Tricuspid Atresia

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.

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.

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.

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.

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.

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.