Background:GATA4 (GATA-binding protein 4), a zinc finger–containing, DNA-binding transcription factor, is essential for normal cardiac development and homeostasis in mice and humans, and mutations in this gene have been reported in human heart defects. Defects in alternative splicing are associated with many heart diseases, yet relatively little is known about how cell type– or cell state–specific

Bendopnea is a clinical symptom of advanced heart failure (HF) with uncertain prognostic value. We aimed to evaluate whether bendopnea and the change in oxygen saturation when bending forward (Bending Oxygen Saturation Index -BOSI-) are associated with adverse outcomes in ambulatory chronic heart failure (CHF) patients.

Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium-glucose

Cardiac amyloidosis (CA) is now recognized as an important cause of heart failure. Increased wall thickness and diastolic dysfunction of the left ventricle (LV) are the most easily detectable manifestations of CA, but amyloid accumulates in all cardiac structures. Involvement of the left and right atria may be due to the haemodynamic effects of ventricular diastolic dysfunction, the effects of amyloid

When a cell is stressed, it often accumulates clumps of misfolded proteins, which in turn trigger reduced protein translation and reprogramming of gene transcription—collectively known as the unfolded protein response (UPR). Because platelets have no nuclei, and thus no transcription, it was possible they lacked a UPR, but Jain and colleagues now show this is not the case. They found that treating

Dr Kanika Jain is an Associate Research Scientist at Yale University School of Medicine. Her fascination with proteostasis and multifaceted Unfolded Protein Response (UPR) began during her PhD. As a postdoctoral fellow under the mentorship of Dr John Hwa, she became interested in the anucleate platelets. She now investigates the role of UPR and stress induced signaling in regulation of platelet function

In the article by Roh et al, “Heart Failure with Preserved Ejection Fraction: Heterogeneous Syndrome, Diverse Preclinical Models,” which was published in the June 10, 2022 issue (Circ Res. 2022;130:1906–1925, doi: 10.1161/CIRCRESAHA.122.320257), a correction was needed. The below reference 117 should be cited on page 10: Sharp TE 3rd, Scarborough AL, Li Z, Polhemus DJ, Hidalgo HA, Schumacher JD, Matsuura

Aims Exercise confers protection against cardiovascular ageing, but the mechanisms remain largely unknown. This study sought to investigate the role of fibronectin type-III domain-containing protein 5 (FNDC5)/irisin, an exercise-associated hormone, in vascular ageing. Moreover, the existence of FNDC5/irisin in circulating extracellular vesicles (EVs) and their biological functions was explored. Methods

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure (HF) and mortality worldwide. Advances in non-invasive diagnosis, coupled with the development of effective treatments, have shifted ATTR-CA from a rare and untreatable disease to a relatively prevalent condition that clinicians should consider on a daily basis. Amyloid fibril formation results from age-related

Aims Trends in characteristics, management, and survival in out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) were studied in the Swedish Cardiopulmonary Resuscitation Registry (SCRR). Methods and results The SCRR was used to study 106 296 cases of OHCA (1990–2020) and 30 032 cases of IHCA (2004–20) in whom resuscitation was attempted. In OHCA, survival increased from 5.7%

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been used to treat patients with type 2 diabetes since 2005 and have become popular because of the efficacy and durability in relation to glycaemic control in combination with weight loss in most patients. Today in 2022, seven GLP-1 RAs, including oral semaglutide are available for treatment of type 2 diabetes. Since the efficacy in relation

Rationale:Myocardial infarction (MI) is one of the most dangerous adverse cardiovascular events. Our previous study found that lysophosphatidic acid (LPA) is increased in human peripheral blood after MI, and LPA has a protective effect on the survival and proliferation of various cell types. However, the role of LPA and its receptors in MI is less understood.Objectives:To study the unknown role of

Background:Ischemic heart disease is a major global public health challenge, and its functional outcomes remain poor. Lysine crotonylation (Kcr) was recently identified as a post-translational histone modification that robustly indicates active promoters. However, the role of Kcr in myocardial injury is unknown. In this study, we aimed to clarify the pathophysiological significance of Kcr in cardiac

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Childbearing cardiologists face a number of challenges before, during and after pregnancy, including radiation concerns, infertility, pregnancy-related complications, and inadequate parental leave and return-to-work structures. Institutions can promote an equitable work environment by creating policies to mitigate these challenges.

Background:Novel targeted treatments increase the need for prompt hypertrophic cardiomyopathy (HCM) detection. However, its low prevalence (0.5%) and resemblance to common diseases present challenges that may benefit from automated machine learning–based approaches. We aimed to develop machine learning models to detect HCM and to differentiate it from other cardiac conditions using ECGs and echocardiograms

Transthyretin amyloid cardiomyopathy (ATTR-CM) is predominantly diagnosed in men. The few available studies suggest affected women have a more favourable cardiac phenotype. We aimed to characterise sex differences among consecutive patients with non-hereditary and two prevalent forms of hereditary ATTR-CM diagnosed over a 20-year period.

To investigate incidence, predictors and prognostic implications of longitudinal New York Heart Association (NYHA) class changes (i.e. improving or worsening vs. stable NYHA class) in heart failure (HF) across the ejection fraction (EF) spectrum.

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Sleep-disordered breathing (SDB), characterized by specific underlying physiological mechanisms, comprises obstructive and central pathophysiology, affects nearly 1 billion individuals worldwide, and is associated with excessive cardiopulmonary morbidity. Strong evidence implicates SDB in cardiac arrhythmogenesis. Immediate consequences of SDB include autonomic nervous system fluctuations, recurrent

Aims The presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFpEF). To date, neither established heart failure therapies nor pulmonary vasodilators proved beneficial. This study investigated the efficacy of chronic treatment with the oral soluble guanylate cyclase stimulator riociguat in patients with PH-HFpEF. Methods

To evaluate short-term changes in tricuspid regurgitation (TR) after transcatheter edge-to-edge repair (M-TEER) in secondary mitral regurgitation (SMR), their predictors and impact on mortality.

Aims We investigated the association of fasting triglycerides with cardiovascular disease (CVD) mortality. Methods and results This cohort study included US adults from the National Health and Nutrition Examination Surveys from 1988 to 2014. CVD mortality outcomes were ascertained by linkage to the National Death Index records. Cox proportional hazards models were used to estimate hazard ratios (HRs)

Aims Hypertension (HTN) can lead to heart and kidney damage. The gut microbiota has been linked to HTN, although it is difficult to estimate its significance due to the variety of other features known to influence HTN. In the present study, we used germ-free (GF) and colonized (COL) littermate mice to quantify the impact of microbial colonization on organ damage in HTN. Methods and results Four-week-old

Background:Inflamed endothelial cells (ECs) trigger atherogenesis, especially at arterial regions experiencing disturbed blood flow. UCP2 (Uncoupling protein 2), a key mitochondrial antioxidant protein, improves endothelium-dependent relaxation in obese mice. However, whether UCP2 can be regulated by shear flow is unknown, and the role of endothelial UCP2 in regulating inflammation and atherosclerosis

Background:Timely and complete restoration of blood flow is the most effective intervention for patients with acute myocardial infarction. However, the efficacy is limited by myocardial ischemia-reperfusion (MI/R) injury. PDE4 (phosphodiesterase-4) hydrolyzes intracellular cAMP and it has 4 subtypes A-D. This study aimed to delineate the role of PDE4B (phosphodiesterase-4 subtype B) in MI/R injury

BACKGROUND:Atherosclerotic cardiovascular disease is the main cause of mortality worldwide and is strongly influenced by circulating low-density lipoprotein (LDL) cholesterol levels. Only a few genes causally related to plasma LDL cholesterol levels have been identified so far, and only 1 gene, ANGPTL3, has been causally related to combined hypocholesterolemia. Here, our aim was to elucidate the genetic

Worsening renal function may impact long-term outcomes in heart failure (HF). However, little is known about the longitudinal trajectories in renal function in relation to the HF hospitalization or how this high-risk clinical event impacts renal outcomes.

Aims To investigate the impact of patiromer on serum potassium level and its ability to enable specified target doses of renin-angiotensin-aldosterone system inhibitor (RAASi) use in patients with heart failure and reduced ejection fraction (HFrEF). Methods and results A total of 1642 patients with HFrEF and current or a history of RAASi-related hyperkalemia were screened and 1195 were enrolled in

Here we review the highlights of cardiovascular basic science in published in 2021 and early 2022 on behalf of the European Society of Cardiology Council for Basic Cardiovascular Science. We begin with non-coding RNAs which have emerged as central regulators cardiovascular biology, and then discuss how technological developments in single-cell ‘omics are providing new insights in cardiovascular development

Rationale:Jacobsen syndrome is a rare chromosomal disorder caused by deletions in the long arm of human chromosome 11, resulting in multiple developmental defects including congenital heart defects. Combined studies in humans and genetically engineered mice implicate that loss of ETS1 (E26 transformation specific 1) is the cause of congenital heart defects in Jacobsen syndrome, but the underlying molecular

BACKGROUND:Accumulating evidence has shown that disorders in the gut microbiota and derived metabolites affect the development of atherosclerotic cardiovascular disease (ASCVD). However, which and how specific gut microbial metabolites contribute to the progression of atherosclerosis and the clinical relevance of their alterations remain unclear.METHODS:We performed integrated microbiome–metabolome

Definition and management of arterial hypertension in children and adolescents are uncertain, due to different positions of current guidelines. The European Society of Cardiology task-force, constituted by Associations and Councils with interest in arterial hypertension, has reviewed current literature and evidence, to produce a Consensus Document focused on aspects of hypertension in the age range

A bidirectional relationship exists between hypertension and psychiatric disorders, including unipolar and bipolar depression, anxiety, post-traumatic stress disorder (PTSD), psychosis, schizophrenia, mania, and dementia/cognitive decline. Repurposing of antihypertensive drugs to treat mental disorders is thus being explored. A systematic knowledge of the mechanisms of action and clinical consequences

Andersen Tawil Syndrome (ATS) is a rare inheritable disease associated with loss-of-function mutations in KCNJ2, the gene coding the strong inward rectifier potassium channel Kir2.1, which forms an essential membrane protein controlling cardiac excitability. ATS is usually marked by a triad of periodic paralysis, life-threatening cardiac arrhythmias and dysmorphic features, but its expression is variable

BACKGROUND:Cellular rejection after heart transplantation imparts significant morbidity and mortality. Current immunosuppressive strategies are imperfect, target recipient T cells, and have adverse effects. The innate immune response plays an essential role in the recruitment and activation of T cells. Targeting the donor innate immune response would represent the earliest interventional opportunity

BACKGROUND:Understanding the predictive utility of previously derived polygenic risk scores (PRSs) for long-term risk of coronary heart disease (CHD) and its additive value beyond traditional risk factors can inform prevention strategies.METHODS:Data from adults 20 to 59 years of age who were free of CHD from the FOS (Framingham Offspring Study) and the ARIC (Atherosclerosis Risk in Communities) study

BACKGROUND:Metabolic disorder increases the risk of abdominal aortic aneurysm (AAA). NRs (nuclear hormone receptors) have been increasingly recognized as important regulators of cell metabolism. However, the role of NRs in AAA development remains largely unknown.METHODS:We analyzed the expression profile of the NR superfamily in AAA tissues and identified NR1D1 (NR subfamily 1 group D member 1) as

Atrial fibrillation (AF) is the most common arrhythmia among patients with heart failure (HF), and HF is the most common cause of death for patients presenting with clinical AF. AF is frequently associated with pathological atrial myocardial dysfunction and remodeling, a triad that has been called atrial myopathy. AF can be the cause or consequence of clinical HF, and the directionality varies between

Highlights from the June issues of the subspecialty journals span a variety of topics. The safety of pulsed field ablation, a novel technology for atrial fibrillation, is reported in Circulation: Arrhythmia and Electrophysiology. Associations of truncating variants in the desmosomal gene with arrhythmogenic right ventricular cardiomyopathy from the UK Biobank are analyzed in Circulation: Genomic and

In the article by Borlaug et al, “Latent Pulmonary Vascular Disease May Alter the Response to Therapeutic Atrial Shunt Device in Heart Failure,” which published in the May 24, 2022, issue of the journal (Circulation.2022; 145:1592-1604. DOI: 10.1161/CIRCULATIONAHA.122.059486), a correction is needed. The disclosures of one the authors, Dr Scott Solomon, was inadvertently excluded from the disclosures

In the article by Dou et al, “Oxidized Phospholipids Promote NETosis and Arterial Thrombosis in LNK(SH2B3) Deficiency,” which published in the December 14, 2021, issue of the journal (Circulation.2021;144:1940-1954. DOI: 10.1161/CIRCULATIONAHA.121.056414), a correction is needed. The disclosures of one the authors, Dr Pradeep Natarajan, was inadvertently excluded from the disclosures statement in the