Circulation

Background: Even on optimal therapy, many patients with heart failure and atrial fibrillation experience cardiovascular complications. Additional treatments are needed to reduce these events, especially in patients with heart failure and preserved left ventricular ejection fraction (HFpEF). Methods: This prespecified subanalysis of the randomized EAST - AFNET 4 trial assessed the effect of systematic, early rhythm control therapy (ERC; using antiarrhythmic drugs or catheter ablation) compared to usual care (UC, allowing rhythm control therapy to improve symptoms) on the two primary outcomes of the trial and on selected secondary outcomes in patients with heart failure, defined as heart failure symptoms NYHA II-III or left ventricular ejection fraction [LVEF] <50%...

Background: Ischemic and hemorrhagic cerebrovascular accidents (ICVA and HCVA, respectively) remain common among patients with centrifugal-flow left ventricular assist devices (CF-LVADs), despite improvements in survival and device longevity. Therefore, the incidence of neurological adverse events (NAEs) associated with two contemporary CF-LVADs, the Abbott HeartMate3® (HM3) and the Medtronic HeartWare™ HVAD® (HVAD), were compared. Methods: Using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), we collected data on adult patients who received a CF-LVAD as a primary isolated implant between 1/1/2017 and 9/30/2019...

Lower extremity peripheral artery disease (PAD) affects >230 million adults worldwide and is associated with increased risk of various adverse clinical outcomes (other cardiovascular diseases such as coronary heart disease and stroke and leg outcomes such as amputation). Despite its prevalence and clinical importance, PAD has been historically underappreciated by health care professionals and patients. This underappreciation seems multifactorial (eg, limited availability of the first-line diagnostic test, the ankle-brachial index, in clinics; incorrect perceptions that a leg vascular disease is not fatal and that the diagnosis of PAD would not necessarily change clinical practice)...

Background: How the extracellular matrix (ECM) microenvironment modulates the contractile phenotype of vascular smooth muscle cells (VSMCs) and confers vascular homeostasis remains elusive. Methods: To explore the key ECM proteins in the maintenance of the contractile phenotype of VSMCs, we applied protein-protein interaction (PPI) network analysis to explore novel ECM proteins associated with the VSMC phenotype. By combining in vitro and in vivo genetic mice vascular injury model, we identified nidogen-2, a basement membrane (BM) glycoprotein, as a key ECM protein for maintenance of vascular smooth muscle cell identity...

Myocarditis has been recognized as a rare complication of coronavirus 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males. According to the U.S. Centers for Disease Control (CDC), myocarditis/pericarditis rates are approximately 12.6 cases per million doses of second dose mRNA vaccine among 12-39-year-olds. In reported cases, patients with myocarditis invariably presented with chest pain, usually 2-3 days after a second dose of mRNA vaccination and had elevated cardiac troponin levels...

Background: Ischemia-reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the build-up of acidic metabolites results in decreased intracellular and extracellular pH that can reach as low as 6.0-6.5. The resulting tissue acidosis exacerbates ischemic injury and significantly impacts cardiac function. Methods: We used genetic and pharmacological methods to investigate the role of acid sensing ion channel 1a (ASIC1a) in cardiac IRI at the cellular and whole organ level...

Background: Although angina is common in patients with stable coronary artery disease (CAD), limited data are available on its prevalence, natural evolution, and outcomes in the era of effective cardiovascular drugs and widespread use of coronary revascularization. Methods: Using data from 32 691 patients with stable CAD from the prospective observational CLARIFY registry, anginal status was mapped each year in patients without new coronary revascularization or new myocardial infarction. The use of medical interventions in the year preceding angina resolution was explored...

Background: Cardiovascular risk in diabetes remains elevated despite glucose lowering therapies. We hypothesised that hyperglycaemia induces trained immunity in macrophages, promoting persistent pro-atherogenic characteristics. Methods: Bone marrow derived macrophages from control and mice with diabetes were grown in physiological glucose (5 mM) and subject to RNA-sequencing (n=6), ATAC-sequencing (n=6) and ChIP-sequencing (n=6) for determination of hyperglycaemia-induced trained immunity. Bone marrow transplantation from mice with (n=9) or without (n=6) diabetes into [normoglycaemic] Ldlr -/- mice was used to assess its functional significance in vivo ...

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No abstract text is available yet for this article.

No abstract text is available yet for this article.

Background: The etiology of life-threatening cardiopulmonary diseases such as Pulmonary Hypertension (PH) and Chronic Obstructive Pulmonary Disease (COPD) originates from a complex interplay of environmental factors and genetic predispositions, which is not fully understood. Likewise, little is known about developmental abnormalities or epigenetic dysregulations that might predispose for PH or COPD in adult individuals. Methods: To identify pathology-associated epigenetic alteration in diseased lung tissues, we screened a cohort of human PH and COPD patients for changes of histone modifications by immunofluorescence staining...

There is growing evidence that people who are transgender and gender diverse (TGD) are impacted by disparities across a variety of cardiovascular risk factors compared with their peers who are cisgender. Prior literature has characterized disparities in cardiovascular morbidity and mortality as a result of a higher prevalence of health risk behaviors. Mounting research has revealed that cardiovascular risk factors at the individual level likely do not fully account for increased risk in cardiovascular health disparities among people who are TGD...

Background: The necrotic core partly formed by ineffective efferocytosis increases the risk of an atherosclerotic plaque rupture. microRNAs contribute to necrotic core formation by regulating efferocytosis and macrophage apoptosis. Atherosclerotic plaque rupture occurs at increased frequency in the early morning, indicating diurnal changes in plaque vulnerability. Although circadian rhythms play a role in atherosclerosis, the molecular clock output pathways that control plaque composition and rupture susceptibility are unclear...

Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is the gold standard for non-invasive myocardial tissue characterization, but requires intravenous contrast agent administration. It is highly desired to develop a contrast-agent-free technology to replace LGE for faster and cheaper CMR scans. Methods: A CMR Virtual Native Enhancement (VNE) imaging technology was developed using artificial intelligence. The deep learning model for generating VNE uses multiple streams of convolutional neural networks to exploit and enhance the existing signals in native T1-maps (pixel-wise maps of tissue T1 relaxation times) and cine imaging of cardiac structure and function, presenting them as LGE-equivalent images...

Background: Current paradigms suggest that nitric oxide (NO) produced by endothelial cells (ECs) via endothelial nitric oxide synthase (eNOS) in the vessel wall is the primary regulator of blood flow and blood pressure. However, red blood cells (RBCs) also carry a catalytically active eNOS, but its role is controversial and remains undefined. This study aimed to elucidate the functional significance of red cell eNOS compared to EC eNOS for vascular hemodynamics and NO metabolism. Methods: We generated tissue-specific "loss-" and "gain-of-function" models for eNOS by using cell-specific Cre-induced gene inactivation or reactivation...

Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a histopathology-based diagnosis such as in the Dallas criteria. Given the invasive and low-sensitivity nature of endomyocardial biopsy, its diagnostic focus shifted to a reliance on clinical suspicion. With the advances of cardiac magnetic resonance, an examination of the whole heart in vivo has gained acceptance in the pursuit of a diagnosis of myocarditis...

Background: Cardiovascular diseases (CVD) and chronic kidney disease (CKD) are highly prevalent, aggravate each other, and account for substantial mortality. Both conditions are characterized by activation of the innate immune system. The alarmin IL-1α is expressed in a variety of cell types promoting (sterile) systemic inflammation. The aim of the present study was to examine the role of IL-1α in mediating inflammation in the setting of acute myocardial infarction (AMI) and CKD. Methods: We assessed the expression of IL-1α on the surface of monocytes from patients with AMI and patients with CKD and determined its association with atherosclerotic CVD events during follow-up in an explorative clinical study...

Cardiac catheterization procedures have rapidly evolved and expanded in scope and techniques over the past few decades. However, although some practices have emerged based on evidence, many traditions have persisted based on beliefs and theoretical concerns. The aim of this review is to highlight common preprocedure, intraprocedure, and postprocedure catheterization laboratory practices where evidence has accumulated over the past few decades to support or discount traditionally held practices.

Background: Activin receptor-like kinase 1 (ALK1) is an endothelial transmembrane serine threonine kinase receptor for BMP family ligands that plays a critical role in cardiovascular development and pathology. Loss-of-function mutations in the ALK1 gene cause type 2 hereditary hemorrhagic telangiectasia (HHT), a devastating disorder that leads to arteriovenous malformations (AVMs). Here we show that ALK1 controls endothelial cell polarization against the direction of blood flow and flow-induced endothelial migration from veins through capillaries into arterioles...