. Furthermore, we provide information on the resources needed to establish a hospital-based 3D printing laboratory.
Zabala, Luis M; Guzzetta, Nina A
Children with cyanotic congenital heart disease (CCHD) have complex alterations in their whole blood composition and coagulation profile due to long-standing hypoxemia. Secondary erythrocytosis is an associated physiological response intended to increase circulating red blood cells and oxygen carrying capacity. However, this response is frequently offset by an increase in whole blood viscosity that paradoxically reduces blood flow and tissue perfusion. In addition, the accompanying reduction in plasma volume leads to significant deficiencies in multiple coagulation proteins including platelets, fibrinogen and other clotting factors. On the one hand, these patients may suffer from severe hyperviscosity and subclinical 'sludging' in the peripheral vasculature with an increased risk of thrombosis. On the other hand, they are at an increased risk for postoperative hemorrhage due to a complex derangement in their hemostatic profile. Anesthesiologists caring for children with CCHD and secondary erythrocytosis need to understand the pathophysiology of these alterations and be aware of available strategies that lessen the risk of bleeding and/or thrombosis. The aim of this review is to provide an updated analysis of the systemic effects of long-standing hypoxemia in children with primary congenital heart disease with a specific focus on secondary erythrocytosis and hemostasis.
Krieger, Eric V; Valente, Anne Marie
Heart failure (HF) is the leading cause of death in adults with repaired congenital heart disease (CHD). However there is currently little evidence to guide treatment strategies in this growing group of patients. Unlike the majority of HF, which is usually caused by LV systolic or diastolic dysfunction, CHD-HF is more often a consequence of RV disease, valve dysfunction, shunting or pulmonary hypertension. It is therefore not appropriate to extrapolate from the acquired HF literature and apply it to this heterogeneous population of CHD patients. Additionally, patients with CHD have been excluded from most large trials of medical or device therapy of HF, which has resulted in small retrospective and underpowered studies in the CHD population. This article critically reviews the current knowledge about CHD-HF, paying particular attention to medical therapy in different CHD populations, cardiac resynchronisation therapy and implantable cardiac defibrillators, and the challenges of heart transplantation and mechanical circulatory support in CHD patients.
Conti, Simon L; Eisenberg, Michael L
As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted). Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age. PMID:26975491
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.
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
Hafner, E; Scholler, J; Schuchter, K; Sterniste, W; Philipp, K
Our purpose was to evaluate the efficacy of level two ultrasound screening for the detection of congenital heart defects (CHD) in a low-risk population by using three standardized cuts. Within a period of four years a total of 6727 pregnant women of a low-risk population undertook several ultrasound examinations on the basis of screening for fetal malformations. All ultrasound examinations were performed by three experienced doctors. At every single scan three standardized cuts (apical and lateral four-chamber view, crossing over of the great arteries) were obtained in order to detect congenital heart defects. Of 87 CHDs (1.33 per cent of the examined women) 39 (43.8 per cent) were diagnosed prenatally. The detection rate was 10/48 (20.8 per cent) in the presence of VSD, ASD2 or combined ASD2 + VSD, the detection rate was 29/39 (74.3 per cent) in the presence of other forms of congenital heart disease. None of the 38 missed cases in the first group but three of the ten missed CHDs in the second group had emergency neonatological problems. Aneuploidy and/or other malformations existed in 22/87 cases of CHD. The obstetrical management was changed in nearly all cases after the diagnosis of a CHD. Twenty-two women opted for termination of pregnancy because of additional fetal malformations or chromosomal defects. Five women were transferred prenatally to a tertiary centre for neonatal cardiac surgery. Ten deliveries were performed in the presence of a neonatologist. Good detection rates for CHD can be achieved in a low-risk population on the basis of level two ultrasound screening by using the above mentioned three cuts and thus, the perinatal mortality and morbidity can be improved.
Yang, Li; Pei, Qiu-Yan; Li, Yun-Tao; Yang, Zhen-Juan
Background: Fetal congenital heart anomalies are the most common congenital anomalies in live births. Fetal echocardiography (FECG) is the only prenatal diagnostic approach used to detect fetal congenital heart disease (CHD). FECG is not widely used, and the antenatal diagnosis rate of CHD varies considerably. Thus, mastering the anatomical characteristics of different kinds of CHD is critical for ultrasound physicians to improve FECG technology. The aim of this study is to investigate the applications of a fetal CHD anatomic database in FECG teaching and training program. Methods: We evaluated 60 transverse section databases including 27 types of fetal CHD built in the Prenatal Diagnosis Center in Peking University People's Hospital. Each original database contained 400–700 cross-sectional digital images with a resolution of 3744 pixels × 5616 pixels. We imported the database into Amira 5.3.1 (Australia Visage Imaging Company, Australia) three-dimensional (3D) software. The database functions use a series of 3D software visual operations. The features of the fetal CHD anatomical database were analyzed to determine its applications in FECG continuing education and training. Results: The database was rebuilt using the 3D software. The original and rebuilt databases can be displayed dynamically, continuously, and synchronically and can be rotated at arbitrary angles. The sections from the dynamic displays and rotating angles are consistent with the sections in FECG. The database successfully reproduced the anatomic structures and spatial relationship features of different fetal CHDs. We established a fetal CHD anatomy training database and a standardized training database for FECG. Ultrasound physicians and students can learn the anatomical features of fetal CHD and FECG through either centralized training or distance education. Conclusions: The database of fetal CHD successfully reproduced the anatomic structures and spatial relationship of different kinds of
Buda, Piotr; Friedman-Gruszczyńska, Joanna; Książyk, Janusz
Congenital diarrhoea of heterogenic etiology is a rare cause of chronic diarrhoea. Characteristic features are: onset in the first weeks of life, life-threatening severe dehydratation and electrolyte disorders leading to a necessity of long-term parenteral nutrition. The clinical onset may be delayed and the degree of diarrhoea may be modest, making the diagnosis difficult. The main causes of congenital diarrhoea such as intestine electrolytes, carbohydrates, lipid and protein transport disorders and congenital enzymatic deficiencies, enterocyte polarization disorders, hormonal, immunological, metabolic, genetic and congenital anatomic disorders are presented in the paper. Some of them, such as: microvillus inclusion disease, tufting enteropathy, intestinal anedocrynosis, IPEX syndrome (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome) have been described recently. One of the basic investigations, when congenital diarrhea is suspected, is general examination of the stool, its electrolyte concentration and serum electrolytes and blood gas analysis. Often, small bowel biopsy with histological examination (with the use of electronic microscopy and PAS staining) is indicated. In some cases molecular examination is possible and indicated. In differential diagnosis other, more frequent causes of chronic diarrhea of infancy, have to be excluded. In most of the cases of congenital diarrhoea there is no casual treatment available - usually long-term parenteral nutrition is necessary.
Ho, Genevieve; Cardamone, Michael; Farrar, Michelle
Myotonic dystrophy type 1 (DM1) is multisystem disease arising from mutant CTG expansion in the non-translating region of the dystrophia myotonica protein kinase gene. While DM1 is the most common adult muscular dystrophy, with a worldwide prevalence of one in eight thousand, age of onset varies from before birth to adulthood. There is a broad spectrum of clinical severity, ranging from mild to severe, which correlates with number of DNA repeats. Importantly, the early clinical manifestations and management in congenital and childhood DM1 differ from classic adult DM1. In neonates and children, DM1 predominantly affects muscle strength, cognition, respiratory, central nervous and gastrointestinal systems. Sleep disorders are often under recognised yet a significant morbidity. No effective disease modifying treatment is currently available and neonates and children with DM1 may experience severe physical and intellectual disability, which may be life limiting in the most severe forms. Management is currently supportive, incorporating regular surveillance and treatment of manifestations. Novel therapies, which target the gene and the pathogenic mechanism of abnormal splicing are emerging. Genetic counselling is critical in this autosomal dominant genetic disease with variable penetrance and potential maternal anticipation, as is assisting with family planning and undertaking cascade testing to instigate health surveillance in affected family members. This review incorporates discussion of the clinical manifestations and management of congenital and childhood DM1, with a particular focus on hypersomnolence and sleep disorders. In addition, the molecular genetics, mechanisms of disease pathogenesis and development of novel treatment strategies in DM1 will be summarised. PMID:26566479
Zhu, Jun-yi; Fu, Yulong; Nettleton, Margaret; Richman, Adam; Han, Zhe
Genomic sequencing has implicated large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system is needed to validate gene associations with pathology. We developed a Drosophila-based functional system to screen candidate disease genes identified from Congenital Heart Disease (CHD) patients. 134 genes were tested in the Drosophila heart using RNAi-based gene silencing. Quantitative analyses of multiple cardiac phenotypes demonstrated essential structural, functional, and developmental roles for more than 70 genes, including a subgroup encoding histone H3K4 modifying proteins. We also demonstrated the use of Drosophila to evaluate cardiac phenotypes resulting from specific, patient-derived alleles of candidate disease genes. We describe the first high throughput in vivo validation system to screen candidate disease genes identified from patients. This approach has the potential to facilitate development of precision medicine approaches for CHD and other diseases associated with genetic factors. DOI: http://dx.doi.org/10.7554/eLife.22617.001 PMID:28084990
Frank, David B.; Hanna, Brian D.
Pulmonary arterial hypertension (PAH) is an uncommon but serious disease characterized by severe pulmonary vascular disease and significant morbidity and mortality. PAH associated with congenital heart disease (APAH-CHD) is one etiology of PAH that has innate characteristics delineating it from other forms of PAH. The patient with APAH-CHD presents with unique challenges consisting of not only pulmonary vascular disease but also the complexity of the cardiac lesion. Eisenmenger syndrome (ES) represents the severe end of the spectrum for disease in APAH-CHD. Over time, systemic-to-pulmonary shunting through cardiac defects increases pulmonary vascular resistance to levels significant enough to reverse shunting across the defect. Historically, ES patients have been reported to have better outcomes than IPAH despite similarities in pulmonary vascular disease. However, recent studies are challenging this notion. Nonetheless, APAH-CHD survival has improved with the advent of modern PAH targeted therapies. New therapeutic options have allowed us to reconsider the dogma of inoperability in APAH-CHD patients with unrepaired defects. Certainly advances have been made, however, investigators must continue to advance the field through controlled clinical trials in both adult and pediatric APAH-CHD patients. PMID:25604592
Derby, Christopher D; Kolcz, Jacek; Kerins, Paul J; Duncan, Daniel R; Quezada, Emilio; Pizarro, Christian
Extracorporeal membrane oxygenation (ECMO) has become the standard technique of mechanical support for the failing circulation following repair of congenital heart lesions. The objective of this study was to identify predictors of survival in patients requiring postcardiotomy ECMO. The Aristotle score, a method developed to evaluate quality of care based on complexity, was investigated as a potential predictor of outcome. Between 2003 and 2005, 37 patients required ECMO following corrective surgery for congenital heart disease. Records were reviewed retrospectively with emphasis on factors affecting survival to discharge. The comprehensive Aristotle complexity score was calculated for each patient. Overall, 28 patients (76%) survived to decannulation and 17 patients (46%) survived to discharge. There were 24 (65%) neonates and 10 patients (27%) with single ventricle physiology, with a hospital survival of 42% (10 of 24) and 50% (5 of 10), respectively. Univariate factors associated with survival included Aristotle score, duration of support, reexploration, multiple organ failure, and number of complications. Age, weight, and single-ventricle physiology were not significant. In a logistic regression model, an Aristotle score < 14 was identified as a predictor of survival (OR 0.12, CI 0.02-0.87). The Aristotle score is predictive of outcome in patients requiring postcardiotomy ECMO and may serve as a uniform criterion when comparing and evaluating quality of care and performance in this complex patient population.
Salazar, Marleny; Villalba, Guiovanny; Mateus, Heidi; Villegas, Victoria; Fonseca, Dora; Núñez, Federico; Caicedo, Víctor; Pachón, Sonia; Bernal, Jaime E
Cardiac defects are the most frequent congenital malformations, with an incidence estimated between 4 and 12 per 1000 newborns. Their etiology is multifactorial and might be attributed to genetic predispositions and environmental factors. Since 1990 these types of pathologies have been associated with 22q11 microdeletion. In this study, the frequency of microdeletion 22q11 was determined in 61 patients with non-syndromic congenital heart disease. DNA was extracted from peripheral blood and TUPLE1 and STR D10S2198 genes were amplified by multiplex PCR and visualized in agarose gels. Gene content was quantified by densitometry. Three patients were found with microdeletion 22q11, representing a 4.9% frequency. This microdeletion was associated with two cases of Tetralogy of Fallot and a third case with atrial septal defect (ASD). In conclusion, the frequency for microdeletion 22q11 in the population analyzed was 4.9%. The cases that presented Teratology of Fallot had a frequency for this microdeletion of 7.4% and for ASD of 11.1%.
Fetal ultrasounds are almost routinely carried out during pregnancies in Western society. It has led to the in-utero diagnosis of congenital malformations, and in skilled hands, complex congenital heart disease which carries a significant morbidity and definite mortality. That has allowed for counselling of the affected parents who may have the option of whether to continue with the pregnancy. Such counselling, however is not without its difficulties and ethical dilemmas. They range from attempting to inform at times very distressed parents, the nature and implications of their fetal abnormality, the outcome and risks involved in the interventions which may be required, while at the same time being asked to prognosticate the long-term outcomes. Such counselling at times is based on incomplete information obtained or refers to lesions that may evolve during the rest of the pregnancy. In addition, the information provided is unable to factor in possible advances that may occur in the future which may alter the quality of life and outcomes of the affected individuals. Other members of the concerned extended family may wish to have a say in the decision making process. The clinicians themselves may wish to take into account not only the burden to the family emotionally and in terms of the possible interventions - surgical or otherwise, hospitalisations, the risks of complications, and so on - but also the financial and other costs borne by the community. This article highlights the problems encountered and raises ethical questions to encourage discussion to guide the clinicians involved.
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
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.
Moreno García, M; Gómez Rodríguez, M J; Barreiro Miranda, E
Congenital heart malformations are the most common of all birth defects, affecting 0.5-1% of all live births. Some of these malformations are due to genetic anomalies. Patterns of autosomal dominant, autosomal recessive and X-linked inheritance have been described. Mitochondrial inheritance and chromosomal anomalies can also be responsible for congenital heart malformations. Several genes for congenital heart defects have been identified. We review current knowledge on the genetic etiology of congenital heart disease.
Collins, R Thomas; Chang, Di; Sandlin, Adam; Goudie, Anthony; Robbins, James M
Most patients with single ventricle (SV) congenital heart disease are expected to survive to adulthood. Women with SV are often counseled against pregnancy; however, data on pregnancies in these women are lacking. We sought to evaluate in-hospital outcomes of pregnancy in women with SV. We used nationally representative data from the 1998 to 2012 National Inpatient Sample to identify women ≥18 years of age admitted to the hospital with International Classification of Diseases-9th Revision codes for an intrauterine pregnancy and a diagnosis of hypoplastic left heart syndrome, tricuspid atresia, or common ventricle. A matched comparison group without a diagnosis of congenital heart disease or pulmonary hypertension was identified from the database. National estimates of hospitalizations were calculated. Length of stay, hospital charges, and complications were analyzed and compared between groups. Charge data were adjusted to 2012 dollars. There were 282 admissions of pregnant women with SV (69% with deliveries) and 1,405 admissions in the control group (88% with deliveries). Vaginal delivery was more common in SV (74% vs 71%, p <0.001). Length of stay (4.1 ± 0.91 vs 2.8 ± 0.18 days, p <0.001) and charges ($30,787 ± 8,109 vs $15,536 ± 1,006, p <0.0001) were higher in the SV group. Complications occurred in most SV admissions and were more common in the SV group than in the control group. No deaths occurred. Cardiovascular complications occurred in 25% of pregnancy-related hospitalizations, although in-hospital pregnancy-related death is rare. Vaginal delivery is common in these patients. These data suggest that pregnancy and vaginal delivery can be tolerated in women with SV, although the risk for a cardiovascular event is significantly higher than in the general population.
Sabzevari, Sakinne; Nematollahi, Monirsadat; Mirzaei, Tayebeh; Ravari, Ali
ABSTRACT Background: Mothers play a key role in caring for their sick children. Their experiences of care were influenced by culture, rules, and the system of health and care services. There are few studies on maternal care of children with congenital heart disease. Also, each of them has studied a particular aspect of care. The present research aimed to understand care experiences of mothers of children with congenital heart disease. Methods: A conventional content analysis was used to obtain rich data. The goal of content analysis is “to provide knowledge and deeper understanding of the phenomenon under the study”. The study was conducted in Kerman, Iran in 2014, on mothers of children with CHD. The purposive sampling technique was used to select the participants. Participants were 14 mothers of children with CHD and one father and one nurse of open heart surgery unit, from two hospitals affiliated with Kerman University of Medical Sciences. Eighteen semi-structured interviews were constructed. Data were analyzed using conventional content analysis. MAXQDA 2007 software (VERBI GmbH, Berlin, Germany) was used to classify and manage the coding. Constant comparative method was done for data analysis. The reliability and validity of the findings, including the credibility, confirm ability, dependability, and transferability, were assessed. Results: According to the content analysis, the main theme was the catastrophic burden of child care on mothers that included three categories: 1) the tension resulting from the disease, 2) involvement with internal thoughts, and 3) difficulties of care process Conclusion: The results of this study may help health care professionals to provide supportive and educational packages to the patients, mothers and Family members until improving the management of patient’s care. PMID:27713900
Soens, Zachry T.; Li, Yuanyuan; Zhao, Li; Eblimit, Aiden; Dharmat, Rachayata; Li, Yumei; Chen, Yiyun; Naqeeb, Mohammed; Fajardo, Norma; Lopez, Irma; Sun, Zhaoxia; Koenekoop, Robert K.; Chen, Rui
Purpose Leber congenital amaurosis (LCA) is an early-onset form of retinal degeneration and six of the 22 known LCA disease genes encode photoreceptor ciliary proteins. Despite the identification of 22 LCA disease genes, the genetic basis of approximately 30% of LCA patients remains unknown. We sought to investigate the cause of disease in the remaining 30% by examining cilia-associated genes. Methods Whole-exome sequencing was performed on an LCA cohort of 212 unsolved probands previously screened for mutations in known retinal disease genes. Immunohistochemistry using mouse retinas was used to confirm protein localization and zebrafish were used to perform rescue experiments. Results A homozygous nonsynonymous mutation was found in a single proband in CLUAP1, a gene required for ciliogenesis and cilia maintenance. Cluap1 knockout zebrafish exhibit photoreceptor cell death as early as five days post fertilization and rescue experiments revealed that our proband’s mutation is significantly hypomorphic. Conclusion Consistent with the knowledge that CLUAP1 plays an important role in cilia function and that cilia are critical to photoreceptor function, our results indicate that hypomorphic mutations in CLUAP1 can result in dysfunctional photoreceptors without systemic abnormalities. This represents the first report linking mutations in CLUAP1 to human disease and establishes CLUAP1 as a candidate LCA gene. PMID:26820066
Dorn, Cornelia; Grunert, Marcel; Sperling, Silke R
Congenital heart diseases (CHD) represent the most common birth defect in human. The majority of cases are caused by a combination of complex genetic alterations and environmental influences. In the past, many disease-causing mutations have been identified; however, there is still a large proportion of cardiac malformations with unknown precise origin. High-throughput sequencing technologies established during the last years offer novel opportunities to further study the genetic background underlying the disease. In this review, we provide a roadmap for designing and analyzing high-throughput sequencing studies focused on CHD, but also with general applicability to other complex diseases. The three main next-generation sequencing (NGS) platforms including their particular advantages and disadvantages are presented. To identify potentially disease-related genomic variations and genes, different filtering steps and gene prioritization strategies are discussed. In addition, available control datasets based on NGS are summarized. Finally, we provide an overview of current studies already using NGS technologies and showing that these techniques will help to further unravel the complex genetics underlying CHD.
Gupta, Kirti; Radotra, Bishan Dass; Suri, Deepti; Sharma, Kusum; Saxena, Akshay Kumar; Singhi, Pratibha
We describe autopsy findings in a 5-month-old infant with disseminated tuberculosis and congenital cytomegalovirus disease. The infant manifested with tubercular meningitis complicating as ruptured mycotic right middle cerebral artery aneurysm. Infiltrative, proliferative, and necrotizing vascular pathologies have been described; however, the occurrence of these is dependent on the duration of illness. The vessel pathology appears to be a payback of its immersion in the local inflammatory cell-rich exudates. Strokes early in the course of the disease are believed to be a consequence of vasospasm, and those occurring later during the disease course are due to proliferative intimal disease. Intracranial mycotic aneurysm following tubercular meningitis developing at such a young age has not been reported in the literature. The lung lesions in a congenitally transmitted tuberculosis and cytomegalovirus disease have also been elaborated.
Moola, Fiona; Fusco, Caroline; Kirsh, Joel A.
Despite the benefits of physical activity for youth with congenital heart disease (CHD), most patients are inactive. Although literature has addressed medical and psychological barriers to participation, little is known about the social barriers that youth encounter. This qualitative study explored sociocultural barriers to physical activity from…
Roberts, Jillian; MacMath, Sheryl
Due to improved medical procedures, more and more children with congenital heart disease are entering the school system. In order to help both school and health professionals involved in the education of children, we provide a brief review of the literature, review real-life dilemmas that school personnel face on a daily basis, and interpret the…
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...
Passantino, Annamaria; Masucci, Marisa
Many of the congenital neurologic diseases can result in incapacity or death of the animal. Some of them, such as idiopathic epilepsy and hydrocephalus, exhibit breed or familial predisposition and a genetic basis was proved or suggested. Some diseases can be presumptively diagnosed after a detailed signalment (breed predisposition), history (e.g. family history because many of these defects have familial tendencies), and through physical exam; other diagnostic methods (radiography, computed tomography, magnetic resonance, electrophysiologic tests, etc.) can provide supportive evidence for the congenital defect and help to confirm the diagnosis. Some cases can lead to civil law-suits when the lesions are congenital, but not easily recognizable, or when the lesions are hereditary but tend to became manifest only after some time (more than 12 months after the date of purchase, e.g., after the vice-free guarantee period has expired). Moreover, quite frequently an early diagnosis is not made because there are delays in consulting the veterinarian or the general practitioner veterinarian does not perceive subtle signs. This study was designed to focus on the medico-legal aspects concerning the buying and selling in Italy of dogs and cats affected by congenital and hereditary neurologic diseases that could constitute vice in these animals. While adequate provisions to regulate in detail the various aspects of pet sale have still to be drawn up by legislators, it may be helpful to involve breeders, by obliging them by contract to extend guarantees in the case of hereditary lesions, including neurologic diseases.
Talwar, Sachin; Keshri, Vikas Kumar; Choudhary, Shiv Kumar; Gupta, Saurabh Kumar; Ramakrishnan, Sivasubramanian; Juneja, Rajnish; Saxena, Anita; Kothari, Shyam Sunder; Airan, Balram
In this review, we discuss specific surgical strategies that are used in patients with congenital heart disease and severe pulmonary arterial hypertension. Our own experience, with the use of unidirectional valved patches in managing these patients, is also discussed in detail. PMID:27326218
Goldman, Allen S.; And Others
There are two general categories (not necessarily mutually exclusive) of congenital defects: (1) abnormalities that have an hereditary basis, such as single and multiple genes, or chromosomal abberration; and (2) abnormalities that are caused by nonhereditary factors, such as malnutrition, maternal disease, radiation, infections, drugs, or…
Newcombe, Jennifer; Fry-Bowers, Eileen
Neonates with critical congenital heart disease (CCHD) are vulnerable to malnutrition during the post-operative period due to hypermetabolism and hypercatabolism. To improve nutritional outcomes during hospitalization, a nurse led post-operative enteral feeding protocol was implemented at a large U.S. children's hospital. During an eight-month implementation period, twenty-one neonates met protocol inclusion criteria. Days for neonates to achieve goal caloric feedings (120kcal/kg/day) were decreased. A one-way repeated measures analysis of variance showed serum albumin levels and serial anthropometric measurements improved significantly throughout hospitalization (p<0.005). Results from this quality improvement project show standardizing nutritional care for neonates with CCHD during the post-operative period is an effective way to improve nutritional outcomes and shorten length of hospital stay.
Gilbert, K; Lam, H-I; Pontré, B; Cowan, B R; Occleshaw, C J; Liu, J Y; Young, A A
Cardiac malformations are the most common birth defect. Better interventions in early life have improved mortality for children with congenital heart disease, but heart failure is a significant problem in adulthood. These patients require regular imaging and analysis of biventricular (left and right ventricular) function. In this study, we describe a rapid method to analyse left and right ventricular shape and function from cardiac MRI examinations. A 4D (3D+time) finite element model template is interactively customized to the anatomy and motion of the biventricular unit. The method was validated in 17 patients and 10 ex-vivo hearts. Interactive model updates were achieved through preconditioned conjugate gradient optimization on a multithread system, and by precomputing points predicted from a coarse mesh optimization.
Matsuda, Hikaru; Fukushima, Norihide; Ichikawa, Hajime; Sawa, Yoshiki
A 41-year-old male with heterotaxy (left isomerism) and dextrocardia composed by single ventricle, absent inferior vena cava, bilateral superior vena cava (SVC), common atrioventricular valve has received orthotopic heart transplantation (HTx) after long waiting period as Status-1. Reconstructions of bilateral SVC and hepatic vein route were successful without use of prosthetic material, and the donor heart was placed in the left mediastinum. In spite of satisfactory early recovery, the patient expired 4 months after transplantation mainly from fungal infection which developed following humoral rejection. HTx for adult patients with complex congenital heart disease is demanding in technical as well as pre- and post-transplant management, and indication should be critically determined.
Chopski, Steven G; Moskowitz, William B; Stevens, Randy M; Throckmorton, Amy L
The use of mechanical circulatory support (MCS) devices is a viable therapeutic treatment option for patients with congestive heart failure. Ventricular assist devices, cavopulmonary assist devices, and total artificial heart pumps continue to gain acceptance as viable treatment strategies for both adults and pediatric patients as bridge-to-transplant, bridge-to-recovery, and longer-term circulatory support alternatives. We present a review of the current and future MCS devices for patients having congenital heart disease (CHD) with biventricular or univentricular circulations. Several devices that are specifically designed for patients with complex CHD are in the development pipeline undergoing rigorous animal testing as readiness experiments in preparation for future clinical trials. These advances in the development of new blood pumps for patients with CHD will address a significant unmet clinical need, as well as generally improve innovation of the current state of the art in MCS technology.
Chu, Peter D; Loynachan, Alan T
A 14-mo-old South American coati (Nasua nasua) was submitted for necropsy to the University of Kentucky Veterinary Diagnostic Laboratory. The coati had a history of progressive neurologic signs beginning 3 mo prior to euthanasia. At necropsy, the coati was in thin body condition, but no other significant findings were evident. Histopathologic findings included moderate distension of neuronal cell bodies by finely vesiculated cytoplasm within the cerebrum, cerebellum, spinal cord, and intestinal ganglia. Hepatocytes and macrophages in the lung, spleen, and liver were similarly affected. Transmission electron microscopy showed numerous electrondense membranous cytoplasmic bodies, swirls, and vesicular profiles within neuronal lysosomes in the brain. To the authors' knowledge, this is the first report of a naturally occurring congenital glycogen storage disease in a South American coati and the family Procyonidae.
Iacobazzi, D; Suleiman, M-S; Ghorbel, M; George, S J; Caputo, M; Tulloh, R M
RV hypertrophy (RVH) is one of the triggers of RV failure in congenital heart disease (CHD). Therefore, improving our understanding of the cellular and molecular basis of this pathology will help in developing strategic therapeutic interventions to enhance patient benefit in the future. This review describes the potential mechanisms that underlie the transition from RVH to RV failure. In particular, it addresses structural and functional remodelling that encompass contractile dysfunction, metabolic changes, shifts in gene expression and extracellular matrix remodelling. Both ischaemic stress and reactive oxygen species production are implicated in triggering these changes and will be discussed. Finally, RV remodelling in response to various CHDs as well as the potential role of biomarkers will be addressed.
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
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
Henningfeld, Jennifer; Loomba, Rohit S; Encalada, Santiago; Magner, Kristin; Pfister, Jennifer; Matthews, Anne; Foy, Andrew; Mikhailov, Theresa
We present the unique case of an 8 month old infant who required extracorporeal membrane oxygenation (ECMO) after neonatal repair of tetralogy of Fallot. While on ECMO, he developed grade 3 intraventricular hemorrhage resulting in hydrocephalus requiring ventriculoperitoneal (VP) shunt placement at 5 months of life. He presented to cardiology clinic with a 2-month history of poor weight gain, tachypnea, and grunting and was found to have a large right sided pleural effusion. This was proven to be cerebrospinal fluid (CSF) accumulation secondary to poor peritoneal absorption with subsequent extravasation of CSF into the thoracic cavity via a diaphragmatic defect. After diaphragm repair, worsening ascites from peritoneal malabsorption led to shunt externalization and ultimate conversion to a ventriculoatrial (VA) shunt. This is the second reported case of VA shunt placement in a child with congenital heart disease and highlights the need to consider CSF extravasation as the cause of pleural effusions in children with VP shunts.
Koyak, Zeliha; de Groot, Joris R; Mulder, Barbara J M
Arrhythmias are a major cause of morbidity, mortality and hospital admission in adults with congenital heart disease (CHD). The etiology of arrhythmias in this population is often multifactorial and includes electrical disturbances as part of the underlying defect, surgical intervention or hemodynamic abnormalities. Despite the numerous existing arrhythmia management tools including drug therapy, pacing and ablation, management of arrhythmias in adults with CHD remains difficult and challenging. Owing to improvement in mapping and ablation techniques, ablation and arrhythmia surgery are being performed more frequently in adults with CHD. However, there is little information on the long-term results of these treatment strategies. The purpose of this article is therefore to review the available data on nonpharmacological treatment of cardiac arrhythmias in adult patients with CHD and to give an overview of the available data on the early and late outcomes of these treatment strategies.
Rothman, K J; Fyler, D C; Goldblatt, A; Kreidberg, M B
A history of oral contraceptive use, hormonal pregnancy tests, prescribed hormones and other drugs was obtained from 390 mothers of infants with congenital heart disease and 1254 mothers of normal infants in Massachusetts. The data show a small positive association between estrogen/progesterone exposure and cardiac malformation, the prevalence ratio estimate of exposed to non-exposed being 1.5 (90 per cent confidence limits are 1.0, 2.1). No association was evident, however, between hormones and trunco-conal or any other class of defect among the cases, an observation which casts doubt on a causal relationship betweem hormones and cardiovascular malformations. Several other drugs were reported more frequently by cases' mothers. These include: ampicillin; aspirin; a combined anti-nausea agent (doxylamine succinate, dicyclomine hydrochloride and pyridoxine hydrochloride); chlordiazopoxide, codeine, diazepam, diphenylhydantoin; insulin; phenobarbital; phenothiazine; phenylephrine; and tetracycline.
Adams Bornemeier, Renee; Fellows, Kenneth E.; Fogel, Mark A.; Weinberg, Paul M.
Anatomic delineation of the heart and great vessels is a necessity when managing children with congenital heart disease. Spatial orientation of the vessels and chambers in the heart and the heart itself may be quite abnormal. Though magnetic resonance imaging provides a noninvasive means for determining the anatomy, the intricate interrelationships between many structures are difficult to conceptualize from a 2-D format. Taking the 2-D images and using a volumetric analysis package allows for a 3-D replica of the heart to be created. This model can then be used to view the anatomy and spatial arrangement of the cardiac structures. This information may be utilized by the physicians to assist in the clinical management of these children.
Hom, Lisa A; Silber, Tomas J; Ennis-Durstine, Kathleen; Hilliard, Mary Anne; Martin, Gerard R
Critical congenital heart disease (CCHD) screening is rapidly becoming the standard of care in the United States after being added to the Recommended Uniform Screening Panel (RUSP) in 2011. Newborn screens typically do not require affirmative parental consent. In fact, most states allow parents to exempt their baby from receiving the required screen on the basis of religious or personally held beliefs. There are many ethical considerations implicated with allowing parents to exempt their child from newborn screening for CCHD. Considerations include the treatment of religious exemptions in our current legal system, as well as medical and ethical principles in relation to the rights of infants. Although there are significant benefits to screening newborns for CCHD, when a parent refuses for religious or personal beliefs, in the case of CCHD screening, the parental decision should stand.
Hoffman, Julien I E
Now that pulse oximetry is used widely to screen for critical congenital heart disease, it is time to consider whether this screening method is applicable to those who live at high altitudes. Consideration of basic physical principles and reports from the literature indicate that not only is the 95 % cutoff point for arterial oxygen saturation incorrect at high altitudes, but the lower saturations are accompanied by greater variability and therefore there is the possibility of a greater percentage of false-positive screening tests at high altitudes. Because of ethnic differences in response to high altitudes, normative data will have to be collected separately in different countries and perhaps for different ethnic groups.
Mutesa, Leon; Jamar, Mauricette; Hellin, Anne Cecile; Pierquin, Genevieve; Bours, Vincent
While the XYY and XXYY syndromes have been several time described in patients, the combination of both syndromes in an individual is a rare event and may result in a severe phenotype. In the present observation, a boy with congenital scoliosis due to segmented thoracic hemivertebra associated with radioulnar synostosis and congenital heart disease is described. Chromosome G-banding and FISH analysis demonstrated a de novo mosaic karyotype 48, XXYY/47, XYY in this patient. To the best of our knowledge, this is the first report of a combination of XYY and XXYY syndromes.
Vida, Vladimiro L; Bacha, Emile; Stellin, Giovanni
The involvement of the hemodynamic expertise in the operating room led to the development of new strategies aimed to improve both early and long-term outcome of patients with congenital heart disease. During the last decade, with the aim of preserving the pulmonary valve function, we embarked on a new surgical approach, which combines surgical and interventional techniques, which are performed in the operating room. We believe that the preservation of the pulmonary valve function can be extended to any patients with classic tetralogy of Fallot and other selected patients with congenital pulmonary valve hypoplasia and dysfunction.
Elder, Robert W; George, Roshan P; McCabe, Nancy M; Rodriguez, Fred H; Book, Wendy M; Mahle, William T; Kirk, Allan D
Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized that lymphopenia in patients with adult congenital heart disease (ACHD) would be reflective of premature T cell maturation and exhaustion. Adults with ACHD who had sternotomy to repair congenital heart disease as infants (<1 year) and age-matched ACHD patients without prior sternotomy were studied using polychromatic flow cytometry interrogating markers of lymphocyte maturation, exhaustion and senescence. Group differences were analyzed using Mann-Whitney U and Fisher's exact tests. Eighteen ACHD patients aged 21-40 years participated: 10 cases and 8 controls. Median age at sternotomy for cases was 52 days. Cases and controls were matched for age (28.9 vs. 29.1 years; p = 0.83), gender (p = 0.15) and race (p = 0.62) and had similar case complexity. Cases had a lower mean percentage of cytotoxic CD8 lymphocytes compared to controls (26.8 vs. 33.9 %; p = 0.016), with fewer naive, undifferentiated CD8 T cells (31.0 vs. 53.6 %; p = 0.027). CD8 cells expressing PD1, a marker of immune exhaustion, trended higher in cases versus controls (25.6 vs. 19.0 %; p = 0.083). Mean percentage of CD4 cells was higher in cases versus controls (65.6 vs. 59.6 %; p = 0.027), without differences in CD4 T cell maturation subtype. In summary, ACHD patients who undergo sternotomy as infants exhibit differences in T lymphocyte composition compared to ACHD controls, suggesting accelerated immunologic exhaustion. Investigation is warranted to assess the progressive nature and clinical impact of this immune phenotypic change.
Hülsmeier, Andreas J.; Tobler, Micha; Burda, Patricie; Hennet, Thierry
Glycosylation is an integral part in health and disease, as emphasized by the growing number of identified glycosylation defects. In humans, proteins are modified with a diverse range of glycoforms synthesized in complex biosynthetic pathways. Glycosylation disorders have been described in congenital disorders of glycosylation (CDG) as well as in acquired disease conditions such and non-alcoholic fatty liver disease (NAFLD). A hallmark in a subset of CDG cases is the reduced glycosylation site occupancy of asparagine-linked glycans. Using an optimized method protocol, we determined the glycosylation site occupancy from four proteins of hepatic and lymphatic origin from CDG and NAFLD patients. We found variable degrees of site occupancy, depending on the tissue of origin and the disease condition. In CDG glycosylation sites of IgG2 and IgA1 were occupied to normal levels. In NAFLD haptoglobin and transferrin glycosylation sites were hyper-glycosylated, a property qualifying for its use as a potential biomarker. Furthermore, we observed, that glycosylation sites of liver-originating transferrin and haptoglobin are differentially occupied under physiological conditions, a further instance not noticed in serum proteins to date. Our findings suggest the use of serum protein hyperglycosylation as a biomarker for early stages of NAFLD. PMID:27725718
Marelli, Ariane; Miller, Steven P; Marino, Bradley Scott; Jefferson, Angela L; Newburger, Jane W
The number of patients surviving with congenital heart disease (CHD) has soared over the last 3 decades. Adults constitute the fastest-growing segment of the CHD population, now outnumbering children. Research to date on the heart-brain intersection in this population has been focused largely on neurodevelopmental outcomes in childhood and adolescence. Mutations in genes that are highly expressed in heart and brain may cause cerebral dysgenesis. Together with altered cerebral perfusion in utero, these factors are associated with abnormalities of brain structure and brain immaturity in a significant portion of neonates with critical CHD even before they undergo cardiac surgery. In infancy and childhood, the brain may be affected by risk factors related to heart disease itself or to its interventional treatments. As children with CHD become adults, they increasingly develop heart failure, atrial fibrillation, hypertension, diabetes mellitus, and coronary disease. These acquired cardiovascular comorbidities can be expected to have effects similar to those in the general population on cerebral blood flow, brain volumes, and dementia. In both children and adults, cardiovascular disease may have adverse effects on achievement, executive function, memory, language, social interactions, and quality of life. Against the backdrop of shifting demographics, risk factors for brain injury in the CHD population are cumulative and synergistic. As neurodevelopmental sequelae in children with CHD evolve to cognitive decline or dementia during adulthood, a growing population of CHD can be expected to require support services. We highlight evidence gaps and future research directions.
Congenital torticollis is a very common postural deformity, characterized by a more or less severe retraction of sternocleidomastoid muscle. Any treatment, else that "good sense" counsels given to the parents, is indicated. The evolution is spontaneously favorable in the majority of cases before the age of one year old. The elimination of differential diagnosis (vertebral and/or neurological malformations, ocular, tumor) is the key-point. Screening of congenital hip dislocation is mandatory because the physiopathology is the same in both diseases. A remaining torticolis after 18 months of age may be an indication to sternocleidomastoid muscle lengthening.
Holst, Kimberly A; Said, Sameh M; Nelson, Timothy J; Cannon, Bryan C; Dearani, Joseph A
Successful outcome in the care of patients with congenital heart disease depends on a comprehensive multidisciplinary team. Surgery is offered for almost every heart defect, despite complexity. Early mortality for cardiac surgery in the neonatal period is ≈10% and beyond infancy is <5%, with 90% to 95% of patients surviving with a good quality of life into the adult years. Advances in imaging have facilitated accurate diagnosis and planning of interventions and surgical procedures. Similarly, advances in the perioperative medical management of patients, particularly with intensive care, has also contributed to improving outcomes. Arrhythmias and heart failure are the most common late complications for the majority of defects, and reoperation for valvar problems is common. Lifelong surveillance for monitoring of recurrent or residual structural heart defects, as well as periodic assessment of cardiac function and arrhythmia monitoring, is essential for all patients. The field of congenital heart surgery is poised to incorporate new innovations such as bioengineered cells and scaffolds that will iteratively move toward bioengineered patches, conduits, valves, and even whole organs.
Geddes, Gabrielle C; Butterly, Mark; Sajan, Imran
The objective of this study is to evaluate the yield of genetic testing in infants with congenital heart disease, who undergo surgical intervention prior to one year of age, and develop a cost-effective strategy to screen infants with congenital heart disease for genetic conditions while providing standard of care. 409 charts of patients with congenital heart disease, who underwent surgical intervention prior to one year of age, were retrospectively reviewed for cytogenetic testing results. 278 patients underwent cytogenetic testing, and 89.6 % of these patients had more than one cytogenetic test completed. The most commonly encountered chromosomal anomaly within the sample was Down Syndrome (12.5 %), followed by 22q11.2 Deletion Syndrome (4.6 %). G-Banded Karyotypes were abnormal in 10.5 % of patients, fluorescence in situ hybridization (FISH) probe for 22q11.2 deletion was abnormal in 7.1 % of patients. SNP microarray testing showed the highest yield and was abnormal in 33 % of patients. Based on the data at our institution, a more directed approach of genetic screening with only microarray would have saved our institution approximately $101, 200 on the 103 patients who underwent genetic evaluation with microarray reviewed. Screening infants with congenital heart disease for 22q11.2 deletion with FISH resulted in a loss of approximately $32,000 per 100 patients at our institution. Institutions should develop microarray-based protocols for genetic screening in patients with congenital heart disease with the anticipation of adding lesion-specific single gene testing as single gene testing becomes routinely available.
Ginde, Salil; Bartz, Peter J.; Hill, Garick D.; Danduran, Michael J.; Biller, Julie; Sowinski, Jane; Tweddell, James S.; Earing, Michael G.
Background/Objectives Following repair of congenital heart disease (CHD), adult patients are at risk for reduced exercise capacity. Restrictive lung disease (RLD) may contribute to reduced exercise capacity in this population. The aim of this study was to determine the prevalence of RLD and its impact on exercise tolerance in the adult with congenital heart disease. Methods One hundred consecutive adult patients with CHD, who underwent routine cardiopulmonary exercise testing with spirometry, were evaluated. Clinical data was obtained by retrospective chart review. Results Patients from 10 major diagnostic groups were identified. The median age for the cohort was 31 years (range 18–63) and included 43 males and 57 females. Most patients, 79%, had at least one previous surgical procedure. Based on spirometry and flow/volume loops, 50 patients were classified as normal pulmonary function, 44 patients had patterns suggestive of RLD, 4 suggestive of mixed (obstructive and restrictive), and 2 indeterminate. Risk factors associated with RLD include history of multiple thoracotomies (odds ratio=9.01, p=0.05) and history of atrial arrhythmias (odd ratio=4.25, p=0.05). Overall, 56% of the patients had abnormal exercise capacity. Spirometry suggestive of RLD was a significant risk factor for decreased exercise capacity (odds ratio=3.65, p=0.03). Patients with spirometry suggesting RLD also had lower exercise duration (p=0.004) and a higher New York Heart Association Functional Class (p=0.02). History of previous surgery and decreased heart rate reserve were also significant risk factors for decreased exercise capacity. Conclusion Abnormal spirometry suggestive of RLD is common in the adult with CHD and is a significant risk factor for decreased exercise tolerance in this population. Further studies, are needed to evaluate the relationship between RLD and exercise intolerance and its relationship to mortality in the adult with CHD. PMID:23075089
Bode-Böger, Stefanie M.; Martens-Lobenhoffer, Jens; Lovric, Svjetlana; Bauersachs, Johann; Schieffer, Bernhard; Westhoff-Bleck, Mechthild; Kielstein, Jan T.
Background Chronic heart failure is an important cause for morbidity and mortality in adults with congenital heart disease (ACHD). While NT-proBNP is an established biomarker for heart failure of non-congenital origin, its value in ACHD has limitations. Asymmetrical dimethylarginine (ADMA) correlates with disease severity and independently predicts adverse clinical events in heart failure of non-congenital origin. Its role in ACHD has not been investigated. Methods In 102 patients ADMA and NT-proBNP were measured and related to NYHA class, systemic ventricular function and parameters of cardiopulmonary exercise testing. Results In contrast to NT-proBNP ADMA differentiated between NYHA classes I-III. Both, ADMA and NT-proBNP showed a good correlation with parameters of cardiopulmonary exercise testing with comparable receiver-operating characteristic curves for identifying patients with severely limited cardiopulmonary exercise capacity. Conclusion ADMA seems to be a better biomarker than NT-proBNP for the assessment of NYHA class and as a good as NT-proBNP for the estimation of maximum exercise capacity in adults with congenital heart disease. Its use in clinical routine should be evaluated. PMID:22470476
Background The incidence of congenital heart disease (CHD) is continuously increasing among infants born alive nowadays, making it one of the leading causes of infant morbidity worldwide. Various studies suggest that both genetic and environmental factors lead to CHD, and therefore identifying its candidate genes and disease-markers has been one of the central topics in CHD research. By using the high-throughput genomic data of CHD which are available recently, network-based methods provide powerful alternatives of systematic analysis of complex diseases and identification of dysfunctional modules and candidate disease genes. Results In this paper, by modeling the information flow from source disease genes to targets of differentially expressed genes via a context-specific protein-protein interaction network, we extracted dysfunctional modules which were then validated by various types of measurements and independent datasets. Network topology analysis of these modules revealed major and auxiliary pathways and cellular processes in CHD, demonstrating the biological usefulness of the identified modules. We also prioritized a list of candidate CHD genes from these modules using a guilt-by-association approach, which are well supported by various kinds of literature and experimental evidence. Conclusions We provided a network-based analysis to detect dysfunctional modules and disease genes of CHD by modeling the information transmission from source disease genes to targets of differentially expressed genes. Our method resulted in 12 modules from the constructed CHD subnetwork. We further identified and prioritized candidate disease genes of CHD from these dysfunctional modules. In conclusion, module analysis not only revealed several important findings with regard to the underlying molecular mechanisms of CHD, but also suggested the distinct network properties of causal disease genes which lead to identification of candidate CHD genes. PMID:22136190
Chiruţa, Daria; Stan, Cristina
Aniridia is a rare congenital, hereditary, bilateral disease which is associated with various systemic and ocular defects. We present the case of a 61 year old patient who was admitted in the hospital of ophthalmology Cluj Napoca, for the symptoms caused by the ocular defects associated with aniridia. In this case, aniridia is autosomal dominant transmitted with incomplete penetrance and it is not accompanied by any systemic defects. The disease also affects three of her sons and two nephews of the patient.
Simões e Silva, Ana Cristina; Valério, Flávia Cordeiro; Vasconcelos, Mariana Affonso; Miranda, Débora Marques; Oliveira, Eduardo Araújo
Fetal hydronephrosis is the most common anomaly detected on antenatal ultrasound, affecting 1-5% of pregnancies. Postnatal investigation has the major aim in detecting infants with severe urinary tract obstruction and clinically significant urinary tract anomalies among the heterogeneous universe of patients. Congenital uropathies are frequent causes of pediatric chronic kidney disease (CKD). Imaging techniques clearly contribute to this purpose; however, sometimes, these exams are invasive, very expensive, and not sufficient to precisely define the best approach as well as the prognosis. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric urological diseases. In this regard, recent studies suggest a role for cytokines and chemokines in the pathophysiology of CAKUT and for the progression to CKD. Some authors proposed that the evaluation of these inflammatory mediators might help the management of postnatal uropathies and the detection of patients with high risk to developed chronic kidney disease. Therefore, the aim of this paper is to revise general aspects of cytokines and the link between cytokines, CAKUT, and CKD by including experimental and clinical evidence.
Simões e Silva, Ana Cristina; Valério, Flávia Cordeiro; Vasconcelos, Mariana Affonso; Miranda, Débora Marques; Oliveira, Eduardo Araújo
Fetal hydronephrosis is the most common anomaly detected on antenatal ultrasound, affecting 1–5% of pregnancies. Postnatal investigation has the major aim in detecting infants with severe urinary tract obstruction and clinically significant urinary tract anomalies among the heterogeneous universe of patients. Congenital uropathies are frequent causes of pediatric chronic kidney disease (CKD). Imaging techniques clearly contribute to this purpose; however, sometimes, these exams are invasive, very expensive, and not sufficient to precisely define the best approach as well as the prognosis. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric urological diseases. In this regard, recent studies suggest a role for cytokines and chemokines in the pathophysiology of CAKUT and for the progression to CKD. Some authors proposed that the evaluation of these inflammatory mediators might help the management of postnatal uropathies and the detection of patients with high risk to developed chronic kidney disease. Therefore, the aim of this paper is to revise general aspects of cytokines and the link between cytokines, CAKUT, and CKD by including experimental and clinical evidence. PMID:24066006
Xin, Yuan-Feng; Xu, Wen-Jun; Liu, Zhong-Min; Qiu, Xing-Biao; Qu, Xin-Kai; Xu, Lei; Li, Xin
Congenital heart disease (CHD) is the most common form of birth defect and is the leading noninfectious cause of infant death. A growing body of evidence demonstrates that genetic risk factors are involved in the pathogenesis of CHD. However, CHD is a genetically heterogeneous disease and the genetic defects underlying CHD in an overwhelming majority of patients remain unclear. In this study, the whole coding region and splice junction sites of the PITX2c gene, which encodes variant 3 of paired-like homeodomain transcription factor 2 crucial for normal cardiovascular morphogenesis, were sequenced in 382 unrelated patients with CHD, and 2 novel heterozygous mutations, p.W147X and p.N153D, were identified in 2 unrelated patients with CHD, respectively, including a 1-year-old male patient with double outlet right ventricle in combination with ventricular septal defect and a 4-year-old female patient with ventricular septal defect. The mutations were absent in 400 control chromosomes and were both predicted to be disease-causing by MutationTaster. Multiple alignments of PITX2c proteins across species displayed that the altered amino acids were completely conserved evolutionarily. Functional analysis revealed that the mutated PITX2c proteins were associated with a significantly reduced transactivational activity compared with their wild-type counterpart. These findings provide a novel insight into the molecular mechanisms implicated in CHD, suggesting potential implications for the antenatal prophylaxis and allele-specific treatment of CHD. PMID:24083357
Furtado, Milena B; Wilmanns, Julia C; Chandran, Anjana; Perera, Joelle; Hon, Olivia; Biben, Christine; Willow, Taylor J; Nim, Hieu T; Kaur, Gurpreet; Simonds, Stephanie; Wu, Qizhu; Willians, David; Salimova, Ekaterina; Plachta, Nicolas; Denegre, James M; Murray, Stephen A; Fatkin, Diane; Cowley, Michael; Pearson, James T; Kaye, David; Ramialison, Mirana; Harvey, Richard P; Rosenthal, Nadia A; Costa, Mauro W
Mutations in the Nkx2-5 gene are a main cause of congenital heart disease. Several studies have addressed the phenotypic consequences of disrupting the Nkx2-5 gene locus, although animal models to date failed to recapitulate the full spectrum of the human disease. Here, we describe a new Nkx2-5 point mutation murine model, akin to its human counterpart disease-generating mutation. Our model fully reproduces the morphological and physiological clinical presentations of the disease and reveals an understudied aspect of Nkx2-5-driven pathology, a primary right ventricular dysfunction. We further describe the molecular consequences of disrupting the transcriptional network regulated by Nkx2-5 in the heart and show that Nkx2-5-dependent perturbation of the Wnt signaling pathway promotes heart dysfunction through alteration of cardiomyocyte metabolism. Our data provide mechanistic insights on how Nkx2-5 regulates heart function and metabolism, a link in the study of congenital heart disease, and confirms that our models are the first murine genetic models to our knowledge to present all spectra of clinically relevant adult congenital heart disease phenotypes generated by NKX2-5 mutations in patients.
Yue, Shuying; Zhang, Kun; Wang, Hui; Dong, Rui; Yang, Xiaomeng; Liu, Yi; Ma, Yanhui
Background High resolution melting (HRM) is a simple, flexible and low-cost mutation screening technique. The methylenetetrahydrofolate reductase (MTHFR) gene encoding a critical enzyme, potentially affects susceptibility to some congenital defects like congenital heart disease (CHD). We evaluate the performance of HRM for genotyping of the MTHFR gene C677T locus in CHD cases and healthy controls of Chinese Han population. Methods A total of 315 blood samples from 147 CHD patients (male72, female 75) and 168 healthy controls (male 92, female 76) were enrolled in the study. HRM was utilized to genotype MTHFR C677T locus of all the samples. The results were compared to that of PCR-RFLP and Sanger sequencing. The association of the MTHFR C677T genotypes and the risk of CHD was analyzed using odds ratio with their 95% confidence interval (CIs) from unconditional logistic regression. Results All the samples were successfully genotyped by HRM within 1 hour and 30 minutes while at least 6 hours were needed for PCR-RFLP and sequencing. The genotypes of MTHFR C677T CC, CT, and TT were 9.52%, 49.66%, and 40.82% in CHD group but 29.17%, 50% and 20.83% in control group, which were identical using both methods of HRM and PCR-RFLP, demonstrating the sensitivity and specificity of HRM were all 100%. Conclusion MTHFR C677T is a potential risk factor for CHD in our local residents of Shandong province in China. HRM is a fast, sensitive, specific and reliable method for clinical application of genotyping. PMID:26990189
Farrar, Genevieve; Suinesiaputra, Avan; Gilbert, Kathleen; Perry, James C; Hegde, Sanjeet; Marsden, Alison; Young, Alistair A; Omens, Jeffrey H; McCulloch, Andrew D
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
Hrycyk, Joris; Kaemmerer, Harald; Nagdyman, Nicole; Hamann, Moritz; Schneider, KTM; Kuschel, Bettina
Background Advances in cardiac surgery and congenital cardiology have led to an increasing number of women with congenital heart disease (CHD) reaching childbearing age. In general, cardiologists recommend vaginal delivery for women with CHD to avoid complications from Caesarean section as many women with CHD tolerate vaginal delivery well. Methods and Results This is a single-center study comparing mode of delivery, pregnancy outcome, indications for Caesarean section and induction of labor between women with and without CHD. A historical cohort study was conducted including 116 patients with CHD. An individual threefold matching with 348 women without CHD was carried out. Caesarean section was performed in 46.6% of pregnancies with CHD (33.6% without CHD, P = 0.012). Primary Caesarean section increases with severity of CHD (P = 0.036), 33.3% of women with CHD had primary planned Caesarean section due to cardiac reasons. Induction of labor was performed in 45.7% of attempted vaginal deliveries in women with CHD (27.9% without CHD, P = 0.001). Lower mean birth weight (P = 0.004) and Small for Gestational Age (SGA) (P < 0.001) were more common in women with CHD. One CHD patient suffered from postpartum hemorrhage. Conclusions Concerns about maternal deterioration resulting in higher rates of induction of labor seem unjustified in most cases. Along with a possible reduction of Caesarean section on maternal request, a reduction of planned vaginal delivery may be expedient in reducing the rate of Caesarean section in women with CHD. PMID:28006009
Pati, Sunil; Pinninti, Swetha; Novak, Zdenek; Chowdhury, Nazma; Patro, Raj; Fowler, Karen; Ross, Shannon; Boppana, Suresh
Background Congenital cytomegalovirus (cCMV) is a common congenital infection and a leading non-genetic cause of sensorineural hearing loss (SNHL). CMV exhibits extensive genetic variability and infection with multiple CMV strains (mixed infection) was shown to be common in cCMV. The role of mixed infections in disease and outcome remains to be defined. Methods Genotyping of envelope glycoproteins, UL55 (gB), UL73 (gN) and UL75 (gH) was performed on saliva specimens from 79 infants from the ongoing CMV and Hearing Multicenter Screening Study (CHIMES) and on blood and urine specimens from 52 infants who participated in natural history studies at the University of Alabama at Birmingham. Genotyping of UL144 and US28 was also performed in the CHIMES cohort. The association of individual genotypes and mixed infection with clinical findings at birth and SNHL was examined. Results Thirty seven of 131 infants (28%) were symptomatic at birth and 26 (20%) had SNHL at birth. All known genotypes of UL55, UL75, UL73, and US28 were represented and no particular genotype was associated with symptomatic infection or SNHL. UL144 subtype C was more common in symptomatic babies but not associated with SNHL. Mixed infection was observed in 59 infants (45%) and not associated with symptoms (p = 0.43) or SNHL at birth (p = 0.82). In the cohort of 52 infants with long-term hearing outcome, mixed infection at birth was not predictive of SNHL. Conclusions Mixed infection is common in infants with cCMV but is neither associated with symptomatic infection nor with SNHL. PMID:23694837
HAN, HUA; CHEN, YU; LIU, GANG; HAN, ZENGQIANG; ZHAO, ZHOU; TANG, YIN
Our previous study indicated that 8 patients from a family with a history of congenital heart disease had simple atrial septal defect (ASD) and carried the same mutation at codon 310 in the GATA4 gene. In the present study, to identify the functional defects caused by this mutation in an in vivo model, the transgene DNA constructs were microinjected into mice to generate a transgenic mouse model. The mice were genotyped using PCR and DNA sequencing. Protein expression was measured by western blot analysis. qPCR was used to determine the copy number of the transgenes. The heart tissue was fixed and sectioned by conventional procedures. The Vevo 2000 system was used to perform echocardiography on the mice. The expression of GATA4 target genes was measured using the real-time PCR system. The incidence of ASD in the heterozygous transgenic mice was found to be greater than that in the wild-type control mice (P<0.05). In addition, the expression of α-myosin heavy chain (α-MHC) in the heart tissues from the homozygous mice was lower than that in the heart tissues from their wild-type littermates (P<0.05). In conclusion, these results suggest that the introduction of GATA4 M310V negatively affects the normal expression of α-MHC. In accordance with previous findings on GATA4 mutation screening and in vitro experiments, this study confirms that GATA4 M310V mutation may lead to the development of the congenital heart defect, ASD. PMID:25873328
Zijlstra, Willemijn M H; Douwes, Johannes M; Ploegstra, Mark-Jan; Krishnan, Usha; Roofthooft, Marcus T R; Hillege, Hans L; Ivy, D Dunbar; Rosenzweig, Erika B; Berger, Rolf M F
Congenital heart disease (CHD) is a frequent cause of pediatric pulmonary arterial hypertension (PAH), with diverse etiology and outcome. We aimed to describe phenotypic heterogeneity in pediatric PAH associated with CHD (PAH-CHD), assess the applicability of the Nice CHD classification, and explore whether this classification accurately reflects patient/disease characteristics and survival. All children with CHD from a contemporary cohort of consecutive pediatric PAH patients followed in three major referral centers (Denver, New York, the Netherlands) were characterized and classified on the basis of the latest proposed clinical classification for PAH-CHD (World Symposium on Pulmonary Hypertension, Nice, 2013). According to this classification, 24% of 134 children were classified into group 1, 14% into group 2, 19% into group 3, and 30% into group 4; 11% could not be classified. Types of CHD and hemodynamic profile differed between groups, with the highest right atrial pressure in group 4 (P < 0.040). Group 3 children had Down syndrome less frequently (P = 0.011) but other (un)defined syndromes most frequently (P = 0.063) and received most intense PAH-targeted therapy (P = 0.003). With 15 deaths and one lung transplant (12%; median follow-up: 4.3 years), survival differences could not be demonstrated between the groups in the Nice CHD classification. Pediatric PAH-CHD is a heterogeneous condition frequently associated with extracardiac, developmental factors that are believed to affect disease development. The Nice CHD classification identifies groups with specific patient/disease characteristics. However, a substantial proportion of children could not be classified. Group 3 forms a distinct disease entity. Its prognostic value could not be determined because of the low number of events. The Nice CHD classification supports clinical characterization of PAH-CHD; however, further refinement is needed to classify all children with PAH-CHD.
Douwes, Johannes M.; Ploegstra, Mark-Jan; Krishnan, Usha; Roofthooft, Marcus T. R.; Hillege, Hans L.; Ivy, D. Dunbar; Rosenzweig, Erika B.; Berger, Rolf M. F.
Abstract Congenital heart disease (CHD) is a frequent cause of pediatric pulmonary arterial hypertension (PAH), with diverse etiology and outcome. We aimed to describe phenotypic heterogeneity in pediatric PAH associated with CHD (PAH-CHD), assess the applicability of the Nice CHD classification, and explore whether this classification accurately reflects patient/disease characteristics and survival. All children with CHD from a contemporary cohort of consecutive pediatric PAH patients followed in three major referral centers (Denver, New York, the Netherlands) were characterized and classified on the basis of the latest proposed clinical classification for PAH-CHD (World Symposium on Pulmonary Hypertension, Nice, 2013). According to this classification, 24% of 134 children were classified into group 1, 14% into group 2, 19% into group 3, and 30% into group 4; 11% could not be classified. Types of CHD and hemodynamic profile differed between groups, with the highest right atrial pressure in group 4 (P < 0.040). Group 3 children had Down syndrome less frequently (P = 0.011) but other (un)defined syndromes most frequently (P = 0.063) and received most intense PAH-targeted therapy (P = 0.003). With 15 deaths and one lung transplant (12%; median follow-up: 4.3 years), survival differences could not be demonstrated between the groups in the Nice CHD classification. Pediatric PAH-CHD is a heterogeneous condition frequently associated with extracardiac, developmental factors that are believed to affect disease development. The Nice CHD classification identifies groups with specific patient/disease characteristics. However, a substantial proportion of children could not be classified. Group 3 forms a distinct disease entity. Its prognostic value could not be determined because of the low number of events. The Nice CHD classification supports clinical characterization of PAH-CHD; however, further refinement is needed to classify all children with PAH-CHD. PMID:27683607
Gurvitz, Michelle; Burns, Kristin M; Brindis, Ralph; Broberg, Craig S; Daniels, Curt J; Fuller, Stephanie M P N; Honein, Margaret A; Khairy, Paul; Kuehl, Karen S; Landzberg, Michael J; Mahle, William T; Mann, Douglas L; Marelli, Ariane; Newburger, Jane W; Pearson, Gail D; Starling, Randall C; Tringali, Glenn R; Valente, Anne Marie; Wu, Joseph C; Califf, Robert M
Congenital heart disease (CHD) is the most common birth defect, affecting about 0.8% of live births. Advances in recent decades have allowed >85% of children with CHD to survive to adulthood, creating a growing population of adults with CHD. Little information exists regarding survival, demographics, late outcomes, and comorbidities in this emerging group, and multiple barriers impede research in adult CHD. The National Heart, Lung, and Blood Institute and the Adult Congenital Heart Association convened a multidisciplinary working group to identify high-impact research questions in adult CHD. This report summarizes the meeting discussions in the broad areas of CHD-related heart failure, vascular disease, and multisystem complications. High-priority subtopics identified included heart failure in tetralogy of Fallot, mechanical circulatory support/transplantation, sudden cardiac death, vascular outcomes in coarctation of the aorta, late outcomes in single-ventricle disease, cognitive and psychiatric issues, and pregnancy.
Patel, V H; Somers, S
MR imaging continues to be an integral problem-solving modality in the evaluation of congenital anomalies and acquired diseases of the female genital tract organs and provides effective clinical information to the practicing gynecologist in those patients in whom sonography is technically suboptimal or the results are equivocal. This article describes the state-of-the art MR imaging of the female pelvis and addresses its current perspectives in the following sections: (1) technical aspects of MR in imaging the female pelvis, (2) normal pelvic anatomy and variations that are seen on MRI, (3) role of MRI in the diagnosis of congenital uterine and vaginal anomalies, (4) MR imaging approach to diagnose congenital uterine and vaginal anomalies, (5) advantages and limitations of MR in the evaluation of various benign diseases and malignant neoplasms of the female genital tract, (6) a MR staging system and criteria for each gynecologic malignancy, (7) fundamental MR criteria to differentiate benign from malignant tumors and recurrent tumors from fibrosis, and (8) the present cost-effective value of MR in pregnancy and obstetrics. Magnetic resonance (MR) technology continues to be an important problem-solving modality in the evaluation of benign, malignant, and recurrent diseases of the female pelvic organs with the development of new software and improved hardware over the last few years. The main issues addressed in this article are (1) to review the basic and expanded applications of the current state-of-the art MR imaging in the diagnosis and management of various congenital and acquired disorders of the female pelvic organs, (2) to illustrate a simplified clinico-radiologic (MRI) approach to the diagnosis of congenital and acquired pathologies of the pelvic organs, (3) to provide relevant information to the clinicians to make rational choices among the competing imaging modalities, and (4) to outline the future potential of this modality in the pelvis.
Umezawa, E S; Nascimento, M S; Kesper, N; Coura, J R; Borges-Pereira, J; Junqueira, A C; Camargo, M E
Immunoblotting with trypomastigote excreted-secreted antigens (TESA blot) of Trypanosoma cruzi was evaluated as a method for diagnosis of chronic and acute phases as well as congenital (in newborn children) Chagas' disease. Serum samples from acute-phase and congenital infections were considered to be positive when they reacted with ladder-like bands of 130- to 200-kDa antigens, recognized by immunoglobulin M (IgM) and IgG antibodies, while IgG from chronic-phase sera recognized a broad band antigen of 150 to 160 kDa. Nonchagasic sera were not reactive to these antigens. The study was carried out on 512 patients, 111 of whom were nonchagasic but included cases of leishmaniasis or other pathologies, and 401 chagasic patients. The latter group comprised 361 chronic cases, 36 acute cases, and 4 congenital cases in newborn children. Among the chronic cases, 256 were from areas in which T. cruzi is endemic but which differed widely in the pathogenic expression of T. cruzi infection and in parasitemia levels. These patients at the same time showed a broad range of low, medium, and high reactivity to conventional enzyme-linked immunosorbent assays and indirect immunofluorescence serotests for Chagas' disease. For these reasons they may better represent the universe of chagasic patients than would a sample of highly reactive sera obtained from chagasic patients in a single area endemic for T. cruzi. All acute and congenital cases showed positivity in the IgM and IgG TESA blots, while chronic cases were 100% positive for IgG antibodies. In nonchagasic sera, including 30 cases of visceral and muco-cutaneous leishmaniasis, the specificity index was 1.000, and no cross-reactions were observed. The TESA blot thus seems to be useful as a sensitive and specific diagnostic assay in cases of suspected acute or congenital T. cruzi infection and as a general confirmatory test for conventional Chagas' disease serology. PMID:8862574
Cytomegalovirus (CMV) is the leading cause of congenital infection in developed countries, affecting 0.3 to 0.6% of all live births in Europe. Primary CMV infection occurs in 1 to 4% of seronegative women during pregnancy and may be transmitted to the fetus in 40% of cases. Up to 10% of intrauterine CMV infections result in symptomatic congenital disease at birth. Half of these children and 13% of those born with asymptomatic infection will develop long-term sequelae, especially neurosensory hearing loss and mental retardation. Accurate diagnosis of primary maternal and fetal infection is now possible using the avidity index of anti-CMV IgG and virological testing to detect the virus in amniotic fluid. Symptomatic congenital infection may be preventable using CMV hyperimmune globulin during pregnancy. The gold standard for diagnosis of congenital CMV infection is the detection of the virus in urine within the first 2 weeks of life by rapid cell culture techniques (shell vial) or nucleic acid amplification of viral DNA (PCR). Retrospective diagnosis can be achieved by detection of viral DNA by PCR in dried blood spots (Guthrie card) collected on filter paper in the first days of life. Currently available drugs for the treatment of congenital CMV include ganciclovir and its oral prodrug valganciclovir. Treatment with intravenous ganciclovir for six weeks may prevent hearing deterioration in children with symptomatic congenital CMV infection and central nervous system involvement. Valganciclovir may be an excellent alternative because of its good bio-availability, providing plasma concentrations similar to those achieved with intravenous ganciclovir.
Furtado, Milena B.; Wilmanns, Julia C.; Chandran, Anjana; Perera, Joelle; Hon, Olivia; Biben, Christine; Willow, Taylor J.; Nim, Hieu T.; Kaur, Gurpreet; Simonds, Stephanie; Willians, David; Salimova, Ekaterina; Plachta, Nicolas; Denegre, James M.; Murray, Stephen A.; Cowley, Michael; Pearson, James T.; Kaye, David; Ramialison, Mirana; Rosenthal, Nadia A.; Costa, Mauro W.
Mutations in the Nkx2-5 gene are a main cause of congenital heart disease. Several studies have addressed the phenotypic consequences of disrupting the Nkx2-5 gene locus, although animal models to date failed to recapitulate the full spectrum of the human disease. Here, we describe a new Nkx2-5 point mutation murine model, akin to its human counterpart disease–generating mutation. Our model fully reproduces the morphological and physiological clinical presentations of the disease and reveals an understudied aspect of Nkx2-5–driven pathology, a primary right ventricular dysfunction. We further describe the molecular consequences of disrupting the transcriptional network regulated by Nkx2-5 in the heart and show that Nkx2-5–dependent perturbation of the Wnt signaling pathway promotes heart dysfunction through alteration of cardiomyocyte metabolism. Our data provide mechanistic insights on how Nkx2-5 regulates heart function and metabolism, a link in the study of congenital heart disease, and confirms that our models are the first murine genetic models to our knowledge to present all spectra of clinically relevant adult congenital heart disease phenotypes generated by NKX2-5 mutations in patients. PMID:28352650
Baquero-Artigao, F; Mellado Peña, M J; Del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L
Tuberculosis (TB) screening in pregnancy using tuberculin skin test (TST) is recommended in case of symptoms of TB disease, close contact with a patient with infectious TB, or high risk of developing active disease. The new interferon gamma release assay (IGRA) tests are recommended in BCG-vaccinated pregnant women with positive TST and no known risk factors for TB, and in those immunocompromised, with clinical suspicion of TB but negative TST. TB diagnosis is difficult due to the non-specific symptoms, the increased frequency of extrapulmonary disease, the delay in radiological examinations, and the high rate of tuberculin anergy. Neonatal TB can be acquired in utero (congenital TB), or through airborne transmission after delivery (postnatal TB). Congenital TB is extremely rare and does not cause fetal malformations. It may be evident at birth, although it usually presents after the second week of life. In newborns with no family history of TB, the disease should be considered in cases of miliary pneumonia, hepatosplenomegaly with focal lesions, or lymphocytic meningitis with hypoglycorrhachia, especially in those born to immigrants from high TB-burden countries. TST is usually negative, and IGRAs have lower sensitivity than in older children. However, the yield of acid-fast smear and culture is higher, mostly in congenital TB. Molecular diagnosis techniques enable early diagnosis and detection of drug resistance mutations. There is a substantial risk of disseminated disease and death.
Karsenty, Clement; Hadeed, Khaled; Acar, Philippe
The recent technical advances allow the use in practice of three-dimensional echocardiography in children especially through the new high frequency matrix probe. It is difficult or even impossible to hold breathing during children' acquisition so to avoid motion full volume artifact, one beat and live 3D modes are suitable. 3D echocardiography is more accurate than 2D to assess the size, location, and relationship with surrounding structures of atrial and ventricular septal defects and thus helps in the therapeutic decision. 3D echocardiography enables to guide precisely percutaneous procedure. The morphology of the valve leaflets, chordal support apparatus, papillary muscle and the annulus are particularly well described in 3D and allows assessment of the regurgitation before repair and after as well for the common valve of the atrioventricular septal defect or in the Ebstein anomaly. Complex heart diseases such as double outlet right ventricle are suitable to a tridimensional assessment to plan surgical strategy. 3D printing, fusion imaging in cathlab and automated volume quantification embody recent innovations of new techniques in congenital heart disease.
Amianto, F; Bergui, G; Abbate-Daga, G; Bellicanta, A; Munno, D; Fassino, S
About 1% of newborn presents some form of congenital heart disease (CHD). Eighty-five percent of these children, thanks to medical and surgical improvement, reaches adulthood. This open up new challenges in patients management, such as the evaluation and optimization of psychosocial functioning and quality of life of CHD subjects. The present review collects research literature regarding neurocognitive and psychopathological adjustment, and personality and quality of life of these patients, analyzing variables that may influence their development. Literature data lean towards a multifactorial process implied into an insufficient outcome of neurocognitive development in many patients. Psychopathological development seems "problematic" with the expression of behavioural disorders both externalising and internalising. But current researches don't consent univocal and definitive conclusions. The need for interventions to improve existential outcome for CHD subjects emerges: research on genetic factors and early recognition of at risk subjects must go with the necessity for research aiming to determine protective and risk factors related to personality, environment and relational aspects entailed in the development of CHD subjects. Finally, some evidences noticed in CHD subjects psychopathological and quality of life outcomes which are even better than normal ones. These results depend on the elaboration of their disease that CHD subjects have carried on. Factors regarding mainly personality development are essential in determining these outcomes.
Amianto, Federico; Bellicanta, Anna; Bergui, Giovanna C; Zuccolin, Maria; Abbate-Daga, Giovanni; Fassino, Secondo
Thank to medical and surgical improvements, a very high percentage of children with congenital heart disease (CHD; about 1% of newborn) reaches adulthood. This population of young surgical and medical patients opens up new challenges in clinical management, including evaluation and optimization of psychosocial functioning and quality of life. Data regarding neurocognitive and psychopathological adaptation, personality and quality of life of CHD patients are rather extensive but still insufficient to guide management approaches to these subjects and to address the numerous emerging problems. The present review analyzes extensively the research literature to find out those variables that may influence development of CHD children. It emerges that a multi-factorial process seems involved in the poor outcome of neurocognitive development in many patients. Notwithstanding the attempts to define risk factors, current researches do not consent definitive conclusions about the determinants of developmental problems in CHD children. An improvement of existential outcome for CHD subjects may be achieved if adequate interventions are carried out. In fact, psychopathological and quality of life in CHD subjects may result even better if elaboration of disease by CHD subjects is adequately supported. On one hand, genetic factors that may contribute to unfavourable evolutions suggest the need for early recognition of subjects at risk. On the other, research should be addressed to the identification of those protective and risk factors related to personality, environmental and relational aspects entailed in the development of CHD subjects.
Chevalier, Robert L; Forbes, Michael S; Galarreta, Carolina I; Thornhill, Barbara A
Most chronic kidney disease in children results from congenital or inherited disorders, which can be studied in mouse models. Following 2 weeks of unilateral ureteral obstruction (UUO) in the adult mouse, nephron loss is due to proximal tubular mitochondrial injury and cell death. In neonatal mice, proximal tubular cell death is delayed beyond 2 weeks of complete UUO, and release of partial UUO allows remodeling of remaining nephrons. Progressive cyst expansion develops in polycystic kidney disease (PKD), a common inherited renal disorder. The polycystic kidney and fibrosis (pcy)-mutant mouse (which develops late-onset PKD) develops thinning of the glomerulotubular junction in parallel with growth of cysts in adulthood. Renal insufficiency in nephropathic cystinosis, a rare inherited renal disorder, results from progressive tubular cystine accumulation. In the Ctns knockout mouse (a model of cystinosis), proximal tubular cells become flattened, with loss of mitochondria and thickening of tubular basement membrane. In each model, persistent obstructive or metabolic stress leads ultimately to the formation of atubular glomeruli. The initial "fight" response (proximal tubular survival) switches to a "flight" response (proximal tubular cell death) with ongoing oxidative injury and mitochondrial damage. Therapies should be directed at reducing proximal tubular mitochondrial oxidative injury to enhance repair and regeneration.
Caesar, R E; Packer, M G; Kaplan, G W; Dudell, G G; Guerrant, A L; Griswold, W R; Lemire, J M; Mendoza, S A; Reznik, V M
Extracorporeal membrane oxygenation (ECMO) is an effective treatment modality for the newborn with refractory hypoxemia. Oligohydramnios can be associated with congenital renal disease (CRD) and can result in respiratory insufficiency from pulmonary hypoplasia, delayed lung maturation, and persistent pulmonary hypertension of the newborn. In this retrospective study, the authors reviewed the outcome of four children with CRD who required ECMO in the neonatal period. Between October 1987 and December 1995, ECMO was used in four newborns with CRD and pulmonary hypoplasia unresponsive to maximal medical management. The causes of CRD were urinary obstruction (2), renal dysplasia (1), and vesicoureteral reflux (1). Neonatal survivors of ECMO with CRD had regular follow-up with a nephrologist, urologist, and pediatrician. Developmental history, assessment of renal function, and a nutritional evaluation were recorded on each visit. The follow-up period ranged from 6 months to 5 years. All patients with CRD were successfully weaned from ECMO. One child died, at 1 month of age, because of renal failure. The estimated glomerular filtration rates in the three survivors were 20, 24, and 60 mL/min/1.73 m2. Growth and development have been delayed in two patients. Based on the author's experience, ECMO may improve the survival of neonates with pulmonary hypoplasia and CRD. Factors associated with successful long-term outcome include (1) renal disease amenable to surgical correction, (2) aggressive nutritional support, and (3) a reliable social support system.
Rama Kumari, N.; Bhaskara Raju, I.; Patnaik, Amar N.; Barik, Ramachandra; Singh, Amarpal; Pushpanjali, A.; Laxmi, V.; Satya Ramakrishna, L.
Objective To determine the prevalence of rheumatic heart disease (RHD) and congenital heart disease (CHD) using clinical and echocardiographic criteria in rural and urban school children in Andhra Pradesh, South India. Materials and methods A total of 4213 school children between 5 and 16 years of age were screened. 1177 were from rural schools and 3036 from urban schools. Prevalence of RHD and CHD was estimated. Results Clinically RHD was present in 3 (prevalence 0.7/1000). Using echocardiography RHD was detected in 32 (7.6/1000), 11 (7.3/1000) from rural and 21 (7/1000) from urban schools. (P = 0.000, O.R = 0.093 and C.I. = 0.023–0.317). Total prevalence of RHD is 8.3/1000. Clinically CHD was present in 39 (9.2/1000) children, rural 9 (7.6/1000) and urban 30 (9.9/1000). Using echocardiography CHD was detected in 44 (10.4/1000) children, rural 11 (9.3/1000) and urban 33 (10.8/1000). Conclusion RHD was detected several fold using echocardiographic screening than by clinical examination alone. Longitudinal follow-up of children with echocardiographically diagnosed subclinical RHD is needed. PMID:24023464
Mertens, L; Friedberg, M K
Cardiac resynchronization therapy (CRT) has been shown to improve mortality and morbidity in adults with refractory heart failure and prolonged QRS-duration. Recent research data suggest that the therapeutic benefit is related to the effect of CRT on interventricular and intraventricular dyssynchrony associated with electrical dyssynchrony. However, around 30-40% of the patients do not respond to CRT when device implantation is based only on QRS-duration. It was hoped that improved description of mechanical dyssynchrony using imaging techniques, might result in improved identification of patients who could benefit from CRT. Different methods have been proposed but a recent multicenter prospective echocardiographic study (PROSPECT) was disappointing. Applying adult criteria for CRT treatment to children and adults with acquired and congenital heart disease is even more challenging due to the age-dependency of QRS-duration and the wide variety of underlying diseases including different ventricular morphology that can result in heart failure. In this review we will overview the adult and pediatric data of CRT treatment and propose a mechanistic approach that could potentially be helpful in trying to identify those patients who might benefit from the treatment.
Trunova, V. A.; Zvereva, V. V.; Okuneva, G. N.; Levicheva, E. N.
It is the myocardium that bears the basic functional loading during heart working, including muscle contractility and enzyme activity. The elemental concentrations in myocardium tissue of heart were determined by SRXRF technique. Our investigation is systematical: the elemental content in each compartment (left and right ventricles, left and right auricles) of hearts of healthy and diseased children (congenital heart diseases, transposition of main vessels (TMV)) was analyzed. The elemental distribution in myocardium of four heart chambers of human fetuses was also analyzed. Following elements were determined: S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb, Sr. It was revealed that the elemental concentrations in myocardium of both ventricles are almost constant in heart of fetuses and healthy children. The transition from pre-natal study (fetus) to post-natal study is accompanied by the redistribution of chemical elements in myocardium. The higher concentrations of S, Fe, Ca, Sr and Cu in myocardium of children are observed, the content of K, Br, Rb and especially Se is lower than in heart of fetuses. The elemental distribution in myocardium of children TMV is considerably different in comparison with the healthy children: the higher levels of Cu are observed. The content of Se is lower.
Ubbink, G J; Stades, F C; Rothuizen, J
The knowledge on the impact of gene defects on the development of disease in companion animals is increasing rapidly. The gene defects may be differentiated in an initiating defect, which is the cause of illness, and a promoting defect, which enhances the chance on illness. Up till now only initiating defects are known in dogs and cats. All this is of great importance for breeding purposes, because within a breed there is narrow relationship which means the genetic diversity is small, and with all the disadvantages thereof. The identification in good time of gene defects in breeding animals, so that these animals being excluded from breeding, is of utmost importance in preventing congenital diseases. For that reason more and more the owners will appeal to veterinary surgeons to cooperate in procedures to screen potential breeding animals, or to declare the animals free from gene defects. The problems with regard to the diagnostic tests, including the DNA-tests, and their predictive values are discussed.
Spadotto, Veronica; Frescura, Carla; Ho, Siew Yen; Thiene, Gaetano
The aim of this study was to estimate the incidence and to analyze the anatomy of double inlet-double outlet right ventricle complex and its associated cardiac anomalies in our autopsy series. Among the 1640 hearts with congenital heart disease of our Anatomical Collection, we reviewed the specimens with double inlet-double outlet right ventricle, according to the sequential-segmental analysis, identifying associated cardiac anomalies and examining lung histology to assess the presence of pulmonary vascular disease. We identified 14 hearts with double inlet-double outlet right ventricle (0.85%). Right atrial isomerism was observed in 10 hearts, situs solitus in 3 and left atrial isomerism in one. Regarding the mode of atrioventricular connection, all hearts but one had a common atrioventricular valve. Systemic or pulmonary venous abnormalities were noted in all patients with atrial isomerism. In nine patients a valvular or subvalvular pulmonary stenosis was present. Among the functionally "univentricular hearts", double inlet- double outlet right ventricle represents a peculiar entity, mostly in association with right atrial isomerism. Multiple cardiac anomalies are associated and may complicate surgical repair.
Zhang, Xi; Hou, Hai-Tao; Wang, Jun; Liu, Xiao-Cheng; Yang, Qin; He, Guo-Wei
Pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) has serious consequence and plasma protein profiles in CHD-PAH are unknown. We aimed to reveal the differential plasma proteins in 272 CHD patients with or without PAH. Various types of CHD-PAH were studied. Differential plasma proteins were first detected by iTRAQ proteomic technology and those with significant clinical relevance were selected for further ELISA validation in new cohort of patients. Among the 190 differential plasma proteins detected by iTRAQ, carbamoyl-phosphate synthetase I (CPSI, related to urea cycle and endogenous nitric oxide production) and complement factor H-related protein 2 (CFHR2, related to complement system and coagulant mechanism) were selected for further ELISA validation in new cohort of 152 patients. Both CPSI and CFHR2 were down-regulated with decreased plasma levels (p < 0.01). Thus, we for the first time in CHD-PAH patients identified a large number of differential plasma proteins. The decreased CPSI expression in CHD-PAH patients may reveal a mechanism related to endogenous nitric oxide and the decrease of CFHR2 protein may demonstrate the deficiency of the immune system and coagulation mechanism. The findings may open a new direction for translational medicine in CHD-PAH with regard to the diagnosis and progress of the disease.
Wheelhouse, Jaimee L; Hulst, Frances; Beatty, Julia A; Hogg, Carolyn J; Child, Georgina; Wade, Claire M; Barrs, Vanessa R
The Sumatran tiger (Panthera tigris ssp. sumatrae) is a critically endangered species in the wild. To ensure that demographic and genetic integrity are maintained in the longer term, those Sumatran tigers held in captivity are managed as a global population under a World Association of Zoos and Aquariums Global Species Management Plan (GSMP). A retrospective study, including segregation and pedigree analysis, was conducted to investigate potential cases of congenital vestibular disease (CVD) in captive Sumatran tigers in Australasian zoos using medical and husbandry records, as well as video footage obtained from 50 tigers between 1975 and 2013. Data from the GSMP Sumatran tiger studbook were made available for pedigree and segregation analysis. Fourteen cases of CVD in 13 Sumatran tiger cubs and one hybrid cub (Panthera tigris ssp. sumatrae × Panthera tigris) were identified. Vestibular signs including head tilt, circling, ataxia, strabismus and nystagmus were observed between birth and 2 months of age. These clinical signs persisted for a median of 237 days and had resolved by 2 years of age in all cases. Pedigree analysis revealed that all affected tigers were closely related and shared a single common ancestor in the last four generations. A genetic cause for the disease is suspected and, based on pedigree and segregation analysis, an autosomal dominant mode of inheritance is likely. Further investigations to determine the world-wide prevalence and underlying pathology of this disorder are warranted.
Zhang, Xi; Hou, Hai-Tao; Wang, Jun; Liu, Xiao-Cheng; Yang, Qin; He, Guo-Wei
Pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) has serious consequence and plasma protein profiles in CHD-PAH are unknown. We aimed to reveal the differential plasma proteins in 272 CHD patients with or without PAH. Various types of CHD-PAH were studied. Differential plasma proteins were first detected by iTRAQ proteomic technology and those with significant clinical relevance were selected for further ELISA validation in new cohort of patients. Among the 190 differential plasma proteins detected by iTRAQ, carbamoyl-phosphate synthetase I (CPSI, related to urea cycle and endogenous nitric oxide production) and complement factor H-related protein 2 (CFHR2, related to complement system and coagulant mechanism) were selected for further ELISA validation in new cohort of 152 patients. Both CPSI and CFHR2 were down-regulated with decreased plasma levels (p < 0.01). Thus, we for the first time in CHD-PAH patients identified a large number of differential plasma proteins. The decreased CPSI expression in CHD-PAH patients may reveal a mechanism related to endogenous nitric oxide and the decrease of CFHR2 protein may demonstrate the deficiency of the immune system and coagulation mechanism. The findings may open a new direction for translational medicine in CHD-PAH with regard to the diagnosis and progress of the disease. PMID:27886187
Gutgesell, Howard P; Hillman, Diane G; McHugh, Kimberly E; Dean, Peter; Matherne, G Paul
We review our 16-year experience using the large, multi-institutional database of the University HealthSystem Consortium to study management and outcomes in congenital heart surgery for hypoplastic left heart syndrome, transposition of the great arteries, and neonatal coarctation. The advantages, limitations, and use of administrative databases by others to study congenital heart surgery are reviewed.
Sandoval, Renata Lazari; Zaconeta, Carlos Moreno; Margotto, Paulo Roberto; Cardoso, Maria Teresinha de Oliveira; França, Evely Mirella Santos; Medina, Cristina Touguinha Neves; Canó, Talyta Matos; de Faria, Aline Saliba
Abstract Objective: To report the case of a newborn with recurrent episodes of apnea, diagnosed with Congenital Central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease (HD), configuring Haddad syndrome. Case description: Third child born at full-term to a non-consanguineous couple through normal delivery without complications, with appropriate weight and length for gestational age. Soon after birth he started to show bradypnea, bradycardia and cyanosis, being submitted to tracheal intubation and started empiric antibiotic therapy for suspected early neonatal sepsis. During hospitalization in the NICU, he showed difficulty to undergo extubation due to episodes of desaturation during sleep and wakefulness. He had recurrent episodes of hypoglycemia, hyperglycemia, metabolic acidosis, abdominal distension, leukocytosis, increase in C-reactive protein levels, with negative blood cultures and suspected inborn error of metabolism. At 2 months of age he was diagnosed with long-segment Hirschsprung's disease and was submitted to segment resection and colostomy through Hartmann's procedure. A genetic research was performed by polymerase chain reaction for CCHS screening, which showed the mutated allele of PHOX2B gene, confirming the diagnosis. Comments: This is a rare genetic, autosomal dominant disease, caused by mutation in PHOX2B gene, located in chromosome band 4p12, which results in autonomic nervous system dysfunction. CCHS can also occur with Hirschsprung's disease and tumors derived from the neural crest. There is a correlation between phenotype and genotype, as well as high intrafamilial phenotypic variability. In the neonatal period it can simulate cases of sepsis and inborn errors of metabolism. PMID:26838603
Abou Zahr, Riad; Faustino, Edward Vincent S; Carpenter, Thomas; Kirshbom, Paul; Hall, E Kevin; Fahey, John T; Kandil, Sarah B
Deficiency in 25-hydroxyvitamin D (25OHD) is associated with increased morbidity and mortality in the critically ill. Children who underwent surgery for congenital heart disease under cardiopulmonary bypass (CPB) are typically deficient in 25OHD. It is unclear whether this deficiency is due to CPB. We hypothesized that CPB reduces the levels of 25OHD in children with congenital heart disease. We conducted a prospective observational study on children aged 2 months to 17 years who underwent CPB. Serum was collected at 3 time points: immediately before, immediately after surgery, and 24 hours after surgery. 25-Hydroxyvitamin D, 1,25-dihydroxyvitamin D, 1,25(OH)2D, vitamin D binding protein, and albumin levels were measured. Levels were compared using repeated measures analysis of variance. We enrolled 20 patients, 40% were deficient in 25OHD with levels <20 ng/mL prior to surgery. Mean (±standard deviation) of 25OHD at the 3 time points was 21.3 ± 8 ng/mL, 19 ± 5.8 ng/mL, and 19.5 ± 6.6 ng/mL, respectively (P = .02). The decrease in 25OHD was observed primarily in children with sufficient levels of 25OHD, with mean levels at the 3 time points: 26.8 ± 4.2 ng/mL, 21.5 ± 5.7 ng/mL, and 23.0 ± 4.9 ng/mL, respectively (P < .001). Calculated means of free fraction of 25OHD at the 3 time points were 6.2 ± 2.8 pg/mL, 5.8 ± 2.2 pg/mL, and 5.5 ± 2.4 pg/mL, respectively, (P = .04). Mean levels of 1,25(OH)2D were 63.7 ± 34.9 ng/mL, 53.2 ± 30.6 ng/mL, and 67.7 ± 23.5 ng/mL (P = .04). Vitamin D binding protein and albumin levels did not significantly change. Cardiopulmonary bypass decreases 25OHD by reducing the free fraction. Current investigations are geared to establish whether vitamin D deficiency is associated with outcomes and if treatment is appropriate.
Mourato, Felipe Alves; Villachan, Lúcia Roberta R.; Mattos, Sandra da Silva
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
Belaval, Vinay; Gadabanahalli, Karthik; Raj, Vimal; Shah, Sejal
Rapid evolution in technology in the recent years has lead to availability of multiple options for cardiac imaging. Availability of multiple options of varying capability, poses a challenge for optimal imaging choice. While new imaging choices are added, some of the established methods find their role re-defined. State of the art imaging practices are limited to few specialist cardiac centres, depriving many radiologists and radiologist in-training of optimal exposure to the field. This presentation is aimed at providing a broad idea about complexity of clinical problem, imaging options and a large library of images of congenital heart disease. Some emphasis is made as to the need of proper balance between performing examination with technical excellence in an ideal situation against the need of the majority of patients who are investigated with less optimal resources. Cases of congenital cardiac disease are presented in an illustrative way, showing imaging appearances in multiple modalities, highlighting specific observations in given instance. PMID:27376034
Bakri, Faris G; Wahbeh, Ayman; Abu Sneina, Awni; Al Khader, Ali; Obeidat, Fatima; AlAwwa, Izzat; Buni, Maryam; Ki, Chang-Seok; Masri, Amira
Patients with congenital insensitivity to pain and anhydrosis syndrome are at risk for renal amyloidosis and inflammatory bowel disease. Physicians caring for such patients should be aware of these complications.
Prendiville, Terence; Jay, Patrick Y; Pu, William T
Study of monogenic congenital heart disease (CHD) has provided entry points to gain new understanding of heart development and the molecular pathogenesis of CHD. In this review, we discuss monogenic CHD caused by mutations of the cardiac transcription factor genes NKX2-5 and GATA4. Detailed investigation of these genes in mice and humans has expanded our understanding of heart development, shedding light on the complex genetic and environmental factors that influence expression and penetrance of CHD gene mutations.
Roston, Thomas M; De Souza, Astrid M; Sandor, George G S; Sanatani, Shubhayan; Potts, James E
Determining safe levels of physical activity for children and adolescents with electrophysiologic and structural congenital heart disease is a challenging clinical problem. The body of evidence for making these recommendations is limited and likely based on expert opinion, medicolegal concerns, and perceived risks of sudden cardiac death (SCD) with activity. The Bethesda Conference has established consensus guidelines for determining the eligibility of athletes with cardiovascular abnormalities for competitive sports and their disqualification from them. However, literature on guidelines for noncompetitive physical activity is not available. A survey was designed to determine practice patterns for patients with electrophysiologic and structural congenital heart disease. Between July 2011 and December 2011, approximately 350 health care providers working with this group of patients were recruited by email or while attending professional meetings. The survey received 81 responses, primarily from pediatric cardiologists (70 %). The findings indicate that the majority of Canadian cardiac care providers surveyed are only partially implementing current recommendations. Areas of variance included physical activity recommendations for hypertrophic cardiomyopathy, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and heart transplantation, among others. The development of comprehensive consensus guidelines for activity recommendations was supported by 96 % of the respondents. The heterogeneity of responses may be attributable to conflicting and poorly evidenced information in the literature, a lack of emphasis on recreational activity, an entrenched tendency toward bed rest in the cardiology community, and a lack of awareness by cardiac care providers regarding the actual risk associated with physical activity in electrophysiologic and structural congenital heart disease. A balanced discussion is required in considering both the significant benefit of
Passantino, Annamaria; Masucci, Marisa
Many of the congenital neurologic diseases can result in incapacity or death of the animal. Some of them, such as idiopathic epilepsy and hydrocephalus, exhibit breed or familial predisposition and a genetic basis was proved or suggested. Some diseases can be presumptively diagnosed after a detailed signalment (breed predisposition), history (e.g. family history because many of these defects have familial tendencies), and through physical exam; other diagnostic methods (radiography, computed tomography, magnetic resonance, electrophysiologic tests, etc.) can provide supportive evidence for the congenital defect and help to confirm the diagnosis. Some cases can lead to civil law-suits when the lesions are congenital, but not easily recognizable, or when the lesions are hereditary but tend to became manifest only after some time (more than 12 months after the date of purchase, e.g., after the vice-free guarantee period has expired). Moreover, quite frequently an early diagnosis is not made because there are delays in consulting the veterinarian or the general practitioner veterinarian does not perceive subtle signs. This study was designed to focus on the medico-legal aspects concerning the buying and selling in Italy of dogs and cats affected by congenital and hereditary neurologic diseases that could constitute vice in these animals. While adequate provisions to regulate in detail the various aspects of pet sale have still to be drawn up by legislators, it may be helpful to involve breeders, by obliging them by contract to extend guarantees in the case of hereditary lesions, including neurologic diseases. PMID:27284217
Zuluaga, Maria A; Burgos, Ninon; Mendelson, Alex F; Taylor, Andrew M; Ourselin, Sébastien
Atlas-based analysis methods rely on the morphological similarity between the atlas and target images, and on the availability of labelled images. Problems can arise when the deformations introduced by pathologies affect the similarity between the atlas and a patient's image. The aim of this work is to exploit the morphological dissimilarities between atlas databases and pathological images to diagnose the underlying clinical condition, while avoiding the dependence on labelled images. We propose a voxelwise atlas rating approach (VoxAR) relying on multiple atlas databases, each representing a particular condition. Using a local image similarity measure to assess the morphological similarity between the atlas and target images, a rating map displaying for each voxel the condition of the atlases most similar to the target is defined. The final diagnosis is established by assigning the condition of the database the most represented in the rating map. We applied the method to diagnose three different conditions associated with dextro-transposition of the great arteries, a congenital heart disease. The proposed approach outperforms other state-of-the-art methods using annotated images, with an accuracy of 97.3% when evaluated on a set of 60 whole heart MR images containing healthy and pathological subjects using cross validation.
Kelsell, David P.; Norgett, Elizabeth E.; Unsworth, Harriet; Teh, Muy-Teck; Cullup, Thomas; Mein, Charles A.; Dopping-Hepenstal, Patricia J.; Dale, Beverly A.; Tadini, Gianluca; Fleckman, Philip; Stephens, Karen G.; Sybert, Virginia P.; Mallory, Susan B.; North, Bernard V.; Witt, David R.; Sprecher, Eli; E. M. Taylor, Aileen; Ilchyshyn, Andrew; Kennedy, Cameron T.; Goodyear, Helen; Moss, Celia; Paige, David; Harper, John I.; Young, Bryan D.; Leigh, Irene M.; Eady, Robin A. J.; O’Toole, Edel A.
Harlequin ichthyosis (HI) is the most severe and frequently lethal form of recessive congenital ichthyosis. Although defects in lipid transport, protein phosphatase activity, and differentiation have been described, the genetic basis underlying the clinical and cellular phenotypes of HI has yet to be determined. By use of single-nucleotide–polymorphism chip technology and homozygosity mapping, a common region of homozygosity was observed in five patients with HI in the chromosomal region 2q35. Sequencing of the ABCA12 gene, which maps within the minimal region defined by homozygosity mapping, revealed disease-associated mutations, including large intragenic deletions and frameshift deletions in 11 of the 12 screened individuals with HI. Since HI epidermis displays abnormal lamellar granule formation, ABCA12 may play a critical role in the formation of lamellar granules and the discharge of lipids into the intercellular spaces, which would explain the epidermal barrier defect seen in this disorder. This finding paves the way for early prenatal diagnosis. In addition, functional studies of ABCA12 will lead to a better understanding of epidermal differentiation and barrier formation. PMID:15756637
Ismail, Eman Abdel Rahman; Youssef, Omneya Ibrahim
Platelet microparticles (PMPs) and function profile in children with congenital heart disease (CHD) have not been widely explored. We investigated platelet aggregation, flow cytometric platelet surface receptors (P-selectin and glycoprotein (GP) IIb/IIIa) and PMPs in 23 children with cyanotic CHD (CCHD), 30 children with acyanotic CHD (ACHD) and 30 healthy controls correlating these variables to hematological and coagulation parameters including von Willebrand factor antigen (vWF Ag) as a marker of endothelial dysfunction. Hemoglobin, hematocrit (HCT), D-dimer, and vWF Ag were significantly higher in CCHD than ACHD group. Platelet MPs and P-selectin expression were increased in patients than controls, particularly in CCHD and positively correlated to HCT, D-dimer, and vWF Ag while platelet count, aggregation, and GP IIb/IIIa expression were decreased in CCHD compared with ACHD group and negatively correlated to HCT. The overproduction of PMPs and platelet activation with suppressed aggregation may be implicated in the pathogenesis of coagulation/hemostatic abnormalities in children with CCHD.
Since the early 1980s prenatal diagnosis of congenital heart disease (CHD) has progressively impacted on the practice of pediatric cardiology and cardiac surgery. Fetal cardiology today raises special needs in screening programs, training of the involved staff, and allocations of services. Due to the increased detection rate and to the substantial number of terminations, the reduced incidence of CHD at birth can affect the workload of centers of pediatric cardiology and surgery. In utero transportation and competition among centers may change the area of referral in favor of the best centers. Echocardiography is a powerful means to diagnose and to guide lifesaving medical treatment of sustained tachyarrhythmias in the fetus. Prenatal diagnosis not only improves the preoperative conditions in most cases but also postoperative morbidity and mortality in selected types of CHD. Intrauterine transcatheter valvuloplasty in severe outflow obstructive lesions has been disappointing so far and this technique remains investigational, until its benefits are determined by controlled trials. Prenatal diagnosis allows counselling of families which are better prepared for the foreseeable management and outcome of the fetus. These benefits can reduce the risks of litigation for missed ultrasound diagnosis. As increased costs can be expected in institutions dealing with a large number of fetal CHD, the administrators of these institutions should receive protected funds, proportional to their needs.
Partington, Sara L; Valente, Anne Marie; Landzberg, Michael; Grant, Frederick; Di Carli, Marcelo F; Dorbala, Sharmila
Non-invasive testing of children with congenital heart disease (CHD) began in the 1950s with the introduction of radionuclide studies to assess shunt fractions, pulmonary blood flow, and ventricular contractile function. Echocardiography and cardiac magnetic resonance imaging have since replaced radionuclide imaging in many of these roles. Concurrently, percutaneous and surgical repairs of complex CHD evolved, creating new roles for radionuclide imaging. In this paper on applications of radionuclide imaging in CHD, we review the multiple mechanisms for myocardial ischemia in CHD. We critically compare optimal radionuclide imaging techniques to other imaging modalities for assessing ischemia in CHD. We present the current role of nuclear imaging for assessing viability and pulmonary blood flow. We highlight the value added by advances in dedicated cardiac SPECT scanners, novel reconstruction software, and cardiac PET in performing low-dose radionuclide imaging in CHD. Finally, we discuss the emerging clinical indications for radionuclide imaging in CHD including coronary flow reserve assessment and evaluation of cardiovascular prosthesis and device infections.
Short, J A; Paris, S T; Booker, P D; Fletcher, R
In children with congenital cyanotic heart disease, right-to-left intracardiac shunting causes an obligatory difference between arterial and end-tidal carbon dioxide tension (PaCO2-PE'CO2) as venous blood, rich in carbon dioxide, is added to the arterial circulation. This obligatory PaCO2-PE'CO2 difference, which can be predicted from knowledge of oxygen saturation, haemoglobin concentration and PaCO2, increases as oxygen saturation decreases, most markedly when the haemoglobin concentration is high. A second possible cause of the PaCO2-PE'CO2 difference is the effect of pulmonary hypoperfusion caused by the shunt. We studied 60 children undergoing cardiac surgery and compared the predicted the PaCO2-PE'CO2 difference with measured values to investigate the extent to which additional factors influence the clinically observed PaCO2-PE'CO2. In many children, observed values were much greater than predicted, which is compatible with some degree of pulmonary hypoperfusion. However, this was not felt to represent the complete picture in all patients. Another cause of ventilation-perfusion mismatch was suspected in those children who showed a considerable improvement in oxygen saturation during ventilation with an increased FIO2. We believe that pulmonary congestion caused by large left-to-right shunts may further increase the PaCO2-PE'CO2 difference.
Embryonic heart development is a very complicated process regulated precisely by a network composed of many genes and signaling pathways in time and space. Forkhead box (Fox, FOX) proteins are a family of transcription factors characterized by the presence of an evolutionary conserved "forkhead"or "winged-helix" DNA-binding domain and able to organize temporal and spatial gene expression during development. They are involved in a wide variety of cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism and DNA damage response. An abundance of studies in model organisms and systems has established that Foxa2, Foxc1/c2, Foxh1 and Foxm1, Foxos and Foxps are important components of the signaling pathways that instruct cardiogenesis and embryonic heart development, playing paramount roles in heart development. The previous studies also have demonstrated that mutations in some of the forkhead box genes and the aberrant expression of forkhead box gene are heavily implicated in the congenital heart disease (CHD) of humans. This review primarily focuses on the current understanding of heart development regulated by forkhead box transcription factors and molecular genetic mechanisms by which forkhead box factors modulate heart development during embryogenesis and organogenesis. This review also summarizes human CHD related mutations in forkhead box genes as well as the abnormal expression of forkhead box gene, and discusses additional possible regulatory mechanisms of the forkhead box genes during embryonic heart development that warrant further investigation.
Manja, Veena; Mathew, Bobby; Carrion, Vivien; Lakshminrusimha, Satyan
Critical congenital heart disease (CCHD) screening is effective in asymptomatic late preterm and term newborn infants with a low false positive rate (0.035%). Objective (1) To compare 2817 NICU discharges before and after implementation of CCHD screening; and (2) to evaluate CCHD screening at < 35 weeks gestation. Methods collection of results of CCHD screening including preductal and postductal SpO2 values. Results During the pre-CCHD screen period, 1247 infants were discharged from the NICU and one case of CCHD was missed. After 3/1/12, 1508 CCHD screens were performed among 1570 discharges and no CCHDs were missed. The preductal and postductal SpO2 values were 98.8±1.4% and 99±1.3% respectively in preterm and 98.9±1.3% and 98.9±1.4% in term infants. Ten infants had false positive screens (10/1508=0.66%). Conclusions Performing universal screening in the NICU is feasible but is associated with a higher false positive rate compared to asymptomatic newborn infants. PMID:25058746
Bianca, Innocenzo; Geraci, Giovanna; Gulizia, Michele Massimo; Egidy-Assenza, Gabriele; Barone, Chiara; Campisi, Marcello; Alaimo, Annalisa; Adorisio, Rachele; Comoglio, Francesca; Favilli, Silvia; Agnoletti, Gabriella; Carmina, Maria Gabriella; Chessa, Massimo; Sarubbi, Berardo; Mongiovì, Maurizio; Russo, Maria Giovanna; Bianca, Sebastiano; Canzone, Giuseppe; Bonvicini, Marco; Viora, Elsa; Poli, Marco
The success of cardiac surgery over the past 50 years has increased numbers and median age of survivors with congenital heart disease (CHD). Adults now represent two-thirds of patients with CHD; in the United States alone the number is estimated to exceed 1 million.In this population many affected women reach reproductive age and wish to have children. While in many CHD patients pregnancy can be accomplished successfully, some special situations with complex anatomy, iatrogenic or residual pathology are associated with an increased risk of severe maternal and fetal complications. Pre-conception counseling allows women to come to truly informed choices. Risk stratification tools can also help high-risk women to eventually renounce to pregnancy and to adopt safe contraception options. Once pregnant, women identified as intermediate or high-risk should receive multidisciplinary care involving a cardiologist, an obstetrician and an anesthesiologist with specific expertise in managing this peculiar medical challenge.This document is intended to provide cardiologists working in hospitals where an Obstetrics and Gynecology Department is available with a streamlined and practical tool, useful for them to select the best management strategies to deal with a woman affected by CHD who desires to plan pregnancy or is already pregnant.
Mistry, Hema; Gardiner, Helena M
We estimated the longer-term cost-effectiveness of using telemedicine screening for prenatal detection of congenital heart disease (CHD). One hospital in south-east England with a telemedicine service was connected to a fetal cardiology unit in London. A UK health service perspective was adopted. Evidence on costs and outcomes for standard-risk pregnant women during the antenatal period was based on patient-level data. Extrapolation beyond the end of the study (just after delivery) was carried out for the lifetime of children born with and without CHD. Expert opinion and data from published sources was used to populate a decision model. Future costs and benefits were discounted. The main outcome was quality-adjusted life years (QALYs) and results were expressed as cost per QALY gained. Various one-way sensitivity analyses were conducted. The model showed that offering telemedicine screening by specialists to all standard-risk pregnant women was the dominant strategy (i.e. cheaper and more effective). The sensitivity analyses found that the model was robust, and that telemedicine remained the most cost-effective strategy. The study showed that it would be cost-effective to provide telemedicine examinations as part of an antenatal screening programme for all standard-risk women.
Mandato, Claudia; Brive, Lena; Miura, Yoshiaki; Davis, Joseph Alex; Di Cosmo, Nicolina; Lucariello, Stefania; Pagliardini, Severo; Seo, Neung-Seon; Parenti, Giancarlo; Vecchione, Raffaella; Freeze, Hudson H; Vajro, Pietro
We investigated the metabolic defect(s) of four children who presented with isolated cryptogenic chronic liver disease, coagulopathy, and abnormalities of several unrelated serum glycoproteins. Analysis of the patients' serum glycoproteins and fibroblasts suggest they have a novel congenital disorder of glycosylation (CDG). All had abnormal transferrin (Tf) isoelectric focusing (IEF) profiles. More detailed analysis of Tf by electrospray ionization mass spectrometry (ESI-MS) showed a plethora of abnormal glycosylations that included loss of 1-2 sialic acids and 1-2 galactose units, typical of Group II defects. Tf from two patients also lacked 1-2 entire oligosaccharide chains, typical of Group One disorders. Total serum N-glycans were analyzed by HPLC and matrix-assisted laser desorption/ionization mass spectrometry and also showed increased proportion of neutral glycan chains lacking sialic acids and galactose units. Analysis of patient fibroblasts eliminated CDG-Ia, through CDG-Ih, -IL and CDG-IId. Our results suggest that a subset of children with clinically asymptomatic, cryptogenic hypertransaminasemia and/or liver steato-fibrosis may represent a novel type of CDG-X with an unknown defect(s). Clinicians are encouraged to test such patients for abnormal Tf glycosylation by ESI-MS.
El-Sayed, Basmah; Abd-Alhakem, Gehan; Ibrahim, Fatma M.
Objectives Oral manifestations recorded for congenital heart disease (CHD) patients include teeth hypoplasia and high caries incidence. These observations suggested that the enamel and dentin of the teeth may be altered, increasing the risk for caries incidence. This study was designed to investigate the effect of CHD on the ultrastructure and composition of deciduous sound teeth. Methods Thirty sound exfoliated human deciduous incisor teeth were selected for this study. They were divided into three groups, Group I (control) from healthy children (n = 6), Group II from acyanotic CHD children (n = 12) and Group III from cyanotic CHD children (n = 12). Each tooth was longitudinally sectioned, providing enough specimens for ultrastructure and chemical analysis using ESEM/EDAX. The results of ESEM/EDAX and dentin image analysis were statistically analyzed using one-way ANOVA test followed by Tukey’s test. Results Enamel of groups II and III showed increased dissolution and irregular orientation of enamel prisms. Orifices of dentinal tubules demonstrated widening and irregular outlines, also lateral branching increased markedly. Image analysis of dentin ESEM photomicrographs showed a highly significant increase in surface area of dentinal tubules. Decrease in calcium (Ca) and phosphorus (P) levels was statistically significant (P < 0.05). Conclusion CHDs affect the structure and chemical composition of deciduous teeth. PMID:25243076
Lopes, Antonio Augusto; dos Anjos Miranda, Rogério; Gonçalves, Rilvani Cavalcante; Thomaz, Ana Maria
BACKGROUND: In patients with congenital heart disease undergoing cardiac catheterization for hemodynamic purposes, parameter estimation by the indirect Fick method using a single predicted value of oxygen consumption has been a matter of criticism. OBJECTIVE: We developed a computer-based routine for rapid estimation of replicate hemodynamic parameters using multiple predicted values of oxygen consumption. MATERIALS AND METHODS: Using Microsoft® Excel facilities, we constructed a matrix containing 5 models (equations) for prediction of oxygen consumption, and all additional formulas needed to obtain replicate estimates of hemodynamic parameters. RESULTS: By entering data from 65 patients with ventricular septal defects, aged 1 month to 8 years, it was possible to obtain multiple predictions for oxygen consumption, with clear between-age groups (P <.001) and between-methods (P <.001) differences. Using these predictions in the individual patient, it was possible to obtain the upper and lower limits of a likely range for any given parameter, which made estimation more realistic. CONCLUSION: The organized matrix allows for rapid obtainment of replicate parameter estimates, without error due to exhaustive calculations. PMID:19641642
D'Alto, Michele; Diller, Gerhard-Paul
The presence of pulmonary arterial hypertension (PAH) increases morbidity and reduces survival in patients with congenital heart disease (CHD). PAH-CHD is a heterogeneous condition, depending on the type of the underlying defect and previous repair strategies. There is growing evidence of the benefits of PAH-specific therapy in the PAH-CHD population, but despite recent advances mortality rates remain relatively high. In the last years, an increasing focus has been placed on patients with PAH-CHD and net left-to-right shunt. Currently, there are limited data to guide the management of these patients and uncertainty on the cut-off values for eventual defect closure. Pregnancy conveys significant risks in PAH-CHD patients: appropriate counselling and care, including psychological support and a multidisciplinary team, should be part of the routine management of women with PAH-CHD of reproductive age. Some subgroups, such as patients with Down's syndrome, Fontan circulation and 'segmental' pulmonary hypertension, present particular challenges in terms of management and therapy. The current review focuses on contemporary treatment strategies in PAH-CHD patients with particular emphasis on challenging patient groups and conditions.
Rietdorf, U.; Riesenkampff, E.; Schwarz, T.; Kuehne, T.; Meinzer, H.-P.; Wolf, I.
The Fontan operation is a surgical treatment for patients with severe congenital heart diseases, where a biventricular correction of the heart can't be achieved. In these cases, a uni-ventricular system is established. During the last step of surgery a tunnel segment is placed to connect the inferior caval vein directly with the pulmonary artery, bypassing the right atrium and ventricle. Thus, the existing ventricle works for the body circulation, while the venous blood is passively directed to the pulmonary arteries. Fontan tunnels can be placed intra- and extracardially. The location, length and shape of the tunnel must be planned accurately. Furthermore, if the tunnel is placed extracardially, it must be positioned between other anatomical structures without constraining them. We developed a software system to support planning of the tunnel location, shape, and size, making pre-operative preparation of the tunnel material possible. The system allows for interactive placement and adjustment of the tunnel, affords a three-dimensional visualization of the virtual Fontan tunnel inside the thorax, and provides a quantification of the length, circumferences and diameters of the tunnel segments. The visualization and quantification can be used to plan and prepare the tunnel material for surgery in order to reduce the intra-operative time and to improve the fit of the tunnel patch.
Biglino, Giovanni; Capelli, Claudio; Bruse, Jan; Bosi, Giorgia M; Taylor, Andrew M; Schievano, Silvia
Computational models of congenital heart disease (CHD) have become increasingly sophisticated over the last 20 years. They can provide an insight into complex flow phenomena, allow for testing devices into patient-specific anatomies (pre-CHD or post-CHD repair) and generate predictive data. This has been applied to different CHD scenarios, including patients with single ventricle, tetralogy of Fallot, aortic coarctation and transposition of the great arteries. Patient-specific simulations have been shown to be informative for preprocedural planning in complex cases, allowing for virtual stent deployment. Novel techniques such as statistical shape modelling can further aid in the morphological assessment of CHD, risk stratification of patients and possible identification of new ‘shape biomarkers’. Cardiovascular statistical shape models can provide valuable insights into phenomena such as ventricular growth in tetralogy of Fallot, or morphological aortic arch differences in repaired coarctation. In a constant move towards more realistic simulations, models can also account for multiscale phenomena (eg, thrombus formation) and importantly include measures of uncertainty (ie, CIs around simulation results). While their potential to aid understanding of CHD, surgical/procedural decision-making and personalisation of treatments is undeniable, important elements are still lacking prior to clinical translation of computational models in the field of CHD, that is, large validation studies, cost-effectiveness evaluation and establishing possible improvements in patient outcomes. PMID:27798056
The prevalence of heart failure in patients with congenital heart disease, mainly due to large left to right shunts, is as high as 20%. Heart failure has a high impact on prognosis, growth and neurodevelopment. Prior to surgery or after palliative procedures children need a medical heart failure therapy. The traditional therapy with digoxin, diuretics and ACE-inhibitors is not supported by prospective randomized trials. Propranolol had a significant beneficial effect on the clinical heart failure score, neurohormonal activation, heart rate variability and cardiac remodeling in the prospective randomized trial CHF-Pro-Infant. Beta-blocker dosages depend on heart rate with a target between 100 and 110 bpm in infants and an average dose of 2mg/kg/day after a titration period of 2 to 3 weeks. Within the last 18 years after the first case the author treated only infants with severe heart failure and highly elevated Pro-BNP-levels (8879 pg/ml on average). However we never observed serious side effects due to worsening heart failure, severe bradycardia or pulmonary obstruction. Diuretics are given as low as necessary to prevent the activation of the renin-angiotensin-aldosterone system with its detrimental effect on cardiac remodeling.
Hom, Lisa A; Martin, Gerard R
Congenital heart disease (CCHD) is the most common birth defect. Screening for the most critical forms (CCHD) using pulse oximetry was added to the Recommended Uniform Screening Panel in the United States in 2011. Since then, CCHD screening has become nearly universal in the United States. Nurses are ideally situated to contribute to the development of best practices for implementation and provide education to families on CCHD screening. Much of the standardization, advocacy, and development of national recommendations occurred with key input from nurses. Nurses often have responsibility for educating parents, performing the screening, interpreting the screening algorithm, and the documentation of results. The nurse role often includes implementing follow-up quality improvement initiatives to ensure that systematic and accurate screening occurs. Smooth implementation can be achieved by identifying champions early, obtaining input from a multidisciplinary team including both physician and nursing leaders, and identifying ways to integrate screening into already existing workflow. By knowing the basics of why screening is important, how to screen, current recommendations on the follow-up for positive screens and the limitations of CCHD screening, nurses can advocate for their patients and positively impact outcomes for infants born with CCHD through early identification before discharge.
Calderon, Johanna; Bellinger, David C
It is widely recognised that children with congenital heart disease (CHD) are at high risk for neurodevelopmental impairments including attention deficit hyperactivity disorder and autism spectrum disorder symptoms. Executive function impairments are one of the most prominent neurodevelopmental features associated with CHD. These deficits can have widespread debilitating repercussions in children's neurocognitive, behavioural, and psycho-social development. There is a crucial gap in research regarding the efficacy of preventive or treatment strategies for these important cognitive morbidities. Executive functions are complex neurocognitive skills highly amenable to improvement. Evidence-based interventions have shown promising results in other paediatric populations, strongly suggesting that they might also benefit the growing population of children with CHD. In this review, we summarise the available data on executive function impairments in children and adolescents with CHD. We underline the important co-morbidity of executive dysfunction with other cognitive and psychiatric issues in CHD, which raises awareness of the crucial need to prevent or at least mitigate these deficits. Finally, we summarise future avenues for research in terms of interventions that may help reduce executive function impairments in youth with CHD.
Zaidi, Samir; Choi, Murim; Wakimoto, Hiroko; Ma, Lijiang; Jiang, Jianming; Overton, John D; Romano-Adesman, Angela; Bjornson, Robert D; Breitbart, Roger E; Brown, Kerry K; Carriero, Nicholas J; Cheung, Yee Him; Deanfield, John; DePalma, Steve; Fakhro, Khalid A; Glessner, Joseph; Hakonarson, Hakon; Italia, Michael J; Kaltman, Jonathan R; Kaski, Juan; Kim, Richard; Kline, Jennie K; Lee, Teresa; Leipzig, Jeremy; Lopez, Alexander; Mane, Shrikant M; Mitchell, Laura E; Newburger, Jane W; Parfenov, Michael; Pe'er, Itsik; Porter, George; Roberts, Amy E; Sachidanandam, Ravi; Sanders, Stephan J; Seiden, Howard S; State, Mathew W; Subramanian, Sailakshmi; Tikhonova, Irina R; Wang, Wei; Warburton, Dorothy; White, Peter S; Williams, Ismee A; Zhao, Hongyu; Seidman, Jonathan G; Brueckner, Martina; Chung, Wendy K; Gelb, Bruce D; Goldmuntz, Elizabeth; Seidman, Christine E; Lifton, Richard P
Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. Here we compare the incidence of de novo mutations in 362 severe CHD cases and 264 controls by analysing exome sequencing of parent-offspring trios. CHD cases show a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging (premature termination, frameshift, splice site) mutations. Similar odds ratios are seen across the main classes of severe CHD. We find a marked excess of de novo mutations in genes involved in the production, removal or reading of histone 3 lysine 4 (H3K4) methylation, or ubiquitination of H2BK120, which is required for H3K4 methylation. There are also two de novo mutations in SMAD2, which regulates H3K27 methylation in the embryonic left-right organizer. The combination of both activating (H3K4 methylation) and inactivating (H3K27 methylation) chromatin marks characterizes 'poised' promoters and enhancers, which regulate expression of key developmental genes. These findings implicate de novo point mutations in several hundreds of genes that collectively contribute to approximately 10% of severe CHD.
Zaidi, Samir; Choi, Murim; Wakimoto, Hiroko; Ma, Lijiang; Jiang, Jianming; Overton, John D.; Romano-Adesman, Angela; Bjornson, Robert D.; Breitbart, Roger E.; Brown, Kerry K.; Carriero, Nicholas J.; Cheung, Yee Him; Deanfield, John; DePalma, Steve; Fakhro, Khalid A.; Glessner, Joseph; Hakonarson, Hakon; Italia, Michael; Kaltman, Jonathan R.; Kaski, Juan; Kim, Richard; Kline, Jennie K.; Lee, Teresa; Leipzig, Jeremy; Lopez, Alexander; Mane, Shrikant M.; Mitchell, Laura E.; Newburger, Jane W.; Parfenov, Michael; Pe'er, Itsik; Porter, George; Roberts, Amy; Sachidanandam, Ravi; Sanders, Stephan J.; Seiden, Howard S.; State, Mathew W.; Subramanian, Sailakshmi; Tikhonova, Irina R.; Wang, Wei; Warburton, Dorothy; White, Peter S.; Williams, Ismee A.; Zhao, Hongyu; Seidman, Jonathan G.; Brueckner, Martina; Chung, Wendy K.; Gelb, Bruce D.; Goldmuntz, Elizabeth; Seidman, Christine E.; Lifton, Richard P.
Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births1. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging mutations. Similar odds ratios were seen across major classes of severe CHD. We found a marked excess of de novo mutations in genes involved in production, removal or reading of H3K4 methylation (H3K4me), or ubiquitination of H2BK120, which is required for H3K4 methylation2–4. There were also two de novo mutations in SMAD2; SMAD2 signaling in the embryonic left-right organizer induces demethylation of H3K27me5. H3K4me and H3K27me mark `poised' promoters and enhancers that regulate expression of key developmental genes6. These findings implicate de novo point mutations in several hundred genes that collectively contribute to ~10% of severe CHD. PMID:23665959
Walker, J. M.
Measurement of the length and width of the ligament of the head of femur (ligamentum teres) in 140 normal human fetuses between 12 weeks and term provides limits for growth changes in this structure. These observations provide no morphological evidence of a significant difference between males and females, or between the right and left sides, to explain the female and left hip preponderance reported in congenital hip disease. The ligament is shown to be variable in length, width, and shape, and it is not a distinctly linear structure through linearity may increase with age. Tests of femoral head mobility support the opinion that this ligament must play a role in fetal and neonatal hip joint stability. Weak correlation only was demonstrated between the ligament variables and acetabular depth, which suggests that ligament shape and socket shape are not closely related. Comparison of measurements from normal and 12 dysplastic or subluxated joints provides no evidence to support previous observations that this structure is unusually long in abnormal hip joints which are not frankly dislocated. Images FIG. 1 PMID:7445537
Amaral, Fernando Tadeu Vasconcelos; Manso, Paulo Henrique; Schmidt, André; Sgarbieri, Ricardo Nilson; Vicente, Walter Villela de Andrade; Carbone Junior, Clovis; Somerville, Jane
During the last decades, advances in diagnosis and treatment of congenital heart disease have allowed many individuals to reach adulthood. Due mainly to the great diagnostic diversity and to the co-morbidities usually present in this age group, these patients demand assistance in a multidisciplinary facility if an adequate attention is aimed. In this paper we reviewed, based in the international literature and also on the authors’ experience, the structural conditions that should be available for these patients. We highlighted aspects like the facility characteristics, the criteria usually adopted for patient transfer from the paediatric setting, the composition of the medical and para- medical staff taking into account the specific problems, and also the model of outpatient and in-hospital assistance. We also emphasized the importance of patient data storage, the fundamental necessity of institutional support and also the compromise to offer professional training. The crucial relevance of clinical research is also approached, particularly the development of multicenter studies as an appropriate methodology for this heterogeneous patient population. PMID:26313729
Sánchez-Gómez, Ma C; García-Mejía, K A; Pérez-Díaz Conti, M; Díaz-Rosas, G; Palma-Lara, I; Sánchez-Urbina, R; Klünder-Klünder, M; Botello-Flores, J A; Balderrábano-Saucedo, N A; Contreras-Ramos, A
Complex congenital heart disease (CHD) affects cardiac blood flow, generating a pressure overload in the compromised ventricles and provoking hypertrophy that over time will induce myocardial dysfunction and cause a potential risk of imminent death. Therefore, the early diagnosis of complex CHD is paramount during the first year of life, with surgical treatment of patients favoring survival. In the present study, we analyzed cardiac tissue and plasma of children with cardiac hypertrophy (CH) secondary to CHD for the expression of 11 miRNAs specific to CH in adults. The results were compared with the miRNA expression patterns in tissue and blood of healthy children. In this way, we determined that miRNAs 1, 18b, 21, 23b, 133a, 195, and 208b constitute the expression profile of the cardiac tissue of children with CHD. Meanwhile, miRNAs 21, 23a, 23b, and 24 can be considered specific biomarkers for the diagnosis of CH in infants with CHD. These results suggest that CH secondary to CHD in children differs in its mechanism from that described for adult hypertrophy, offering a new perspective to study the development of this pathology and to determine the potential of hypertrophic miRNAs to be biomarkers for early CH.
Ortmann, Laura A; Manimtim, Winston M; Lachica, Charisse I
Outcomes after discharge in children requiring tracheostomy after cardiac surgery have not been fully described. A retrospective, single-center study was performed on all children <18 years of age requiring both tracheostomy and surgery for congenital heart disease from January 2002 to May 2015. Forty-six tracheostomies were placed after surgery and four before. Single-ventricle anatomy was present in 12 (33%) patients. Incidence of tracheostomy after heart surgery increased from 0.8% the first half of the study period to 2% the second half. Median time between cardiac surgery and tracheostomy was 58 days. The most common indication for tracheostomy was multifactorial (30%) followed by airway malacia (22%). Median length to follow-up for survivors was 3.9 years (range 0.4-11.8 years). Survival to hospital discharge was 72%, and intermediate survival was 48%. Survival in those with systemic to pulmonary artery shunts at the time of tracheostomy was 22% compared to 59% for those with biventricular anatomy. Heart failure and multiple indications for tracheostomy were associated with worse outcome. There was no difference in survival for those discharged with a ventilator compared to those that were not. The most common cause of death after discharge was tracheostomy tube dislodgement/obstruction, accounting for 5 of 11 that died. Survival with a tracheostomy after cardiac surgery is poor, and children with systemic to pulmonary artery shunts are at especially high risk of death.
Peters, Bjoern; Ewert, Peter; Berger, Felix
Intravascular or intracardiac stenoses occur in many forms of congenital heart disease (CHD). Therefore, the implantation of stents has become an accepted interventional procedure for stenotic lesions in pediatric cardiology. Furthermore, stents are know to be used to exclude vessel aneurysm or to ensure patency of existing or newly created intracardiac communications. With the further refinement of the first generation of devices, a variety of “modern” stents with different design characteristics have evolved. Despite the tremendous technical improvement over the last 20 years, the “ideal stent” has not yet been developed. Therefore, the pediatric interventionalist has to decide which stent is suitable for each lesion. On this basis, currently available stents are discussed in regard to their advantages and disadvantages for common application in CHD. New concepts and designs developed to overcome some of the existing problems, like the failure of adaptation to somatic growth, are presented. Thus, in the future, biodegradable or growth stents might replace the currently used generation of stents. This might truly lead to widening indications for the use of stents in the treatment of CHD. PMID:20300265
Romley, John A; Chen, Alex Y; Goldman, Dana P; Williams, Roberta
Objective To determine the association between hospital costs and risk-adjusted inpatient mortality among children undergoing surgery for congenital heart disease (CHD) in U.S. acute-care hospitals. Data Sources/Study Settings Retrospective cohort study of 35,446 children in 2003, 2006, and 2009 Kids' Inpatient Database (KID). Study Design Cross-sectional logistic regression of risk-adjusted inpatient mortality and hospital costs, adjusting for a variety of patient-, hospital-, and community-level confounders. Data Collection/Extraction Methods We identified relevant discharges in the KID using the AHRQ Pediatric Quality Indicator for pediatric heart surgery mortality, and linked these records to hospital characteristics from American Hospital Association Surveys and community characteristics from the Census. Principal Findings Children undergoing CHD surgery in higher cost hospitals had lower risk-adjusted inpatient mortality (p = .002). An increase from the 25th percentile of treatment costs to the 75th percentile was associated with a 13.6 percent reduction in risk-adjusted mortality. Conclusions Greater hospital costs are associated with lower risk-adjusted inpatient mortality for children undergoing CHD surgery. The specific mechanisms by which greater costs improve mortality merit further exploration. PMID:24138064
... of infancy Great Ormond Street Hospital for Children (UK) Merck Manual Consumer Version: Hypoglycemia Orphanet: Congenital isolated ... Diseases Congenital Hyperinsulinism International The Children's Hyperinsulinism Fund (UK) GeneReviews (1 link) Familial Hyperinsulinism ClinicalTrials.gov (1 ...
Lomtadze, M; Chkhaidze, M; Mgeladze, E; Metreveli, I; Tsintsadze, A
Nosocomial infections still remain a serious problem in patients undergoing open heart surgery. The aim of the study was to determine the incidence, etiology and main risk factors of nosocomial infections (NI) following cardiac surgery in congenital heart diseases population. Retrospective case study was conducted. 387 patients with congenital heart disease (CHD), who underwent cardiac surgery from January 2007 to December 2008 were studied. The age of the most patients varied between 1 day to 15 years, 73 patients (18,8%) were older than 15 years. All 387 patients underwent cardiac surgery. The rate of NI was 16%. The most common infections were bloodstream infections (BSI) (7,75%) and respiratory tract infections (7%) respectively. The rate of NI was higher in patients under 1 year of age, after urgent surgery and urgent reoperation, long cardiopulmonary bypass (CPB) and aortic cross-clamp time, also in patients with prolonged mechanical ventilation, massive haemotransfusion, with open heart bone after surgery, reintubation, hospitalization in another hospital during last three month. It was concluded that the most common nosocomial infection after cardiac surgery congenital heart diseases in Georgian population was blood stream infection. The main risk factors of NI in the same setting were age under 1 year, urgent surgery, urgent reoperation, long CPB and aortic cross-clamp time, long duration of mechanical ventilation, massive haemotransfusion, open heart bone after surgery, reintubation, hospitalization in another hospital during last three month.
Harrison, Tondi M.; Ludington-Hoe, Susan
Background Infants with complex congenital heart disease requiring surgical intervention within the first days or weeks of life may be the most seriously ill infants needing intensive nursing and medical care immediately after birth. Skin to skin contact (SSC) is well-accepted and practiced as a positive therapeutic intervention in premature infants, but is not routinely offered to infants in cardiac intensive care units. Physiologic effects of SSC in the congenital heart disease population must be examined before recommending incorporation of SSC into standard care routines. Objective The purpose of this case study was to describe the physiologic response to a single session of SSC in an 18-day-old infant with hypoplastic left heart syndrome. Methods Repeated measures of heart rate, respiratory rate, oxygen saturation, blood pressure, and temperature were recorded 30 minutes prior to SSC, during SSC (including interruptions for bottle and breast feedings), and 10 minutes after SSC was completed. Results All physiologic parameters were clinically acceptable throughout the 135-minute observation. Conclusion This case study provides beginning evidence that SSC is safe in full-term infants following surgery for complex congenital heart disease. Further research with a larger sample is needed to examine effects of SSC on infant physiology before surgery and earlier in the postoperative time period as well as on additional outcomes such as length of stay, maternal-infant interaction, and neurodevelopment. PMID:25325374
Lee, Yu-Sheng; Jeng, Mei-Jy; Tsao, Pei-Chen
Background The mortality risk associated with congenital airway anomalies (CAA) in children with congenital heart disease (CHD) is unclear. This study aimed to investigate the factors associated with CAA, and the associated mortality risk, among children with CHD. Methods This nationwide, population-based study evaluated 39,652 children with CHD aged 0–5 years between 2000 and 2011, using the Taiwan National Health Insurance Research Database (NHIRD). We performed descriptive, logistic regression, Kaplan–Meier, and Cox regression analyses of the data. Results Among the children with CHD, 1,591 (4.0%) had concomitant CAA. Children with CHD had an increased likelihood of CAA if they were boys (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.33–1.64), infants (OR, 5.42; 95%CI, 4.06–7.24), or had a congenital musculoskeletal anomaly (OR, 3.19; 95%CI, 2.67–3.81), and were typically identified 0–3 years after CHD diagnosis (OR, 1.33; 95%CI 1.17–1.51). The mortality risk was increased in children with CHD and CAA (crude hazard ratio [HR], 2.05; 95%CI, 1.77–2.37), even after adjusting for confounders (adjusted HR, 1.76; 95%CI, 1.51–2.04). Mortality risk also changed by age and sex (adjusted HR and 95%CI are quoted): neonates, infants, and toddlers and preschool children, 1.67 (1.40–2.00), 1.93 (1.47–2.55), and 4.77 (1.39–16.44), respectively; and boys and girls, 1.62 (1.32–1.98) and 2.01 (1.61–2.50), respectively. Conclusion The mortality risk is significantly increased among children with CHD and comorbid CAA. Clinicians should actively seek CAA during the follow-up of children with CHD. PMID:26334302
Repair of congenital heart disease with associated pulmonary hypertension in children: what are the minimal investigative procedures? Consensus statement from the Congenital Heart Disease and Pediatric Task Forces, Pulmonary Vascular Research Institute (PVRI)
Abstract Standardization of the diagnostic routine for children with congenital heart disease associated with pulmonary arterial hypertension (PAH-CHD) is crucial, in particular since inappropriate assignment to repair of the cardiac lesions (e.g., surgical repair in patients with elevated pulmonary vascular resistance) may be detrimental and associated with poor outcomes. Thus, members of the Congenital Heart Disease and Pediatric Task Forces of the Pulmonary Vascular Research Institute decided to conduct a survey aimed at collecting expert opinion from different institutions in several countries, covering many aspects of the management of PAH-CHD, from clinical recognition to noninvasive and invasive diagnostic procedures and immediate postoperative support. In privileged communities, the vast majority of children with congenital cardiac shunts are now treated early in life, on the basis of noninvasive diagnostic evaluation, and have an uneventful postoperative course, with no residual PAH. However, a small percentage of patients (older at presentation, with extracardiac syndromes or absence of clinical features of increased pulmonary blood flow, thus suggesting elevated pulmonary vascular resistance) remain at a higher risk of complications and unfavorable outcomes. These patients need a more sophisticated diagnostic approach, including invasive procedures. The authors emphasize that decision making regarding operability is based not only on cardiac catheterization data but also on the complete diagnostic picture, which includes the clinical history, physical examination, and all aspects of noninvasive evaluation. PMID:25006452
Wang, Bo; Chen, Sun; Fu, Qihua; Sun, Kun
Background Congenital heart disease (CHD) is the most prevalent type of birth defect in human, with high morbidity in infant. Several genes essential for heart development have been identified. GATA4 is a pivotal transcription factor that can regulate the cardiac development. Many GATA4 mutations have been identified in patients with different types of CHD. Aims In this study, the NKX2-5, HAND1 and GATA4 coding regions were sequenced in a family spanning three generations in which seven patients had CHD. Disease-causing potential variation in this family was evaluated by bioinformatics programs and the transcriptional activity of mutant protein was analyzed by the dual luciferase reporter assay. Results A novel GATA4 mutation, c.C931T (p.R311W), was identified and co-segregated with the affected patients in this family. The bioinformatics programs predicted this heterozygous mutation to be deleterious and the cross-species alignment of GATA4 sequences showed that the mutation occurred within a highly conserved amino acid. Even though it resided in the nuclear localization signal domain, the mutant protein didn’t alter its intracellular distribution. Nevertheless, further luciferase reporter assay demonstrated that the p.R311W mutation reduced the ability of GATA4 to activate its downstream target gene. Conclusions Our study identified a novel mutation in GATA4 that likely contributed to the CHD in this family. This finding expanded the spectrum of GATA4 mutations and underscored the pathogenic correlation between GATA4 mutations and CHD. PMID:27391137
Smemo, Scott; Campos, Luciene C; Moskowitz, Ivan P; Krieger, José E; Pereira, Alexandre C; Nobrega, Marcelo A
Recent studies have identified the genetic underpinnings of a growing number of diseases through targeted exome sequencing. However, this strategy ignores the large component of the genome that does not code for proteins, but is nonetheless biologically functional. To address the possible involvement of regulatory variation in congenital heart diseases (CHDs), we searched for regulatory mutations impacting the activity of TBX5, a dosage-dependent transcription factor with well-defined roles in the heart and limb development that has been associated with the Holt-Oram syndrome (heart-hand syndrome), a condition that affects 1/100 000 newborns. Using a combination of genomics, bioinformatics and mouse genetic engineering, we scanned ∼700 kb of the TBX5 locus in search of cis-regulatory elements. We uncovered three enhancers that collectively recapitulate the endogenous expression pattern of TBX5 in the developing heart. We re-sequenced these enhancer elements in a cohort of non-syndromic patients with isolated atrial and/or ventricular septal defects, the predominant cardiac defects of the Holt-Oram syndrome, and identified a patient with a homozygous mutation in an enhancer ∼90 kb downstream of TBX5. Notably, we demonstrate that this single-base-pair mutation abrogates the ability of the enhancer to drive expression within the heart in vivo using both mouse and zebrafish transgenic models. Given the population-wide frequency of this variant, we estimate that 1/100 000 individuals would be homozygous for this variant, highlighting that a significant number of CHD associated with TBX5 dysfunction might arise from non-coding mutations in TBX5 heart enhancers, effectively decoupling the heart and hand phenotypes of the Holt-Oram syndrome.
Silva, Karina Peres; Rocha, Luciane Alves; Leslie, Ana Teresa Figueiredo Stochero; Guinsburg, Ruth; Silva, Célia Maria Camelo; Nardozza, Luciano Marcondes Machado; Moron, Antonio Fernandes; Araujo Júnior, Edward
Summary Objective to describe the epidemiological data of the population born with the diagnosis of Congenital Heart Disease (CHD); to compare diagnoses made using fetal echocardiography with the findings from postnatal echocardiography or anatomopathological examination of the heart; and to evaluate mortality among newborns that underwent surgical treatment. Methods this was a cohort study with information gathered from the medical records of the pregnant women and their newborns diagnosed with CHD during the fetal or postnatal periods, between January 2008 and December 2012. Means, standard deviations and maximum and minimum values were calculated for the quantitative variables. Relative and absolute values were calculated for the qualitative variables. The heart malformations were categorized in four groups: complex lesions, significant lesions, minor lesions and others. Results we detected postnatal incidence of CHD of 1.9% at our service. The mean maternal age was 28.3 years and 10 (21.3%) of the pregnant women were ≥ 35 years old. The mean gestational age at the time of performing the fetal echocardiogram was 27.8 weeks. Mean gestational age at delivery was 38 weeks, and the mean weight of the newborns was 2,644.5 grams. Regarding the diagnosis of CHD, there were: 23 complex lesions (39%); 15 significant lesions (26%); 10 minor lesions (17%); 4 other lesions (7%) and 6 normal anatomies (10%). The diagnosis of CHD made on the fetus and postnatally coincided in 77.6% of the cases. A total of 27 patients (60%) underwent surgery, and the outcome was neonatal death in five cases. Conclusion we detected postnatal incidence of CHD of 1.9%, and it was more common among older pregnant women and with late detection in the intrauterine period. Complex heart diseases predominated, thus making it difficult to have a good result regarding neonatal mortality rates. PMID:25332754
Li, You; Klena, Nikolai T.; Gabriel, George C; Liu, Xiaoqin; Kim, Andrew J.; Lemke, Kristi; Chen, Yu; Chatterjee, Bishwanath; Devine, William; Damerla, Rama Rao; Chang, Chien-fu; Yagi, Hisato; San Agustin, Jovenal T.; Thahir, Mohamed; Anderton, Shane; Lawhead, Caroline; Vescovi, Anita; Pratt, Herbert; Morgan, Judy; Haynes, Leslie; Smith, Cynthia L.; Eppig, Janan T.; Reinholdt, Laura; Francis, Richard; Leatherbury, Linda; Ganapathiraju, Madhavi K.; Tobita, Kimimasa; Pazour, Gregory J.; Lo, Cecilia W.
Congenital heart disease (CHD) is the most prevalent birth defect, affecting nearly 1% of live births1, but the incidence of CHD is up to ten fold higher in human fetuses2,3. A genetic contribution is strongly suggested by the association of CHD with chromosome abnormalities and high recurrence risk4. Here we report findings from a recessive forward genetic screen in fetal mice, showing the cilium and cilia transduced cell signaling play important roles in the pathogenesis of CHD. The cilium is an evolutionarily conserved organelle projecting from the cell surface with essential roles in diverse cellular processes. Using echocardiography, we ultrasound scanned 87,355 chemically mutagenized C57BL/6J fetal mice and recovered 218 CHD mouse models. Whole exome sequencing identified 91 recessive CHD mutations in 61 genes. This included 34 cilia-related genes, 16 genes involved in cilia transduced cell signaling, and 10 genes regulating vesicular trafficking, a pathway important for ciliogenesis and cell signaling. Surprisingly, many CHD genes encoded interacting proteins, suggesting an interactome protein network may provide a larger genomic context for CHD pathogenesis. These findings provide novel insights into the potential Mendelian genetic contribution to CHD in the fetal population, a segment of the human population not well studied. We note pathways identified show overlap with CHD candidate genes recovered in CHD patients5, suggesting they may have relevance to the more complex genetics of CHD overall. These CHD mouse models and >8,000 incidental mutations are sperm archived, creating a rich public resource for human disease modeling. PMID:25807483
Rosenthal, E; Qureshi, S A; Kakadekar, A P; Anjos, R; Baker, E J; Tynan, M
OBJECTIVE--To investigate the efficacy and safety of transcatheter laser-assisted valve dilatation for atretic valves in children with congenital heart disease. DESIGN--Prospective clinical study. SETTING--Supraregional paediatric cardiology centre. SUBJECTS--Eleven children (aged 1 day-11 years; weight 2.1-35.7 kg) with atresia of pulmonary (10) or tricuspid (one) valve underwent attempted laser-assisted valve dilatation as part of the staged treatment of their cyanotic heart disease. INTERVENTION--After delineating the atretic valve by angiography and/or echocardiography a 0.018 inch "hot tip" laser wire was used to perforate the atretic valve. Subsequently the valve was dilated with conventional balloon dilatation catheters up to the valve annulus diameter. RESULTS--Laser-assisted valve dilatation was successfully accomplished in nine children. In two neonates with pulmonary valve atresia, intact ventricular septum, and coexistent infundibular atresia the procedure resulted in cardiac tamponade: one died immediately and one later at surgery. During a follow up of 1-17 months (mean 11) two infants with pulmonary valve atresia and intact ventricular septum died (one with congestive cardiac failure). The remainder are either well palliated and do not require further procedures (three), or are awaiting further transcatheter or surgical procedures because of associated defects (four). CONCLUSIONS--Laser-assisted valve dilatation is a promising adjunct to surgery in this high risk group of patients. It may avoid surgery in some patients, and may reduce the number of surgical procedures in those requiring staged operations. Images PMID:8343325
Thompson, Jennifer L.; Kuklina, Elena V.; Bateman, Brian T.; Callaghan, William M.; James, Andra H.; Grotegut, Chad A.
OBJECTIVE To estimate nationwide trends in the prevalence of maternal congenital heart disease (CHD) and determine whether women with CHD are more likely than women without maternal CHD to have medical and obstetric complications. METHODS The 2000–2010 Nationwide Inpatient Sample was queried for International Classification of Diseases, 9th Revision, Clinical Modification codes to identify delivery hospitalizations of women with and without CHD. Trends in the prevalence of CHD were determined and then rates of complications were reported for CHD per 10,000 delivery hospitalizations. For Nationwide Inpatient Sample 2008–2010, logistic regression was used to examine associations between CHD and complications. RESULTS From 2000 to 2010, there was a significant linear increase in the prevalence of CHD from 6.4 to 9.0 per 10,000 delivery hospitalizations (P<.001). Multivariable logistic regression demonstrated that all selected medical complications, including mortality (17.8 compared with 0.7/10,000 deliveries, adjusted odds ratio [OR] 22.10, 95% confidence interval [CI] 13.96–34.97), mechanical ventilation (91.9 compared with 6.9/10,000, adjusted OR 9.94, 95% CI 7.99–12.37), and a composite cardiovascular outcome (614 compared with 34.3/10,000, adjusted OR 10.54, 95% CI 9.55–11.64) were more likely to occur among delivery hospitalizations with maternal CHD than without. Obstetric complications were also common among women with CHD. Delivery hospitalizations with maternal CHD that also included codes for pulmonary circulatory disorders had higher rates of medical complications compared with hospitalizations with maternal CHD without pulmonary circulatory disorders. CONCLUSION The number of delivery hospitalizations with maternal CHD in the United States is increasing, and although we were not able to determine whether correction of the cardiac lesion affected outcomes, these hospitalizations have a high burden of medical and obstetric complications. PMID
Parkinson, William M.; Dookwah, Michelle; Dear, Mary Lynn; Gatto, Cheryl L.; Aoki, Kazuhiro; Tiemeyer, Michael; Broadie, Kendal
ABSTRACT Congenital disorders of glycosylation (CDGs) constitute a rapidly growing family of human diseases resulting from heritable mutations in genes driving the production and modification of glycoproteins. The resulting symptomatic hypoglycosylation causes multisystemic defects that include severe neurological impairments, revealing a particularly critical requirement for tightly regulated glycosylation in the nervous system. The most common CDG, CDG-Ia (PMM2-CDG), arises from phosphomannomutase type 2 (PMM2) mutations. Here, we report the generation and characterization of the first Drosophila CDG-Ia model. CRISPR-generated pmm2-null Drosophila mutants display severely disrupted glycosylation and early lethality, whereas RNAi-targeted knockdown of neuronal PMM2 results in a strong shift in the abundance of pauci-mannose glycan, progressive incoordination and later lethality, closely paralleling human CDG-Ia symptoms of shortened lifespan, movement impairments and defective neural development. Analyses of the well-characterized Drosophila neuromuscular junction (NMJ) reveal synaptic glycosylation loss accompanied by defects in both structural architecture and functional neurotransmission. NMJ synaptogenesis is driven by intercellular signals that traverse an extracellular synaptomatrix and are co-regulated by glycosylation and matrix metalloproteinases (MMPs). Specifically, trans-synaptic signaling by the Wnt protein Wingless (Wg) depends on the heparan sulfate proteoglycan (HSPG) co-receptor Dally-like protein (Dlp), which is regulated by synaptic MMP activity. Loss of synaptic MMP2, Wg ligand, Dlp co-receptor and downstream trans-synaptic signaling occurs with PMM2 knockdown. Taken together, this Drosophila CDG disease model provides a new avenue for the dissection of cellular and molecular mechanisms underlying neurological impairments and is a means by which to discover and test novel therapeutic treatment strategies. PMID:26940433
Friedman, Marcia A.; Miletta, Nathanial; Roe, Cheryl; Wang, Dongliang; Morrow, Bernice E.; Kates, Wendy R.; Higgins, Anne Marie; Shprintzen, Robert J.
Objective Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion of approximately 40 genes from one copy of chromosome 22. Expression of the syndrome is a variable combination of over 190 phenotypic characteristics. As of yet, little is known about how these phenotypes correlate with one another or whether there are predictable patterns of expression. Two of the most common phenotypic categories, congenital heart disease and cleft palate, have been proposed to have a common genetic relationship to the deleted T-box 1 gene (TBX1). The purpose of this study is to determine if congenital heart disease and cleft palate are correlated in a large cohort of human subjects with VCFS. Methods This study is a retrospective chart review including 316 Caucasian non-Hispanic subjects with FISH or CGH microarray confirmed chromosome 22q11.2 deletions. All subjects were evaluated by the interdisciplinary team at the Velo-Cardio-Facial Syndrome International Center at Upstate Medical University, Syracuse, NY. Each combination of congenital heart disease, cleft palates, and retrognathia was analyzed by chi square or Fisher exact test. Results For all categories of congenital heart disease and cleft palate or retrognathia no significant associations were found, with the exception of submucous cleft palate and retrognathia (nominal p=0.0325) and occult submucous cleft palate and retrognathia (nominal p=0.000013). Conclusions Congenital heart disease and cleft palate do not appear to be correlated in human subjects with VCFS despite earlier suggestions from animal models. Possible explanations include modification of the effect of TBX1 by genes outside of the 22q11.2 region that may further influence the formation of the palate or heart, or the presence of epigenetic factors that may effect genes within the deleted region, modifying genes elsewhere, or polymorphisms on the normal copy of chromosome 22. Lastly, it is possible that TBX1 plays a role in palate formation in some
Wedenoja, Satu; Ormälä, Timo; Berg, Ulla B; Halling, Stella F Edström; Jalanko, Hannu; Karikoski, Riitta; Kere, Juha; Holmberg, Christer; Höglund, Pia
Congenital chloride diarrhea is due to mutations in the intestinal Cl(-)/HCO(3)(-) exchange (SLC26A3) which results in sodium chloride and fluid depletion leading to hypochloremic and hypokalemic metabolic alkalosis. Although treatment with sodium and potassium chloride offers protection from renal involvement in childhood, the long-term renal outcome remains unclear. Here we describe two cases of congenital chloride diarrhea-associated end-stage renal disease with transplantation. Further, we show that there is a high incidence of mild chronic kidney disease in 35 other patients with congenital chloride diarrhea. The main feature of the renal injury was nephrocalcinosis, without hypercalciuria or nephrolithiasis with small sized kidneys and commensurately reduced glomerular filtration rates. This suggests that diarrhea-related sodium chloride and volume depletion, the first signs of non-optimal salt substitution, promote urine supersaturation and crystal precipitation. The poor compliance with salt substitution along with long-lasting hypochloremic and hypokalemic metabolic alkalosis is likely to induce progressive calcification and renal failure. Both our patients developed nephrocalcinosis in the transplanted kidneys suggesting that this complication is a consequence of intestinal SLC26A3 deficiency. Interestingly, the transporter is expressed in the distal nephron but the recurrence of nephrocalcinosis in the transplanted kidney suggests that it does not play a significant renal role in this syndrome.
... Listen Español Text Size Email Print Share Congenital Abnormalities Page Content Article Body About 3% to 4% ... of congenital abnormalities earlier. 5 Categories of Congenital Abnormalities Chromosome Abnormalities Chromosomes are structures that carry genetic ...
Rassart, Jessica; Luyckx, Koen; Goossens, Eva; Apers, Silke; Moons, Philip
The present study examined associations between parenting and perceived health in adolescents with congenital heart disease (CHD) using a longitudinal trajectory approach. Adolescents with CHD were selected from the database of pediatric and congenital cardiology of the University Hospitals Leuven. A total of 429 adolescents (M age = 16 at T1) participated in the present study, comprising four measurement waves spanning approximately 3 years. Latent class growth analysis was used to identify trajectory classes of parenting and perceived health. Whereas adolescents from democratic households reported the most favorable health outcomes, adolescents from authoritarian, overprotective, and psychologically controlling families (all characterized by relatively high levels of psychological control) showed an increased risk for poor perceived health over time. Hence, the present study found substantial developmental associations between parenting and perceived health in adolescents with CHD. Future research should investigate whether working on the parent-adolescent relationship can foster patients' health.
Gosnell, Jordan; Pietila, Todd; Samuel, Bennett P; Kurup, Harikrishnan K N; Haw, Marcus P; Vettukattil, Joseph J
Three-dimensional (3D) printing is an emerging technology aiding diagnostics, education, and interventional, and surgical planning in congenital heart disease (CHD). Three-dimensional printing has been derived from computed tomography, cardiac magnetic resonance, and 3D echocardiography. However, individually the imaging modalities may not provide adequate visualization of complex CHD. The integration of the strengths of two or more imaging modalities has the potential to enhance visualization of cardiac pathomorphology. We describe the feasibility of hybrid 3D printing from two imaging modalities in a patient with congenitally corrected transposition of the great arteries (L-TGA). Hybrid 3D printing may be useful as an additional tool for cardiologists and cardiothoracic surgeons in planning interventions in children and adults with CHD.
Report from the international society for nomenclature of paediatric and congenital heart disease: creation of a visual encyclopedia illustrating the terms and definitions of the international pediatric and congenital cardiac code.
Giroud, Jorge M; Jacobs, Jeffrey P; Spicer, Diane; Backer, Carl; Martin, Gerard R; Franklin, Rodney C G; Béland, Marie J; Krogmann, Otto N; Aiello, Vera D; Colan, Steven D; Everett, Allen D; William Gaynor, J; Kurosawa, Hiromi; Maruszewski, Bohdan; Stellin, Giovanni; Tchervenkov, Christo I; Walters, Henry L; Weinberg, Paul; Anderson, Robert H; Elliott, Martin J
Tremendous progress has been made in the field of pediatric heart disease over the past 30 years. Although survival after heart surgery in children has improved dramatically, complications still occur, and optimization of outcomes for all patients remains a challenge. To improve outcomes, collaborative efforts are required and ultimately depend on the possibility of using a common language when discussing pediatric and congenital heart disease. Such a universal language has been developed and named the International Pediatric and Congenital Cardiac Code (IPCCC). To make the IPCCC more universally understood, efforts are under way to link the IPCCC to pictures and videos. The Archiving Working Group is an organization composed of leaders within the international pediatric cardiac medical community and part of the International Society for Nomenclature of Paediatric and Congenital Heart Disease (www.ipccc.net). Its purpose is to illustrate, with representative images of all types and formats, the pertinent aspects of cardiac diseases that affect neonates, infants, children, and adults with congenital heart disease, using the codes and definitions associated with the IPCCC as the organizational backbone. The Archiving Working Group certifies and links images and videos to the appropriate term and definition in the IPCCC. These images and videos are then displayed in an electronic format on the Internet. The purpose of this publication is to report the recent progress made by the Archiving Working Group in establishing an Internet-based, image encyclopedia that is based on the standards of the IPCCC.
... heart disease. Google+ Hangout on the first large-scale gene sequencing analysis of congenital heart disease 05/ ... in the journal Nature, about the first large-scale sequencing analysis of congenital heart disease. This NHLBI- ...
Tulloh, Robert; Marsh, Michael; Blackburn, Michael; Casey, Frank; Lenney, Warren; Weller, Peter; Keeton, Barry R
New data are emerging on the use of palivizumab as prophylaxis against infection with the respiratory syncytial virus in infants with congenital cardiac disease. Following a 4-year multicentre randomised trial, it was shown that prophylactic injections with palivizumab were effective and safe for such children. Prophylaxis consists of 5, monthly, intramuscular injections of palivizumab, at a dose of 15 mg/kg, given during the season for infection with the respiratory syncytial virus. Timing is at the discretion of the physician, depending on the onset of the season locally. It is suggested that, in the United Kingdom, this should be commenced in mid-September. To help clinicians to identify appropriate candidates for palivizumab, a working group of the British Paediatric Cardiac Association has developed recommendations. Infants, namely those under 1 year old, with congenital cardiac disease likely to benefit from prophylaxis include those with haemodynamically significant lesions, particularly increased pulmonary blood flow with or without cyanosis; pulmonary venous congestion, pulmonary hypertension or long-term pulmonary complications, residual haemodynamic abnormalities following medical or surgical intervention (patients who have undergone cardiopulmonary bypass should receive an injection as soon as they are medically stable), cardiomyopathy requiring treatment, and congenital cardiac disease likely to need hospital admission for medical or surgical intervention during the season of infection with the virus. Prophylaxis with palivizumab may also be indicated, at the discretion of the physician, in some children with complex cardiac disease over the age of 1 year. Children less likely to benefit from prophylaxis are those with haemodynamically insignificant disease, or those with lesions adequately corrected by medical or surgical intervention.
Li, Huixia; Luo, Miyang; Zheng, Jianfei; Luo, Jiayou; Zeng, Rong; Feng, Na; Du, Qiyun; Fang, Junqun
Abstract An artificial neural network (ANN) model was developed to predict the risks of congenital heart disease (CHD) in pregnant women. This hospital-based case-control study involved 119 CHD cases and 239 controls all recruited from birth defect surveillance hospitals in Hunan Province between July 2013 and June 2014. All subjects were interviewed face-to-face to fill in a questionnaire that covered 36 CHD-related variables. The 358 subjects were randomly divided into a training set and a testing set at the ratio of 85:15. The training set was used to identify the significant predictors of CHD by univariate logistic regression analyses and develop a standard feed-forward back-propagation neural network (BPNN) model for the prediction of CHD. The testing set was used to test and evaluate the performance of the ANN model. Univariate logistic regression analyses were performed on SPSS 18.0. The ANN models were developed on Matlab 7.1. The univariate logistic regression identified 15 predictors that were significantly associated with CHD, including education level (odds ratio = 0.55), gravidity (1.95), parity (2.01), history of abnormal reproduction (2.49), family history of CHD (5.23), maternal chronic disease (4.19), maternal upper respiratory tract infection (2.08), environmental pollution around maternal dwelling place (3.63), maternal exposure to occupational hazards (3.53), maternal mental stress (2.48), paternal chronic disease (4.87), paternal exposure to occupational hazards (2.51), intake of vegetable/fruit (0.45), intake of fish/shrimp/meat/egg (0.59), and intake of milk/soymilk (0.55). After many trials, we selected a 3-layer BPNN model with 15, 12, and 1 neuron in the input, hidden, and output layers, respectively, as the best prediction model. The prediction model has accuracies of 0.91 and 0.86 on the training and testing sets, respectively. The sensitivity, specificity, and Yuden Index on the testing set (training set) are 0.78 (0.83), 0.90 (0
Perricone, Giovanna; Polizzi, Concetta; De Luca, Francesco
Child development may be subject to forms of motor, physical, cognitive and self-representation impairments when complex congenital heart disease (CHD) occurs. In some cases, inadequacy of both self-representation as well as the family system are displayed. It seems to be important to search the likely internal and external resources of the CHD child, and the possible connections among such resources, which may help him/her to manage his/her own risk condition. The research project inquires the possible resources related to the self-representation and self-esteem levels of the CHD child, and those related to maternal self-perception as competent mothers. A group of 25 children (mean age = 10.2; SD=1.8) suffering from specific forms of CHD, and a group made up of their relative mothers (mean age = 38.2; SD=5) were studied. The tools used were the Human Figure Drawing, to investigate child body-related self-representation; the TMA scale (Self-esteem Multidimensional Test), to investigate the child's self-esteem; and the Q-sort questionnaire, to assess how mothers perceived their maternal competence. Data concerning the likely correlations between the child's self-representation and the maternal role competence show [that] positive correlations between some indicators of maternal competence, specific aspects of CHD children's self-representation (mothers' emotional coping and children's self-image adequacy) and self-esteem (mothers' emotional scaffolding and children's self-esteem at an emotional level). By detecting the occurrence of specific correlations among resources of both child and mother, the study provides cardiologists with information that is useful for building a relationship with the families concerned, which would seem to enhance the quality of the process of the cure itself. PMID:23667730
Liu, Caixia; Shen, Adong; Li, Xiaofeng; Jiao, Weiwei; Zhang, Xingen; Li, Zhongzhi
Despite animal studies having demonstrated that Tbx20 is essential for heart development, few studies have been conducted about TBX20 and congenital heart disease (CHD) in humans. Recently two TBX20 mutations have been associated with human heart defects in two Caucasian families, but TBX20 mutations underlying the more common isolated forms of CHD are still unknown. To explore this question and to analyze the association between TBX20 and susceptibility to CHD 203 Chinese patients with a variety of predominantly sporadic CHD and 300 control subjects were investigated for TBX20 mutations. The exon 2-6 contributing to the T-box DNA-binding domain and their flanking intron sequences were amplified by polymerase chain reaction (PCR) and then were sequenced after purification. Three non-synonymous mutations (A63T, I121F, and T262M) were identified in 3 patients, which were not seen in 300 controls. I121F and T262M mutations occurred within the highly conserved T-box DNA-binding domain. Two synonymous sequence variants (N222N, T262T) and one intervening variant (IVS2-5insCT) were observed in 3 patients but not in the controls. In addition, eight SNPs were observed both in patients and controls and four (S167S, P177P, A181A, and I219I) of them are novel. These data indicate that the frequency of TBX20 missense mutations occurred in Chinese CHD children is low, but they probably contribute to the risk of atrial septal defect (ASD), total anomalous pulmonary venous connection (TAPVC) and tetralogy of Fallot (TOF) in a small subset of Chinese. The findings provide the first insight into TBX20 mutations for TOF and TAPVC. Functional study involved in the new sequence variants should be subject of further investigation.
Rosenblum, Omer; Katz, Uriel; Reuveny, Ronen; Williams, Craig A; Dubnov-Raz, Gal
Few previous studies have addressed exercise capacity in patients with corrected congenital heart disease (CHD) and significant anatomical residua. The aim of this study was to determine the aerobic fitness and peak cardiac function of patients with corrected CHD with complete or incomplete repairs, as determined by resting echocardiography. Children, adolescents and young adults (<40 years) with CHD from both sexes, who had previously undergone biventricular corrective therapeutic interventions (n = 73), and non-CHD control participants (n = 76) underwent cardiopulmonary exercise testing. The CHD group was further divided according to the absence/presence of significant anatomical residua on a resting echocardiogram ("complete"/"incomplete" repair groups). Aerobic fitness and cardiac function were compared between groups using linear regression and analysis of covariance. Peak oxygen consumption, O2 pulse and ventilatory threshold were significantly lower in CHD patients compared with controls (all p < 0.01). Compared with the complete repair group, the incomplete repair group had a significantly lower mean peak work rate, age-adjusted O2 pulse (expressed as % predicted) and a higher VE/VCO2 ratio (all p ≤ 0.05). Peak oxygen consumption was comparable between the subgroups. Patients after corrected CHD have lower peak and submaximal exercise parameters. Patients with incomplete repair of their heart defect had decreased aerobic fitness, with evidence of impaired peak cardiac function and lower pulmonary perfusion. Patients that had undergone a complete repair had decreased aerobic fitness attributed only to deconditioning. These newly identified differences explain why in previous studies, the lowest fitness was seen in patients with the most hemodynamically significant heart malformations.
Movahedian, Amir Hosein; Mosayebi, Ziba; Sagheb, Setareh
Background: Delayed or missed diagnosis of critical and cyanotic congenital heart disease (CHD) in asymptomatic newborns may result in significant morbidity and mortality. The aim of this study was to determine the accuracy of pulse oximetry screening performed on the first day of life for the early detection of critical and cyanotic CHD in apparently normal newborns. Methods: This cross-sectional study used postductal pulse oximetry to evaluate term neonates born between 2008 and 2011 with normal physical examinations. Functional oxygen saturation < 95% was considered abnormal, and second measurement was done 2 hours later. If the second measurement remained < 95%, an echocardiogram was performed. On enrolment in the study, the following data for each neonate were recorded: gestational age, gender, birth weight, mode of delivery, and mother’s age. Results: During the study period, totally 3,846 newborns were evaluated. Of the whole study population, 304 (7.9%) babies had a postductal functional saturation < 95%. The second measurement was also < 95% in 104 (2.7%) neonates. The mean age of the neonates at the time of pulse oximetry was 18.91 ± 8.61 (min = 4.5 and max = 49) hours. Forty-nine percent of the subjects were female and 51% were male. Echocardiography was performed on 81 out of 104 newborns, and 14 (0.36%) of them had CHD. The types of CHD in our patients were tetralogy of Fallot (3 cases), transposition of the great vessels (2 cases), double-outlet right ventricle (2 cases), truncus arteriosus, total anomalous pulmonary venous return, atrioventricular septal defect, pulmonary atresia, persistent pulmonary hypertension, ventricular septal defect, and atrial septal defect (1 case for each type). The best time for pulse oximetry was within 8-24 hours of the newborns’ life. Conclusion: Pulse oximetry screening along with clinical examination may be able to assist in the early detection of critical and cyanotic CHD in asymptomatic newborns. PMID:27928258
Perricone, Giovanna; Polizzi, Concetta; De Luca, Francesco
Child development may be subject to forms of motor, physical, cognitive and self-representation impairments when complex congenital heart disease (CHD) occurs. In some cases, inadequacy of both self-representation as well as the family system are displayed. It seems to be important to search the likely internal and external resources of the CHD child, and the possible connections among such resources, which may help him/her to manage his/her own risk condition. The research project inquires the possible resources related to the self-representation and self-esteem levels of the CHD child, and those related to maternal self-perception as competent mothers. A group of 25 children (mean age = 10.2; SD=1.8) suffering from specific forms of CHD, and a group made up of their relative mothers (mean age = 38.2; SD=5) were studied. The tools used were the Human Figure Drawing, to investigate child body-related self-representation; the TMA scale (Self-esteem Multidimensional Test), to investigate the child's self-esteem; and the Q-sort questionnaire, to assess how mothers perceived their maternal competence. Data concerning the likely correlations between the child's self-representation and the maternal role competence show [that] positive correlations between some indicators of maternal competence, specific aspects of CHD children's self-representation (mothers' emotional coping and children's self-image adequacy) and self-esteem (mothers' emotional scaffolding and children's self-esteem at an emotional level). By detecting the occurrence of specific correlations among resources of both child and mother, the study provides cardiologists with information that is useful for building a relationship with the families concerned, which would seem to enhance the quality of the process of the cure itself.
Monfredi, Oliver; Griffiths, Linda; Clarke, Bernard; Mahadevan, Vaikom S
The dual endothelin receptor antagonist, bosentan, has been shown to be well tolerated and effective in improving pulmonary arterial hypertension (PAH) symptoms in patients with Eisenmenger syndrome but data from longer-term studies are lacking. The aim of this study was to retrospectively analyze the long-term efficacy and safety of bosentan in adults with PAH secondary to congenital heart disease (PAH-CHD). Prospectively collected data from adult patients with PAH-CHD (with and without Down syndrome) initiated on bosentan from October 2007 through June 2010 were analyzed. Parameters measured before bosentan initiation (62.5 mg 2 times/day for 4 weeks titrated to 125 mg 2 times/day) and at each follow-up (1 month and 3, 6, 9, 12, 18, and 24 months) included exercise capacity (6-minute walk distance [6MWD]), pretest oxygen saturation, liver enzymes, and hemoglobin. Data were analyzed from 39 patients with PAH-CHD (10 with Down syndrome) who had received ≥ 1 dose of bosentan (mean duration of therapy 2.1 ± 1.5 years). A significant (p < 0.0001) average improvement in 6MWD of 54 m over a 2-year period in patients with PAH-CHD without Down syndrome was observed. Men patients had a 6MWD of 33 m greater than women (p < 0.01). In all patients, oxygen saturation, liver enzymes, and hemoglobin levels remained stable. There were no discontinuations from bosentan owing to adverse events. In conclusion, patients with PAH-CHD without Down syndrome gain long-term symptomatic benefits in exercise capacity after bosentan treatment. Men seem to benefit more on bosentan treatment. Bosentan appears to be well tolerated in patients with PAH-CHD with or without Down syndrome.
Dawson, April; Cassell, Cynthia H.; Riehle-Colarusso, Tiffany; Grosse, Scott D.; Tanner, Jean Paul; Kirby, Russell S.; Watkins, Sharon M.; Correia, Jane A.; Olney, Richard S.
Objectives Critical congenital heart disease (CCHD) was added recently to the U.S. Recommended Uniform Screening Panel for newborns. This study assessed whether maternal/household and infant characteristics were associated with late CCHD detection. Methods This was a state-wide, population-based, retrospective, observational study of infants with CCHD born 1998-2007 identified by the Florida Birth Defects Registry. We examined 12 CCHD conditions that are primary and secondary targets of newborn CCHD screening by pulse oximetry. We used Poisson regression models to analyze associations between selected characteristics (e.g., maternal age, CCHD type, and birth hospital nursery level [highest level available in the hospital]) and late CCHD detection, which was defined as diagnosis after the birth hospitalization. Results Of 3,603 infants with CCHD and linked hospitalizations, CCHD was not detected during the birth hospitalization for 22.9% (n=825) of infants. The likelihood of late detection varied by CCHD condition. Infants born in a birth hospital with a Level I nursery only (adjusted prevalence ratio [aPR] 1.9, 95% confidence interval (CI) 1.6-2.2) or Level II nursery (aPR 1.5, 95% CI 1.3-1.7) were significantly more likely to have late-detected CCHD compared to infants born in a birth hospital with a Level III (highest) nursery. Conclusions After controlling for the selected characteristics, hospital nursery level appears to have an independent association with late CCHD detection. Thus, perhaps universal newborn screening for CCHD could be particularly beneficial in Levels I and II nurseries and may reduce differences in the frequency of late diagnosis between birth hospital facilities. PMID:23940249
Peterson, Cora; Dawson, April; Grosse, Scott D.; Riehle-Colarusso, Tiffany; Olney, Richard S.; Tanner, Jean Paul; Kirby, Russell S.; Correia, Jane A.; Watkins, Sharon M.; Cassell, Cynthia H.
BACKGROUND Critical congenital heart disease (CCHD) was recently added to the U.S. Recommended Uniform Screening Panel for newborns. States considering screening requirements may want more information about the potential impact of screening. This study examined potentially avoidable mortality among infants with late detected CCHD and assessed whether late detection was associated with increased hospital resource use during infancy. METHODS This was a state-wide, population-based, observational study of infants with CCHD (n =3603) born 1998 to 2007 identified by the Florida Birth Defects Registry. We examined 12 CCHD conditions that are targets of newborn screening. Late detection was defined as CCHD diagnosis after the birth hospitalization. Deaths potentially avoidable through screening were defined as those that occurred outside a hospital following birth hospitalization discharge and those that occurred within 3 days of an emergency readmission. RESULTS For 23% (n =825) of infants, CCHD was not detected during the birth hospitalization. Death occurred among 20% (n =568/2,778) of infants with timely detected CCHD and 8% (n =66/825) of infants with late detected CCHD, unadjusted for clinical characteristics. Potentially preventable deaths occurred in 1.8% (n =15/825) of infants with late detected CCHD (0.4% of all infants with CCHD). In multivariable models adjusted for selected characteristics, late CCHD detection was significantly associated with 52% more admissions, 18% more hospitalized days, and 35% higher inpatient costs during infancy. CONCLUSION Increased CCHD detection at birth hospitals through screening may lead to decreased hospital costs and avoid some deaths during infancy. Additional studies conducted after screening implementation are needed to confirm these findings. PMID:24000201
Mussatto, Kathleen A.; Hoffmann, Raymond; Hoffman, George; Tweddell, James S.; Bear, Laurel; Cao, Yumei; Tanem, Jena; Brosig, Cheryl
Background Children with congenital heart disease (CHD) are at risk for developmental delay (DD). This study sought to identify early risk factors for abnormal developmental trajectories in children with CHD. Methods and Results Children with CHD at high risk for DD, without known genetic abnormality, and with ≥3 assessments using the Bayley Scales of Infant Development-III (BSID-III) were studied. Logistic regression was used to assess the impact of patient and clinical factors on cognitive, language, and motor score trajectories; classified as: “Average or Improved” if all scores were ≥ 85 (< 1SD below mean) or increased to ≥ 85 and never decreased; or “Abnormal” if all scores were < 85, fell to < 85 and never improved, or fluctuated above and below 85. Data on 131 children with 527 BSID-III assessments were analyzed. Subject age was 5.5–37.4 months. Overall, 56% had cognitive, language, and motor development in the average range. Delays occurred in single domains in 23%. Multiple domains were delayed in 21%. More cardiac surgeries, longer hospital stay, poorer linear growth, and tube feeding were associated with worse outcomes in all domains (p<0.05). In the multivariable model, need for tube feeding was a risk factor for having an abnormal developmental trajectory (OR = 5.1–7.9). Minority race and lack of private insurance had significant relationships with individual domains. Conclusions Longitudinal developmental surveillance identified early factors that can help quantify risk of DD over time. Strategies to improve modifiable factors and early therapeutic intervention can be targeted to children at highest risk. PMID:26304667
Hoffmann, Raymond G.; Hoffman, George M.; Tweddell, James S.; Bear, Laurel; Cao, Yumei; Brosig, Cheryl
BACKGROUND AND OBJECTIVE: Children with congenital heart disease (CHD) are at risk for developmental delay (DD). Changes in cognitive, language, and motor skills in early childhood have not been described. We report the results of a structured approach using longitudinal testing to identify problems and ensure early intervention in accordance with published guidelines. METHODS: Bayley Scales of Infant Development, Third Edition, were used to assess cognitive, language, and motor skills in 99 children with CHD. Subjects were evaluated 3 to 6 times in the first 3 years of life. DD was defined as scores >1 SD below the population mean. RESULTS: Cardiac anatomy was single ventricle (1V) in 34 subjects and 2 ventricles (2V) in 65. Medical comorbidities were present in 21% and genetic syndromes in 19%. Most subjects (75%) had DD in ≥1 area at ≥1 assessments. Subjects with 1V anatomy had equivalent outcomes to those with 2V. Cognitive and language scores declined in subjects with genetic syndromes but were stable and within the average range for subjects with 1V and 2V. Motor scores improved for subjects with 1V and 2V but remained low for those with genetic syndromes. In addition to age, need for supplemental tube feeding, longer cardiopulmonary bypass time, and shorter time since last hospitalization were significant predictors of developmental outcomes. CONCLUSIONS: DDs in young children with CHD are both common and dynamic. Providers should encourage longitudinal surveillance for children with CHD because exposure to risk and prevalence of DD change over time. PMID:24488746
Block, AJ; McQuillen, PS; Chau, V; Glass, H; Poskitt, KJ; Barkovich, AJ; Esch, M; Soulikias, W; Azakie, A; Campbell, A; Miller, SP
Objective Preoperative brain injury, particularly stroke and white matter injury (WMI), is common in newborns with congenital heart disease (CHD). The objective of this study was to determine the risk of hemorrhage or extension of preoperative brain injury with cardiac surgery. Methods This dual-center prospective cohort study recruited 92 term newborns: 62 with transposition of the great arteries (TGA), and 30 with single ventricle physiology from two tertiary referral centers. Newborns underwent brain MRI scans before and after cardiac surgery. Results Brain injury was identified in 40 (43%) newborns on the preoperative MRI scan (median five days of life): stroke in 23, WMI in 21, and intraventricular hemorrhage in 7. None of the brain lesions presented clinically with overt signs or seizures. Preoperative brain injury was associated with balloon atrial septostomy (BAS) (P=0.003) and lowest SaO2 (P=0.007); in a multivariable model, only the effect of BAS remained significant when adjusting for lowest SaO2. On postoperative MRI in 78 newborns (median 21 days of life), none of the preoperative lesions showed evidence of extension or hemorrhagic transformation (0/40 [95% CI: 0-7%]). The presence of preoperative brain injury was not a significant risk factor for acquiring new injury on the postoperative MRI (P=0.8). Conclusion Clinically silent brain injuries identified preoperatively in newborns with CHD, including stroke, have a low risk of progression with surgery and cardiopulmonary bypass, and should therefore not delay clinically indicated cardiac surgery. In this multi-center cohort, BAS remains an important risk factor for preoperative brain injury, particularly stroke. PMID:20434174
Soares, R.P.S.; Bydlowski, S.P.; Nascimento, N.M.; Thomaz, A.M.; Bastos, E.N.M.; Lopes, A.A.
Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF. PMID:23558858
Oliver, Jose Maria; Garcia-Hamilton, Diego; Gonzalez, Ana Elvira; Ruiz-Cantador, Jose; Sanchez-Recalde, Angel; Polo, Maria Luz; Aroca, Angel
The incidence and risk factors for prosthetic pulmonary valve failure (PPVF) should be considered when determining optimal timing for pulmonary valve replacement (PVR) in asymptomatic patients with congenital heart disease (CHD). The cumulative freedom for reintervention due to PPVF after 146 PVR in 114 patients with CHD was analyzed. Six potential risk factors (underlying cardiac defect, history of palliative procedures, number of previous cardiac interventions, hemodynamic indication for PVR, type of intervention, and age at intervention) were analyzed using Cox proportional hazard modeling. Receiver operating characteristic (ROC) curves were used for discrimination. Internal validation in patients with tetralogy of Fallot was also performed. Median age at intervention was 23 years. There were 60 reinterventions due to PPVF (41%). Median event-free survival was 14 years (95% confidence interval [CI] 12 to 16 years). The only independent risk factor was the age at intervention (hazard ratio [HR] 0.93, 95% CI 0.90 to 0.97; p = 0.001; area under the ROC curve 0.95, 95% CI 0.92 to 0.98; p <0.001). The best cut-off point was 20.5 years. Freedom from reintervention for PPVF 15 years after surgery was 70% when it was performed at age >20.5 years compared with 33% when age at intervention was <20.5 years (p = 0.004). Internal validation in 102 PVR in patient cohort with tetralogy of Fallot (ROC area 0.98, 95% CI 0.96 to 1.0; p <0.001) was excellent. In conclusion, age at intervention is the main risk factor of reintervention for PPVF. The risk of reintervention is 2-fold when PVR is performed before the age of 20.5 years.
Lee, Namheon; Banerjee, Rajit; Taylor, Michael; Hor, Kan
Surgical correction or palliation of congenital heart disease (CHD) often requires augmenting the main pulmonary artery (MPA) with non-native material or placing a cylindrical graft. The degree to which this intervention affects PA compliance is largely unknown. In this study, the MPA stiffness characteristics were assessed by its compliance, distensibility, and pressure-strain modulus. Coregistered velocity encoded phase-contrast MRI and cardiac catheterization data were available for a cohort of repaired CHD patients (n=8) and controls (n=3). All patients were repaired with either an RV-PA conduit or a RV outflow tract patch. We measured the MPA area change by MRI and MPA pressure during the cath. The measurements were taken through or just distal to the conduit. The MPA compliance and distensibility for the patients were significantly lower than the controls: compliance (9.8±10.8 vs 28.3±7.7mm^2/mmHg, p<0.05), distensibility (2.2±1.5 vs 6.6±2.1%Area change/mmHg, p=0.05). The patients had a significantly higher pressure-strain modulus (152.3±116.4mmHg, p<0.05) than the controls (35.8±10.6mmHg). The abnormally elevated PA stiffness due to the rigidity of the conduit or patch material may cause a compliance mismatch resulting in high stress levels contributing to the observed progressive PA dilatation. This may be a factor in the progressive RV dilatation seen in this cohort of repaired CHD patients.
Levin, A.R.; Goldberg, H.L.; Borer, J.S.; Rothenberg, L.N.; Nolan, F.A.; Engle, M.A.; Cohen, B.; Skelly, N.T.; Carter, J.
Digital subtraction angiography (DSA) permits high-resolution cardiac imaging with relatively low doses of contrast medium and reduced radiation exposure. These are potential advantages in children with congenital heart disease. Computer-based DSA (30 frames/sec) and conventional cutfilm angiography (6 frames/sec) or cineangiography (60 frames/sec) were compared in 42 patients, ages 2 months to 18 years (mean 7.8 years) and weighing 3.4 to 78.5 kg (mean 28.2 kg). There were 29 diagnoses that included valvular regurgitant lesions, obstructive lesions, various shunt abnormalities, and a group of miscellaneous anomalies. For injections made at a site distant from the lesion and on the right side of the circulation, the mean dose of contrast medium was 60% to 100% of the conventional dose given during standard angiography. With injections made close to the lesion and on the left side of the circulation, the mean dose of contrast medium was 27.5% to 42% of the conventional dose. Radiation exposure for each technique was markedly reduced in all age groups. A total of 92 digital subtraction angiograms were performed. Five studies were suboptimal because too little contrast medium was injected; in the remaining 87 injections, DSA and conventional studies resulted in identical diagnoses in 81 instances (p less than .001 vs chance). The remaining six injections made during DSA failed to confirm diagnoses made angiographically by standard cutfilm angiography or cineangiography. We conclude that DSA usually provides diagnostic information equivalent to that available from cutfilm angiography and cineangiography, but DSA requires considerably lower doses of contrast medium and less radiation exposure than standard conventional methods.
Stoupel, E.; Dulskiene, V.; Kuciene, R.; Abramson, E.; Israelevich, P.; Sulkes, J.
Recent studies described a number of fetal development sides related to the environmental physical activity. The aim of this study was to check the possible links between congenital heart disease (CHD) born in a non-selected medical network and indices of environmental physical activity. Children born with CHD in Kaunas, Lithuania, in years 1995-2005 were analyzed at the end of the first year of life (including also those died after birth from this condition). Monthly distribution of CHD (total - 371, both gender (178 boys and 193 girls), 41435 births) were compared with parameters of solar (SA), geomagnetic (GMA) and cosmic ray (CRA) activity, as well as the year, at the month of birth, 9 months before and at year of birth and one year before. CRA was represented by neutron activity on the Earth's surface. Heliogeophysical data were obtained from space research centers in the USA, Russia and Finland. There was found a significant correlation between yearly number of births (r = - 0.9, p = 0.00012). Monthly number of CHD was correlated with SA and CRA often highly at the beginning of pregnancy both in monthly and yearly (r = - 0.7, p = 0.025 for SA, r = 0.8, p = 0.005 for CRA) comparison. For boys the correlation was stronger, but also it was significant for girls. GMA has not shown significant effects. It is concluded that the number of yearly and monthly CHD is connected with SA and CRA in pregnancy. Boys show high levels in these correlations. The mechanism of the cosmophysical effects on human development and temporal distribution of CHD deserve special studies.
Xu, Zhuoming; Zhu, Limin; Liu, Xinrong; Gong, Xiaolei; Gattrell, William; Liu, Jinfen
Congenital heart disease (CHD) can cause pulmonary hypertension (PH) in children, and surgery to correct CHD may be complicated by postoperative pulmonary hypertensive crises (PHC). Clinical data regarding the use of inhaled iloprost to treat children with PH are scarce. Our aim was to determine the efficacy and safety of iloprost in children with PH following surgery to correct CHD. This was a randomized, placebo-controlled study of 22 children (median age 7 months) undergoing surgery to achieve biventricular repair. The combined clinical endpoint was a decrease of more than 20% in the ratio of systolic pulmonary arterial pressure to systolic arterial pressure or pulmonary resistance to systemic resistance, with no PHC or death. Patients were randomized to receive low-dose iloprost (30 ng/kg/min), high-dose iloprost (50 ng/kg/min), or placebo, for 10 min every 2 hr in the first 48 hr after surgery. PHC were experienced by two patients who received placebo and one patient treated with high-dose iloprost. The combined clinical endpoint was reached by six patients administered low-dose iloprost (P = 0.005) and four administered high-dose iloprost (P = 0.077), compared with none in the placebo group. Patients treated with iloprost showed a significant reduction from baseline in mean pulmonary vascular resistance index (-2.2 Wood units, P < 0.05), whereas patients who received placebo showed no significant change. This study supports the use of iloprost to treat children with PH following surgery to correct CHD.
Flores, Patricia C.; Diaz, Gabriel F.; Mesquita, Sonia M. F.
Abstract South America is a territory of 17,819,100 km2, where ∼388 million people live in 13 countries. In the region, access to medical assistance (e.g., for treatment of cardiovascular disorders) is relatively easy in metropolitan areas but difficult in remote places such as the Andes and the Amazon. Altitudes up to ∼6,700 m influence the prevalence of congenital heart disease (CHD) and pulmonary arterial hypertension (PAH). In tertiary centers, CHD is now treated earlier in life but remains an important etiology of PAH. In adolescents and adults with PAH assisted at institutions devoted to treatment of cardiovascular disorders, the relative frequency of PAH-CHD (∼50%–60%) is even higher than that of idiopathic PAH. In one big tertiary center in São Paulo, Brazil, the prevalence of advanced PAH in children and adults with CHD is 1.2% and 4.2%, respectively. In young patients with cardiac septal defects (aged up to 2 years), pulmonary vascular abnormalities are a matter of concern in the decision about operability in 4.9% of cases. Access to specific PAH drugs is not uniform in South America, being unrealistic in remote places. In big cities, there are real possibilities for management of complex CHD, neonatal disorders, and even cardiac transplantation. Research activities have been implemented at clinical, translational, and basic levels. However, because of social and economic inequalities and political issues, access to best standards of medical care remains a problem in the region as a whole. PMID:25621150
Sanaa, Benhaourech,; Abdenasser, Drighil,; Ayoub, El Hammiri
Summary Background Congenital heart disease (CHD) is frequently described in patients with Down syndrome (DS) and is the main cause of death in this population during the first two years of life. The spectrum of CHD patterns in DS varies widely worldwide; this variation could be due to sociodemographic, genetic and geographic factors. Methods A six-year retrospective, descriptive study was carried out from December 2008 to October 2014, based on the Paediatric Unit CHD registry of Ibn Rochd University Hospital. Clinical, echocardiographic and outcomes data were collected and sorted according to confirmation of the syndrome. Results Among 2 156 patients with CHD, 128 were identified with Down syndrome. The genders were equally represented (gender ratio 1) and the median age at diagnosis was 9.5 months (2 days to 16 years). The median age of mothers at delivery was 39 years (16–47). Of the 186 CHD lesions reported, the most common was atrioventricular septal defect (AVSD, 29%), followed by ventricular septal defect (VSD,21.5%) and atrial septal defect (ASD, 19.9%). The most common associations of CHD were AVSD + ASD (10%) and VSD + ASD (7.8%). Surgery was the most common modality of treatment (54.3%). The overall mortality rate was 14.1%. Conclusion Our study confirmed that the profile and type of CHD in DS in the Moroccan setting exhibited slight differences in the distribution of these CHDs compared with European neighbours and other Western countries. Further studies are needed to determine which variables have an impact on these differences. PMID:27805241
Kim, Ah Young; Jung, Se Yong; Choi, Jae Young; Kim, Gi Beom; Kim, Young-Hwue; Shim, Woo Sup; Kang, I-Seok
Background and Objectives We conducted a review of current data on respiratory syncytial virus (RSV) prophylaxis with palivizumab, in Korean children with congenital heart diseases (CHD). In 2009, the Korean guideline for RSV prophylaxis had established up to five shots monthly per RSV season, only for children <1 year of age with hemodynamic significance CHD (HS-CHD). Subjects and Methods During the RSV seasons in 2009-2015, we performed a retrospective review of data for 466 infants with CHD, examined at six centers in Korea. Results Infants received an average of 3.7±1.9 (range, 1-10) injections during the RSV season. Fifty-seven HS-CHD patients (12.2%) were hospitalized with breakthrough RSV bronchiolitis, with a recurrence in three patients, one year after the initial check-up. Among patients with simple CHD, only five (1.1%) patients received one additional dose postoperatively, as per the limitations set by the Korean guideline. Among the 30 deaths (6.4%), five (1.1%) were attributed to RSV infection; three to simple CHD, one to Tetralogy of Fallot, and one to hypertrophic cardiomyopathy (HCM). Of the three HCM patients that exceeded guidelines for RSV prophylaxis, two (66.6%) were hospitalized, and one died of RSV infection (33.3%). Conclusion In accordance to the Korean guideline, minimal injections of palivizumab were administered to patients having HS-CHD
Becker, Kristian C.; Hornik, Christoph P.; Cotten, C. Michael; Clark, Reese H.; Hill, Kevin D.; Smith, P. Brian; Lenfestey, Robert W.
Objective Infants with congenital heart disease (CHD) receiving prostaglandins (PGE) may be at increased risk for necrotizing enterocolitis (NEC). Enteral feeding may further increase risk of NEC in these patients. We evaluated the incidence of NEC and its association with enteral feeding in infants with ductal-dependent CHD. Study Design We examined a cohort of infants with CHD receiving PGE in neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2010. We used logistic regression to evaluate the association between NEC and enteral feeding, as well as other risk factors including antacid medications, inotropic and ventilator support, and anatomic characteristics, controlling for gestational age. Results We identified 6710 infants with ductal-dependent CHD receiving PGE for 17,158 infant days. NEC occurred in 21 of 6710 (0.3%) infants, of whom 12/21(57%) were <37 weeks gestational age. The incidence of NEC was 1.2/1000 infant days while on enteral feeds versus 0.4/1000 infant days while not on enteral feeds (p=0.27). Enteral feeding was not associated with a statistically significant increased odds of NEC on the day of diagnosis (odds ratio [OR] 2.08; 95% confidence interval [CI] 0.38, 11.7). Risk factors associated with a significant increased odds of NEC included a diagnosis of single-ventricle heart defect (OR 2.82; 95% CI 1.23, 6.49), although the overall risk in this population remained low (8/1631, 0.5%). Conclusion The incidence of NEC in our cohort of infants with ductal-dependent CHD on PGE therapy was low and did not increase with enteral feeding. PMID:25486286
Barros, Thayanny Lopes do Vale; Dias, Marly de Jesus Sá; Nina, Rachel Vilela de Abreu Haickel
Introduction Congenital heart defects, cardiac malformations that occur in the embryonic period, constitute a serious health problem. They cover a proportion of 8-10 per 1000 live births and contribute to infant mortality. Objective To identify the socioeconomic status of children undergoing cardiac surgery at the Hospital Universitário da Universidade Federal do Maranhão, in São Luis, the existence of material elements that contribute to worsening conditions. Methods We conducted a retrospective study with a quantitative approach, descriptive and reflective, from the interviews conducted by the Social Service Social with families of children with heart disease from January 2011 to July 2012. Results A total of 95 interviews, the results reveal that (75.79%) of children have elements that suggest poor socioeconomic conditions. It also shows that only 66.33% lived in brick house, while (31.73%) in mud, adobe and straw houses. With regard to income, it showed that only 4.08% received 1-2 minimum wages, while the remaining (95.9%) with benchmarks oscillating half the minimum wage (27.55%), 1/4 of the minimum wage and (24.48%) and income below 70 dollars per person, featuring extreme poverty. On the social security situation prevailing at children with no ties to 61.22%. With respect to benefits, we found that only (12.24%) of children were in the enjoyment of the Continuous Cash Benefit - CCB. Conclusion Poor socioeconomic conditions listed as major obstacles in meeting the needs, resulting in the maintenance of health conditions and even allowing the aggravation of an existing pathology. PMID:25372921
Kang, Guanyang; Xiao, Jianmin; Wang, Jieying; Chen, Jiuhao; Li, Wei; Wang, Yitong; Liu, Qingchun; Wang, Zhiming; Xia, Jinxi; Huang, Jianzhong; Cheng, Ling; Chen, Yuqiang; Chen, Qiaozhu; Yang, Fan
The aim of this study was to determine the prevalence and treated status of congenital heart disease (CHD) in elementary schoolchildren and facilitate the long-term planning of health care, resource allocation, and development of targeted primary prevention strategies. From November 2011 to November 2012, 540,574 schoolchildren from 449 elementary schools were screened for CHD by trained doctors in Dongguan City. The schoolchildren who were suspected to have CHD were referred to a pediatric cardiologist and/or an echocardiographist for complete evaluation. Of them, 214,634 (39.7%) were local children and 325,940 (60.3%) were migrant children. The total prevalence of CHD was 2.14‰, and there was a significant difference (p <0.05) of the CHD prevalence between local (1.97‰) and migrant children (2.26‰). The treatment rates of CHD in local children and in migrant children were 63.51% and 47.21%, respectively (p <0.01). The commonest CHD was ventricular septal defect (43.13%), followed by atrial septal defect (25.84%) and patent ductus arteriosus (12.79%). With respect to gender, CHD was equally distributed between men and women. In conclusion, social, economic, and environmental risk factors that affect health of migrant children with CHD call for more attention from health policy makers and researchers in contemporary China. Efforts should be made to increase public health investment, establish health care manage system for children from migrant families, and increase the parents' awareness of preventing the CHD.
Lopes, Antonio Augusto; Flores, Patricia C; Diaz, Gabriel F; Mesquita, Sonia M F
South America is a territory of 17,819,100 km(2), where ∼388 million people live in 13 countries. In the region, access to medical assistance (e.g., for treatment of cardiovascular disorders) is relatively easy in metropolitan areas but difficult in remote places such as the Andes and the Amazon. Altitudes up to ∼6,700 m influence the prevalence of congenital heart disease (CHD) and pulmonary arterial hypertension (PAH). In tertiary centers, CHD is now treated earlier in life but remains an important etiology of PAH. In adolescents and adults with PAH assisted at institutions devoted to treatment of cardiovascular disorders, the relative frequency of PAH-CHD (∼50%-60%) is even higher than that of idiopathic PAH. In one big tertiary center in São Paulo, Brazil, the prevalence of advanced PAH in children and adults with CHD is 1.2% and 4.2%, respectively. In young patients with cardiac septal defects (aged up to 2 years), pulmonary vascular abnormalities are a matter of concern in the decision about operability in 4.9% of cases. Access to specific PAH drugs is not uniform in South America, being unrealistic in remote places. In big cities, there are real possibilities for management of complex CHD, neonatal disorders, and even cardiac transplantation. Research activities have been implemented at clinical, translational, and basic levels. However, because of social and economic inequalities and political issues, access to best standards of medical care remains a problem in the region as a whole.
Fadnes, Solveig; Nyrnes, Siri Ann; Torp, Hans; Lovstakken, Lasse
High-frame-rate ultrasound speckle tracking was used for quantification of peak velocity in shunt flows resulting from septal defects in congenital heart disease. In a duplex acquisition scheme implemented on a research scanner, unfocused transmit beams and full parallel receive beamforming were used to achieve a frame rate of 107 frames/s for full field-of-view flow images with high accuracy, while also ensuring high-quality focused B-mode tissue imaging. The setup was evaluated in vivo for neonates with atrial and ventricular septal defects. The shunt position was automatically tracked in B-mode images and further used in blood speckle tracking to obtain calibrated shunt flow velocities throughout the cardiac cycle. Validation toward color flow imaging and pulsed wave Doppler with manual angle correction indicated that blood speckle tracking could provide accurate estimates of shunt flow velocities. The approach was less biased by clutter filtering compared with color flow imaging and was able to provide velocity estimates beyond the Nyquist range. Possible placements of sample volumes (and angle corrections) for conventional Doppler resulted in a peak shunt velocity variations of 0.49-0.56 m/s for the ventricular septal defect of patient 1 and 0.38-0.58 m/s for the atrial septal defect of patient 2. In comparison, the peak velocities found from speckle tracking were 0.77 and 0.33 m/s for patients 1 and 2, respectively. Results indicated that complex intraventricular flow velocity patterns could be quantified using high-frame-rate speckle tracking of both blood and tissue movement. This could potentially help increase diagnostic accuracy and decrease inter-observer variability when measuring peak velocity in shunt flows.
Li, Fei Feng; Deng, Xia; Zhou, Jing; Yan, Peng; Zhao, Er Ying; Liu, Shu Lin
Congenital heart disease (CHD) is a complex illness with high rates of morbidity and mortality. In embryonic development, the heart is the first formed organ, which is strictly controlled by gene regulatory networks, including transcription factors, signaling pathways, epigenetic factors and microRNAs. Bone morphogenetic protein (BMP)-2 and -4 are essential in cardiogenesis as they can induce the expression of transcription factors, NKX2-5 and GATA binding protein 4, which are important in the development of the heart. The inhibition of BMP-2 and 4- inhibits the late expression of NKX2-5 and affects cardiac differentiation. The aim of the present study was to investigate whether BMP-2 and -4 variations may be associated with CHD in Chinese Han populations. The rs1049007, rs235768 and rs17563 single nucleotide polymorphisms (SNPs), which are genetic variations located within the translated region of the BMP-2 and -4, were evaluated in 230 patients with CHD from the Chinese Han population and 160 non CHD control individuals. Statistical analyses were performed using the χ2 test, implemented using SPSS software (version 13.0). The Hardy Weinberg equilibrium test was performed on the population using online Online Encyclopedia for Genetic Epidemiology studies software, and multiple-sequence alignments of the BMP proteins were performed using Vector NTI software. No statistically significant associations were identified between these genetic variations and the risk of CHD (rs1049007, P value=0.560; rs235768, P value=0.972; rs17563, P value=0.787). In addition, no correlation was found between the patients with CHD and the non-CHD control individuals. Therefore, the rs1049007, rs235768 and rs17563 genetic variations of BMP-2 were not associated with CHD in the Chinese Han population. PMID:27357418
Chiang, Szu-Hui; Ho, Hui-Chen; Liu, Yu-Ling; Chung, Yuan-Fang; Lin, Li-Ju; Chen, Ming-Ren; Chang, Jia-Kan; Soong, Wen-Jue; Lin, Hsiu-Lian; Hwang, Betau; Hsiao, Kwang-Jen
Background Early detection of critical congenital heart disease (CCHD) can significantly reduce morbidity and mortality among newborns. We investigate the feasibility of implementing a community-based newborn CCHD screening program in Taipei. Methods Twelve birthing facilities in Taipei participated in a trial screening program between October 1, 2013, and March 31, 2014. Newborns underwent pulse oximetry at 24–36 h old, with probes attached to the right hand and one lower limb. Any screening saturation ≥95% in either extremity, with an absolute difference of ≤3% between the right hand and foot, was accepted as a screening pass. A screening result was considered as a fail if the oxygen saturation was <95% at either probe site, on 3 separate occasions, each separated by 30 min or the first result was <95% at either probe site, and any subsequent oxygen saturation measurement was <90%. Public health nurses would follow up all missed or refused cases. Results Of the 6,387 live births, 6,296 newborns (coverage rate: 6,296/6,387 = 98.6%) underwent appropriate pulse oximetry screening. Sixteen newborns (0.25%) were reported to have a failed screening result. Five of these screen positive newborns were confirmed with CCHD; two of them were diagnosed solely attributed to the failed screening results. The false-positive rate was 0.18%. Implementing a 6-month screening program for CCHD produced good case detection rate, while using efficient screening and referral systems. Conclusion This program was successful in integrating screening, referral and public health tracking systems. The protocol outlined in this report could provide a community-based model for worldwide implementation. PMID:27073996
Liu, Min; Zhao, Luosha; Yuan, Jiaying
Purpose. The purpose of present study was to construct the best screening model of congenital heart disease serum markers and to provide reference for further prevention and treatment of the disease. Methods. Documents from 2006 to 2014 were collected and meta-analysis was used for screening susceptibility genes and serum markers closely related to the diagnosis of congenital heart disease. Data of serum markers were extracted from 80 congenital heart disease patients and 80 healthy controls, respectively, and then logistic regression analysis and support vector machine were utilized to establish prediction models of serum markers and Gene Ontology (GO) functional annotation. Results. Results showed that NKX2.5, GATA4, and FOG2 were susceptibility genes of congenital heart disease. CRP, BNP, and cTnI were risk factors of congenital heart disease (p < 0.05); cTnI, hs-CRP, BNP, and Lp(a) were significantly close to congenital heart disease (p < 0.01). ROC curve indicated that the accuracy rate of Lp(a) and cTnI, Lp(a) and BNP, and BNP and cTnI joint prediction was 93.4%, 87.1%, and 97.2%, respectively. But the detection accuracy rate of the markers' relational model established by support vector machine was only 85%. GO analysis suggested that NKX2.5, GATA4, and FOG2 were functionally related to Lp(a) and BNP. Conclusions. The combined markers model of BNP and cTnI had the highest accuracy rate, providing a theoretical basis for the diagnosis of congenital heart disease. PMID:27118988
Peres, Murilo Bertazzo; Croti, Ulisses Alexandre; de Godoy, Moacir Fernandes; Marchi, Carlos Henrique De; Hassem Sobrinho, Sírio; Beani, Lilian; Moscardini, Airton Camacho; Braile, Domingo Marcolino
Objective To evaluate the height and weight development of children with congenital heart disease undergoing surgery with the goal of determining when they reach the threshold of normal development and whether there are differences between patients with developmental pattern below the level of normality preoperatively (z-score<-2 for the analyzed parameter) in comparison to the total group of cardiac patients. Methods We prospectively followed up 27 children undergoing operation into five time periods: preoperatively and at four subsequent outpatient appointments: 1st month, 3rd month, 6th month and 12th month after hospital discharge. The anthropometric parameters used were median z-score (MZ), weight (WAZ), height (HAZ), subscapular skinfold (SSFAZ), upper arm circumference (UAC) and triceps skinfold (TSFAZ). The evolution assessment of the parameters was performed by analysis of variance and comparison with the general normal population from unpaired t test, both in the total group of cardiac patients, and in subgroups with preoperative parameters below the normal level (Zm<-2). Results In the total group there was no significant evolution of MZ of all parameters. WAZ was statistically lower than the normal population until the 1st month of follow-up (P=0.028); HAZ only preoperatively (P=0.044), SSFAZ in the first month (P=0.015) and at 12th month (P=0.038), UAC and TSFAZ were always statistically equal to the general population. In patients whose development was below the level of normality, there were important variation of WAZ (P=0.002), HAZ (P=0.001) and UAC (P=0.031) after the operation, and the WAZ was lower than the normal population until the 3rd month (P=0.015); HAZ and UAC, until the first month (P=0.024 and P=0.039 respectively), SSFAZ, up to the 12th month (P=0.005), the TSFAZ only preoperatively (P=0.011). Conclusion The operation promoted the return to normalcy for those with heart disease in general within up to three months, but for the group of
Wang, Yu; Cao, Hai-yan; Xie, Ming-xing; He, Lin; Han, Wei; Hong, Liu; Peng, Yuan; Hu, Yun-fei; Song, Ben-cai; Wang, Jing; Wang, Bin; Deng, Cheng
To investigate the application and effectiveness of vascular corrosion technique in preparing fetal cardiovascular cast models, 10 normal fetal heart specimens with other congenital disease (control group) and 18 specimens with severe congenital heart disease (case group) from induced abortions were enrolled in this study from March 2013 to June 2015 in our hospital. Cast models were prepared by injecting casting material into vascular lumen to demonstrate real geometries of fetal cardiovascular system. Casting effectiveness was analyzed in terms of local anatomic structures and different anatomical levels (including overall level, atrioventricular and great vascular system, left-sided and right-sided heart), as well as different trimesters of pregnancy. In our study, all specimens were successfully casted. Casting effectiveness analysis of local anatomic structures showed a mean score from 1.90±1.45 to 3.60±0.52, without significant differences between case and control groups in most local anatomic structures except left ventricle, which had a higher score in control group (P=0.027). Inter-group comparison of casting effectiveness in different anatomical levels showed no significant differences between the two groups. Intra-group comparison also revealed undifferentiated casting effectiveness between atrioventricular and great vascular system, or left-sided and right-sided heart in corresponding group. Third-trimester group had a significantly higher perfusion score in great vascular system than second-trimester group (P=0.046), while the other anatomical levels displayed no such difference. Vascular corrosion technique can be successfully used in fabrication of fetal cardiovascular cast model. It is also a reliable method to demonstrate three-dimensional anatomy of severe congenital heart disease and normal heart in fetus.
Sochet, Anthony A; Ayers, Mark; Quezada, Emilio; Braley, Katherine; Leshko, Jennifer; Amankwah, Ernest K.; Jacobs, Jeffrey; Dadlani, Gul
Background Infants with critical congenital heart disease who require cardiothoracic surgical intervention may have significant postoperative mortality and morbidity. Infants who are small for gestational age (SGA) <10th percentile with foetal growth restriction may have end-organ dysfunction that may predispose them to increased morbidity or mortality. Methods A single institution retrospective review was performed in 230 infant with congenital heart disease who had cardiothoracic surgical intervention <60 days of age. Pre-, peri-, and post-operative morbidity and mortality markers were collected along with demographics and anthropometric measurements. Results There were 230 infants 57 (23.3%) small for gestational age and 173 (70.6%) appropriate for gestational age (AGA). No significant difference was noted in pre-operative markers - gestational age, age at surgery, corrected gestational age, Society for Thoracic Surgeons and –European Association for Cardiothoracic Surgery mortality score; or post-operative factors - length of stay, ventilation days, arrhythmias, need for extracorporeal membrane oxygenation, vocal cord dysfunction, hearing loss; or end-organ dysfunction - gastro-intestinal, renal, central nervous system, or genetic. Small for gestational age infants were more likely to have failed vision tests (p=0.006). Small for gestational age infants were more likely to have increased 30-day (p=0.005) and discharge mortality (p=0.035). Small for gestational age infants with normal birth weight (>2500 grams) were also at increased risk of 30-day mortality compared to AGA infants (p=0.045). Conclusions Small for gestational age infants with congenital heart disease who undergo cardiothoracic surgery <60days of age have increased risk of mortality and failed vision screening. Assessment of foetal growth restriction as part of routine preoperative screening may be beneficial. PMID:24401264
Shen, Zheng; Zou, Chao Chun; Shang, Shi Qiang; Jiang, Ke Wen
Congenital heart disease (CHD) is extremely rarely reported in 48, XYY, +21 karyotype. Herein, we reported one case of 48,XYY,+21 karyotype with CHD and reviewed the available literature. The phenotypic characteristics of the 4-month-old child showed the presence of features typical of mongoloid slant. X-ray detection showed the form of heart was corpulent and the bilateral mediastinum was broad. Doppler echocardiogram detection showed atrial septal and ventricular septal defects with patent ductus arteriosus, pulmonary hypertension and mild tricuspid regurgitation. Including this case, 63 cases of 48, XYY, +21 chromosome pattern have been reported. However, only 9 cases have CHD.
Lisanti, Amy Jo; Cribben, Jeanne; Connock, Erin McManus; Lessen, Rachelle; Medoff-Cooper, Barbara
Newborn infants with complex congenital heart disease are at risk for developmental delay. Developmental care practices benefit prematurely born infants in neonatal intensive care units. Cardiac intensive care units until recently had not integrated developmental care practices into their care framework. Interdisciplinary developmental care rounds in our center have helped in the promotion of developmentally supportive care for infants before and after cardiac surgery. This article discusses basic principles of developmental care, the role of each member of the interdisciplinary team on rounds, common developmental care practices integrated into care from rounds, and impacts to patients, families, and staff.
Yeong, Michael; Hamilton, Mark; Manghat, Nathan
Cardiac computed tomography (CCT) has become an invaluable cross-sectional imaging modality in congenital heart disease (CHD) patients. However, altered anatomical connections and cardiovascular physiology makes CHD arguably the most challenging area in CCT imaging, which remains a complimentary modality to cardiac magnetic resonance and echocardiography. A bespoke CT protocol is often required to achieve a diagnostic examination; this can be achieved through careful consideration of the basic principles of image acquisition and contrast administration. This article reviews these principles and demonstrates how they can be applied to CCT in CHD using the Fontan circulation as an example. PMID:28275561
Smith, Andrew H; Owen, Jill; Borgman, Kristie Y; Fish, Frank A; Kannankeril, Prince J
Milrinone reduces the risk of low cardiac output syndrome for some pediatric patients after congenital heart surgery. Data from adults undergoing cardiac surgery suggest an association between milrinone and an increased risk of postoperative arrhythmias. We tested the hypothesis that milrinone is an independent risk factor for tachyarrhythmias after congenital heart surgery. Subjects undergoing congenital heart surgery at our institution were consecutively enrolled for 38 months, through September 2010. The data were prospectively collected, including a review of full-disclosure telemetry and the medical records. Within 38 months, 603 enrolled subjects underwent 724 operative procedures. The median age was 5.5 months (range 0.0 to 426), the median weight was 6.0 kg (range 0.7 to 108), and the cohort was 45% female. The overall arrhythmia incidence was 50%, most commonly monomorphic ventricular tachycardia (n = 85, 12%), junctional ectopic tachycardia (n = 69, 10%), accelerated junctional rhythm (n = 58, 8%), and atrial tachyarrhythmias (including atrial fibrillation, atrial flutter, and ectopic or chaotic atrial tachycardia, n = 58, 8%). Multivariate logistic regression analysis demonstrated that independent of age <1 month, the use of cardiopulmonary bypass, the duration of cardiopulmonary bypass, Risk Adjusted classification for Congenital Heart Surgery, version 1, score >3, and the use of epinephrine or dopamine, milrinone use on admission to the cardiac intensive care unit remained independently associated with an increase in the odds of postoperative tachyarrhythmia resulting in an intervention (odds ratio 2.8, 95% confidence interval 1.3 to 6.0, p = 0.007). In conclusion, milrinone use is an independent risk factor for clinically significant tachyarrhythmias in the early postoperative period after congenital heart surgery.
Moalla, Wassim; Elloumi, Mohamed; Chamari, Karim; Dupont, Grégory; Maingourd, Yves; Tabka, Zouhair; Ahmaidi, Said
We investigated the effect of training on peripheral muscular performance and oxygenation during exercise and recovery in children with congenital heart diseases (CHD). Eighteen patients with CHD aged 12 to 15 years were randomly assigned into either an individualized 12-week aerobic cycling training group (TG) or a control group (CG). Maximal voluntary contraction (MVC) and endurance at 50% MVC (time to exhaustion, T(lim)) of the knee extensors were measured before and after training. During the 50% MVC exercise and recovery, near-infrared spectroscopy (NIRS) was used to assess the fall in muscle oxygenation, i.e., deoxygenation ([Formula: see text]) of the vastus lateralis, the mean rate of decrease in muscle oxygenation, the half time of recovery (T(1/2R)), and the recovery speed to maximal oxygenation (R(S)). There was no effect of time on any parameter in the CG. After training, significant improvements were observed in TG for MVC (101.6 ± 14.0 vs. 120.2 ± 19.4 N·m, p < 0.01) and T(lim) (66.2 ± 22.6 vs. 86.0 ± 23.0 s, p< 0.01). Increased oxygenation (0.20 ± 0.13 vs. 0.15 ± 0.07 a.u., p < 0.01) and faster mean rate of decrease in muscle oxygenation were also shown after training in TG (1.22 ± 0.45 vs. 1.71 ± 0.78%·s(-1), p < 0.001). Moreover, a shorter recovery time was observed in TG after training for T(1/2R) (27.2 ± 6.1 vs. 20.8 ± 4.2 s, p < 0.01) and R(S) (63.1 ± 18.4 vs. 50.3 ± 11.4 s, p < 0.01). A significant relationship between the change in [Formula: see text] and both MVC (r = 0.95, p < 0.001) and T(lim) (r = 0.90, p < 0.001) in TG was observed. We concluded that exercise training improves peripheral muscular function by enhancing strength and endurance performance in children with CHD. This improvement was associated with increased oxygenation of peripheral muscles and faster recovery.
Shi, William Y; Saxena, Pankaj; Yong, Matthew S; Marasco, Silvana F; McGiffin, David C; Shipp, Anne; Weintraub, Robert G; d'Udekem, Yves; Brizard, Christian P; Konstantinov, Igor E
Owing to improved surgical results, there is a growing population of patients with repaired congenital heart disease (CHD) requiring heart transplantation. The objective of the study was to review our experience in these patients. A retrospective review of the outcomes of heart transplantation in patients with CHD (n = 77) between 1988 and 2014 was performed. Outcomes of early (1988-1999) and late (2000-2014) eras were compared. In results, the mean age was 18 ± 14 years (range: 16 days-58 years). Seventy (91%) patients underwent a mean of 2.6 ± 1.3 (range: 1-6) cardiac operations before transplantation, whereas 7 were primary transplants. Univentricular palliation had been performed in 44 (57%) patients. Patients with CHD in the later era had longer mean cardiopulmonary bypass time (early: 190 ± 70 minute vs late: 271 ± 115 minute; P < 0.001), ischemic times (early: 222 ± 98 minute vs late: 275 ± 102 minute; P = 0.039), and more often required reconstruction of the great arteries at the time of transplantation (8% vs 28%; P = 0.036). In those with prior univentricular palliations, the ratio of ischemic to cardiopulmonary bypass time decreased in the later era (early: 1.41 ± 0.60 vs late: 0.99 ± 0.37; P = 0.016), reflecting increased intraoperative complexity. Following transplantation, hospital mortality was 13% (10/77; 7 due to primary graft failure). There was no difference in inhospital mortality between the 2 eras (P = 0.52); however, patients in the later era more often required postoperative extracorporeal membrane oxygenation (early: 8%, 3/38 vs late: 28%, 11/39; P = 0.036). In patients with prior univentricular palliations, those in the late era were more likely to experience postoperative renal impairment (early: 1/21, 5% vs late: 9/23, 39%; P = 0.01). Patients with CHD had higher 30-day mortality (CHD: n = 8, 10% vs non-CHD: n = 17, 3.8%; P = 0.021), but similar survival at 10 years (67% ± 12% vs 70% ± 4.7%; P = 0.87) compared to those without
Background Signaling by the vitamin A-derived morphogen retinoic acid (RA) is required at multiple steps of cardiac development. Since conversion of retinaldehyde to RA by retinaldehyde dehydrogenase type II (ALDH1A2, a.k.a RALDH2) is critical for cardiac development, we screened patients with congenital heart disease (CHDs) for genetic variation at the ALDH1A2 locus. Methods One-hundred and thirty-three CHD patients were screened for genetic variation at the ALDH1A2 locus through bi-directional sequencing. In addition, six SNPs (rs2704188, rs1441815, rs3784259, rs1530293, rs1899430) at the same locus were studied using a TDT-based association approach in 101 CHD trios. Observed mutations were modeled through molecular mechanics (MM) simulations using the AMBER 9 package, Sander and Pmemd programs. Sequence conservation of observed mutations was evaluated through phylogenetic tree construction from ungapped alignments containing ALDH8 s, ALDH1Ls, ALDH1 s and ALDH2 s. Trees were generated by the Neighbor Joining method. Variations potentially affecting splicing mechanisms were cloned and functional assays were designed to test splicing alterations using the pSPL3 splicing assay. Results We describe in Tetralogy of Fallot (TOF) the mutations Ala151Ser and Ile157Thr that change non-polar to polar residues at exon 4. Exon 4 encodes part of the highly-conserved tetramerization domain, a structural motif required for ALDH oligomerization. Molecular mechanics simulation studies of the two mutations indicate that they hinder tetramerization. We determined that the SNP rs16939660, previously associated with spina bifida and observed in patients with TOF, does not affect splicing. Moreover, association studies performed with classical models and with the transmission disequilibrium test (TDT) design using single marker genotype, or haplotype information do not show differences between cases and controls. Conclusion In summary, our screen indicates that ALDH1A2 genetic
Baraona, Fernando; Gurvitz, Michelle; Landzberg, Michael J; Opotowsky, Alexander R
Congenital heart disease (CHD) is common in patients with Down syndrome (DS), and these patients are living longer lives. The aim of this study was to describe the epidemiology of hospitalizations in adults with DS and CHD in the United States. Hospitalizations from 1998 to 2009 for adults aged 18 to 64 years with and without DS with CHD diagnoses associated with DS (atrioventricular canal defect, ventricular septal defect, tetralogy of Fallot, and patent ductus arteriosus) were analyzed using the Nationwide Inpatient Sample. Outcomes of interest were (1) in-hospital mortality, (2) common co-morbidities, (3) cardiac procedures, (4) hospital charges, and (5) length of stay. Multivariate modeling adjusted for age, gender, CHD diagnosis, and co-morbidities. There were 78,793 ± 2,653 CHD admissions, 9,088 ± 351 (11.5%) of which were associated with diagnoses of DS. The proportion of admissions associated with DS (DS/CHD) decreased from 15.2 ± 1.3% to 8.5 ± 0.9%. DS was associated with higher in-hospital mortality (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.4 to 2.4), especially in women (OR 2.4, 95% CI 1.7 to 3.4). DS/CHD admissions were more commonly associated with hypothyroidism (OR 7.7, 95% CI 6.6 to 9.0), dementia (OR 82.0, 95% CI 32 to 213), heart failure (OR 2.2, 95% CI 1.9 to 2.5), pulmonary hypertension (OR 2.5, 95% CI 2.2 to 2.9), and cyanosis or secondary polycythemia (OR 4.6, 95% CI 3.8 to 5.6). Conversely, DS/CHD hospitalizations were less likely to include cardiac procedures or surgery (OR 0.3, 95% CI 0.2 to 0.4) and were associated with lower charges ($23,789 ± $1,177 vs $39,464 ± $1,371, p <0.0001) compared to non-DS/CHD admissions. In conclusion, DS/CHD hospitalizations represent a decreasing proportion of admissions for adults with CHD typical of DS; patients with DS/CHD are more likely to die during hospitalization but less likely to undergo a cardiac procedure.
Sanders, D B; Smith, B P; Sowell, S R; Nguyen, D H; Derby, C; Eshun, F; Nigro, J J
Sickle cell anemia and thalassemia are hemoglobinopathies rarely encountered in the United States. Compounded with congenital heart disease, patients with sickle cell disease (SCD) requiring cardiopulmonary bypass and open-heart surgery represent the proverbial "needle in the haystack". As such, there is some trepidation on the part of clinicians when these patients present for complex cardiac surgery. SCD is an autosomal, recessive condition that results from a single nucleotide polymorphism in the β-globin gene. Hemoglobin SS molecules (HgbSS) with this point mutation can polymerize under the right conditions, stiffening the erythrocyte membrane and distorting the cellular structure to the characteristic sickle shape. This shape change alters cellular transit through the microvasculature. As a result, circumstances such as hypoxia, hypothermia, acidosis or diminished blood flow can lead to aggregation, vascular occlusion and thrombosis. Chronically, SCD can give rise to multiorgan damage secondary to hemolysis and vascular obstruction. This review and case study details an 11-year-old African-American male with known SCD who presented to the cardiothoracic surgical service with congenital heart disease consisting of an anomalous, intramural right coronary artery arising from the left coronary sinus for surgical consultation and subsequent surgical correction. This case report will include a review of the pathophysiology and current literature regarding preoperative, intraoperative and postoperative management of SCD patients.
Bouveret, Romaric; Waardenberg, Ashley J; Schonrock, Nicole; Ramialison, Mirana; Doan, Tram; de Jong, Danielle; Bondue, Antoine; Kaur, Gurpreet; Mohamed, Stephanie; Fonoudi, Hananeh; Chen, Chiann-mun; Wouters, Merridee A; Bhattacharya, Shoumo; Plachta, Nicolas; Dunwoodie, Sally L; Chapman, Gavin; Blanpain, Cédric; Harvey, Richard P
We take a functional genomics approach to congenital heart disease mechanism. We used DamID to establish a robust set of target genes for NKX2-5 wild type and disease associated NKX2-5 mutations to model loss-of-function in gene regulatory networks. NKX2-5 mutants, including those with a crippled homeodomain, bound hundreds of targets including NKX2-5 wild type targets and a unique set of "off-targets", and retained partial functionality. NKXΔHD, which lacks the homeodomain completely, could heterodimerize with NKX2-5 wild type and its cofactors, including E26 transformation-specific (ETS) family members, through a tyrosine-rich homophilic interaction domain (YRD). Off-targets of NKX2-5 mutants, but not those of an NKX2-5 YRD mutant, showed overrepresentation of ETS binding sites and were occupied by ETS proteins, as determined by DamID. Analysis of kernel transcription factor and ETS targets show that ETS proteins are highly embedded within the cardiac gene regulatory network. Our study reveals binding and activities of NKX2-5 mutations on WT target and off-targets, guided by interactions with their normal cardiac and general cofactors, and suggest a novel type of gain-of-function in congenital heart disease. DOI: http://dx.doi.org/10.7554/eLife.06942.001 PMID:26146939
Otaigbe, BE; Tabansi, PN
Summary Introduction Echocardiographic evaluation remains the gold standard for the diagnosis of structural cardiac disease. No previous prospective studies have been done on the prevalence of congenital heart disease (CHD) in the Niger Delta area. This study was done to determine the frequency and pattern of congenital heart disease, using echocardiography as a diagnostic tool. Methods All patients presenting to the Paediatric Cardiology clinics of two centres, the University of Port Harcourt Teaching Hospital and the Paediatric Care Hospital between April 2009 and March 2013, were recruited and all had echocardiography performed. Results Prevalence of CHD in this study was 14.4 per 1 000 children; 277 (83.4%) of the patients had acyanotic CHD and 55 (16.6%) had cyanotic CHD. Ventricular septal defect and tetralogy of Fallot were the commonest acyanotic and cyanotic heart defects, respectively Conclusion The high prevalence of CHD in this study is the highest in the country and Africa, and may be attributable to the increased oil spillage and gas flaring from petroleum exploitation in this region. PMID:25388927
McAuley, James B.
Toxoplasmosis is caused by infection with the parasite Toxoplasma gondii. It is one of the most common parasitic infections in humans and is most typically asymptomatic. However, primary infection in a pregnant woman can cause severe and disabling disease in the developing fetus. Recent developments have included increased understanding of the role of parasite genotype in determining infectivity and disease severity. Risk factors for acquisition of infection have been better defined, and the important role of foodborne transmission has been further delineated. In addition, strategies have emerged to decrease mother-to-child transmission through prompt identification of acutely infected pregnant women followed by appropriate treatment. Refined diagnostic tools, particularly the addition of immunoglobulin G avidity testing, allow for more accurate timing of maternal infection and hence better decision making during pregnancy. Congenitally infected children can be treated, beginning in utero and continuing through the first year of life, to ameliorate the severity of disease. However, despite these many advances in our understanding of congenital toxoplasmosis prevention and treatment, significant areas of study remain: we need better drugs, well defined strategies for screening of pregnant women, improved food safety, and improved diagnostic tests. PMID:25232475
The care of adults with congenital heart disease across the globe: Current assessment and future perspective: A position statement from the International Society for Adult Congenital Heart Disease (ISACHD).
Webb, Gary; Mulder, Barbara J; Aboulhosn, Jamil; Daniels, Curt J; Elizari, Maria Amalia; Hong, Gu; Horlick, Eric; Landzberg, Michael J; Marelli, Ariane J; O'Donnell, Clare P; Oechslin, Erwin N; Pearson, Dorothy D; Pieper, Els P G; Saxena, Anita; Schwerzmann, Markus; Stout, Karen K; Warnes, Carole A; Khairy, Paul
The number of adults with congenital heart disease (CHD) has increased markedly over the past few decades as a result of astounding successes in pediatric cardiac care. Nevertheless, it is now well understood that CHD is not cured but palliated, such that life-long expert care is required to optimize outcomes. All countries in the world that experience improved survival in CHD must face new challenges inherent to the emergence of a growing and aging CHD population with changing needs and medical and psychosocial issues. Founded in 1992, the International Society for Adult Congenital Heart Disease (ISACHD) is the leading global organization of professionals dedicated to pursuing excellence in the care of adults with CHD worldwide. Recognizing the unique and varied issues involved in caring for adults with CHD, ISACHD established a task force to assess the current status of care for adults with CHD across the globe, highlight major challenges and priorities, and provide future direction. The writing committee consisted of experts from North America, South America, Europe, South Asia, East Asia, and Oceania. The committee was divided into subgroups to review key aspects of adult CHD (ACHD) care. Regional representatives were tasked with investigating and reporting on relevant local issues as accurately as possible, within the constraints of available data. The resulting ISACHD position statement addresses changing patterns of worldwide epidemiology, models of care and organization of care, education and training, and the global research landscape in ACHD.
Blok, Ilja M; van Riel, Annelieke C M J; Mulder, Barbara J M; Bouma, Berto J
Pulmonary arterial hypertension is a serious complication of adult congenital heart disease associated with systemic-to-pulmonary shunts. Although early shunt closure restricts development of pulmonary arterial hypertension, patients remain at risk even after repair. The development of pulmonary arterial hypertension is associated with a markedly increased morbidity and mortality. It is important to identify patients with a poor prognosis using disease specific markers. Echocardiography and biomarkers arise as practical tools to determine the risk of mortality. Although pulmonary arterial hypertension cannot be cured, four classes of disease-targeting therapies are currently available and several promising therapies are being studied. There is a shift in drug studies towards more clinically relevant endpoints such as time to clinical worsening and morbidity and mortality events.
... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Genetic Counseling for Congenital Heart Defects Updated:Oct 26, ... person with congenital heart disease considers having children. Genetic counseling can help answer these questions and address ...
Li, Zheng; Yu, Xin; Shen, Jianxiong
Growing evidence has proved that many aspects of our lifestyle and the environment contribute to the development of congenital disease. Congenital spinal deformities are due to anomalous development of the vertebrae including failure of formation and segmentation during embryogenesis. The causes of congenital scoliosis have not been fully identified. A variety of factors are implicated in the development of vertebral abnormalities. Previous studies have demonstrated that both genetics and environmental factors are implicated in the development of vertebral abnormalities. However, no specific cause for congenital scoliosis has been identified. In our review, we focus on the environmental factors for the development of congenital scoliosis. Various maternal exposures during pregnancy including hypoxia, alcohol use, vitamin deficiency, valproic acid, boric acid, and hyperthermia have been observed to be associated with the occurrence of congenital scoliosis. This review describes the major environmental contributors of congenital scoliosis with an emphasis on treatment aspects associated with environmental disposition in congenital scoliosis.
DiNardo, James A
Despite remarkable improvements in perioperative care, adverse neurobehavioral outcomes following neonatal and infant cardiac surgery are commonplace and are associated with substantial morbidity. It is becoming increasingly clear that complex congenital heart disease is associated with both abnormalities in neuroanatomic development and a delay in fetal brain maturation. Substantial cerebral ischemic/hypoxic injury has been detected in neonates with complex congenital heart disease both prior to and following corrective cardiac surgery. The brain of the neonate with complex congenital heart disease appears to be uniquely vulnerable to the types of ischemic/hypoxic injury associated with perioperative care. It remains to be determined whether delaying surgical correction to allow for brain maturation will be associated with improvements in neurobehavioral outcomes.
D'Arcy, Colleen; Pertile, Mark; Goodwin, Tess; Bittinger, Sophie
Congenital adrenal agenesis is an extremely rare condition wherein the adrenal glands fail to develop. The absence of adrenal tissue results in the complete absence of hormones produced in the adrenal cortex (cortisol, aldosterone) and medulla (catecholamines), and is not compatible with postnatal life without artificial hormone replacement therapy. To date, 9 cases of adrenal agenesis have been reported, many of which are associated with additional congenital anomalies. Most cases were not detected on antenatal imaging and were detected incidentally at postmortem examination. We present a case of adrenal agenesis, detected incidentally at postmortem examination after termination of pregnancy for suspected fetal hydrops, and review the heterogeneous phenotype of this condition with associated abnormalities and molecular genetics. This case reinforces the role of the perinatal autopsy to investigate cause of perinatal mortality, allowing correlation of pathology with antenatal imaging findings and clinical details.
Grot, Przemyslaw; Dunajski, Zbigniew
Fetal magnetocardiography - a modern method of measuring electroactivity of fetal's heart is gaining more popularity interest among scientists and doctor's. For the method to become a useful tool in diagnosing congenital heart disease there has been created an international database composed of data taken from various scientific centers in the world (e.g. Institute of Precision and Biomedical Engineering of Warsaw University of Technology). Cardiograms which are recorded during fMCG (fetal magnetocardiography) and fECG (fetal electrocardiography) examination can be used to classify if the fetal heart is developing in healthy or pathological way. Thus, it has been extremely vital to create the universal and univocal pattern of discrimination between healthy or pathological fetuses. In order to do this an international database with normal values of the parameters describing the cardiograms was needed. The database is a compilation of data measured at various centers using different but similar devices and different signal processing techniques. This work analyses helpfulness of the international database in establishing the universal pattern which in future could serve as the basis for the proper congenital heart disease diagnosis.
Hom, Lisa A; Martin, Gerard R
An estimated 90% of births or more in the United States will be screened for critical congenital heart disease (CCHD) by the end of 2014. Europe has made less progress despite providing the population-based studies that were critical in driving support for efforts within the United States. Congenital Heart Disease (CHD) advocacy groups, investigators in screening for CCHD and international health organizations have been meeting with health care providers and government officials on a country by country basis. Countries that are implementing or have pilot projects have been identified to track global implementation. The Nordic countries, the United States, Switzerland and the United Arab Emirates are closest to universal screening for CCHD in newborns. Significant pilot projects tailored to unique care delivery systems screen through the use of midwives in the Netherlands, on maternity wards in the United Kingdom and while developing newborn care infrastructure in China. In Africa, South and Central America, individual countries are in the early stages of organization. Screening for CCHD is spreading across the globe. Early recognition has the ability to improve care in countries providing CHD treatment and prepare parents for adverse events in countries where care is not accessible. Impact of screening in regions with less access to intervention will be important to track.
Stephens, Elizabeth H.; Kearney, Debra L.; Grande-Allen, K. Jane
Congenitally diseased valves are relatively frequent causes of significant morbidity and mortality. Pathology descriptions of such valves have primarily focused on gross structural features including the number of leaflets or commissures (bicuspid/bicommissural valve) and alterations in the contour, thickness and consistency of the leaflets (dysplastic valve). Functional correlates of these pathologic alterations are valvar stenosis, insufficiency or both. Further characterization of the microstructural abnormalities seen in these malformed valves may not only provide insight into the correlation of distinct pathologies with their respective pathogenesis and clinical sequelae, but also may prove pivotal in uncovering new avenues for therapeutic interventions and prevention regimens. This review summarizes microstructural findings in congenital semilunar valve disease (CSVD) and discusses their relevance in light of recent advances in knowledge of normal valve microstructure, biology, and function. Specifically, the biological and mechanical roles of various matrix components and their interactions are discussed in the context of CSVD. Indeed, recent research in normal valves adds significant insight into CSVD, and raises many hypotheses that will need to be addressed by future studies. PMID:21349746
Medeiros-Neto, G; Kim, P S; Yoo, S E; Vono, J; Targovnik, H M; Camargo, R; Hossain, S A; Arvan, P
Recent advances in understanding the molecular pathogenesis of congenital hypothyroid goiter in cog/cog mice, have raised important questions concerning the maturation of thyroglobulin (the thyroid prohormone) in certain human kindreds with congenital goiter. We have now examined affected siblings from two unrelated families that synthesize an apparently normally glycosylated, > 300 kD immunoreactive thyroglobulin, yet have a reduced quantity of intraglandular thyroglobulin and that secreted into the circulation. From thyroid tissues of the four patients, light microscopic approaches demonstrated presence of intracellular thyroglobulin despite its absence in thyroid follicle lumina, while electron microscopy indicated abnormal distention of the endoplasmic reticulum (ER). We have confirmed biochemically that most intrathyroidal thyroglobulin fails to reach the (Golgi) compartment where complex carbohydrate modification takes place. Moreover, the disease in the affected patients is associated with massive induction of specific ER molecular chaperones including the hsp90 homolog, GRP94, and the hsp70 homolog, BiP. The data suggest that these patients synthesize a mutant thyroglobulin which is defective for folding/assembly, leading to a markedly reduced ability to export the protein from the ER. Thus, these kindreds suffer from a thyroid ER storage disease, a cell biological defect phenotypically indistinguishable from that found in cog/cog mice. PMID:8981932
Lin, C Huie; Hegde, Sanjeet; Marshall, Audrey C; Porras, Diego; Gauvreau, Kimberlee; Balzer, David T; Beekman, Robert H; Torres, Alejandro; Vincent, Julie A; Moore, John W; Holzer, Ralf; Armsby, Laurie; Bergersen, Lisa
Continued advancements in congenital cardiac catheterization and interventions have resulted in increased patient and procedural complexity. Anticipation of life-threatening events and required rescue measures is a critical component to preprocedural preparation. We sought to determine the incidence and nature of life-threatening adverse events in congenital and pediatric cardiac catheterization, risk factors, and resources necessary to anticipate and manage events. Data from 8905 cases performed at the 8 participating institutions of the Congenital Cardiac Catheterization Project on Outcomes were captured between 2007 and 2010 [median 1,095/site (range 133-3,802)]. The incidence of all life-threatening events was 2.1 % [95 % confidence interval (CI) 1.8-2.4 %], whereas mortality was 0.28 % (95 % CI 0.18-0.41 %). Fifty-seven life-threatening events required cardiopulmonary resuscitation, whereas 9 % required extracorporeal membrane oxygenation. Use of a risk adjustment model showed that age <1 year [odd ratio (OR) 1.9, 95 % CI 1.4-2.7, p < 0.001], hemodynamic vulnerability (OR 1.6, 95 % CI 1.1-2.3, p < 0.01), and procedure risk (category 3: OR 2.3, 95 % CI 1.3-4.1; category 4: OR 4.2, 95 % CI 2.4-7.4) were predictors of life-threatening events. Using this model, standardized life-threatening event ratios were calculated, thus showing that one institution had a life-threatening event rate greater than expected. Congenital cardiac catheterization and intervention can be performed safely with a low rate of life-threatening events and mortality; preprocedural evaluation of risk may optimize preparation of emergency rescue and bailout procedures. Risk predictors (age < 1, hemodynamic vulnerability, and procedure risk category) can enhance preprocedural patient risk stratification and planning.
Rashid, Usman; Qureshi, Ahmad U; Hyder, Syed N; Sadiq, Masood
Objective: To determine the delay in diagnosis of various types of congenital heart defects in children and factors associated with such delay. Patients and Methods: For this observational study, 354 patients having congenital heart disease (CHD) presenting for the first time to the Department of Cardiology, Children’s Hospital, Lahore, Pakistan, between January 1, 2015 and June 30, 2015, were enrolled after obtaining informed verbal consent from the guardian of each child. Demographical profile and various factors under observation were recorded. Results: Among the 354 enrolled children (M: F 1.7:1) with age ranging from 1 to 176 months (median 24 months), 301 (85.1%) had delayed diagnosis of CHD (mainly acyanotic 65.3%), with median delay (8 months). Main factors for delay were delayed first consultation to a doctor (37.2%) and delayed diagnosis by a health professional (22.5%). Other factors included delayed referral to a tertiary care hospital (13.3%), social taboos (13.0%), and financial constraints (12.3%). Most children were delivered outside hospital settings (88.7%). Children with siblings less than two (40%) were less delayed than those having two or more siblings (60%, P < 0.001). Conclusion: Diagnosis of congenital heart defect was delayed in majority of patients. Multiple factors such as lack of adequately trained health system and socioeconomic constraints were responsible for the delay. There is a need to develop an efficient referral system and improve public awareness in developing countries for early diagnosis and management of such children. PMID:27625517
Bodian, M; Ngaïdé, A A; Mbaye, A; Sarr, S A; Jobe, M; Ndiaye, M B; Kane, A D; Aw, F; Gaye, N D; Ba, F G; Bah, M B; Tabane, A; Dioum, M; Diagne, D; Diao, M; Diack, B; Sarr, M; Kane, A; Bâ, S A
Congenital heart diseases are one of the major cardiovascular diseases in developing countries. Most prevalence studies were based on clinical examination of children with echocardiographic confirmation of suspected cases and underestimate its prevalence. The objective of this study was to investigate the prevalence of congenital heart disease in "daara" (Koranic schools) in the city of Dakar and its suburbs on the basis of clinical examination and Doppler echocardiography in school children. This cross-sectional survey was carried out from 9(th) August to 24(th) December 2011, and included a population of 2019 school children aged 5 to 18 years in 16 selected "daaras" under the Academic Inspectorate of Dakar and its suburbs. Anamnestic, clinical and echocardiographic data were recorded in a validated questionnaire. A p < 0.05 was considered to be statistically significant in bivariate analysis. 2 019 school children were included out of which 60.1% were male (sex-ratio: 0.66). The average age was 9.7 years (± 3.3 years). 18 cases of congenital heart diseases were detected being a prevalence of 8.9 per 1 000 (95 % CI: 1.8 to 7.9). This included 6 cases of inter-atrial septal aneurysm, 5 cases of peri-membranous ventricular septal defects, 4 cases of patent ductusarteriosus and 3 cases of tetralogy of Fallot. Factors correlated with the presence of congenital heart disease were ageless than 8 (p <0.001) and residence in the suburbs of Dakar (p <0.001). We also detected 10 cases of rheumatic valvular disease, a prevalence of 4.9 per 1 000 (95% CI: 2.4 to 9.1). Our study shows a high prevalence of congenital heart diseases, which is almost identical to the WHO estimates and that ultrasound screening is more sensitive than clinical screening. Reducing the prevalence of these diseases requires implementation of appropriate policies, focusing on awareness and early detection.
Lin, Yuan; Ding, Chenyue; Zhang, Kai; Ni, Bixian; da, Min; Hu, Liang; Hu, Yuanli; Xu, Jing; Wang, Xiaowei; Chen, Yijiang; Mo, Xuming; Cui, Yugui; Shen, Hongbing; Sha, Jiahao; Liu, Jiayin; Hu, Zhibin
OCT4 is a transcription factor of the POU family, which plays a key role in embryonic development and stem cell pluripotency. Previous studies have shown that Oct4 is required for cardiomyocyte differentiation in mice and its depletion could result in cardiac morphogenesis in embryo. However, whether the genetic variations in OCT4 coding gene, POU5F1, confer the predisposition to congenital heart disease (CHD) is unclear. This study sought to investigate the associations between low-frequency (defined here as having minor allele frequency (MAF) between 0.1%-5%) and rare (MAF below 0.1%) variants with potential function in POU5F1 and risk of CHD. We conducted association analysis in a two-stage case-control study with a total of 2,720 CHD cases and 3,331 controls in Chinese. The low-frequency variant rs3130933 was observed to be associated with a significantly increased risk of CHD [additive model: adjusted odds ratio (OR) = 2.15, adjusted P = 3.37 × 10-6]. Furthermore, luciferase activity assay showed that the variant A allele led to significantly lower expression levels as compared to the G allele. These findings indicate for the first time that low-frequency functional variant in POU5F1 may contribute to the risk of congenital heart malformations.
Buonocore, E.; Pavlicek, W.; Modic, M.T.; Meaney, T.F.; O'Donovan, P.B.; Grossman, L.B.; Moodie, D.S.; Yiannikas, J.
Digital subtraction angiography (DSA) of the heart was performed in 54 patients for the evaluation of congenital heart diagnostic images and accurate physiologic shunt data that compared favorably with catheter angiography and nuclear medicine studies. Retrospective analysis of this series of patients indicated that DSA studies contributed sufficient informantion to shorten significantly or modify cardiac catheterization in 85% (79/93) of the defects that were identified. Interatrial septal defects were particularly well diagnosed, with identification occurring in 10 of 10 cases, wheseas intraventricular septal defects were identified in only 6 of 9 patients. Evaluation of postsurgical patients was accurate in 19 of 20 cases.
Werner, Petra; Paluru, Prasuna; Simpson, Anisha M.; Latney, Brande; Iyer, Radhika; Brodeur, Garrett M.; Goldmuntz, Elizabeth
Congenital heart defects (CHDs) are the most common major birth defects and the leading cause of death from congenital malformations. The etiology remains largely unknown, though genetic variants clearly contribute. In a previous study, we identified a large copy number variant (CNV) that deleted 46 genes in a patient with a malalignment type ventricular septal defect (VSD). The CNV included the gene NTRK3 encoding neurotrophic tyrosine kinase receptor C (TrkC), which is essential for normal cardiogenesis in animal models. To evaluate the role of NTRK3 in human CHDs, we studied 467 patients with related heart defects for NTRK3 mutations. We identified four missense mutations in four patients with VSDs that were not found in ethnically matched controls and were predicted to be functionally deleterious. Functional analysis using neuroblastoma cell lines expressing mutant TrkC demonstrated that one of the mutations (c.278C>T, p.T93M) significantly reduced autophosphorylation of TrkC in response to ligand binding, subsequently decreasing phosphorylation of downstream target proteins. In addition compared to WT, three of the four cell lines expressing mutant TrkC showed altered cell growth in low-serum conditions without supplemental NT-3. These findings suggest a novel pathophysiological mechanism involving NTRK3 in the development of VSDs. PMID:25196463
Malawski, Stefan; Malawski, Piotr
The authors categorised congenital malformations of the spine into five different pathomorphologic groups basing on a series of 61 cases (age ranging from 1 to 50 years): defects of the vertebra, of the vertebral body, intervertebral synostosis, rib synostosis, and defects of the vertebral arch. A total of over 30 different kinds of malformations were obtained in this classification. In the analysed series 34 patients had a predominant kind of malformation, while in 27 cases mixed malformations were noted. These malformations lead to spine deformities: 21 cases with arch scoliosis, 15 cases with kyphoscoliosis, 13 cases with angular scoliosis and 12 cases with kyphosis. Deformities had a tendency to progress with age. In 20 patients neurological deficits (increased spasticity, spastic paresis, spastic and flaccid paralysis) increased after reaching skeletal maturity. Prognosis as to deformity regression was made difficult be the large variety of different pathomorphologic types of deformity. Only general patterns were visible e.g. a tendency to progress in cases were hemivertebra were found. In cases were more than one type of deformity was noted, growth balance of the spine was not a rule. On the contrary, even small mixed deformities of ten progressed. This paper indicates that most congenital deformities of the spine should be treated operatively, either to correct the deformity or to attain spine growth balance.
Spijkerboer, A. W.; Utens, E. M. W. J.; Bogers, A. J. J. C.; Verhulst, F. C.; Helbing, W. A.
In this study, long-term intellectual functioning and school-related behavioural outcomes were assessed in a patient sample that underwent invasive treatment for congenital heart disease (ConHD) between 1990 and 1995. The Wechsler Intelligence Scale for Children-Revised was used to measure intellectual functioning and the Teacher's Report Form to…
Hong, Haifa; Xia, Yu; Sun, Yanjun; Ye, Lincai; Liu, Jinfen; Bai, Jie; Zhang, Haibo
Patency of the ductus arteriosus (DA) after birth is essential in ductal-dependent congenital heart disease. The Na(+)/Ca(2+) exchanger (NCX) has been demonstrated to play a key role in regulating vascular tone. The potassium-dependent Na(+)/Ca(2+) exchanger (NCKX) is a related family of NCX depending on the K(+) gradients which triggers DA constriction. The present study investigated the comparative expression of NCX and NCKX between a constricted DA and patent DA in human ductal-dependant congenital heart disease. Human DAs, which were patent (n = 10, age = 20.2 ± 4.3 days) or constricted (n = 10, age = 18.3 ± 3.9 days), were excised during surgery from neonates with ductal-dependent congenital heart disease. Western blotting analysis, real-time quantitative polymerase chain reaction analysis and immunofluorescence studies were performed to detect the protein and mRNA levels of NCX1, NCKX3, and NCKX4. The expressions of NCX1 and NCKX4 were significantly higher in the patent DA group at both the protein and mRNA levels, and expression was localized to the smooth muscle layer. These findings indicate that NCX1 and NCKX4 are up-regulated in human postnatal patent DAs and may represent potential therapeutic targets for maintaining DA patency in ductal-dependent congenital heart disease.
Mohammad, Misbahuddin; James, Anish F.; Qureshi, Raheel S.; Saraf, Sapan; Ahluwalia, Tina; Mukherji, Joy Dev; Kole, Tamorish
BACKGROUND: Stroke is a common presentation in geriatric patients in emergency department but rarely seen in pediatric patients. In case of acute ischemic stroke in pediatric age group, management is different from that of adult ischemic stroke where thrombolysis is a good op. METHODS: We report a case of a 17-year-old male child presenting in emergency with an episode of acute ischemic stroke causing left hemiparesis with left facial weakness and asymmetry. The patient suffered from cyanotic congenital heart disease for which he had undergone Fontan operation previously. He had a history of missing his daily dose of warfarin for last 3 days prior to the stroke. RESULTS: The patient recovered from acute ischemic stroke without being thrombolyzed. CONCLUSION: In pediatric patients, acute ischemic stroke usually is evolving and may not require thrombolysis. PMID:25215056
Batra, Anjan S; Alexander, Mark E; Silka, Michael J
Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood, and congenital heart disease (CHD) is the most common form of birth defect. Children with CHD are at increased risk for neurodevelopmental disorders such as ADHD. Stimulant medications, specifically methylphenidates and amphetamines, are frequently prescribed and effective in reducing the symptoms of ADHD. Despite their efficacy and long history of use, the safety of these medications has recently come into question due to isolated reports describing sudden unexplained death of children undergoing treatment. This review summarizes the current literature on the cardiovascular risks associated with the use of pharmacologic therapy for ADHD, with an emphasis on patients who had CHD.
Cerebral palsy is one of the symptoms of congenital Minamata disease associated with exposure to methyl mercury. Cerebral palsy hospitalization rates for 17 Canadian Areas of Concern have been used as a health index in evaluating the effectiveness of the United States and Canadian governments in implementing their Great Lakes Water Quality Agreement. Elevated rates in males in several locations was associated with historic uses of mercury and with natural sources indicating that the governments have failed to protect human health from exposures to this persistent toxic substance. Advances in epidemiological theory indicate that the reasons for this failure cannot be explained solely in scientific and technical frames but that the social, economic, and political contexts of the two nations need to be examined.
Ch'ng, Julie; Chan, William; Lee, Paul; Joshi, Subodh; Grigg, Leanne E.; Ajani, Andrew E
Staphylococcus aureus is a leading cause of septicaemia and infective endocarditis. The overall incidence of staphylococcal bacteraemia is increasing, contributing to 16% of all hospital-acquired bacteraemias. The use of cardiac pacemakers has revolutionized the management of rhythm disturbances, yet this has also resulted in a group of patients at risk of pacemaker lead endocarditis and seeding in the range of 1% to 7%. We describe a 26-year-old man with transposition of the great arteries who had a pacemaker implanted and presented with S. aureus septicaemia 2 years postpacemaker implantation and went on to develop pacemaker lead endocarditis. This report illustrates the risk of endocarditis in the population with congenital heart disease and an intracardiac device.
Morris, Cullen D; Gregoric, Igor D; Cooley, Denton A; Cohn, William E; Loyalka, Pranav; Frazier, O H
For patients with end-stage heart failure and contraindications to transplantation, insertion of a continuous-flow left ventricular assist device (LVAD) is an effective treatment strategy. We present a case of LVAD insertion in a 46-year-old man with cyanotic complex congenital heart disease and an extensive surgical history who presented with failure of his systemic ventricle. The insertion of an LVAD in our patient restored cardiac output and improved cyanosis and native ventricular function. As the number of patients with congenital heart defects surviving to adulthood increases, destination LVAD therapy may be increasingly considered as an alternative.
Otani, Hiroki; Udagawa, Jun; Hatta, Toshihisa; Kagohashi, Yukiko; Hashimoto, Ryuju; Matsumoto, Akihiro; Satow, Fumio; Nimura, Masayuki
Morphological studies of congenital anomalies have mainly focused on abnormal shape (i.e. malformation) and thus on disturbed organogenesis. However, in regard to postnatal functions of organs that develop through branching mechanisms, organ size is another important morphological feature. These organs consist of a large number of structural and functional units, such as nephrons in the kidney, and the total number of these units, that is approximately proportional to the organ size, has been shown to vary widely among individuals. Organ-specific cells are differentiated and organized to form structural units and realize organ-specific functions during the histogenetic period (i.e. from mid-gestation to the early postnatal period). The total number of units is attained at the end of histogenesis and determines the total functional capacity, including the functional reserve of the organ, and thus may be related to predispositions to postnatal organ-based diseases, because the functional reserve decreases during the course of life and eventually become short of the minimum requirement of each organ. Therefore, it may be hypothesized that a smaller number of units of organs at the end of histogenesis is one of the predisposing factors for postnatal diseases (i.e. a form of unnoticed but late-manifested congenital anomalies), in this era of extended longevity. However, the mechanisms that control the total number of units in each organ during histogenesis and the possible relationship among the numbers of units in different organs remain unknown. Here, we review our trials based on the above hypothesis in order to (1) mathematically analyze the morphometric data of the different organs in fetuses to elucidate relationship among developing organs, (2) analyze the developing neuro-immuno-endocrine network as a series of mechanisms to systemically correlate the histogenesis of multiple organs, and (3) examine the maternal environment, including dietary fat, as a factor to
Preston, L; Turner, J; Booth, A; O'Keeffe, C; Campbell, F; Jesurasa, A; Cooper, K; Goyder, E
Objective To identify and synthesise the evidence on the relationship between surgical volume and patient outcomes for adults and children with congenital heart disease. Design Evidence synthesis of interventional and observational studies. Data sources MEDLINE, EMBASE, CINAHL, Cochrane Library and Web of Science (2009–2014) and citation searching, reference lists and recommendations from stakeholders (2003–2014) were used to identify evidence. Study selection Quantitative observational and interventional studies with information on volume of surgical procedures and patient outcomes were included. Results 31 of the 34 papers identified (91.2%) included only paediatric patients. 25 (73.5%) investigated the relationship between volume and mortality, 7 (20.6%) mortality and other outcomes and 2 (5.9%) non-mortality outcomes only. 88.2% were from the US, 97% were multicentre studies and all were retrospective observational studies. 20 studies (58.8%) included all congenital heart disease conditions and 14 (41.2%) single conditions or procedures. No UK studies were identified. Most studies showed a relationship between volume and outcome but this relationship was not consistent. The relationship was stronger for single complex conditions or procedures. We found limited evidence about the impact of volume on non-mortality outcomes. A mixed picture emerged revealing a range of factors, in addition to volume, that influence outcome including condition severity, individual centre and surgeon effects and clinical advances over time. Conclusions The heterogeneity of findings from observational studies suggests that, while a relationship between volume and outcome exists, this is unlikely to be a simple, independent and directly causal relationship. The effect of volume on outcome relative to the effect of other, as yet undetermined, health system factors remains a complex and unresolved research question. PMID:26685029
Puri, Inder; Vibha, Deepti; Prasad, Kameshwar; Bhatia, Rohit
A 22-year-old man presented with a history of progressive weakness and wasting of the right hand and forearm for 12 months followed by similar symptoms in the left upper limb for the past 5 months. He also gave a history of episodes of loss of consciousness for the past 5 years with a frequency of one per 3 months. On examination, there were melanocytic naevi-one large lesion in the nape of the neck and multiple satellite lesions. On investigation, the cervical cord MRI was normal. The brain MRI and angiography showed a moyamoya pattern. Thus, this patient had congenital melanocytic naevi with Hirayama disease and moyamoya pattern. He was treated with extracranial-intracranial bypass for moyamoya disease. During 6-month follow-up, he has been stable. Although moyamoya syndrome has been associated with several systemic diseases and conditions, the coexistence of a moyamoya pattern with Hirayama disease and melanocytic naevi has not been described so far.
Doyle, Michelle J; Lohr, Jamie L; Chapman, Christopher S; Koyano-Nakagawa, Naoko; Garry, Mary G; Garry, Daniel J
Congenital heart disease (CHD) remains a significant health problem, with a growing population of survivors with chronic disease. Despite intense efforts to understand the genetic basis of CHD in humans, the etiology of most CHD is unknown. Furthermore, new models of CHD are required to better understand the development of CHD and to explore novel therapies for this patient population. In this review, we highlight the role that human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes can serve to enhance our understanding of the development, pathophysiology and potential therapeutic targets for CHD. We highlight the use of hiPSC-derived cardiomyocytes to model gene regulatory interactions, cell-cell interactions and tissue interactions contributing to CHD. We further emphasize the importance of using hiPSC-derived cardiomyocytes as personalized research models. The use of hiPSCs presents an unprecedented opportunity to generate disease-specific cellular models, investigate the underlying molecular mechanisms of disease and uncover new therapeutic targets for CHD.
Raimondi, Francesca; Warin-Fresse, Karine
Computed tomography (CT) technology is acquiring a key role in the diagnostic process of complex cardiac congenital anomalies. Recent advances and improvements in spatial and temporal resolution and radiation dose are encouraging the use of CT scanning in children. Paediatric cardiologists should have a good knowledge of the potential of CT techniques and their limitations to plan and properly perform CT examinations without forgetting radiation concerns. In this paper, we will discuss the principal indications for CT scans in newborns and children in our clinical practice. We will also outline the most-used strategies for dose reduction. Basic knowledge about the various CT techniques is crucial, not only to perform, but also to interpret CT results, thus helping the medical and surgical management of patients.
Cheeran, Maxim C.-J.; Lokensgard, James R.; Schleiss, Mark R.
Congenital cytomegalovirus (CMV) infection is the leading infectious cause of mental retardation and hearing loss in the developed world. In recent years, there has been an improved understanding of the epidemiology, pathogenesis, and long-term disabilities associated with CMV infection. In this review, current concepts regarding the pathogenesis of neurological injury caused by CMV infections acquired by the developing fetus are summarized. The pathogenesis of CMV-induced disabilities is considered in the context of the epidemiology of CMV infection in pregnant women and newborn infants, and the clinical manifestations of brain injury are reviewed. The prospects for intervention, including antiviral therapies and vaccines, are summarized. Priorities for future research are suggested to improve the understanding of this common and disabling illness of infancy. PMID:19136436
Wright, Lydia K; Ehrlich, Alexandra; Stauffer, Nanci; Samai, Cyrus; Kogon, Brian; Oster, Matthew E
Prenatal diagnosis of congenital heart defects (CHDs) is increasingly common, but it is still unclear whether it translates to improved postoperative outcomes. We performed a retrospective cohort study of all infants (aged <1 year) who underwent surgery for CHDs from 2006 to 2011 at a single institution. Primary outcomes were in-hospital and 1-year mortality rates. Secondary outcomes were readmission within 30 days of discharge, postoperative length of intensive care unit and hospital stay, unplanned reoperation, and extracorporeal membrane oxygenation use. We used chi-square analyses, Wilcoxon rank-sum tests, Kaplan-Meier survival curves, and adjusted Cox proportional hazards models to compare outcomes. Of the 1,642 patients with CHDs, 539 (33%) were diagnosed prenatally. Patients with prenatal diagnoses were of a younger age and less weight at the time of surgery, had greater Risk Adjustment for Congenital Heart Surgery scores, and were more likely to be white, to have an identified syndrome, or to be born at term. Compared with those diagnosed postnatally, those diagnosed prenatally had a significantly higher unadjusted 1-year mortality rate (11% vs 5.5%, respectively, p = 0.03). Controlling for weight, surgical severity, race, age at surgery, prematurity, and the presence or absence of genetic syndrome, patients with prenatal diagnoses had significantly greater mortality at 1 year (adjusted hazard ratio 1.5, p = 0.03), as well as significantly longer intensive care unit and hospital stays. Infants with CHDs diagnosed prenatally had worse outcomes compared with those diagnosed postnatally. Prenatal diagnosis likely captures patients with more severe phenotypes within given surgical risk categories and even within diagnoses and thus may be an important prognostic factor when counseling families.
Jacobs, Jeffrey Phillip; Jacobs, Marshall Lewis; Mavroudis, Constantine; Backer, Carl Lewis; Lacour-Gayet, Francois G; Tchervenkov, Christo I; Franklin, Rodney C G; Béland, Marie J; Jenkins, Kathy J; Walters, Hal; Bacha, Emile A; Maruszewski, Bohdan; Kurosawa, Hiromi; Clarke, David Robinson; Gaynor, J William; Spray, Thomas L; Stellin, Giovanni; Ebels, Tjark; Krogmann, Otto N; Aiello, Vera D; Colan, Steven D; Weinberg, Paul; Giroud, Jorge M; Everett, Allen; Wernovsky, Gil; Elliott, Martin J; Edwards, Fred H
This review discusses the historical aspects, current state of the art, and potential future advances in the areas of nomenclature and databases for the analysis of outcomes of treatments for patients with congenitally malformed hearts. We will consider the current state of analysis of outcomes, lay out some principles which might make it possible to achieve life-long monitoring and follow-up using our databases, and describe the next steps those involved in the care of these patients need to take in order to achieve these objectives. In order to perform meaningful multi-institutional analyses, we suggest that any database must incorporate the following six essential elements: use of a common language and nomenclature, use of an established uniform core dataset for collection of information, incorporation of a mechanism of evaluating case complexity, availability of a mechanism to assure and verify the completeness and accuracy of the data collected, collaboration between medical and surgical subspecialties, and standardised protocols for life-long follow-up. During the 1990s, both The European Association for Cardio-Thoracic Surgery and The Society of Thoracic Surgeons created databases to assess the outcomes of congenital cardiac surgery. Beginning in 1998, these two organizations collaborated to create the International Congenital Heart Surgery Nomenclature and Database Project. By 2000, a common nomenclature, along with a common core minimal dataset, were adopted by The European Association for Cardio-Thoracic Surgery and The Society of Thoracic Surgeons, and published in the Annals of Thoracic Surgery. In 2000, The International Nomenclature Committee for Pediatric and Congenital Heart Disease was established. This committee eventually evolved into the International Society for Nomenclature of Paediatric and Congenital Heart Disease. The working component of this international nomenclature society has been The International Working Group for Mapping and Coding
Fang, Pingping; Weemhoff, James L.; Apte, Udayan
Autosomal recessive polycystic kidney disease (ARPKD) is a severe monogenic disorder that occurs due to mutations in the PKHD1 gene. Congenital hepatic fibrosis (CHF) associated with ARPKD is characterized by the presence of hepatic cysts derived from dilated bile ducts and a robust, pericystic fibrosis. Cyst growth, due to cyst wall epithelial cell hyperproliferation and fluid secretion, is thought to be the driving force behind disease progression. Liver fibrosis is a wound healing response in which collagen accumulates in the liver due to an imbalance between extracellular matrix synthesis and degradation. Whereas both hyperproliferation and pericystic fibrosis are hallmarks of CHF/ARPKD, whether or not these two processes influence one another remains unclear. Additionally, recent studies demonstrate that inflammation is a common feature of CHF/ARPKD. Therefore, we propose a “pathogenic triumvirate” consisting of hyperproliferation of cyst wall growth, pericystic fibrosis, and inflammation which drives CHF/ARPKD progression. This review will summarize what is known regarding the mechanisms of cyst growth, fibrosis, and inflammation in CHF/ARPKD. Further, we will discuss the potential advantage of identifying a core pathogenic feature in CHF/ARPKD to aid in the development of novel therapeutic approaches. If a core pathogenic feature does not exist, then developing multimodality therapeutic approaches to target each member of the “pathogenic triumvirate” individually may be a better strategy to manage this debilitating disease. PMID:27891514
Rostirola Guedes, Renata; Kieling, Carlos Oscar; Rossato Adami, Marina; Cerski, Carlos Thadeu Schmidt
Neonatal liver failure (NLF) is a major cause of neonatal morbidity and mortality, presenting as acute liver failure and/or congenital cirrhosis. Many affected patients show antenatal signs of fetal injury. There are several causes of NLF and early diagnosis is mandatory to elucidate the etiology and determine a specific treatment or the best management strategy. Gestational alloimmune liver disease associated with neonatal hemochromatosis (GALD-NH) is a rare but potentially treatable cause of NLF. It should be considered in any neonate with fetal signs of disease and postnatal signs of liver failure with no other identifiable causes. GALD-NH is often diagnosed late and patients are therefore referred late to specialized centers, delaying treatment. This case highlights the consequences of late diagnosis and treatment of GALD-NH and emphasizes the importance of a high grade of suspicion of this disease in order to refer the patient to a specialized center soon enough to perform the appropriate treatment. PMID:28251010
Costello, John P; Weiderhold, Allison; Louis, Clauden; Shaughnessy, Conner; Peer, Syed M; Zurakowski, David; Jonas, Richard A; Nath, Dilip S
The objective of this study was to examine a large institutional experience of patients with trisomy 13 and trisomy 18 in the setting of comorbid congenital heart disease and present the outcomes of surgical versus expectant management. It is a retrospective single-institution cohort study. Institutional review board approved this study. Thirteen consecutive trisomy 18 patients and three consecutive trisomy 13 patients (sixteen patients in total) with comorbid congenital heart disease who were evaluated by our institution's Division of Cardiovascular Surgery between January 2008 and December 2013 were included in the study. The primary outcome measures evaluated were operative mortality (for patients who received surgical management), overall mortality (for patients who received expectant management), and total length of survival during follow-up. Of the thirteen trisomy 18 patients, seven underwent surgical management and six received expectant management. With surgical management, operative mortality was 29 %, and 80 % of patients were alive after a median follow-up of 116 days. With expectant management, 50 % of patients died before hospital discharge. Of the three patients with trisomy 13, one pat