Valproic Acid-Associated Hyperammonemia: A Systematic Review.

Background: Hyperammonemia is an adverse effect that poses clinical uncertainty around valproic acid (VPA) use. The prevalence of symptomatic and asymptomatic hyperammonemia and its relationship to VPA concentration is not well established. There is also no clear guidance regarding its management.

Biventricular Repair in Borderline Left Hearts: Insights From Cardiac Magnetic Resonance Imaging.

Background: Cardiac magnetic resonance imaging (CMR) may augment 2-dimensional (2D) echocardiography in decision-making for biventricular repair in borderline hypoplastic left hearts.

Objectives: This study evaluates: 1) the relationship between 2D echocardiography and CMR; 2) imaging variables affecting assignment to biventricular vs non-biventricular management; and 3) variables affecting transplant-free biventricular survival.

Methods: We reviewed clinical, echocardiographic, and CMR data in 67 infants, including CMR-determined ascending aortic (AAo) flow and comparable left ventricular end-diastolic volume indexed (LVEDVi) by 2D-echocardiography and CMR.

Current-Era Outcomes of Balloon Aortic Valvotomy in Neonates and Infants.

Background: The optimal initial treatment pathway for aortic valve stenosis remains debated.

Objectives: The objective of this study was to review current outcomes of balloon aortic valvotomy (BAV) in neonates and infants.

Methods: Neonates and infants with a biventricular circulation treated with BAV between 2004 and 2019 were reviewed.

Palliative Care?! But This Child's Not Dying: The Burgeoning Partnership Between Pediatric Cardiology and Palliative Care.

The field of pediatric cardiology has witnessed major changes over the past few decades that have considerably altered patient outcomes, including decreasing mortality rates for many previously untreatable conditions. Despite this, some pediatric cardiology programs are increasingly choosing to partner with their institutional palliative care teams. Why is this? The field of palliative care also has experienced significant shifts over a similar period of time.

Warfarin Reinitiation After Intracranial Hemorrhage: A Case Series of Heart Valve Patients.

Patients with mechanical heart valves are at high thrombotic risk and require warfarin. Among those developing intracranial hemorrhage, limited data are available to guide clinicians with antithrombotic reinitiation. This 13-patient case series of warfarin-associated intracranial hemorrhages found the time to reinitiate antithrombotic therapy (17 days, interquartile range 21.

A case series of left main coronary artery ostial atresia and a review of the literature.

Left main coronary artery ostial atresia (LMCAOA) is a rare congenital anomaly of the coronary arteries. The published literature regarding the current diagnostic and management recommendations are limited. We present three case series of LMCAOA from our institution, including one with a unique association with anomalous origin of left coronary artery (LCA) from pulmonary artery.

Evaluation of Prescribing Appropriateness and Initiatives to Improve Prescribing of Proton Pump Inhibitors at Vancouver General Hospital.

Background: Proton pump inhibitors (PPIs) have proven clinical efficacy for a variety of indications. However, there is emerging evidence of adverse events associated with their long-term use. The emergence of these adverse events has reinforced the need to regularly evaluate the appropriateness of continuing PPI therapy, and to use only the lowest effective dose for the minimally indicated duration.

Dual effects of hyperglycemia on endothelial cells and cardiomyocytes to enhance coronary LPL activity.

In the diabetic heart, there is excessive dependence on fatty acid (FA) utilization to generate ATP. Lipoprotein lipase (LPL)-mediated hydrolysis of circulating triglycerides is suggested to be the predominant source of FA for cardiac utilization during diabetes. In the heart, the majority of LPL is synthesized in cardiomyocytes and secreted onto cell surface heparan sulfate proteoglycan (HSPG), where an endothelial cell (EC)-releasable β-endoglycosidase, heparanase cleaves the side chains of HSPG to liberate LPL for its onward movement across the EC.

Loss of VEGFB and its signaling in the diabetic heart is associated with increased cell death signaling.

Vascular endothelial growth factor B (VEGFB) is highly expressed in metabolically active tissues, such as the heart and skeletal muscle, suggesting a function in maintaining oxidative metabolic and contractile function in these tissues. Multiple models of heart failure have indicated a significant drop in VEGFB. However, whether there is a role for decreased VEGFB in diabetic cardiomyopathy is currently unknown.

Heparanase Overexpression Induces Glucagon Resistance and Protects Animals From Chemically Induced Diabetes.

Heparanase, a protein with enzymatic and nonenzymatic properties, contributes toward disease progression and prevention. In the current study, a fortuitous observation in transgenic mice globally overexpressing heparanase (hep-tg) was the discovery of improved glucose homeostasis. We examined the mechanisms that contribute toward this improved glucose metabolism.

High glucose facilitated endothelial heparanase transfer to the cardiomyocyte modifies its cell death signature.

Aims: The secretion of enzymatically active heparanase (Hep) has been implicated as an essential metabolic adaptation in the heart following diabetes. However, the regulation and function of the enzymatically inactive heparanase (Hep) remain poorly understood. We hypothesized that in response to high glucose (HG) and secretion of Hep from the endothelial cell (EC), Hep uptake and function can protect the cardiomyocyte by modifying its cell death signature.

Endothelial cell-cardiomyocyte crosstalk in diabetic cardiomyopathy.

The incidence of diabetes is increasing globally, with cardiovascular disease accounting for a substantial number of diabetes-related deaths. Although atherosclerotic vascular disease is a primary reason for this cardiovascular dysfunction, heart failure in patients with diabetes might also be an outcome of an intrinsic heart muscle malfunction, labelled diabetic cardiomyopathy. Changes in cardiomyocyte metabolism, which encompasses a shift to exclusive fatty acid utilization, are considered a leading stimulus for this cardiomyopathy.

Cardiomyocyte-endothelial cell control of lipoprotein lipase.

In people with diabetes, inadequate pharmaceutical management predisposes the patient to heart failure, which is the leading cause of diabetes related death. One instigator for this cardiac dysfunction is change in fuel utilization by the heart. Thus, following diabetes, when cardiac glucose utilization is impaired, the heart undergoes metabolic transformation wherein it switches to using fats as an exclusive source of energy.

Cardiomyocyte VEGF Regulates Endothelial Cell GPIHBP1 to Relocate Lipoprotein Lipase to the Coronary Lumen During Diabetes Mellitus.

Objective: Lipoprotein lipase (LPL)-mediated triglyceride hydrolysis is the major source of fatty acid for cardiac energy. LPL, synthesized in cardiomyocytes, is translocated across endothelial cells (EC) by its transporter glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). Previously, we have reported an augmentation in coronary LPL, which was linked to an increased expression of GPIHBP1 following moderate diabetes mellitus.

Lipoprotein lipase and angiopoietin-like 4 - Cardiomyocyte secretory proteins that regulate metabolism during diabetic heart disease.

Cardiac diseases have been extensively studied following diabetes and altered metabolism has been implicated in its initiation. In this context, there is a shift from glucose utilization to predominantly fatty acid metabolism. We have focused on the micro- and macro-environments that the heart uses to provide fatty acids to the cardiomyocyte.

Direct measurement of aortic regurgitation with phase-contrast magnetic resonance is inaccurate: proposal of an alternative method of quantification.

Background: Phase-contrast magnetic resonance (MR) has been widely used for quantification of aortic regurgitation. However there is significant practice variability regarding where and how the blood flow data are acquired.

Objective: To compare the accuracy of flow quantification of aortic regurgitation at three levels: the ascending aorta at the level of the right pulmonary artery (level 1), the aortic valve hinge points at end-diastole (level 2) and the aortic valve hinge points at end-systole (level 3).

Endothelial cell regulation of cardiac metabolism following diabetes.

The earliest change that occurs in the diabetic heart is reduced glucose consumption, with a switch to utilization of fatty acids (FA) predominantly as an energy resource. Although this adaptation might be beneficial in the short-term, over a protracted duration, it is potentially catastrophic given the malicious effects produced by high FA in cardiomyocytes. In this review, we describe how the endothelial cell (EC), a "first-responder" to hyperglycemia, communicates with the underlying cardiomyocyte.

Endothelial cells respond to hyperglycemia by increasing the LPL transporter GPIHBP1.

In diabetes, when glucose uptake and oxidation are impaired, the heart is compelled to use fatty acid (FA) almost exclusively for ATP. The vascular content of lipoprotein lipase (LPL), the rate-limiting enzyme that determines circulating triglyceride clearance, is largely responsible for this FA delivery and increases following diabetes. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein [GPIHBP1; a protein expressed abundantly in the heart in endothelial cells (EC)] collects LPL from the interstitial space and transfers it across ECs onto the luminal binding sites of these cells, where the enzyme is functional.

Endothelial cell heparanase taken up by cardiomyocytes regulates lipoprotein lipase transfer to the coronary lumen after diabetes.

After diabetes, the heart has a singular reliance on fatty acid (FA) for energy production, which is achieved by increased coronary lipoprotein lipase (LPL) that breaks down circulating triglycerides. Coronary LPL originates from cardiomyocytes, and to translocate to the vascular lumen, the enzyme requires liberation from myocyte surface heparan sulfate proteoglycans (HSPGs), an activity that needs to be sustained after chronic hyperglycemia. We investigated the mechanism by which endothelial cells (EC) and cardiomyocytes operate together to enable continuous translocation of LPL after diabetes.

The function of heparanase in diabetes and its complications.

Heparan sulfate proteoglycans are ubiquitous glycoproteins that contain several heparan sulfate polysaccharide side chains attached to a core protein. They function not only as a primary structural component of the extracellular matrix, but also provide a storage depot for bioactive molecules, such as basic fibroblast growth factor, vascular endothelial growth factor and lipoprotein lipase. Heparanase is an endoglycosidase that specifically hydrolyzes heparan sulfate into oligosaccharides.

Hyperglycemia-induced secretion of endothelial heparanase stimulates a vascular endothelial growth factor autocrine network in cardiomyocytes that promotes recruitment of lipoprotein lipase.

Objective: During diabetes mellitus, coronary lipoprotein lipase increases to promote the predominant use of fatty acids. We have reported that high glucose stimulates active heparanase secretion from endothelial cells to cleave cardiomyocyte heparan sulfate and release bound lipoprotein lipase for transfer to the vascular lumen. In the current study, we examined whether heparanase also has a function to release cardiomyocyte vascular endothelial growth factor (VEGF), and whether this growth factor influences cardiomyocyte fatty acid delivery in an autocrine manner.

Infolding of covered stents used for aortic coarctation: report of two cases.

Covered stents have been used for the treatment of aortic coarctation to protect the arterial wall during dilation. Early results have shown them to be safe and effective. We report two cases of infolding of the proximal edge of a covered aortic coarctation stent.

Endothelial heparanase regulates heart metabolism by stimulating lipoprotein lipase secretion from cardiomyocytes.

Objective: After diabetes mellitus, transfer of lipoprotein lipase (LPL) from cardiomyocytes to the coronary lumen increases, and this requires liberation of LPL from the myocyte surface heparan sulfate proteoglycans with subsequent replenishment of this reservoir. At the lumen, LPL breaks down triglyceride to meet the increased demand of the heart for fatty acid. Here, we examined the contribution of coronary endothelial cells (ECs) toward regulation of cardiomyocyte LPL secretion.

Complex Interventions in the Adult with Congenital Heart Disease: Percutaneous Solutions for Venous Baffles, Coronary Artery Fistulas, and Ruptured Sinus of Valsalva Aneurysms.

We describe 3 distinct ACHD lesions amenable to percutaneous repair: (1) venous baffle obstruction in transposition of the great arteries, (2) coronary artery fistulas, and (3) ruptured sinus of Valsalva aneurysms. For each entity, we chronicle the typical clinical scenario and indications for intervention to supplement the technical approach and potential pitfalls with treatment.