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

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

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

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

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

Background: The 2018 physical activity guidelines for Americans recommend a minimum of 150 to 300 min/wk of moderate physical activity (MPA), 75 to 150 min/wk of vigorous physical activity (VPA), or an equivalent combination of both. However, it remains unclear whether higher levels of long-term VPA and MPA are, independently and jointly, associated with lower mortality.Methods: A total of 116221 adults

Background:African Americans continue to have suboptimal cardiovascular health (CVH) based on the American Heart Association Life’s Simple 7 (LS7), 7 health-promoting behaviors and biological risk factors (eg, physical activity, blood pressure). Innovative, community-level interventions in partnership with trusted institutions such as African American churches are potential means to improve CVH in

Background:Black adults experience a disproportionately higher burden of cardiovascular risk factors and disease in comparison with White adults in the United States. Less is known about how sex-based disparities in cardiovascular mortality between these groups have changed on a national scale over the past 20 years, particularly across geographic determinants of health and residential racial segregation

Background:Despite improvements in population health, marked racial and ethnic disparities in longevity and cardiovascular disease (CVD) mortality persist. This study aimed to describe risks for all-cause and CVD mortality by race and ethnicity, before and after accounting for socioeconomic status (SES) and other factors, in the MESA study (Multi-Ethnic Study of Atherosclerosis).Methods:MESA recruited

Cardiovascular disease is the leading contributor to years lost due to disability or premature death among adults. Current efforts focus on risk prediction and risk factor mitigation‚ which have been recognized for the past half-century. However, despite advances, risk prediction remains imprecise with persistently high rates of incident cardiovascular disease. Genetic characterization has been proposed

BACKGROUND:Clinical and anatomical characteristics are often considered key factors in deciding between percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with complex coronary artery disease (CAD) such as left-main CAD or 3-vessel disease. However, little is known about the interaction between self-reported preprocedural physical/mental health and clinical

BACKGROUND:Abnormalities in Ca2+ homeostasis are associated with cardiac arrhythmias and heart failure. Triadin plays an important role in Ca2+ homeostasis in cardiomyocytes. Alternative splicing of a single triadin gene produces multiple triadin isoforms. The cardiac-predominant isoform, mouse MT-1 or human Trisk32, is encoded by triadin exons 1 to 8. In humans, mutations in the triadin gene that

This science advisory focuses on the need to better understand the epidemiology, pathophysiology, and treatment of pulmonary hypertension in patients with heart failure with preserved ejection fraction. This clinical phenotype is important because it is common, is strongly associated with adverse outcomes, and lacks evidence-based therapies. Our goal is to clarify key knowledge gaps in pulmonary hypertension

BACKGROUND:The cardiorenal effects of sodium-glucose cotransporter 2 inhibition (empagliflozin 25 mg QD) combined with angiotensin-converting enzyme inhibition (ramipril 10 mg QD) were assessed in this mechanistic study in patients with type 1 diabetes with potential renal hyperfiltration.METHODS:Thirty patients (out of 31 randomized) completed this double-blind, placebo-controlled, crossover trial

Background:More than one-fifth of the world’s population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation.Methods:A multicenter, patient- and outcome assessor–blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines

BACKGROUND:Although transcatheter aortic valve replacement (TAVR) therapy continues to grow, there have been concerns about the occurrence of hypoattenuating leaflet thickening (HALT), which may affect prosthesis function or durability. This study aimed to examine prosthesis frame factors and correlate their extent to the frequency of HALT and clinical outcomes.METHODS:We prospectively examined 565

BACKGROUND:Clinical worsening (CW) is a composite end point commonly used in pulmonary arterial hypertension (PAH) trials. We aimed to assess the trial-level surrogacy of CW for mortality in PAH trials, and whether the various CW components were similar in terms of frequency of occurrence, treatment-related relative risk (RR) reduction, and importance to patients.METHODS:We searched MEDLINE, Embase

BACKGROUND:Recent trial data suggest that stratification of patients with heart failure with preserved ejection fraction (HFpEF) according to left ventricular ejection fraction (LVEF) provides a means for dissecting different treatment responses. However, the differential pathophysiologic considerations have rarely been described.METHODS:This prospective, single-center study analyzed consecutive symptomatic

BACKGROUND:Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis. A majority of patients exhibit improvements in left ventricular ejection fraction (LVEF) after TAVR in response to TAVR-associated afterload reduction. However, a specific role for circulating microRNAs (miRNAs) in the

The use of temporary mechanical circulatory support in cardiogenic shock has increased dramatically despite a lack of randomized controlled trials or evidence guiding clinical decision-making. Recommendations from professional societies on temporary mechanical circulatory support escalation and de-escalation are limited. This scientific statement provides pragmatic suggestions on temporary mechanical

In the article by Yang et al, “Genetic Landscape of the ACE2 Coronavirus Receptor” which published in the May 3, 2022, issue of the journal (Circulation. 2021;145:1398–1411. doi: 10.1161/CIRCULATIONAHA.121.057888), a correction is needed. The incorrect author was listed in the first line of the Disclosures section. The Disclosures should read as follows: Dr Butterworth has received grants outside of

Background:The human heart has limited capacity to generate new cardiomyocytes and this capacity declines with age. Because loss of cardiomyocytes may contribute to heart failure, it is crucial to explore stimuli of endogenous cardiac regeneration to favorably shift the balance between loss of cardiomyocytes and the birth of new cardiomyocytes in the aged heart. We have previously shown that cardiomyogenesis

The 2021 American Heart Association/American College of Cardiology/American Society of Echocardiography/American College of Chest Physicians/Society for Academic Emergency Medicine/Society of Cardiovascular Computed Tomography/Society for Cardiovascular Magnetic Resonance guidelines for the evaluation and diagnosis of acute chest pain make important recommendations that include the recognition of high-sensitivity

Appropriately designed and conducted randomized clinical trials (RCTs) are foundational for the practice of evidence-based medicine, including the regulatory approval of therapeutics and the inclusion of those therapies in clinical practice guidelines. Broadly defined, RCTs can be considered in 2 categories: explanatory or mechanistic trials that examine the effect of an intervention on biological

BACKGROUND:Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain.METHODS:The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment

BACKGROUND:Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance that primarily affects women of childbearing age. The underlying pathophysiology of POTS is not fully understood, but it has been suggested that autoimmunity may play a role. The aim of this study was to compare concentrations of autoantibodies to cardiovascular G protein–coupled receptors between patients

Background: The American Heart Association (AHA) recently published an updated algorithm for quantifying cardiovascular health (CVH)—the "Life's Essential 8™" score. We quantified US levels of CVH using the new score.Methods: We included non-pregnant, non-institutionalized individuals ages 2 through 79 years who were free of cardiovascular disease from the National Health and Nutrition Examination

In 2010, the American Heart Association defined a novel construct of cardiovascular health to promote a paradigm shift from a focus solely on disease treatment to one inclusive of positive health promotion and preservation across the life course in populations and individuals. Extensive subsequent evidence has provided insights into strengths and limitations of the original approach to defining and

Background:Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear.Methods:In

BACKGROUND:Empagliflozin improves outcomes in patients with heart failure with a preserved ejection fraction, but whether the effects are consistent in patients with and without diabetes remains to be elucidated.METHODS:Patients with class II through IV heart failure and a left ventricular ejection fraction >40% were randomized to receive empagliflozin 10 mg or placebo in addition to usual therapy

Background:Immune checkpoint inhibitors (ICIs) are monoclonal antibodies used to activate the immune system against tumor cells. Despite therapeutic benefits, ICIs have the potential to cause immune-related adverse events such as myocarditis, a rare but serious side effect with up to 50% mortality in affected patients. Histologically, patients with ICI myocarditis have lymphocytic infiltrates in the

Background:REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl—Intervention Trial) reported a 25% relative risk reduction in major adverse cardiovascular events with use of icosapent ethyl compared with pharmaceutical grade mineral oil. The mechanisms underlying this benefit remain uncertain. We explored whether treatment allocation in REDUCE-IT might affect a series of biomarkers in

BACKGROUND:Ca2+ signals in smooth muscle cells (SMCs) contribute to vascular resistance and control blood pressure. Increased vascular resistance in hypertension has been attributed to impaired SMC Ca2+ signaling mechanisms. In this regard, transient receptor potential vanilloid 4 (TRPV4SMC) ion channels are a crucial Ca2+ entry pathway in SMCs. However, their role in blood pressure regulation has

Background:Socioeconomic deprivation is associated with higher cardiovascular morbidity and mortality. Whether deprivation status should be incorporated in more cardiovascular risk estimation scores remains unclear. This study evaluates how socioeconomic deprivation status affects the performance of 3 primary prevention cardiovascular risk scores.Methods:The Generation Scotland Scottish Family Health

BACKGROUND:Genome-wide association studies have identified many genetic loci that are robustly associated with coronary artery disease (CAD). However, the underlying biological mechanisms are still unknown for most of these loci, hindering the progress to medical translation. Evidence suggests that the genetic influence on CAD susceptibility may act partly through vascular smooth muscle cells (VSMCs)

A 58-year-old male with a history of type 2 diabetes, hypertension, chronic kidney disease, a severe ischemic cardiomyopathy (left ventricular [LV] ejection fraction 19%), paroxysmal atrial fibrillation, and ventricular tachycardia (VT) which had been treated with amiodarone and a defibrillator, was admitted with worsening heart failure and palpitations. He was found to be volume overloaded with acute

BACKGROUND:In the CABANA trial (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation), catheter ablation did not significantly reduce the primary end point of death, disabling stroke, serious bleeding, or cardiac arrest compared with drug therapy by intention-to-treat, but did improve the quality of life and freedom from atrial fibrillation recurrence. In the heart failure subgroup

Background:Extreme-heat events are increasing as a result of climate change. Prior studies, typically limited to urban settings, suggest an association between extreme heat and cardiovascular mortality. However, the extent of the burden of cardiovascular deaths associated with extreme heat across the United States and in different age, sex, or race and ethnicity subgroups is unclear.Methods:County-level

Background:Cerebral microbleeds (CMBs) have been observed in healthy elderly people undergoing systematic brain magnetic resonance imaging. The potential role of acute triggers on the appearance of CMBs remains unknown. We aimed to describe the incidence of new CMBs after transcatheter aortic valve replacement (TAVR) and to identify clinical and procedural factors associated with new CMBs including

Background:There is a paucity of data regarding the phenotype of dilated cardiomyopathy (DCM) gene variants in the general population. We aimed to determine the frequency and penetrance of DCM-associated putative pathogenic gene variants in a general adult population, with a focus on the expression of clinical and subclinical phenotype, including structural, functional, and arrhythmic disease features

A 59-year-old woman presented to the emergency department after her primary care provider discovered an abnormal ECG at an office visit (Figure 1). She had been experiencing intermittent atypical chest pain for months. Thorough ischemic work-up was unremarkable, although the patient was found to have mild global left ventricular systolic dysfunction with preserved chamber size and borderline left atrial

Cardiovascular interventions using x-ray guidance are increasing in both volume and complexity. The long-term biological effects of chronic low-dose radiation exposure in operators performing these procedures are, however, largely unknown. Occupational safety limits are based on physical dosimetry only and do not consider individual biological sensitivity to radiation. We previously reported DNA damage

In the article by Reynolds et al, “Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity” which published online on September 9, 2021 and appeared in the September 28, 2021, issue of Circulation (Circulation. 2021;144:1024–1038. doi: 10.1161/CIRCULATIONAHA.120.049755), corrections are needed. The analysis population for CAD and outcomes is correct as stated, at 2475

Background:Black adults have a higher incidence of peripheral artery disease and limb amputations than White adults in the United States. Given that peripheral endovascular intervention (PVI) is now the primary revascularization strategy for peripheral artery disease, it is important to understand whether racial differences exist in PVI incidence and outcomes.Methods:Data from fee-for-service Medicare

Background:The role of diabetes in the development of valvular heart disease, and, in particular, the relation with risk factor control, has not been extensively studied.Methods:We included 715 143 patients with diabetes registered in the Swedish National Diabetes Register and compared them with 2 732 333 matched controls randomly selected from the general population. First, trends were analyzed with