Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

Background: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD).

The Future of Kawasaki Disease Diagnosis: Liquid Biopsy May Hold the Key.

Kawasaki disease (KD) is a febrile illness characterised by systemic inflammation of small- and medium-sized blood vessels, which commonly occurs in young children. Although self-limiting, there is a risk of developing coronary artery lesions as the disease progresses, with delay in diagnosis and treatment. Unfortunately, the diagnosis of KD continues to remain a clinical dilemma.

Fetal congenital heart diseases: Diagnosis by anatomical scans, echocardiography and genetic tests.

Objective: To determine the distribution of major fetal congenital heart diseases (CHDs) diagnosed antenatally during routine second-trimester obstetric anatomical scans in an unselected population at a single tertiary centre and to characterise and stratify risk factors, genetic diagnosis and long-term health at 4 years old.

Method: A single-centre cohort study of all major fetal CHDs detected on routine obstetric fetal anatomical ultrasound scans between January 2014 and December 2017 was performed in an unselected population. Demographic details, fetal echocardiogram reports, genetic test results, delivery outcomes and postnatal progress were stratified by CHD subtype.

The Associations Between Preoperative Anthropometry and Postoperative Outcomes in Infants Undergoing Congenital Heart Surgery.

Aim: We explored the association between preoperative anthropometry and biochemistry, and postoperative outcomes in infants with CHD after cardiac surgery, as infants with congenital heart disease (CHD) often have feeding difficulties and malnutrition.

Methodology: This was a retrospective review of infants (≤ 1-year-old) who underwent congenital heart surgery. Preoperative anthropometryin terms of preoperative weight-for-age z-score (WAZ), length-for-age z-score (LAZ), as well as preoperative serum albumin and hemoglobin concentrations, were evaluated against 6-month mortality, and morbidity outcomes including postoperative complications, vasoactive inotrope score, duration of mechanical ventilation, length of stay in the pediatric intensive care unit and in hospital, using the logistic regression or median regression models accounting for infant-level clustering.

8-Oxoguanine DNA Glycosylase (OGG1) Deficiency Exacerbates Doxorubicin-Induced Cardiac Dysfunction.

Doxorubicin is an anthracycline widely used for the treatment of various cancers; however, the drug has a common deleterious side effect, namely a dose-dependent cardiotoxicity. Doxorubicin treatment increases the generation of reactive oxygen species, which leads to oxidative stress in the cardiac cells and ultimately DNA damage and cell death. The most common DNA lesion produced by oxidative stress is 7,8-dihydro-8-oxoguanine (8-oxoguanine), and the enzyme responsible for its repair is the 8-oxoguanine DNA glycosylase (OGG1), a base excision repair enzyme.

Causative Variants for Inherited Cardiac Conditions in a Southeast Asian Population Cohort.

Background: Variable penetrance and late-onset phenotypes are key challenges for classifying causal as well as incidental findings in inherited cardiac conditions. Allele frequencies of variants in ancestry-specific populations, along with clinical variant analysis and interpretation, are critical to determine their true significance.

Methods: Here, we carefully reviewed and classified variants in genes associated with inherited cardiac conditions based on a population whole-genome sequencing cohort of 4810 Singaporeans representing Southeast Asian ancestries.

The Role of Epigenetics in Congenital Heart Disease.

Congenital heart disease (CHD) is the most common birth defect among newborns worldwide and contributes to significant infant morbidity and mortality. Owing to major advances in medical and surgical management, as well as improved prenatal diagnosis, the outcomes for these children with CHD have improved tremendously so much so that there are now more adults living with CHD than children. Advances in genomic technologies have discovered the genetic causes of a significant fraction of CHD, while at the same time pointing to remarkable complexity in CHD genetics.

Mending a broken heart: , and models of congenital heart disease.

Birth defects contribute to ∼0.3% of global infant mortality in the first month of life, and congenital heart disease (CHD) is the most common birth defect among newborns worldwide. Despite the significant impact on human health, most treatments available for this heterogenous group of disorders are palliative at best.

Cardiotoxicity After Anthracycline Chemotherapy for Childhood Cancer in a Multiethnic Asian Population.

Anthracyclines are widely used to treat childhood cancers; however, they cause cardiotoxicity. To address the paucity of clinical data from Asian populations, this study investigated the epidemiology of pediatric anthracycline-induced cardiotoxicity, during and after chemotherapy, in a multiethnic Asian population. This was a single-center, retrospective analysis of 458 anthracycline-treated pediatric oncology patients at KK Women's and Children's Hospital, a tertiary children's hospital in Singapore from 2005 through 2015.

Echocardiographic assessment of fetal cardiac function in the uterine artery ligation rat model of IUGR.

Background: Intrauterine growth restriction (IUGR) leads to cardiac dysfunction and adverse remodeling of the fetal heart, as well as a higher risk of postnatal cardiovascular diseases. The rat model of IUGR, via uterine artery ligation, is a popular model but its cardiac sequelae is not well investigated. Here, we performed an echocardiographic evaluation of its cardiac function to determine how well it can represent the disease in humans.

Multiscale modeling of a modified Blalock-Taussig surgery in a patient-specific tetralogy of Fallot.

Tetralogy of Fallot (TOF) is a congenital heart anomaly that causes a drastic reduction in the oxygen level. In this study, we coupled a lumped-parameter model with a patient-specific three-dimensional (3D) model which included a modified Blalock-Taussig (MBT) shunt. By forming a closed loop, we investigated the effects of certain parameters on the flow rates and the pressures at different locations of the developed network.

Human fetal hearts with tetralogy of Fallot have altered fluid dynamics and forces.

Studies have suggested the effect of blood flow forces in pathogenesis and progression of some congenital heart malformations. It is therefore of interest to study the fluid mechanic environment of the malformed prenatal heart, such as the tetralogy of Fallot (TOF), especially when little is known about fetal TOF. In this study, we performed patient-specific ultrasound-based flow simulations of three TOF and seven normal human fetal hearts.

Dynamic Myocardial Response to Exercise in Childhood Cancer Survivors Treated with Anthracyclines.

Background: Anthracycline cardiotoxicity can cause significant long-term morbidity in childhood cancer survivors (CCS), but many CCS do not manifest clinical symptoms until adulthood. The aims of this study were to characterize the dynamic myocardial response to exercise of CCS at long-term follow-up by combining semisupine bicycle exercise stress echocardiography with myocardial imaging techniques and to establish whether semisupine bicycle exercise stress echocardiography could identify CCS with abnormal exercise response.

Methods: This was a single-center prospective cross-sectional study.

Prelisting predictions of early postoperative survival in infant heart transplantation using classification and regression tree analysis.

Infants listed for heart transplantation experience high waitlist and early post-transplant mortality, and thus, optimal allocation of scarce donor organs is required. Unfortunately, the creation and validation of multivariable regression models to identify risk factors and generate individual-level predictions are challenging. We sought to explore the use of data mining methods to generate a prediction model.

The Utility of Cardiopulmonary Exercise Testing for the Prediction of Outcomes in Ambulatory Children With Dilated Cardiomyopathy.

Background: Unlike adult patients, the utility of cardiopulmonary exercise testing (CPET) in children as a prognostic tool is unclear. We sought to examine the associations of CPET with outcomes in children with dilated cardiomyopathy (DCM).

Methods: This was a single-center, retrospective review of children with DCM who underwent CPET.

Intramyocardial Hematoma After Ebstein Anomaly Repair.

Intramyocardial hematoma is a rare condition and is an incomplete form of myocardial rupture, which may occur after myocardial infarction, cardiac surgery, trauma, percutaneous coronary intervention, or spontaneously. We describe a case of a 16-year-old girl with intramyocardial hematoma mimicking an intracavitary thrombus following repair of Ebstein anomaly. The intramyocardial hematoma was incorrectly diagnosed on echocardiography as a right ventricular thrombus, and the true nature of the lesion was only realized during repeat surgical intervention for severe tricuspid regurgitation.

Left Ventricular Myocardial and Hemodynamic Response to Exercise in Young Patients after Endovascular Stenting for Aortic Coarctation.

Background: Endovascular stenting has emerged as a treatment option for children with coarctation of the aortic (CoA), but the impact on left ventricular (LV) function has been poorly documented. The aim of this study was to characterize the LV myocardial and hemodynamic response to exercise in young patients who underwent endovascular stenting for CoA during childhood using semisupine bicycle exercise stress echocardiography.

Methods: This was a single-center prospective cross-sectional study including 30 patients with CoA and 30 age- and gender-matched control subjects who underwent semisupine bicycle exercise stress echocardiography.

Patterns of Mechanical Inefficiency in Pediatric Dilated Cardiomyopathy and Their Relation to Left Ventricular Function and Clinical Outcomes.

Background: Pediatric dilated cardiomyopathy (DCM) is associated with death or transplantation and is typically considered a homogeneous process affecting global left ventricular (LV) function. However, assessment of regional abnormalities that contribute to pumping inefficiencies is lacking. The aim of this study was to define regional strain patterns of mechanical inefficiency in the broader context of LV discoordination (dysfunction and timing abnormalities) and to evaluate their associations with LV function and clinical outcomes.

Diffuse Myocardial Fibrosis in Children After Heart Transplantations: A Magnetic Resonance T1 Mapping Study.

Background: It is unclear whether the myocardium undergoes accelerated fibrotic remodeling in children after heart transplantation (HTx).

Methods: In this prospective study, cardiac magnetic resonance (CMR) studies in 17 patients 1.3 years (median, range 0.

Classic-pattern dyssynchrony and electrical activation delays in pediatric dilated cardiomyopathy.

Background: Progressive heart failure leading to transplantation or death is common in pediatric dilated cardiomyopathy (DCM), and treatment options are limited. Select children with DCM have improved after cardiac resynchronization therapy (CRT), but predicting response is challenging. Nonetheless, considering the frequency of death or transplantation in this population, identifying any candidate would be valuable.

Association of trisomy 18 with hepatoblastoma and its implications.

Unlabelled: Hepatoblastoma is a highly malignant embryonal liver tumor that occurs almost exclusively in infants and toddlers. Trisomy 18 is the second most common autosomal trisomy after trisomy 21 and is generally considered a lethal disorder. Ten cases of hepatoblastoma in children with trisomy 18 have been published to date.

Successful drainage of a traumatic haemopericardium with pericardiocentesis through an intercostal approach.

A case of traumatic haemopericardium, sustained after blunt thoracic trauma, is described in a paediatric patient that was successfully drained by needle pericardiocentesis under 2D-echocardiographic guidance, via an intercostal approach, in the Children's Intensive Care Unit. The patient was haemodynamically unstable with obvious signs of cardiac tamponade. Drainage of the haemopericardium resulted in immediate improvement in haemodynamics.