Identification of a SCN5A Genetic Variant Associated With Type 1 Brugada Syndrome (BrS) in a Family.

The Brugada pattern is associated with a genetic disorder characterized by ST-segment elevation in the right precordial leads on electrocardiogram (EKG) in the absence of structural heart disease. Patients with the Brugada pattern have an increased risk for ventricular tachyarrhythmia and sudden cardiac death. Loss-of-function mutations in the SCN5A gene which encodes the alpha subunit of the cardiac sodium channel have been associated with Brugada syndrome (BrS).

Implementation of Novel Lipid Therapies in a Refractory Heterozygous Familial Hypercholesterolemia Patient With Atherosclerotic Disease.

Compound heterozygous familial hypercholesterolemia patients are phenotypically similar to homozygous familial hypercholesterolemia patients, present with significant elevations of low-density lipoprotein cholesterol, and are at risk of cardiovascular disease. Although new treatment options are emerging, the stepwise approach to the use of different therapies has not been well described. ().

Acute COVID-19 Pneumonia Unmasking a Large Left Atrial Myxoma.

This is a case of acute coronavirus disease 2019 pneumonia that revealed an incidental large atrial myxoma with obstructive physiology that ultimately required emergent treatment with a definitive atriotomy and resection of the underlying myxoma.

Management of COVID-19 myopericarditis with reversal of cardiac dysfunction after blunting of cytokine storm: a case report.

Background: Coronavirus disease 2019 (COVID-19) is a syndrome that has been associated with multiple cardiac complications including myopericarditis. The pathophysiology and treatment for myopericarditis in the setting of COVID-19 infection is still under investigation.

Case Summary: We present a case of a 60-year-old male admitted for dyspnoea due to COVID-19.

A Novel Treatment for a Rare Cause of Cardiogenic Shock.

Drug rash with eosinophilia and systemic symptoms (DRESS)-associated myocarditis is a rare but life-threatening adverse drug reaction with a very high mortality rate and no effective therapies. We report a case of DRESS-associated myocarditis complicated by cardiogenic shock successfully treated with a novel targeted therapy. ().

CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation.

Factors that underlie the clustering of metabolic syndrome traits are not fully known. We performed whole-exome sequence analysis in kindreds with extreme phenotypes of early-onset atherosclerosis and metabolic syndrome, and identified novel loss-of-function mutations in the gene encoding the pancreatic elastase chymotrypsin-like elastase family member 2A (CELA2A). We further show that CELA2A is a circulating enzyme that reduces platelet hyperactivation, triggers both insulin secretion and degradation, and increases insulin sensitivity.

Application of Whole Exome Sequencing in the Clinical Diagnosis and Management of Inherited Cardiovascular Diseases in Adults.

Background: With the advent of high throughput sequencing, the identification of genetic causes of cardiovascular disease (CVD) has become an integral part of medical diagnosis and management and at the forefront of personalized medicine in this field. The use of whole exome sequencing for clinical diagnosis, risk stratification, and management of inherited CVD has not been previously evaluated.

Methods And Results: We analyzed the results of whole exome sequencing in first 200 adult patients with inherited CVD, who underwent genetic testing at the Yale Program for Cardiovascular Genetics.

Transcription and translation of human F11R gene are required for an initial step of atherogenesis induced by inflammatory cytokines.

Background: The F11 Receptor (F11R; aka JAM-A, JAM-1) is a cell adhesion protein present constitutively on the membrane surface of circulating platelets and within tight junctions of endothelial cells (ECs). Previous reports demonstrated that exposure of ECs to pro-inflammatory cytokines causes insertion of F11R molecules into the luminal surface of ECs, ensuing with homologous interactions between F11R molecules of platelets and ECs, and a resultant adhesion of platelets to the inflamed ECs. The main new finding of the present report is that the first step in this chain of events is the de-novo transcription and translation of F11R molecules, induced in ECs by exposure to inflammatory cytokines.

Silencing of the F11R gene reveals a role for F11R/JAM-A in the migration of inflamed vascular smooth muscle cells and in atherosclerosis.

Rationale And Objective: Our previous studies have determined that the F11 receptor (F11R; aka JAM-A) exerts a critical force in the adhesion of human platelets to inflamed endothelial cells (ECs), and thus can play a significant role in the initiation of atherosclerotic plaque formation. In the present study, we focus on a subsequent event in plaque development--the migration of smooth muscle cells (SMCs) from the media to the intima of inflamed vessels. Here we report our investigation of the expression of F11R in atherosclerotic arteries of coronary artery disease (CAD) patients, and of the role of F11R in the migration of SMCs involved in atherogenesis.

The F11 receptor (F11R/JAM-A) in atherothrombosis: overexpression of F11R in atherosclerotic plaques.

F11R is the gene name for an adhesion protein, called the F11-receptor, aka JAM-A, which under normal physiological conditions is expressed constitutively on the surface of platelets and localized within tight junctions of endothelial cells (EC). Previous studies of the interactions between human platelets and EC suggested that F11R/JAM-A plays a crucial role in inflammatory thrombosis and atherosclerosis. The study reported here obtained in-vivo confirmation of this conclusion by investigating F11R/JAM-A protein and mRNA in patients with aortic and peripheral vascular disease and in an animal model of atherosclerosis.