Congenital Cardiovascular Disease Research Articles

Introduction: December 2015 HeartWeek Issue of Cardiology in the Young - Highlights of HeartWeek 2015: Challenges and Dilemmas of Pediatric Cardiac Care including Heart Failure in Children and Congenital Abnormalities of the Coronary Arteries.

This December Issue of Cardiology in the Young represents the 13th annual publication in Cardiology in the Young generated from the two meetings that composed "HeartWeek in Florida". "HeartWeek in Florida", the joint collaborative project sponsored by the Cardiac Centre at the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, together with Johns Hopkins All Children's Heart Institute of Saint Petersburg, Florida, averages over 1000 attendees every year and is now recognised as one of the major planks of continuing medical and nursing education for those working in the fields of diagnosis and treatment of cardiac disease in the foetus, neonate, infant, child, and adult. "HeartWeek in Florida" combines the International Symposium on Congenital Heart Disease, organised by All Children's Hospital and Johns Hopkins Medicine, and entering its 16th year, with the Annual Postgraduate Course in Paediatric Cardiovascular Disease, organised by The Children's Hospital of Philadelphia entering its 19th year. This December 2015 Issue of Cardiology in the Young features highlights of the two meetings that compose HeartWeek. Johns Hopkins All Children's Heart Institute's 15th Annual International Symposium on Congenital Heart Disease was held at the Renaissance Vinoy Resort & Golf Club, Saint Petersburg, Florida, from Friday, 6 February, 2015, to Monday, 9 February, 2015. This Symposium was co-sponsored by The American Association for Thoracic Surgery and its special focus was "Congenital Abnormalities of the Coronary Arteries". The Children's Hospital of Philadelphia's annual meeting - Cardiology 2015, the 18th Annual Update on Paediatric and Congenital Cardiovascular Disease: "Challenges and Dilemmas" - was held at the Hyatt Regency Scottsdale Resort and Spa at Gainey Ranch, Scottsdale, Arizona, from Wednesday, 11 February, 2015, to Sunday, 15 February, 2015. We would like to acknowledge the tremendous contributions made to paediatric and congenital cardiac care by Juan Valentín Comas, MD, PhD (13 May, 1960 to 16 June, 2015) and Donald Nixon Ross, FRCS (4 October, 1922 to 7 July, 2014); and therefore, we dedicate this December 2015 HeartWeek Issue of Cardiology in the Young to them.

Manejo quirúrgico de aneurismas poscirugía de coartación aórtica

Introduction and objectiveAortic coarctation is one of the most common congenital cardiovascular diseases and its surgical correction implies an 11% morbidity at long term follow up, among which are the aneurysms and pseudoaneurysms. The purpose of this study is to describe our experience regarding the surgical management of descending aortic aneurysms after surgery for aortic coarctation. MethodsRetrospective analysis of 6 surgeries performed between January 2006 and April 2014 in patients with history of patch aortoplasty for coarctation of the aorta during their childhood and who were diagnosed with descending aortic aneurysm during follow up. ResultsFrom a total of 6 patients, 4 were male and 2 female, the mean age at time of the first surgery for correction of the coarctation of the aorta was 8.2±2.9years, and for the descending aortic aneurysm surgery it was 34.3±5.1years. The mean time elapsed between the first surgery and the re-intervention was 26±5years. Replacement of the descending thoracic aorta was performed using a collagen coated braided polyester prosthesis. Two perfusion strategies were used; in 5 patients surgery was performed using extracorporeal circulation, and in one patient atrial femoral bypass with centrifuge pump was used. Four patients had minor complications (haemothorax, pneumothorax, chylothorax, Horner's syndrome, dysphonia, and headache), and one patient died. All patients were asymptomatic at a mean follow up of 44.8months. ConclusionsIn young patients with few comorbidities, surgery offers a definitive solution for postoperative aneurysms of the descending aorta with an acceptable morbidity and mortality.

Decreasing matrix modulus of PEG hydrogels induces a vascular phenotype in human cord blood stem cells

Adult and congenital cardiovascular diseases are significant health problems that are often managed using surgery. Bypass grafting is a principal therapy, but grafts fail at high rates due to hyperplasia, fibrosis, and atherosclerosis. Biocompatible, cellularized materials that attenuate these complications and encourage healthy microvascularization could reduce graft failure, but an improved understanding of biomaterial effects on human stem cells is needed to reach clinical utility. Our group investigates stem-cell-loaded biomaterials for placement along the adventitia of at-risk vessels and grafts. Here, the effects of substrate modulus on human CD34+ stem cells from umbilical cord blood were evaluated. Cells were isolated by immunomagnetic separation and encapsulated in 3, 4, and 6 weight% PEG hydrogels containing 0.032% gelatin and 0.0044% fibronectin. Gels reached moduli of 0.34, 4.5, and 9.1 kPa. Cell viability approached 100%. Cell morphologies appeared similar across gels, but proliferation was significantly lower in 6 wt% gels. Expression profiling using stem cell signaling arrays indicated enhanced self-renewal and differentiation into vascular endothelium among cells in the lower weight percent gels. Thus, modulus was associated with cell proliferation and function. Gels with moduli in the low kilopascal range may be useful in stimulating cell engraftment and microvascularization of graft adventitia.

Computed Tomography and Magnetic Resonance Imaging in Neonates With Congenital Cardiovascular Disease

Most cardiac diseases in the newborn are caused by structural abnormalities developed in utero. With few exceptions, palliative and definitive treatments require cardiac surgery. The diagnosis and management decisions regarding uncomplicated lesions, such as atrial septal defect, ventricular septal defect, patent ductus arteriosus, and tetralogy of Fallot, can be accomplished by echocardiography alone. Abnormalities beyond the sonographic window, complex 3-dimensional lesions, and detailed functional information require additional imaging. In the past, this was fulfilled by catheter angiography, but today much of the information can be obtained from noninvasive computed tomography angiography and magnetic resonance imaging. This article discusses the design and application of these imaging techniques to the newborn, with emphasis on safety, efficacy, and image quality. Understanding the capabilities and limitations of these techniques is crucial for making rational choices among imaging options based on sound risk and benefit considerations. Important examples of congenital heart lesions have been illustrated with 3-dimensional reconstruction from computed tomography and magnetic resonance images.

Use of 3D prototyping in congenital cardiovascular diseases - initial experience in Hong Kong

Background The use of 3D prototyping in medical practice is becoming increasingly important, due to the development of 3D printing and the recent rapid advances in relevant techniques and equipments. The use of 3D model is especially important in the field of paediatric cardiology and congenital cardiovascular disease, where there is a clear advantage over conventional 2D images in demonstrating complex anatomies and relationships between different structures.

Anxiety determinants in mothers of children with congenital heart diseases undergoing cardiac surgery.

Background:The infants with congenital cardiovascular diseases are faced with too much problems in the case of their ongoing life. Mothers’ stress investigation would be important because can receive the stress from his parents. The aim of the following study was determined anxiety in mothers of children undergoing cardiac surgery.Materials and Methods:The present study was conducted by an analytical study on 69 infants’ mothers who were operated due to their cardiovascular abnormalities in Yazd Afshar Hospital (2012). In this study, some demographic information and influential factors were recorded germane to mothers’ stress, including residential location, history of infant hospitalization or congenital disease as well as some questions in the case of stimuli of the hospital environment, family support, economic situation and the mothers’ awareness of their stress.Results:There are statistically significant differences between mothers’ stress and their age (P = 0.03) and infants’ age (P < 0.0001). There are not statically significant differences between mothers’ stress score mean and their educational level (P = 0.75), the infants’ hospitalization history (P = 0.57), the history of congenital of disease in family (P = 0.24) and the family support in infant care (P = 0.08).Conclusion:Those mothers who asserted the stimuli of the hospital environment, infant and its mother support, economic situation and the mothers’ awareness lack of disease and infant status as strong stress-making stimuli enjoy a stress high mean.

The Role of Medical Air Rescue Services in Medical Transport of Organ Recipients in Poland: Organizational Solutions Supporting Transplantation Medicine.

The aim of this study was to analyze the use of fixed-wing air ambulance (FWAA) services in Poland during the period 2012-2013, with particular emphasis on air transport of organ recipients to transplantation centers. This was a retrospective, cross-sectional analysis of data derived from standard FWAA medical documentation. In the years 2012-2013 there were 500 emergency (52.7%) and 447 elective (47.3%) missions. Children who were 1-10 years old comprised the single largest group in both emergency (EM) and elective (EL) missions, accounting for 17% of all flights. EM transports carried mainly patients aged 49-59 (18.5%), and 35.1% of all EM transports concerned patients with end-stage renal disease qualified as organ recipients who were transported to transplantation centers. With a total of 2278 kidney transplantations performed in Poland within the period analyzed, up to 7.8% recipients were transported by air medical services. For EL flights, the most numerous group were patients aged 1-10 (25.4%) and this group comprised mainly patients with congenital disorders (17.9%) and cardiovascular diseases (15.8%). The average flight duration was similar for both EM and EL groups (41.7±10.5 min vs. 40.4±8.7 min, respectively) (p=NS), as was the average distance covered (321.8±99.4 km vs. 310.5±87.4 km, respectively) (p=NS). In the case of patients with end-stage renal disease, the average distance and flight time were significantly longer than those for all other groups in total: 382.5±96.4 km vs. 302.6±87.3 km (p<0.001) and 74.9±10.2 min vs. 39.7±8.8 min (p<0.001), respectively. The most frequent clinical indication for FWAA transport was end-stage renal disease and most of those flights were carried out as EM. The FWAA service plays a vital role in the organization of pre-transplantation transport to referral centers in Poland. This analysis supports the data for evaluation and potential changes in the Polish distribution and allocation rules for kidney transplantation.

Select Abstracts From the 18th Annual Update on Pediatric and Congenital Cardiovascular Disease, Scottsdale, Arizona, February 11-15, 2015

Restricted accessAbstractFirst published online December 29, 2014Select Abstracts From the 18th Annual Update on Pediatric and Congenital Cardiovascular Disease, Scottsdale, Arizona, February 11-15, 2015Volume 6, Issue 1https://doi.org/10.1177/2150135114562369

Computed Tomography Pulmonary Angiography in Evaluation of Congenital Heart Diseases

Congenital heart disease (CHD) still accounts for signifi cant morbidity and mortality, despite major advances in diagnosis and management. A signifi cant proportion of CHD is still undiagnosed at birth emphasizing the need for a detailed history and meticulous clinical examination. CHD is common and early detection and comprehensive functional and physiological evaluation is very important. Usually echocardiography is the initial diagnostic modality for patients with suspected CHD; in some patients this modality can be limited in its ability to delineate great artery and intracardiac anomalies, pulmonary veins, and coronary arteries. Magnetic resonance imaging is an excellent tool due to its non-ionizing nature and exquisite anatomic and functional capabilities. Computed tomography (CT) pulmonary angiography can be used to assess complex cardiovascular anatomic features both before and after surgery and of a variety of post-treatment complications. In CHD it is very important to have extensive knowledge of cardiovascular anatomy, physiology, and surgical techniques. Recent developments in CT technology primarily by reducing the cardiac motion and the radiation dose usage in CHD evaluation have helped expand the indications for CT usage. It has become a very useful complementary tool to guide the proper medical and surgical management. The purpose of the article is to review the role of CT pulmonary angiography in the evaluation of congenital cardiovascular disease with emphasis on its type, nature and anatomic details. Key words: Cardiac anomalies, congenital heart disease, computed tomography pulmonary angiography, imaging.

Pediatric intensive care outcomes: development of new morbidities during pediatric critical care.

To investigate significant new morbidities associated with pediatric critical care. Randomly selected, prospective cohort. PICU patients from eight medical and cardiac PICUs. This was a randomly selected, prospective cohort of PICU patients from eight medical and cardiac PICUs. The main outcomes measures were hospital discharge functional status measured by Functional Status Scale scores and new morbidity defined as an increase in the Functional Status Scale of more than or equal to 3. Of the 5,017 patients, there were 242 new morbidities (4.8%), 99 PICU deaths (2.0%), and 120 hospital deaths (2.4%). Both morbidity and mortality rates differed (p < 0.001) among the sites. The worst functional status profile was on PICU discharge and improved on hospital discharge. On hospital discharge, the good category decreased from a baseline of 72% to 63%, mild abnormality increased from 10% to 15%, moderate abnormality status increased from 13% to 14%, severe status increased from 4% to 5%, and very severe was unchanged at 1%. The highest new morbidity rates were in the neurological diagnoses (7.3%), acquired cardiovascular disease (5.9%), cancer (5.3%), and congenital cardiovascular disease (4.9%). New morbidities occurred in all ages with more in those under 12 months. New morbidities involved all Functional Status Scale domains with the highest proportions involving respiratory, motor, and feeding dysfunction. The prevalence of new morbidity was 4.8%, twice the mortality rate, and occurred in essentially all types of patients, in relatively equal proportions, and involved all aspects of function. Compared with historical data, it is possible that pediatric critical care has exchanged improved mortality rates for increased morbidity rates.

Collaborative quality improvement in the cardiac intensive care unit: development of the Paediatric Cardiac Critical Care Consortium (PC4).

Despite many advances in recent years for patients with critical paediatric and congenital cardiac disease, significant variation in outcomes remains across hospitals. Collaborative quality improvement has enhanced the quality and value of health care across specialties, partly by determining the reasons for variation and targeting strategies to reduce it. Developing an infrastructure for collaborative quality improvement in paediatric cardiac critical care holds promise for developing benchmarks of quality, to reduce preventable mortality and morbidity, optimise the long-term health of patients with critical congenital cardiovascular disease, and reduce unnecessary resource utilisation in the cardiac intensive care unit environment. The Pediatric Cardiac Critical Care Consortium (PC4) has been modelled after successful collaborative quality improvement initiatives, and is positioned to provide the data platform necessary to realise these objectives. We describe the development of PC4 including the philosophical, organisational, and infrastructural components that will facilitate collaborative quality improvement in paediatric cardiac critical care.

A stepwise model for delivering medical humanitarian aid requiring complex interventions

Cardiothoracic surgeons and practitioners of cardiovascular medicine have a long history of humanitarian aid. Although this is worthwhile at multiple levels and occasionally described in some detail, few efforts have a proven algorithm with demonstrable outcomes that suggest effective educational methodology or clinical results approaching accepted standards in developed countries. Our report provides a stepwise approach to developing highly successful self-sustainable, replicable, and scalable humanitarian congenital cardiac surgical programs, and provides data to allow insight into the efficacy of our model. This program model has evolved over 25 years, during which it has been replicated several times and scaled throughout a vast and populous country. Since 1989, Russia has undergone considerable social, political, and economic changes. Our program model proved successful throughout this time despite dynamic social, political, and medical landscapes. The positive results of our program model indicate that these methodologies may be helpful to others attempting to address the worldwide shortage of cardiovascular care and particularly the complex interventions required in the management of congenital cardiovascular disease.

Pregnancy and cardiovascular risk for women with Turner syndrome.

Most women with Turner syndrome (TS) are infertile due to primary ovarian failure. However, approximately 5% experience spontaneous pregnancy, and recently, more women with TS have used assisted reproductive technology with donated oocytes (ART-OD) to become pregnant. The firstgeneration of Turner patients undergoing ART-OD demonstrated a high rate of fatal aortic dissection in late pregnancy or postpartum. More recent observations, particularly from Nordic countries, suggest a lesser risk of dissection, but confirm a high rate of pre-eclampsia in ART-OD pregnancies. This article reviews publications since 2000 concerning maternal outcomes for pregnancies in women with TS to determine if specific risk factors such as type of pregnancy, age, or presence of underlying congenital cardiovascular disease may identify women at special risk.

HIC2 is a novel dosage-dependent regulator of cardiac development located within the distal 22q11 deletion syndrome region.

22q11 deletion syndrome arises from recombination between low-copy repeats on chromosome 22. Typical deletions result in hemizygosity for TBX1 associated with congenital cardiovascular disease. Deletions distal to the typically deleted region result in a similar cardiac phenotype but lack in extracardiac features of the syndrome, suggesting that a second haploinsufficient gene maps to this interval. The transcription factor HIC2 is lost in most distal deletions, as well as in a minority of typical deletions. We used mouse models to test the hypothesis that HIC2 hemizygosity causes congenital heart disease. We created a genetrap mouse allele of Hic2. The genetrap reporter was expressed in the heart throughout the key stages of cardiac morphogenesis. Homozygosity for the genetrap allele was embryonic lethal before embryonic day E10.5, whereas the heterozygous condition exhibited a partially penetrant late lethality. One third of heterozygous embryos had a cardiac phenotype. MRI demonstrated a ventricular septal defect with over-riding aorta. Conditional targeting indicated a requirement for Hic2 within the Nkx2.5+ and Mesp1+ cardiovascular progenitor lineages. Microarray analysis revealed increased expression of Bmp10. Our results demonstrate a novel role for Hic2 in cardiac development. Hic2 is the first gene within the distal 22q11 interval to have a demonstrated haploinsufficient cardiac phenotype in mice. Together our data suggest that HIC2 haploinsufficiency likely contributes to the cardiac defects seen in distal 22q11 deletion syndrome.

Asymptomatic severe aortic coarctation at old age

Aortic coarctation (AC) is a relatively frequent congenital cardiovascular disease, defined as a narrowing or constriction of the lumen of the aorta [1]. Clinical presentation of affected patients depends on the site and extent of obstruction and associated cardiovascular anomalies. AC is generally diagnosed in early childhood, but sometimes it might be detected in apparently healthy adults, especially when efficient collateral vessels compensate this vascular anomaly. However, survival of non-corrected severe AC is impaired, with mortality rates as high as 90% at the end of the fifth decade of life [2].

Select Abstracts From Cardiology 2014

Restricted accessAbstractFirst published online January 8, 2014Select Abstracts From Cardiology 2014: The 17th Annual Update on Pediatric and Congenital Cardiovascular Disease Orlando, Florida, February 19-23, 2014Volume 5, Issue 1https://doi.org/10.1177/2150135113516281

The Forensic Implications of Turner's Syndrome

Turner's syndrome, the most common sex chromosome disorder of females, is caused by complete or partial loss of one X chromosome and is associated with a wide range of internal and external manifestations and increased mortality rates (three to nine times the background population). While individuals with Turner's syndrome may survive for many decades, premature and unexpected deaths can occur that bring decedents to the attention of forensic examiners. Causes of death in Turner's syndrome are often linked to underlying cardiovascular conditions such as aortic dissection, congenital cardiovascular disease, ischemic heart, and cerebrovascular disease, but deaths due to noncardiac causes also occur with increased frequency. The latter include epilepsy, diabetes mellitus, chronic renal disease, pneumonia, chronic liver disease, and malignancy. Thus, the autopsy evaluation of these cases requires careful examination of all major organ systems, with the consideration of confirmatory cytogenetic testing.

Cardiovascular manifestations of Williams syndrome: Imaging findings

Williams syndrome is a relatively common (1 in 10,000 live births) genetic disorder caused by a deletion involving chromosome 7 that results in a variety of clinically significant abnormalities, including developmental delay, behavioral changes, hypercalcemia, and a distinct "elfin" facial appearance. Congenital cardiovascular disease that presents in childhood is responsible for most of the morbidity and mortality associated with this disorder. The purpose of this pictorial essay is to review imaging findings of some of the more common cardiovascular manifestations of Williams syndrome and to highlight some of the unique anatomic variations that can be seen in these patients.

P11.03: Low‐level 45,X/46,XX mosaicism up to 10% of aneuploidy seems not to be associated with higher prevalence of congenital cardiovascular disease and thoracic aorta dilatation: a prospective study

<scp>P11</scp>.03: Low‐level 45,X/46,<scp>XX</scp> mosaicism up to 10% of aneuploidy seems not to be associated with higher prevalence of congenital cardiovascular disease and thoracic aorta dilatation: a prospective study

Ventricular septal defects in mice targeted deletion of versican in vascular smooth muscle cells

Purpose: To determine the function of versican (Vcan) in the cardiovascular system in vivo, we generated the versican conditional knockout mice, in which the Vcan gene was selectively ablated in vascular smooth muscle cells (SMCs). Versican is a large secreted chondroitin sulfate proteoglycan, which is important for cardiac development, and is also implicated in adult cardiovascular disease. Four splice variants of versican (V0, V1, V2, V3) have been identified, each containing two invariant domains, an N-terminal G1 domain that interact with hyaluronan, and a C-terminal G3 domain that interact with other extracellular matrix (ECM) molecules. As it has been reported that versican knockout mice died of cardiac defects at E10.5, the role of versican in cardiac development and disease has not been completely elucidated. Methods: SM22-Cre+:Vcanflox/flox conditional knockout mice were generated by combining Cre/loxP with a Flp/FRT system. In brief, a targeting vector harboring the Vcan flox allele was constructed by franking exon2 including start codon with loxP sites in the combination of a PGK-neoR cassette flanked by the FRT sequence. After obtaining Vcanflox/flox mice, they crossbred with SM22-Cre Tg mice, and the Vcan gene was selectively ablated in SMCs. The expression of different cardiac markers and ECM molecules were analyzed using histological and biochemical methods. Results: SM22-Cre+:Vcanflox/flox mice were viable and fertile, and they can reach their lifespan. The hearts in SM22-Cre+:Vcanflox/flox newborn mice showed normal cardiac looping; however, exhibited dilated heart and ventricular septal defects (VSD). The expressions of the a-actinin in their ventricular wall, which is a marker of cardiac muscle cell, decreased compared to wild type. Furthermore, though their arterial walls were thinner than wild type, elastic lamina was formed. Conclusions: Previously we generated the versican mutant mice (VcanΔ3/Δ3) whose versican lacked the A-subdomain of the G1 domain. The VcanΔ3/Δ3 mice died at neonatal period day 0, exhibiting the dilated heart and VSD. In this study, the targeted deletion of versican in SMCs leads to moderate cardiovascular defects with the dilated heart and VSD. SMCs transduce a variety of signals from a highly structured ECM that modulate cellular differentiation, migration, and proliferation. Our results suggest that the versican expression from SMCs is important for the cardiovascular development, and this study can lead to the treatment for congenital cardiovascular disease.