Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater

Background: Various non-invasive intermittent rhythm monitoring strategies have been used to assess arrhythmia recurrences in trials of atrial fibrillation (AF) ablation. We determined whether a frequency and duration of non-invasive rhythm monitoring could be identified that accurately detects arrhythmia recurrences and approximates the AF burden derived from continuous monitoring using an implantable

Background: Smaller randomized studies have reported conflicting results regarding the optimal electrode position for cardioverting atrial fibrillation. However, anterior-posterior electrode position is widely used as a standard and believed to be superior to anterior-lateral electrode position. Therefore, we aimed to compare anterior-lateral and anterior-posterior electrode position for cardioverting

Background:Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an abnormal cardiac energetic state underpins this process.Methods:We recruited patients across the spectrum of diastolic dysfunction and HFpEF (controls, n=11; type 2 diabetes, n=9; HFpEF

Heart failure with preserved ejection fraction (HFpEF) has been previously defined by various criteria,1 with a common theme being the presence of preserved left ventricular ejection fraction. Defining a heart disease on the basis of a normal cardiac finding should beg the question: What is distinctly abnormal about the heart in HFpEF? Answering this question may aid in overcoming a track record of

Background:In the past 2 decades, hypertension control in the US population has not improved and there are widening disparities. Little is known about progress in reducing hospitalizations for acute hypertension.Methods:We conducted serial cross-sectional analysis of Medicare fee-for-service beneficiaries age 65 years or older between 1999 and 2019 using Medicare denominator and inpatient files. We

Background:Barth syndrome (BTHS) is caused by mutations of the gene encoding tafazzin, which catalyzes maturation of mitochondrial cardiolipin and often manifests with systolic dysfunction during early infancy. Beyond the first months of life, BTHS cardiomyopathy typically transitions to a phenotype of diastolic dysfunction with preserved ejection fraction, blunted contractile reserve during exercise

Background:Hypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At the cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure–function relationships, there is still much to be learned about

For the American Heart Association’s 2019 Resuscitation Science Symposium abstract #03 by Tulasi Jinka, Adam D Chalek, Joseph M Wider, Kathleen J Maheras, Amanda Qvigstad, Erin Gruley, Sarita Raghunayakula, Jinhui Liao, Xiaodan Ren, Rui Zhang, Thomas H Sanderson, and Robert W Neumar (“High-Dose Intranasal Insulin During CPR Improves Neurological Outcomes in a Rat Model of Cardiac Arrest” Circulation

In the article by Lu et al, “National Trends and Disparities in Hospitalization for Acute Hypertension Among Medicare Beneficiaries (1999–2019),” which appears in the November 23, 2021, issue of the journal (Circulation.2021;144:1683–1693. DOI: 10.1161/CIRCULATIONAHA.121.057056), a correction is needed. In the What Are the Clinical Implications? section, the sentence “The marked increase in hospitalizations

Background: Remodelling of the extracellular matrix (ECM) is a hallmark of heart failure (HF). Our previous analysis of the secretome of murine cardiac fibroblasts returned ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) as one of the most abundant proteases. ADAMTS5 cleaves chondroitin sulphate proteoglycans (CSPGs) such as versican. The contribution of ADAMTS5 and its substrate

Background: Cardiac fibrosis is a lethal outcome of excessive formation of myofibroblasts that are scar-forming cells accumulated after heart injury. It has been reported that cardiac endothelial cells (ECs) contribute to a substantial portion of myofibroblasts through EndoMT. Recent lineage tracing studies demonstrate that myofibroblasts are derived from expansion of resident fibroblasts rather than

Background: Acute myocardial infarction (MI) results in overzealous production and infiltration of neutrophils to the ischemic heart. This is mediated in-part by granulopoiesis induced by the S100A8/A9-NLRP3-IL-1β signaling axis in injury-exposed neutrophils. Despite the transcriptional upregulation of the NLRP3 inflammasome and associated signaling components in neutrophils, the serum levels of IL-1β

Background:Prescription opioids are a major contributor to the ongoing epidemic of persistent opioid use (POU). The incidence of POU among opioid-naïve patients after cardiac implantable electronic device (CIED) procedures is unknown.Methods:This retrospective cohort study used data from a national administrative claims database from 2004 to 2018 of patients undergoing CIED procedures. Adult patients

Background:Filamin C truncating variants (FLNCtv) cause a form of arrhythmogenic cardiomyopathy: the mode of presentation, natural history, and risk stratification of FLNCtv remain incompletely explored. We aimed to develop a risk profile for refractory heart failure and life-threatening arrhythmias in a multicenter cohort of FLNCtv carriers.Methods:FLNCtv carriers were identified from 10 tertiary

Background:Endothelial cells depend on glycolysis for much of their energy production. Impaired endothelial glycolysis has been associated with various vascular pathobiologies, including impaired angiogenesis and atherogenesis. IFN-γ (interferon-γ)–producing CD4+ and CD8+ T lymphocytes have been identified as the predominant pathological cell subsets in human atherosclerotic plaques. Although the immunologic

Background:PALMD (palmdelphin) belongs to the family of paralemmin proteins implicated in cytoskeletal regulation. Single nucleotide polymorphisms in the PALMD locus that result in reduced expression are strong risk factors for development of calcific aortic valve stenosis and predict severity of the disease.Methods:Immunodetection and public database screening showed dominant expression of PALMD in

Arrhythmogenic cardiomyopathy (ACM) is a primary disease of the myocardium, predominantly caused by genetic defects in proteins of the cardiac intercalated disc, particularly, desmosomes. Transmission is mostly autosomal dominant with incomplete penetrance. ACM also has wide phenotype variability, ranging from premature ventricular contractions to sudden cardiac death and heart failure. Among other

The introduction of Mission: Lifeline significantly increased timely access to percutaneous coronary intervention for patients with ST-segment–elevation myocardial infarction (STEMI). In the years since, morbidity and mortality rates have declined, and research has led to significant developments that have broadened our concept of the STEMI system of care. However, significant barriers and opportunities

Background: Patients with heart failure and preserved ejection fraction (HFpEF) have significant impairment in health-related quality of life (HRQoL). In EMPEROR-Preserved, we evaluated the efficacy of empagliflozin on HRQoL in patients with HFpEF and whether the clinical benefit observed with empagliflozin varies according to baseline health status.Methods: HRQoL was measured using the Kansas City

Background: The PRAETORIAN trial showed non-inferiority of the subcutaneous implantable cardioverter-defibrillator (S-ICD) compared to the transvenous ICD (TV-ICD) with regard to inappropriate shocks and complications. In contrast to the TV-ICD, the S-ICD cannot provide antitachycardia pacing (ATP) for monomorphic ventricular tachycardia (VT). This pre-specified secondary analysis evaluates appropriate

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) both reduce cardiovascular (CV) events among patients with type 2 diabetes. However, no CV outcome trial has evaluated the long-term effects of their combined use. The AMPLITUDE-O trial reported that once weekly injections of the GLP-1 RA efpeglenatide (vs. placebo) reduced major

Background: Surgical aortic valve replacement (SAVR) represents a class I indication in symptomatic patients with severe aortic stenosis (AS). However, indications for early SAVR in asymptomatic patients with severe AS and normal left ventricular function remain debated.Methods: The Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR) trial is an i

Background: Chronic kidney disease (CKD) and type 2 diabetes (T2D) are independently associated with heart failure (HF), a leading cause of morbidity and mortality. In the FIDELIO-DKD and FIGARO DKD trials, finerenone (a selective, nonsteroidal mineralocorticoid receptor antagonist) improved cardiovascular outcomes in patients with albuminuric CKD and T2D. These prespecified analyses from FIGARO-DKD

Background: Despite the acknowledged importance of socioeconomic factors as regards cardiovascular-disease onset, and survival, the relationship between individual-level socioeconomic factors and survival after out-of-hospital cardiac arrest (OHCA) is not fully established. Our aim was to investigate whether socioeconomic variables are associated with 30-day survival after OHCA.Methods: We linked data

Background: Many heart diseases can develop a reduced pumping capacity of the heart muscle. A mismatch between ATP demand and ATP production of cardiomyocytes is one of the possible causes. Assessment of the relation between the myocardial ATP production (MVATP) and cardiac workload is important for better understanding disease development and choice of nutritional or pharmacological treatment strategies

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review

Improving cancer survival represents the most significant effect of precision medicine and personalized molecular and immunologic therapeutics. Cardiovascular health becomes henceforth a key determinant for the direction of overall outcomes after cancer. Comprehensive tissue diagnostic studies undoubtedly have been and continue to be at the core of the fight against cancer. Will a systemic approach

Background:The associations of changes in noncombustible nicotine or tobacco product (NNTP) and combustible cigarette (CC) use habits with subsequent cardiovascular disease (CVD) risk are still unclear.Methods:The study population consisted of 5 159 538 adult men who underwent health screening examinations during both the first (2014–2015) and second (2018) health screening periods from the Korean

Background:There are few contemporary cohorts of Trypanosoma cruzi–seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with T. cruzi seropositivity.Methods:Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as T. cruzi–seropositive blood donors.

Background:Long noncoding RNAs (lncRNAs) are important regulators of biological processes involved in vascular tissue homeostasis and disease development. The present study assessed the functional contribution of the lncRNA myocardial infarction-associated transcript (MIAT) to atherosclerosis and carotid artery disease.Methods:We profiled differences in RNA transcript expression in patients with advanced

Myocardial injury after noncardiac surgery is defined by elevated postoperative cardiac troponin concentrations that exceed the 99th percentile of the upper reference limit of the assay and are attributable to a presumed ischemic mechanism, with or without concomitant symptoms or signs. Myocardial injury after noncardiac surgery occurs in ≈20% of patients who have major inpatient surgery, and most

In the article by Choi et al, “Combined Associations of Changes in Noncombustible Nicotine or Tobacco Product and Combustible Cigarette Use Habits With Subsequent Short-Term Cardiovascular Disease Risk Among South Korean Men: A Nationwide Cohort Study,” which published online October 4, 2021, and appears in the November 9, 2021, issue of the journal (Circulation. 2021;144:1528–1538. DOI: 10.1161/CIRCULATIONAHA

Background: Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies concerning this topic have been published. We investigated the association between hypertension/elevated BP and AD in two cohorts and conducted a meta-analysis of published prospective studies, including these two studies.Methods: We analyzed data from the

Background: Differences in patient characteristics, changes in treatment algorithms, and advances in medical technology could each influence the applicability of older randomized trial results to contemporary clinical practice. The Dual Antiplatelet Therapy (DAPT) Study found that longer duration DAPT decreased ischemic events at the expense of greater bleeding, but subsequent evolution in stent technology

Background: Artificial intelligence (AI)-enabled analysis of 12-lead electrocardiograms (ECGs) may facilitate efficient estimation of incident atrial fibrillation (AF) risk. However, it remains unclear whether AI provides meaningful and generalizable improvement in predictive accuracy beyond clinical risk factors for AF.Methods: We trained a convolutional neural network ("ECG-AI") to infer 5-year incident

Background: The microvasculature, the smallest blood vessels in the body, has key roles in maintenance of organ health as well as tumorigenesis. The retinal fundus is a window for human in vivo non-invasive assessment of the microvasculature. Large-scale complementary machine learning-based assessment of the retinal vasculature with phenome-wide and genome-wide analyses may yield new insights into

Background: Socioeconomic disadvantage is a strong determinant of adverse outcomes in patients with heart failure (HF). However, the contribution of community-level economic distress to adverse outcomes in HF may differ across races.Methods: Patients of self-reported Black, White, and Hispanic race/ethnicity hospitalized with HF between 2014 and 2019 were identified from the 100% CMS MedPAR database

Background: Circulating high-sensitivity cardiac troponin T (hsTnT) predominantly reflects myocardial injury, and higher levels are associated with a higher risk of worsening heart failure (HF) and death in patients with HF with reduced ejection fraction (HFrEF). Less is known about the prognostic significance of changes in hsTnT over time, the effects of dapagliflozin on clinical outcomes in relation

Background: No study has so far compared Amulet with the new Watchman FLX in terms of residual left atrial appendage (LAA) patency or clinical outcomes in patients undergoing percutaneous LAA closure (LAAC).Methods: In the investigator-initiated SWISS APERO trial, patients undergoing LAAC were randomized (1:1) open-label to receive Amulet or Watchman 2.5 or FLX (Watchman) across 8 European centres

Background: Transcatheter aortic valve replacement (TAVR) is an established treatment option for patients with severe symptomatic aortic stenosis (AS), and is most commonly performed through the transfemoral access route. Percutaneous access site closure can be achieved using dedicated plug-based or suture-based vascular closure device (VCD) strategies, but randomized comparative studies are scarce

Cardiovascular disease predominates as the leading health burden among middle-aged and older American adults, but progress in improving cardiovascular health remains slow. Comprehensive, evidenced-based behavioral counseling interventions in primary care are a recommended first-line approach for promoting healthy behaviors and preventing poor cardiovascular disease outcomes in adults with cardiovascular

Poor diet quality is strongly associated with elevated risk of cardiovascular disease morbidity and mortality. This scientific statement emphasizes the importance of dietary patterns beyond individual foods or nutrients, underscores the critical role of nutrition early in life, presents elements of heart-healthy dietary patterns, and highlights structural challenges that impede adherence to heart-healthy

Background:Acute cellular rejection is a major determinant of mortality and retransplantation after heart transplantation. We sought to evaluate the prognostic implications of coronary microcirculatory dysfunction assessed by index of microcirculatory resistance (IMR) for the risk of acute cellular rejection after heart transplantation.Methods:The present study prospectively enrolled 154 heart transplant

Background:Observational and small, randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease.Methods:We conducted an investigator-initiated, randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infarction (MI; 99.7% of patients) or high-risk stable coronary

Background:In the VICTORIA trial (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction), anemia occurred more often in patients treated with vericiguat (7.6%) than with placebo (5.7%). We explored the association between vericiguat, randomization hemoglobin, development of anemia, and whether the benefit of vericiguat related to baseline hemoglobin.Methods:Anemia was