Tricuspid Atresia

Submaximal Field Walking Tests Applied in the Cardiopulmonary Assessment in Congenital Heart Diseases: A Systematic Review

Introduction: Submaximal field walking tests are easy to apply and low cost, but it is necessary to standardize their application, especially in the pediatric population. The feasibility and its use in patients with congenital heart disease have been studied. The goal of this study was to verify which are the submaximal field walking tests applied in the cardiopulmonary assessment of children and adolescents with CHD and to verify if they are being performed as recommended by the standardization protocols/guidelines.

Methods: Literature review through a search in six electronic databases, structured in PICO format, without date restrictions. Looking for studies that used submaximal field walking tests in children and adolescents with congenital heart disease aged 5 to 18 years. Methodological quality, effectiveness and safety and risk of bias were assessed.

Results: Five studies met the eligibility criteria with a sample of 160 individuals with congenital heart disease, and all used the six-minute walk test. Note that different methodologies and modifications are used. Only the clinical trial showed good methodological quality.Four studies had low risk of bias and one study had moderate risk.

Conclusion: Although the six-minute walk test is the only test used as a field test found in our research, there is no standardization in the application of the test, making it difficult to compare the results. In this sense, reducing the limitations and heterogeneity in the application of the test will enable more concrete outcomes and facilitate their reproduction in clinical practice.

MicroRNAs as Biomarkers for Birth Defects

It is estimated that 2-4% of live births will have a birth defect (BD). The availability of biomarkers for the prenatal detection of BDs will facilitate early risk assessment, prompt medical intervention and ameliorating disease severity. miRNA expression levels are often found to be altered in many diseases. There is, thus, a growing interest in determining whether miRNAs, particularly extracellular miRNAs, can predict, diagnose, or monitor BDs. These miRNAs, typically encapsulated in exosomes, are released by cells (including those of the fetus and placenta) into the extracellular milieu, such as blood, urine, saliva and cerebrospinal fluid, thereby enabling interaction with target cells. Exosomal miRNAs are stable, protected from degradation, and retain functionality. The observation that placental and fetal miRNAs can be detected in maternal serum, provides a strong rationale for adopting miRNAs as noninvasive prenatal biomarkers for BDs. In this mini-review, we examine the current state of research involving the use of miRNAs as prognostic and diagnostic biomarkers for BD.

Current Treatment Options for the Failing Fontan Circulation

The Fontan operation was introduced in 1968. For congenital malformations, where biventricular repair is unsuitable, the Fontan procedure has provided a long-term palliation strategy with improved outcomes compared to the initially developed procedures. Despite these improvements, several complications merely due to a failing Fontan circulation, including myocardial dysfunction, arrhythmias, increased pulmonary vascular resistance, protein-losing enteropathy, hepatic dysfunction, plastic bronchitis, and thrombo-embolism, may occur, thereby limiting the life-expectancy in this patient cohort. This review provides an overview of the most common complications of Fontan circulation and the currently available treatment options.

Cardiovascular Diseases in Pregnancy - A Brief Overview

Even though, there have been many advances in maternal medical care and fertility treatments, the presence of cardiovascular disease has a significant impact on pregnancy. In pregnant women, several heart conditions, such as valvular heart disease, chronic hypertension, congenital heart defects and non-ischemic cardiomyopathies are linked to increased risk of fetal as well as maternal morbidity and mortality. To date, the management of the co-existing conditions of pregnancy and heart disease has been challenging. Therefore, in-depth information may be beneficial to tackle a difficult case scenario. Towards this end, this paper provides an overview of the recent updated knowledge of pregnancy-related cardiovascular diseases in women.

Fontan Circulation Might be Associated with Peripartum Cardiomyopathy: A Review of Mechanistic and Clinical Aspects

Fontan operation has been defined as a palliative surgery connecting systemic venous return and pulmonary circulation in patients with certain forms of complex congenital heart disease (CHD). Fortunately, it has improved overall survival and chance of successful pregnancies among these patients. However, Fontan circulation (FC), as a potential trade-off, might be associated with specific late or post-gestational complications, including peripartum cardiomyopathy (PPCM) largely through its adverse effects on the placenta and inflammation-oxidation stress. Importantly, diagnosis of superimposed PPCM in women with FC might be a diagnostic challenge, requiring a high index of suspicion. Accordingly, the present paper aims to highlight the potential association of FC with PPCM evolution largely based on certain mechanistic and clinical perspectives.

Critical Congenital Heart Disease in Neonates: A Review Article

Critical congenital heart defects (CCHDs) are serious malformations that remain to be an important cause of neonatal mortality and morbidity. The clinical presentations of CCHD are shock, cyanosis, or respiratory distress, which may be similar to that of other neonatal conditions. Failure to diagnose these conditions early on after birth may result in acute cardiovascular collapse and death. Screening with routine pulse oximetry is efficient in distinguishing newborns with CCHD and other hypoxemic illnesses, which may otherwise be potentially life-threatening. If the cardiovascular system cannot be observed by echocardiography, then treatment with continuous prostaglandin-E1(PGE1) infusion should be started in any newborn whose condition deteriorates in the first few days of life. This review aims to provide a concise summary of the presentation and management of various CCHDs and to emphasize the role of timely diagnosis in the management.

Therapeutic Utilities of Pediatric Cardiac Catheterization

In an era when less invasive techniques are favored, therapeutic cardiac catheterization constantly evolves and widens its spectrum of usage in the pediatric population. The advent of sophisticated devices and well-designed equipment has made the management of many congenital cardiac lesions more efficient and safer, while providing more comfort to the patient. Nowadays, a large variety of heart diseases are managed with transcatheter techniques, such as patent foramen ovale, atrial and ventricular septal defects, valve stenosis, patent ductus arteriosus, aortic coarctation, pulmonary artery and vein stenosis and arteriovenous malformations. Moreover, hybrid procedures and catheter ablation have opened new paths in the treatment of complex cardiac lesions and arrhythmias, respectively. In this article, the main therapeutic utilities of cardiac catheterization in children are discussed.

Diagnostic Cardiac Catheterization in the Pediatric Population

Although the utility of diagnostic cardiac catheterization in the clinical setting has diminished over the last years, due to the emergence of noninvasive imaging modalities, such as echocardiography, magnetic resonance imaging and computed tomography, catheterization for diagnostic reasons still constitutes a valuable tool in certain parts in the workup of pediatric heart disease. As a result, awareness of the main aspects of diagnostic catheterization is of great importance for the clinical cardiologist. In this article, the main variables measured and the main actions performed during diagnostic cardiac catheterization in children are discussed.

Therapeutic Potential of N-Acetylcysteine for Wound Healing, Acute Bronchiolitis, and Congenital Heart Defects

Background: Wound healing is a composite and vital process in which devitalized tissue layers and cellular structures repair themselves. Bronchiolitis is generally prompted by respiratory syncytial virus or human metapneumovirus; this condition is an acute inflammatory injury of bronchioles. Heart problems that develop before birth are known as congenital heart defects (CHDs), and pregestational diabetes is considered a major predisposing factor of CHDs. N-Acetylcysteine (NAC) is a transformed kind of amino acid cysteine which restores the intracellular levels of the natural antioxidant glutathione when taken internally, thereby assisting the cells’ ability to diminish the damaging effects of reactive oxygen species (ROS).

Objective: In the present communication, NAC’s therapeutic potential for wound healing, acute bronchiolitis, and congenital heart defects (CHDs) is critically analyzed by reviewing its effect on the various targets of these diseases. The multifunctional nature of NAC is outlined in a review of evidence from in vitro and in vivo studies.

Conclusion: In conclusion, NAC could be used as a therapeutic agent in the treatment of wound healing, acute bronchiolitis and congenital heart defects (CHDs). The focus of future research should be the following; (1) to examine NAC clinically to be considered in the treatment of wound healing; (2) to investigate whether NAC could be used alone or with insulin to prevent CHDs in infants with pregestational diabetes; (3) to evaluate the application of NAC as a potential agent for PAH treatment.

New Insights into the Surgical Management of Tetralogy of Fallot: Physiological Fundamentals and Clinical Relevance

The surgical treatment of tetralogy of Fallot can be considered as a success story in the history of congenital heart diseases. Since the early outcome is no longer the main issue, the focus moved to the late sequelae of TOF repair, i.e. the pulmonary insufficiency and the secondary adaptation of the right ventricle. This review provides recent insights into the pathophysiological alterations of the right ventricle in relation to the reconstruction of the right ventricular outflow tract after repair of tetralogy of Fallot. Its clinical relevance is documented by addressing the policy changes regarding the optimal management at the time of surgical repair as well as properly defining criteria and timing for late pulmonary valve implantation.

Atrial Macroreentry in Congenital Heart Disease

Macroreentrant atrial tachycardia is a common complication following surgery for congenital heart disease (CHD), and is often highly symptomatic with potentially significant hamodynamic consequences. Medical management is often unsuccessful, requiring the use of invasive procedures. Cavotricuspid isthmus dependent flutter is the most common circuit but atypical circuits also exist, involving sites of surgical intervention or areas of scar related to abnormal hemodynamics. Ablation can be technically challenging, due to complex anatomy, and difficulty with catheter stability. A thorough assessment of the patients status and pre-catheter ablation planning is critical to successfully managing these patients.

Atrial Tachycardias Occurring Late After Open Heart Surgery

Atrial tachycardias are common after open heart surgery. Most commonly these are macro-reentrant including cavotricuspid isthmus dependent atrial flutter, incisional right atrial flutter and left atrial flutter. Focal atrial tachycardias occur less frequently. The specific type of atrial tachycardia highly depends on the type of surgical incision. Catheter ablation can be very effective, however requires a thorough understanding of anatomy and surgical technique.

Left Ventricular Non-compaction: From Recognition to Treatment

We have gained considerable insight and understanding about the etiology, embryogenesis of the myocardium, genetic background, diagnosis and outcome of left ventricular non-compaction (LVNC) over the last 2 decades. LVNC has a distinct morphological appearance with a thickened, two-layered myocardium consisting of an epicardial compacted and a thicker endocardial non-compacted layer. These features make the recognition with non-invasive imaging modalities highly feasible.

We now recognize LVNC is a distinct phenotype of the myocardium with genetic heterogeneity. In several cases, LVNC shares a common genetic background with other forms of cardiomyopathy. Therefore, most likely it is not a distinct form of cardiomyopathy but rather a morphological expression of different diseases.

LVNC can present as an isolated condition or associated with congenital heart disease, neuromuscular disease or genetic syndromes. It may be sporadic or a familial disease, with an autosomal dominant or X-linked mode of transmission. The clinical features associated with LVNC vary from asymptomatic individuals diagnosed during screening to symptomatic patients, with the potential for heart failure, arrhythmias, thromboembolic events, and sudden cardiac death.

A comprehensive diagnostic approach includes clinical history, electrocardiogram, imaging (in many instances with more than one technique), genetic assessment, and screening of first-degree relatives. This increases the chances of instituting the most appropriate therapy. Therapy for the most part is very similar to the general heart failure population with the exception that anticoagulation is started at a lower threshold.

Congenital Heart Disease: The Crossroads of Genetics, Epigenetics and Environment

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.

Advanced Echocardiographic Imaging of the Congenitally Malformed Heart

There have been significant advancements in the ability of echocardiography to provide both morphological and functional information in children with congenitally malformed hearts. This progress has come through the development of improved technology such as matrix array probes and software which allows for the off line analysis of images to a high standard. This article focuses on these developments and discusses some newer concepts in advanced echocardiography such is multi-planar reformatting [MPR] and tissue motion annular displacement [TMAD].

Our aim is to discuss important aspects related to the quality and reproducibility of data, to review the most recent published data regarding advanced echocardiography in the malformed heart and to guide the reader to appropriate text for overcoming the technical challenges of using these methods. Many of the technical aspects of image acquisition and post processing have been discussed in recent reviews by the authors and we would urge readers to study these texts to gain a greater understanding [1]. The quality of the two dimensional image is paramount in both strain analysis and three dimensional echocardiography. An awareness of how to improve image quality is vital to acquiring accurate and usable data.

Three dimensional echocardiography (3DE) is an attempt to visualise the dynamic morphology of the heart. Although published media is the basis for theoretical knowledge of how to practically acquire images, electronic media [eg.www.3dechocardiography.com] is the only way of visualising the advantages of this technology in real time.

It is important to be aware of the limitations of this technology and that much of the data gleaned from using these methods is at a research stage and not yet in regular clinical practice.

Mutation p.S335X in GATA4 Reduces its DNA Binding Affinity and Enhances Cell Apoptosis Associated with Ventricular Septal Defect

Genetic mutations in GATA4, a transcriptional factor, have been found to cause congenital heart diseases. The underlying mechanism, however, remains largely unknown. We previously reported 7 heterozygous variants in patients with ventricular septal defects (VSD). Here we functionally characterized a de novo mutation p.S335X and demonstrated that this mutation led to the pre-termination of its translation, producing a truncated GATA4 lacking a conservative region at C-terminus. Truncated GATA4 did not disturb its subcellular localization; however, it delayed the cardiomyocyte differentiation in P19cl6 model and prohibited Bcl2 expression that led to apoptosis proved by fragmented genomic DNA and positive TUNEL staining in H9C2 cells. By ChIP assay, we showed that GATA4 without C-terminus reduced its DNA binding affinity and suppressed the expressions of its target genes. These findings suggest that C-terminus of GATA4 is critical to maintain DNA binding, and genetic mutations in this region may affect genes important for myocyte apoptosis and differentiation associated with congenital heart defects.

Perinatal and Neonatal Outcomes of Lithium-Treated and Untreated Bipolar Women During Pregnancy: A Review of Present Literature

Many women with a bipolar disorder are in their reproductive age and will need to continue their psychopharmacological treatment during pregnancy, being abrupt discontinuation of these medications associated with an increase of the probability of relapse, high-risk behaviours, significant family dysfunction, and suicide. Lithium is a first line drug for acute and maintenance treatment of bipolar disorder. Its teratogenic and perinatal effects are controversial, so as its longterm effects on neurodevelopment of the children. Our purpose is to review the most up-to-date literature dealing with growth, neurological, cognitive and behavioural development of children exposed to Lithium in utero. A PubMed search was performed with the following keywords: bipolar disorder, Lithium, pregnancy, lactation, perinatal disease, child development. Studies were included in the review if they investigated one or more of the adverse events of interest. Of the 26 studies included in our review, some show an association between Lithium treatment and several grades of malformations (most commonly minor), both cardiac and involving other organs, and dysfunctions which are often reversible. Some studies reported no collateral effects due to in utero exposure to Lithium. Even though literature points out a slightly increased risk of major malformations due to Lithium therapy during pregnancy, the drug should not be discontinued, yet monitoring of serum Lithium levels and foetal echocardiography are recommended.

Resuscitation of the Patient with the Functionally Univentricular Heart

Neonates and infants with functional single ventricle anatomy face nearly certain early mortality without cardiac transplantation or successive palliation through a pathway of staged interventions. Patients with single ventricle variants typically have multiple hospitalizations and high incidence of cardiac arrest. Few studies have directly addressed the physiology, pharmacology, techniques or outcomes of resuscitation of this high-risk group. The unique challenge posed by resuscitation of this patient group was recently recognized within the 2010 International Liaison Committee on Resuscitation consensus statement, where, for the first time, two worksheets were devoted exclusively to the resuscitation of the single ventricle patient before and after S1P and those patients with bidirectional Glenn/hemi-Fontan and Fontan physiology. This article will review the consensus on science, treatment recommendations, and areas of uncertainty in the resuscitation of the infants and children with single ventricle physiology during each stage of surgical repair.

Clinical and Pharmacological Aspects of Immunoprophylaxis for Respiratory Syncytial Virus Infection in High-Risk Infants

Respiratory syncytial virus (RSV) is the leading cause of respiratory tract infection in infants and young children throughout the world. Although preterm birth has been considered for years the major risk factor for severe disease and hospitalization, recent findings indicate that prematurity is not a necessary condition, but one of the independent risk factors for severe RSV infection, together with chronic lung diseases, congenital heart disease and immunodeficiency. Furthermore, over 50% of infants hospitalized for RSV infections during the first year of life are healthy, full-term newborns, suggesting that other environmental and individual factors may be involved. Unfortunately, there is still no specific therapy against RSV infection and therefore prophylactic measures seem to be the only intervention to avoid disease complications. No safe and effective RSV vaccine is available for the prevention of serious RSV infection. Therefore, in addition to hygienic measures, the only approach is passive immunoprophylaxis with humanized monoclonal anti-RSV antibodies, such as palivizumab that have been developed for clinical use. Because of the high cost of these antibodies, a better definition of the individual risk profile for severe RSV infection and timing of administration is needed for optimal effectiveness and careful use of limited health care resources.

In this article, we have reviewed the clinical and pharmacological aspects of immunoprophylaxis with monoclonal antibodies for preventing RSV infection in high-risk infants.

The Patient with a Single Cardiac Ventricle

Patients born with a single cardiac ventricle are one of the most complex and challenging subgroups of congenital heart disease to manage, from their initial diagnosis to their long-term post-surgical sequelae. Advances in antenatal detection, operative techniques, and post-operative strategies have led to improved outcomes over the past two decades, yet morbidity and mortality remain high relative to other congenital heart lesions. Optimal management and outcome depend in part on a thorough understanding of the anatomy and physiology unique to these infants by all caregivers that may be involved including neonatologists, primary care pediatricians, emergency medicine physicians, and pediatric intensivists. This review will discuss in detail the course of these infants, from their birth through to their three stage surgical palliations and beyond. This review will also highlight many of the most recent medical and surgical innovations available to these infants.

The Role of Venous Abnormalities in Neurological Disease

The role of the venous circulation has long been underestimated in clinical practice and in research into neurological diseases. In this review, we present an overview of the existing evidence that venous abnormalities can play a key role in the development and manifestation of neurological and neurodegenerative diseases. We review the history behind the role of venous diseases in multiple sclerosis and their connections with the disease landmarks, the links of chronic venous hypertension to cerebral hydrodynamics and the role of iron in MS. In addition, we highlight the role of venous abnormalities in other diseases including jugular venous reflux, developmental anomalies, hydrocephalus and cerebrospinal fluid flow. Finally, and based on the information presented throughout the whole review, we conclude with the link between chronic cerebrospinal venous insufficiency and MS and the role and power of magnetic resonance imaging in diagnosing venous anomalies.

Mechanical Ventilation Following Cardiac Surgery in Children

The application of positive pressure mechanical ventilation can result in complex changes in pulmonary and cardiovascular physiology. These cardiopulmonary interactions are particularly important in pediatric patients undergoing surgery for repair or palliation of congenital cardiac defects. In this article, we review the various effects of mechanical ventilation on right and left ventricular preload, afterload and contractility. We also address specific clinical scenarios, such as mechanical ventilation of the uncomplicated patient following cardiac surgery, ventilation of patients with delayed sternal closure, the Norwood procedure, bidirectional and total cavopulmonary anastomoses and patients with right ventricular diastolic dysfunction.

Current Pharmacologic Management of Pediatric Heart Failure in Congenital Heart Disease

Pharmacologic therapy represents the mainstay of treatment for heart failure in children. However, medical therapy for this population is not widely standardized. This is mainly due to the heterogeneity of potential etiologies, the specific challenge of patients with univentricular physiology and the lack of evidence-based prospective randomized clinical trials in pediatric patients. In fact, most current strategies are based largely on extrapolated data from adult studies. Although the classic drugs for heart failure i.e. diuretics, angiotensin-converting enzyme inhibitors, β-blockers and cardiac glycosides, still play a major role in the treatment of pediatric heart failure, newer alternative therapies such as levosimendan and nesiritide are increasingly utilized with promising early results. A systematic literature search of PubMed and MEDLINE databases using relevant terms was performed. All clinical trials and relevant manuscripts about the current pharmacologic treatment of heart failure in the pediatric population were reviewed. New drugs such as levosimendan and nesiritide and the treatment of single-ventricle patients were also included.

Effects of Onion Extract on Endogenous Vascular H2S and Adrenomedulin in Rat Atherosclerosis

Objective: This study aimed to explore the effect of onion extract on endogenous hydrogen sulfide (H2S) and adrenomedulin (ADM) and on atherosclerotic progression in rats with atherosclerosis (AS). Methods And Results: Male Sprague-Dawley rats were randomly divided into control, AS and AS+onion groups. Ultrastructure of aorta and atherosclerotic lesions both in aorta and in coronary artery were detected. Plasma and aortic H2S were detected by using a sulfide- sensitive electrode. Plasma and aortic ADM was determined with radioimmunoassay. Cystathionine-γ-lyase (CSE), calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP1, RAMP2 and RAMP3) mRNA expressions were analysed. Glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and NO synthase (NOS) contents in plasma, SOD1, SOD2 and ICAM-1 expressions in aorta were detected. Rats in the AS group showed marked atherosclerotic lesions both in aorta and in coronary artery but decreased aortic H2S production. Decreased plasma and aortic ADM content, but increased levels of aortic CRLR, RAMP2 and RAMP3 mRNAs were observed. Plasma GSH-PX and SOD were reduced but MDA elevated. Plasma ICAM-1 and NO contents and iNOS activity were increased. Onion extract, however, lessened atherosclerotic lesions and increased endogenous aortic H2S production, but decreased plasma ADM content, aortic ADM content and aortic CRLR, RAMP2 and RAMP3 mRNAs. In addition, it increased plasma GSH-PX level and SOD activities but reduced MDA; it decreased inflammatory response but increased plasma eNOS activity and NO content. Conclusions: Onion extract exerted a marked antiatherogenic effect in association with the up-regulation of the endogenous CSE/H2S pathway but down-regulation of the ADM/CRLR family in atherosclerotic rats.

Heart Transplantation in Biventricular Congenital Heart Disease: Indications, Techniques, and Outcomes

Heart transplantation is an accepted therapeutic modality for end-stage congenital heart disease for both biventricular and univentricular anomalies. Many transplant centers have pushed the limits of transplantation to include patients with high pulmonary vascular resistance, high panel reactive antibodies, positive cross-matches, and ABOincompatibility. Excellent results have been possible, particularly with the development of improved diagnostic and therapeutic algorithms to prevent and treat rejection, infection, and post-transplant lymphoproliferative disease. Late graft failure and chronic rejection remain vexing problems. The vast majority of patients with biventricular congenital heart disease have undergone prior cardiac surgical procedures. Indications for transplantation in this subgroup are primarily progressive refractory heart failure following prior cardiac surgical reconstructive procedures. Contraindications to transplantation mimic those for other forms of end-stage heart disease. A determination of pulmonary vascular resistance is important in listing patients with biventricular congenital heart disease for heart transplantation. Modifications in the implant technique are necessary and vary depending on underlying recipient anatomy. Risk factors for perioperative outcomes in patients with biventricular congenital heart disease include the need for reoperation, the degree of anatomic reconstruction necessary during the implant procedure, and the degree of antibody sensitization, in addition to a number of other recipient and donor factors. Postoperative outcomes and survival are very good but remain inferior to those with cardiomyopathy in most series. In conclusion, patients with end-stage biventricular congenital heart disease represent a complex group of patients for heart transplantation, and require careful evaluation and management to ensure optimal outcomes.

Heart Transplantation for Congenital Heart Disease in the First Year of Life

Successful infant heart transplantation has now been performed for over 25 years. Assessment of long term outcomes is now possible. We report clinical outcomes for322 patients who received their heart transplant during infancy. Actuarial graft survival for newborn recipients is 59% at 25 years. Survival has improved in the most recent era. Cardiac allograft vasculopathy is the most important late cause of death with an actuarial incidence at 25 years of 35%. Posttransplant lymphoma is estimated to occur in 20% of infant recipients by25 years. Chronic kidney disease grade 3 or worse is present in 31% of survivors. The epidemiology of infant heart transplantation has changed through the years as the results for staged repair improved and donor resources remained stagnant. Most centers now employ staged repair for hypoplastic left heart syndrome and similar extreme forms of congenital heart disease. Techniques for staged repair, including the hybrid procedure, are described. The lack of donors is described with particular note regarding decreased donors due to newer programs for appropriate infant sleep positioning and infant car seats. ABO incompatible donors are a newer resource for maximizing donor resources, as is donation after circulatory determination of death and techniques to properly utilize more donors by expanding the criteria for what is an acceptable donor. An immunological advantage for the youngest recipients has long been postulated, and evaluation of this phenomenon may provide clues to the development of accommodation and/or tolerance.

Interaction of the Heart and Lungs During Exercise: Physiology and Pathophysiology in Children with Congenital Heart Disease

The modern era of surgical palliation, perioperative strategies, and myocardial preservation has dramatically altered the long-term outcome for children with congenital heart disease. Even children surgically corrected for more complex heart disease are now surviving to ages where physical activity and sports participation are not only considered but encouraged by pediatric cardiologists secondary to the benefits of regular physical activity on cardiovascular risk factors. In this review, basic cardiovascular and pulmonary responses to exercise performance are reviewed. In addition, the interaction of the cardiovascular and pulmonary systems during exercise in children with simple and complex congenital heart disease is reviewed.

Arrhythmias and Left Ventricular Hypertrabeculation/Noncompaction

Arrhythmias in left ventricular hypertrabeculation/noncompaction (LVHT) comprise sustained or non-sustained ventricular tachycardia (VT) (n=135), atrial fibrillation (AF) (n=96) AV block (n=55) and QT prolongation (n=47). The prevalence differs between children and adults. In children most frequent are WPW-syndrome (n=24), AV block (n=24), VT (n=17) and bradycardia (n=15). In adults most frequent arrhythmias are VT (n=118), AF (n=95), QT prolongation (n=42) and AV block (n=31). Some arrhythmias are more frequently reported in children than in adults like WPW-syndrome (24 vs. 17 patients), second-degree AV block (4 vs. 0 patients), bradycardia (15 vs. 3 patients) and ventricular fibrillation (VF) (9 vs. 5 patients). There are nearly no pediatric cases with AF (1 vs. 95 patients). In 120 patients implantable cardioverters/defibrillators have been implanted for primary or secondary prevention of sudden cardiac death. The pathomechanisms of arrhythmias in LVHT are largely unknown, especially if patients with LVHT and neuromuscular disorders are more prone to arrhythmias than patients without. There is a need to clarify risk factors for VT or VF because 19% of LVHT patients with VT or VF have a normal systolic function and demonstration of systolic dysfunction is no reliable risk marker. Data about long-term follow- up of LVHT patients with implanted cardioverters/defibrillators are necessary since the indication for prophylactic implantation is still unclear. AF in LVHT increases the embolic risk, thus it would be useful to know which LVHT patients who have sinusrhythm at baseline are prone to develop AF in order to start early with anticoagulant therapy.

Arterial Duct Stenting in Congenital Heart Disease with Duct-Dependent Pulmonary Circulation

Background: Despite current trends toward early primary repair, surgical systemic-to-pulmonary artery shunt is still an invaluable palliative option in some high-risk patients with congenital heart disease and duct-dependent pulmonary blood flow. However, maintaining arterial duct patency by stent implantation has been proposed as an effective alternative to surgical palliation in neonates who are unsuitable for primary repair or in whom there is anticipated spontaneous improvement of oxygen saturation as the pulmonary vascular resistance decreases. Recent advances in technology has made arterial duct stenting a safe and feasible tool for short-term palliation of newborns and young infants with this pathophysiologic arrangement. This option might be even more advisable in low-weight newborns, who are at higher risk for surgical palliation or repair and in whom repeat stent dilatations could be effective in tailoring the pulmonary flow to the patients growth. This paper highlights history, methodology and results of this innovative and minimally-invasive palliative option. Methods and Results: Following duct morphology evaluation, the stent is chosen to completely cover the entire ductal length and is dilated to about 75% of the proposed surgical shunt. The procedure can be performed from arterial or venous approach and is successfully completed in the vast majority of cases. Procedural failure mainly depends on ductal tortuosity, typically found in complex conotruncal anomalies such as tetralogy of Fallot or pulmonary atresia with ventricular septal defect. The morbidity rate ranges from 8 to 11% and mainly consists in stent embolization or thrombosis as well as vascular access injury. The mid-term fate of the stented duct is spontaneous, slow and progressive closure within a few months. However, the stented arterial duct promotes similar and more balanced pulmonary artery growth than surgical shunt over a mid-term follow-up. Conclusions: Arterial duct stenting is a technically feasible, safe and effective palliation in congenital heart disease with duct-dependent pulmonary circulation. The stented arterial duct is less durable than conventional surgical shunt but is highly effective in promoting global and balanced pulmonary artery growth.

Genetics of Congenital Heart Disease

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.

Cardiac Resynchronization Therapy in Children

Cardiac Resynchronization therapy has become an important management tool in adults with heart failure and dilated cardiomyopathy. The role of CRT in children with CHF is still unclear. Evidence is slowly emerging in the pediatric cardiology literature that CRT may have an important and useful role in certain select populations with CHF. These include patients with complete heart block who develop pacing-induced cardiomyopathy, certain forms of congenital heart disease associated with systemic ventricular failure (even if the systemic ventricle is a morphologic RV) and in patients with idiopathic dilated cardiomyopathy. Studies in children supporting the use of CRT include many case reports, a few studies of CRT in post-operative patients, and one multi-center registry reporting the use of CRT in children. These papers will be summarized.

Managing the Suicidal Risk in Pregnant Women with Severe and Persistent Psychiatric Disorder: Focus on Antisuicidal Drugs and Somatic Interventions

Suicide remains a significant public issue. Several concordant information exists suggesting that patients diagnosed with severe and persistent psychiatric disorder (SPPD) show relatively higher rates of deaths by suicide compared with patients suffering from other mental illness. In particular, recent researches have demonstrated that, in pregnant women with history of SPPD, a percentage ranging from 13.1% to 33.0% of mothers may have suicidal ideation. Both psychopathological and social specificities of women with SPPD must force clinicians to consider any suicidal expression shown by these mothers as a signal of possible high-lethality suicide attempts. Because of the vast majority of maternal suicidal deaths due to psychiatric disorder usually occur before week 20 of gestation, the necessity exists to analyze and summarize published literature information on the teratogenic risk of antisuicidal drugs and somatic treatments also associated with the property to reduce the rate of self-aggressive behaviors, in order to identify the safest option to treat suicidal risk during early pregnancy. Further, the difficulties of managing the suicidal risk during the last stages of pregnancy are briefly summarized.

Staged Starnes Operation Preserving Patent Ductus Arteriosus for Neonates with Ebsteins Anomaly and Pulmonary Atresia

We herein reported 2 successful neonates with Ebsteins anomaly and small pulmonary arteries undergoing Starnes operation preserving the patent ductus arteriosus. Subsequent Blalock-Taussig shunt was carried out 1 or 2 months after the first surgery. One case had already undergone a successful Fontan operation, and the other had a successful bidirectional Glenn shunt so far. This staged Starnes strategy might be a safe and simple choice for neonates with Ebsteins anomaly and small pulmonary arteries.

Neurocognitive Monitoring and Care During Pediatric Cardiopulmonary Bypass — Current and Future Directions

Neurologic injury in patients with congenital heart disease remains an important source of morbidity and mortality. Advances in surgical repair and perioperative management have resulted in longer life expectancies for these patients. Current practice and research must focus on identifying treatable risk factors for neurocognitive dysfunction, advancing methods for perioperative neuromonitoring, and refining treatment and care of the congenital heart patient with potential neurologic injury. Techniques for neuromonitoring and future directions will be discussed.

Remote Control of Pulmonary Blood Flow

Pulmonary artery banding is a suitable approach for complex heart defects suitable to later bi-ventricular repair, functionally uni-ventricular hearts, and left ventricular retraining. Despite the existence of a very large spectrum of congenital heart defects and clinical situations with potential indication for pulmonary artery banding, the availability of only the conventional surgical technique is still limiting the application of this approach. A solution to the clinical need for an adjustable pulmonary artery banding has been found with a telemetrically controlled adjustable pulmonary artery banding, FloWatch® (EndoArt, Lausanne, Switzerland). This new implantable, wireless, bat-tery free, device (FloWatch®), demonstrated the feasibility of repeated progressive occlusions and re-openings of the de-vice at the wanted percentage of occlusion through a remote control, with long-term experimental evaluation in animals, followed by successful introduction in clinical practice in different institutions. The availability of a reliable adjustable pulmonary artery banding, avoiding any re-operation and the need for pulmonary artery reconstruction at the moment of de-banding, has substantially modified the clinical management of infants with congenital heart defects with increased pulmonary artery blood flow and pressures. New therapeutic strategies can now be considered to expand the applicability of this device.

Twin-to-Twin Transfusion Syndrome: From Placental Anastomoses to Long-Term Neurodevelopmental Outcome

Twin-to-twin transfusion syndrome (TTTS) is a complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity. Placental vascular anastomoses, almost invariably present in monochorionic placentas, are the essential anatomical substrate for the development of TTTS. According to recent studies, different pathophysiological mechanisms may play a role. Diagnosis of TTTS is no longer based on neonatal criteria such as birth weight discordance and hemoglobin difference, but on strict prenatal ultrasound criteria. A significant evolution in prenatal care strategies and management options for patients with TTTS has occurred during the last decade. Endoscopical laser ablation of communicating placental vessels is a new treatment modality that has led to an increase in survival rates. In perinatology, a decrease in mortality rates may be associated with an increase in morbidity rates. Follow-up studies in infants with TTTS are shedding more light on the wide range of morbidity associated with TTTS, such as neurological, cardiac and renal sequelae. This review analyzes the possible pathophysiological mechanisms involved, discusses the latest findings in diagnosis, therapy and prognosis, and focuses on neonatal and pediatric morbidity associated with TTTS.