<div><h4>The cardiovascular effects of novel weight loss therapies.</h4><i>Usman MS, Davies M, Hall ME, Verma S, ... Rosenstock J, Butler J</i><br /><AbstractText>The prevalence of overweight and obesity has reached pandemic proportions. Obesity is known to increase the risk for Type 2 diabetes and hypertension, as well as the risk for overt cardiovascular (CV) disease, including myocardial infarction, heart failure, and stroke. The rising prevalence of obesity may counteract the recent advances in primary and secondary prevention of CV disease. Overweight and obesity are common in patients with CV disease; however, cardiologists face several challenges in managing body weight in this population. Many may not consider obesity as a therapeutic target probably because there were no previous highly effective and safe pharmacologic interventions to consider. In addition, they may not have the expertise or resources to implement lifestyle interventions and may have limited familiarity with obesity pharmacotherapy. Moreover, the long-term CV effects of obesity pharmacotherapy remain uncertain due to limited CV outcome data with weight loss as the primary intervention. Although current CV guidelines recognize the importance of weight loss, they primarily focus on lifestyle modifications, with fewer details on strategies to utilize obesity pharmacotherapy and surgery. However, the recent 2022 American Diabetes Association/European Association for the Study of Diabetes consensus on the management of Type 2 diabetes has moved up weight management to the front of the treatment algorithm, by prioritizing the use of pharmacologic interventions such as glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists, which have potent weight-lowering effects, in addition to glucose-lowering effects. This review appraises the current evidence regarding the CV effects of weight-loss interventions. Considering this evidence, practical guidance is provided to assist cardiologists in developing and implementing treatment plans, which may allow optimal weight management while maximizing CV benefits and minimizing side effects to improve the overall well-being of people with CV disease.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 14 Nov 2023; epub ahead of print</small></div>

<div><h4>Dynamic ECG Changes Are a Novel Risk Marker for Sudden Cardiac Death.</h4><i>Pham HN, Holmstrom L, Chugh H, Uy-Evanado A, ... Reinier K, Chugh SS</i><br /><b>Background:</b><br/>and aims</b><br />ECG abnormalities have been evaluated as static risk markers for sudden cardiac death (SCD) but the potential importance of dynamic ECG remodeling has not been investigated. In this study, the nature and prevalence of dynamic ECG remodeling were studied among individuals who eventually suffered SCD.<br /><b>Methods</b><br />The study population was drawn from two prospective community-based SCD studies in Oregon, USA (2002-, discovery cohort) and California, USA (2015-, validation cohort). For this present sub-study, 231 discovery cases (2015-2017) and 203 validation cases (2015-2021) with ≥2 archived pre-SCD ECGs were ascertained, and were matched to 234 discovery and 203 validation controls based on age, sex, and duration between the ECGs. Dynamic ECG remodeling was measured as progression of a previously validated cumulative 6-variable ECG electrical risk score (ERS).<br /><b>Results</b><br />Oregon SCD cases displayed greater ERS increase over time vs. controls [+1.06 (95% CI +0.89 to +1.24) vs. -0.05 (-0.21 to +0.11); p < 0.001]. These findings were successfully replicated in California [+0.87 (+0.7 to +1.04) vs. -0.11 (-0.27 to 0.05); p < 0.001]. In multivariable models, abnormal dynamic ECG remodeling improved SCD prediction over baseline ECG, demographics, and clinical SCD risk factors in both Oregon [AUC 0.770 (95% CI 0.727-0.812) increased to AUC 0.869 (95% CI 0.837-0.902)] and California cohorts.<br /><b>Conclusions</b><br />Dynamic ECG remodeling improved SCD risk prediction beyond clinical factors combined with the static ECG, with successful validation in a geographically distinct population. These findings introduce a novel concept of SCD dynamic risk and warrant further detailed investigation.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 12 Nov 2023; epub ahead of print</small></div>

<div><h4>Anticoagulation with edoxaban in patients with long Atrial High-Rate Episodes ≥24 hours.</h4><i>Becher N, Toennis T, Bertaglia E, Blomström-Lundqvist C, ... Zapf A, Kirchhof P</i><br /><b>Background:</b><br/>and aims</b><br />Patients with long atrial high-rate episodes (AHRE) ≥ 24 hours and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared to no anticoagulation in these patients.<br /><b>Methods</b><br />This secondary prespecified analysis of NOAH-AFNET 6 examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared to placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and ECG-diagnosed atrial fibrillation.<br /><b>Results</b><br />AHRE ≥24 hours were present at baseline in 259/2389 patients enrolled in NOAH-AFNET 6 (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc score 4). Clinical characteristics were not different from patients with shorter AHRE. During a median follow-up of 1.8 years, the primary outcome occurred in 9/132 patients with AHRE ≥24 hours (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). AHRE duration did not interact with the efficacy (p-interaction = 0.65) or safety (p-interaction = 0.98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 hours developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; p < 0.001).<br /><b>Conclusions</b><br />This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 11 Nov 2023; epub ahead of print</small></div>

<div><h4>Cardiovascular Hospitalizations and Mortality Among Adults Aged 25 to 64 years in the United States.</h4><i>Henry CM, Oseran AS, Zheng Z, Dong H, Wadhera RK</i><br /><b>Background:</b><br/>and aims</b><br />Declines in cardiovascular mortality have stagnated in the United States since 2011. There is growing concern that these patterns reflect worsening cardiovascular health in younger adults. However, little is known about how the burden of acute cardiovascular hospitalizations and mortality have changed in this population. Changes in cardiovascular hospitalizations and mortality among adults aged 25-64 years were evaluated, overall and by community-level income.<br /><b>Methods</b><br />Using the National Inpatient Sample, age-standardized annual hospitalization and inhospital mortality rates for acute myocardial infarction (AMI), heart failure, and ischemic stroke were determined among adults aged 25-64 years. Quasi-Poisson and quasi-binominal regression models were fitted to compare outcomes between individuals residing in low- and higher-income communities.<br /><b>Results</b><br />Between 2008 and 2019, age-standardized hospitalization rates for AMI increased among younger adults from 155.0 (95% CI 154.6, 155.4) per 100,000 to 160.7 (160.3, 161.1) per 100,000 (absolute change +5.7 [5.0, 6.3], p<0.001). Heart failure hospitalizations also increased (165.3 [164.8, 165.7] to 225.3 [224.8, 225.8], absolute change +60.0 (59.3, 60.6), p<0.001), as ischemic stroke hospitalizations (76.3 [76.1, 76.7] to 108.1 [107.8, 108.5], absolute change +31.7 (31.2, 32.2), p<0.001). Across all conditions, hospitalizations rates were significantly higher among younger adults residing in low-income compared with higher-income communities, and disparities did not narrow between groups. In-hospital mortality decreased for all conditions over the study period.<br /><b>Conclusions</b><br />There was an alarming increase in cardiovascular hospitalizations among younger adults in the US from 2008 to 2019, and disparities between those residing in low- and higher-income communities did not narrow.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 10 Nov 2023; epub ahead of print</small></div>

<div><h4>Clonal haematopoiesis of indeterminate potential predicts incident cardiac arrhythmias.</h4><i>Schuermans A, Vlasschaert C, Nauffal V, Cho SMJ, ... Natarajan P, Honigberg MC</i><br /><b>Background:</b><br/>and aims</b><br />Clonal haematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutations, is associated with atherosclerotic cardiovascular disease and heart failure. This study aimed to test the association of CHIP with new-onset arrhythmias.<br /><b>Methods</b><br />UK Biobank participants without prevalent arrhythmias were included. Co-primary study outcomes were supraventricular arrhythmias, bradyarrhythmias, and ventricular arrhythmias. Secondary outcomes were cardiac arrest, atrial fibrillation, and any arrhythmia. Associations of any CHIP [variant allele fraction (VAF) ≥ 2%], large CHIP (VAF ≥10%), and gene-specific CHIP subtypes with incident arrhythmias were evaluated using multivariable-adjusted Cox regression. Associations of CHIP with myocardial interstitial fibrosis [T1 measured using cardiac magnetic resonance (CMR)] were also tested.<br /><b>Results</b><br />This study included 410 702 participants [CHIP: n = 13 892 (3.4%); large CHIP: n = 9191 (2.2%)]. Any and large CHIP were associated with multi-variable-adjusted hazard ratios of 1.11 [95% confidence interval (CI) 1.04-1.18; P = .001] and 1.13 (95% CI 1.05-1.22; P = .001) for supraventricular arrhythmias, 1.09 (95% CI 1.01-1.19; P = .031) and 1.13 (95% CI 1.03-1.25; P = .011) for bradyarrhythmias, and 1.16 (95% CI, 1.00-1.34; P = .049) and 1.22 (95% CI 1.03-1.45; P = .021) for ventricular arrhythmias, respectively. Associations were independent of coronary artery disease and heart failure. Associations were also heterogeneous across arrhythmia subtypes and strongest for cardiac arrest. Gene-specific analyses revealed an increased risk of arrhythmias across driver genes other than DNMT3A. Large CHIP was associated with 1.31-fold odds (95% CI 1.07-1.59; P = .009) of being in the top quintile of myocardial fibrosis by CMR.<br /><b>Conclusions</b><br />CHIP may represent a novel risk factor for incident arrhythmias, indicating a potential target for modulation towards arrhythmia prevention and treatment.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 10 Nov 2023; epub ahead of print</small></div>

<div><h4>Device-measured physical activity and cardiometabolic health: the Prospective Physical Activity, Sitting, and Sleep (ProPASS) consortium.</h4><i>Blodgett JM, Ahmadi MN, Atkin AJ, Chastin S, ... Hamer M, ProPASS Collaboration</i><br /><b>Background:</b><br/>and aims</b><br />Physical inactivity, sedentary behaviour (SB), and inadequate sleep are key behavioural risk factors of cardiometabolic diseases. Each behaviour is mainly considered in isolation, despite clear behavioural and biological interdependencies. The aim of this study was to investigate associations of five-part movement compositions with adiposity and cardiometabolic biomarkers.<br /><b>Methods</b><br />Cross-sectional data from six studies (n = 15 253 participants; five countries) from the Prospective Physical Activity, Sitting and Sleep consortium were analysed. Device-measured time spent in sleep, SB, standing, light-intensity physical activity (LIPA), and moderate-vigorous physical activity (MVPA) made up the composition. Outcomes included body mass index (BMI), waist circumference, HDL cholesterol, total:HDL cholesterol ratio, triglycerides, and glycated haemoglobin (HbA1c). Compositional linear regression examined associations between compositions and outcomes, including modelling time reallocation between behaviours.<br /><b>Results</b><br />The average daily composition of the sample (age: 53.7 ± 9.7 years; 54.7% female) was 7.7 h sleeping, 10.4 h sedentary, 3.1 h standing, 1.5 h LIPA, and 1.3 h MVPA. A greater MVPA proportion and smaller SB proportion were associated with better outcomes. Reallocating time from SB, standing, LIPA, or sleep into MVPA resulted in better scores across all outcomes. For example, replacing 30 min of SB, sleep, standing, or LIPA with MVPA was associated with -0.63 (95% confidence interval -0.48, -0.79), -0.43 (-0.25, -0.59), -0.40 (-0.25, -0.56), and -0.15 (0.05, -0.34) kg/m2 lower BMI, respectively. Greater relative standing time was beneficial, whereas sleep had a detrimental association when replacing LIPA/MVPA and positive association when replacing SB. The minimal displacement of any behaviour into MVPA for improved cardiometabolic health ranged from 3.8 (HbA1c) to 12.7 (triglycerides) min/day.<br /><b>Conclusions</b><br />Compositional data analyses revealed a distinct hierarchy of behaviours. Moderate-vigorous physical activity demonstrated the strongest, most time-efficient protective associations with cardiometabolic outcomes. Theoretical benefits from reallocating SB into sleep, standing, or LIPA required substantial changes in daily activity.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 09 Nov 2023; epub ahead of print</small></div>

<div><h4>Neutrophil counts and cardiovascular disease.</h4><i>Luo J, Thomassen JQ, Nordestgaard BG, Tybjærg-Hansen A, Frikke-Schmidt R</i><br /><b>Background:</b><br/>and aims</b><br />Anti-inflammatory trials have shown considerable benefits for cardiovascular disease. High neutrophil counts, an easily accessible inflammation biomarker, are associated with atherosclerosis in experimental studies. This study aimed to investigate the associations between neutrophil counts and risk of nine cardiovascular endpoints using observational and genetic approaches.<br /><b>Methods</b><br />Observational studies were conducted in the Copenhagen General Population Study (n = 101 730). Genetic studies were firstly performed using one-sample Mendelian randomization (MR) with individual-level data from the UK Biobank (n = 365 913); secondly, two-sample MR analyses were performed using summary-level data from the Blood Cell Consortium (n = 563 085). Outcomes included ischaemic heart disease, myocardial infarction, peripheral arterial disease, ischaemic cerebrovascular disease, ischaemic stroke, vascular-related dementia, vascular dementia, heart failure, and atrial fibrillation.<br /><b>Results</b><br />Observational analyses showed associations between high neutrophil counts with high risks of all outcomes. In the UK Biobank, odds ratios (95% confidence intervals) per 1-SD higher genetically predicted neutrophil counts were 1.15 (1.08, 1.21) for ischaemic heart disease, 1.22 (1.12, 1.34) for myocardial infarction, and 1.19 (1.04, 1.36) for peripheral arterial disease; similar results were observed in men and women separately. In two-sample MR, corresponding estimates were 1.14 (1.05, 1.23) for ischaemic heart disease and 1.11 (1.02, 1.20) for myocardial infarction; multiple sensitivity analyses showed consistent results. No robust associations in two-sample MR analyses were found for other types of leucocytes.<br /><b>Conclusions</b><br />Observational and genetically determined high neutrophil counts were associated with atherosclerotic cardiovascular disease, supporting that high blood neutrophil counts is a causal risk factor for atherosclerotic cardiovascular disease.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 08 Nov 2023; epub ahead of print</small></div>

<div><h4>4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification.</h4><i>Kiyuna LA, Candido DS, Bechara LRG, Jesus ICG, ... Ferreira LRP, Ferreira JCB</i><br /><b>Background:</b><br/>and aims</b><br />Developing novel therapies to battle the global public health burden of heart failure remains challenging. This study investigates the underlying mechanisms and potential treatment for 4-hydroxynonenal (4-HNE) deleterious effects in heart failure.<br /><b>Methods</b><br />Biochemical, functional, and histochemical measurements were applied to identify 4-HNE adducts in rat and human failing hearts. In vitro studies were performed to validate 4-HNE targets.<br /><b>Results</b><br />4-HNE, a reactive aldehyde by-product of mitochondrial dysfunction in heart failure, covalently inhibits Dicer, an RNase III endonuclease essential for microRNA (miRNA) biogenesis. 4-HNE inhibition of Dicer impairs miRNA processing. Mechanistically, 4-HNE binds to recombinant human Dicer through an intermolecular interaction that disrupts both activity and stability of Dicer in a concentration- and time-dependent manner. Dithiothreitol neutralization of 4-HNE or replacing 4-HNE-targeted residues in Dicer prevents 4-HNE inhibition of Dicer in vitro. Interestingly, end-stage human failing hearts from three different heart failure aetiologies display defective 4-HNE clearance, decreased Dicer activity, and miRNA biogenesis impairment. Notably, boosting 4-HNE clearance through pharmacological re-activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) using Alda-1 or its improved orally bioavailable derivative AD-9308 restores Dicer activity. ALDH2 is a major enzyme responsible for 4-HNE removal. Importantly, this response is accompanied by improved miRNA maturation and cardiac function/remodelling in a pre-clinical model of heart failure.<br /><b>Conclusions</b><br />4-HNE inhibition of Dicer directly impairs miRNA biogenesis in heart failure. Strikingly, decreasing cardiac 4-HNE levels through pharmacological ALDH2 activation is sufficient to re-establish Dicer activity and miRNA biogenesis; thereby representing potential treatment for patients with heart failure.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 06 Nov 2023; epub ahead of print</small></div>

<div><h4>Discontinuation vs. continuation of renin-angiotensin system inhibition before non-cardiac surgery: the SPACE trial.</h4><i>Ackland GL, Patel A, Abbott TEF, Begum S, ... Pearse RM, Stopping Perioperative ACE-inhibitors or angiotensin-II receptor blockers (SPACE) trial investigators </i><br /><b>Background:</b><br/>and aims</b><br />Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury remains unclear.<br /><b>Methods</b><br />From 31 July 2017 to 1 October 2021, patients aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned to either discontinue or continue RAS inhibitors prescribed for existing medical conditions in six UK centres. Renin-angiotensin system inhibitors were withheld for different durations (2-3 days) before surgery, according to their pharmacokinetic profile. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury [plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 h after surgery, or ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L]. Pre-specified adverse haemodynamic events occurring within 48 h of surgery included acute hypertension (>180 mmHg) and hypotension requiring vasoactive therapy.<br /><b>Results</b><br />Two hundred and sixty-two participants were randomized to continue (n = 132) or stop (n = 130) RAS inhibitors. Myocardial injury occurred in 58 (48.3%) patients randomized to discontinue, compared with 50 (41.3%) patients who continued, RAS inhibitors [odds ratio (for continuing): 0.77; 95% confidence interval (CI) 0.45-1.31]. Hypertensive adverse events were more frequent when RAS inhibitors were stopped [16 (12.4%)], compared with 7 (5.3%) who continued RAS inhibitors [odds ratio (for continuing): 0.4; 95% CI 0.16-1.00]. Hypotension rates were similar when RAS inhibitors were stopped [12 (9.3%)] or continued [11 (8.4%)].<br /><b>Conclusions</b><br />Discontinuing RAS inhibitors before non-cardiac surgery did not reduce myocardial injury, and could increase the risk of clinically significant acute hypertension. These findings require confirmation in future studies.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 06 Nov 2023; epub ahead of print</small></div>

<div><h4>Amiodarone and pulmonary toxicity in atrial fibrillation: a nationwide Israeli study.</h4><i>Tsaban G, Ostrovsky D, Alnsasra H, Burrack N, ... Konstantino Y, Haim M</i><br /><b>Background:</b><br/>and aims</b><br />Amiodarone-related interstitial lung disease (ILD) is the most severe adverse effect of amiodarone treatment. Most data on amiodarone-related ILD are derived from periods when amiodarone was given at higher doses than currently used.<br /><b>Methods</b><br />A nationwide population-based study was conducted among patients with incident atrial fibrillation (AF) between 1 December 1999 and 31 December 31 2021. Amiodarone-exposed patients were matched 1:1 with controls unexposed to amiodarone based on age, sex, ethnicity, and AF diagnosis duration. The final patient cohort included only matched pairs where amiodarone therapy was consistent throughout follow-up. Directed acyclic graphs and inverse probability treatment weighting (IPTW) modelling were used. Patients with either prior ILD or primary lung cancer (PLC) were excluded. The primary outcome was the incidence of any ILD. Secondary endpoints were death and PLC.<br /><b>Results</b><br />The final cohort included 6039 amiodarone-exposed patients who were matched with unexposed controls. The median age was 73.3 years, and 51.6% were women. After a mean follow-up of 4.2 years, ILD occurred in 242 (2.0%) patients. After IPTW, amiodarone exposure was not significantly associated with ILD [hazard ratio (HR): 1.45, 95% confidence interval (CI): 0.97, 2.44, P = 0.09]. There was a trivial higher relative risk of ILD among amiodarone-exposed patients between Years 2 and 8 of follow-up [maximal risk ratio (RR): 1.019]. Primary lung cancer occurred in 97 (0.8%) patients. After IPTW, amiodarone was not associated with PLC (HR: 1.18, 95% CI: 0.76, 2.08, P = 0.53). All-cause death occurred in 2185 (18.1%) patients. After IPTW, amiodarone was associated with reduced mortality risk (HR: 0.65, 95% CI: 0.60, 0.72, P < 0.001). The results were consistent across a variety of sensitivity analyses.<br /><b>Conclusion</b><br />In a contemporary AF population, low-dose amiodarone was associated with a trend towards increased risk of ILD (15%-45%) but a clinically negligible change in absolute risk (maximum of 1.8%), no increased risk of PLC, and a lower risk of all-cause mortality.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 05 Nov 2023; epub ahead of print</small></div>

<div><h4>Fulminant myocarditis proven by early biopsy and outcomes.</h4><i>Huang F, Ammirati E, Ponnaiah M, Montero S, ... Schmidt M, FULLMOON Study Group </i><br /><b>Background:</b><br/>and aims</b><br />While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear.<br /><b>Methods</b><br />Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders.<br /><b>Results</b><br />Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016).<br /><b>Conclusions</b><br />Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 05 Nov 2023; epub ahead of print</small></div>

<div><h4>Autoantibodies against the chemokine receptor 3 predict cardiovascular risk.</h4><i>Müller FS, Aherrahrou Z, Grasshoff H, Heidorn MW, ... Riemekasten G, Wild PS</i><br /><b>Background:</b><br/>and aims</b><br />Chronic inflammation and autoimmunity contribute to cardiovascular (CV) disease. Recently, autoantibodies (aAbs) against the CXC-motif-chemokine receptor 3 (CXCR3), a G protein-coupled receptor with a key role in atherosclerosis, have been identified. The role of anti-CXCR3 aAbs for CV risk and disease is unclear.<br /><b>Methods</b><br />Anti-CXCR3 aAbs were quantified by a commercially available enzyme-linked immunosorbent assay in 5000 participants (availability: 97.1%) of the population-based Gutenberg Health Study with extensive clinical phenotyping. Regression analyses were carried out to identify determinants of anti-CXCR3 aAbs and relevance for clinical outcome (i.e. all-cause mortality, cardiac death, heart failure, and major adverse cardiac events comprising incident coronary artery disease, myocardial infarction, and cardiac death). Last, immunization with CXCR3 and passive transfer of aAbs were performed in ApoE(-/-) mice for preclinical validation.<br /><b>Results</b><br />The analysis sample included 4195 individuals (48% female, mean age 55.5 ± 11 years) after exclusion of individuals with autoimmune disease, immunomodulatory medication, acute infection, and history of cancer. Independent of age, sex, renal function, and traditional CV risk factors, increasing concentrations of anti-CXCR3 aAbs translated into higher intima-media thickness, left ventricular mass, and N-terminal pro-B-type natriuretic peptide. Adjusted for age and sex, anti-CXCR3 aAbs above the 75th percentile predicted all-cause death [hazard ratio (HR) (95% confidence interval) 1.25 (1.02, 1.52), P = .029], driven by excess cardiac mortality [HR 2.51 (1.21, 5.22), P = .014]. A trend towards a higher risk for major adverse cardiac events [HR 1.42 (1.0, 2.0), P = .05] along with increased risk of incident heart failure [HR per standard deviation increase of anti-CXCR3 aAbs: 1.26 (1.02, 1.56), P = .03] may contribute to this observation. Targeted proteomics revealed a molecular signature of anti-CXCR3 aAbs reflecting immune cell activation and cytokine-cytokine receptor interactions associated with an ongoing T helper cell 1 response. Finally, ApoE(-/-) mice immunized against CXCR3 displayed increased anti-CXCR3 aAbs and exhibited a higher burden of atherosclerosis compared to non-immunized controls, correlating with concentrations of anti-CXCR3 aAbs in the passive transfer model.<br /><b>Conclusions</b><br />In individuals free of autoimmune disease, anti-CXCR3 aAbs were abundant, related to CV end-organ damage, and predicted all-cause death as well as cardiac morbidity and mortality in conjunction with the acceleration of experimental atherosclerosis.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 05 Nov 2023; epub ahead of print</small></div>

<div><h4>Platelet biology and function: plaque erosion vs. rupture.</h4><i>Baaten CCFMJ, Nagy M, Bergmeier W, Spronk HMH, van der Meijden PEJ</i><br /><AbstractText>The leading cause of heart disease in developed countries is coronary atherosclerosis, which is not simply a result of ageing but a chronic inflammatory process that can lead to acute clinical events upon atherosclerotic plaque rupture or erosion and arterial thrombus formation. The composition and location of atherosclerotic plaques determine the phenotype of the lesion and whether it is more likely to rupture or to erode. Although plaque rupture and erosion both initiate platelet activation on the exposed vascular surface, the contribution of platelets to thrombus formation differs between the two phenotypes. In this review, plaque phenotype is discussed in relation to thrombus composition, and an overview of important mediators (haemodynamics, matrix components, and soluble factors) in plaque-induced platelet activation is given. As thrombus formation on disrupted plaques does not necessarily result in complete vessel occlusion, plaque healing can occur. Therefore, the latest findings on plaque healing and the potential role of platelets in this process are summarized. Finally, the clinical need for more effective antithrombotic agents is highlighted.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 05 Nov 2023; epub ahead of print</small></div>

<div><h4>Disparities in donor heart acceptance between the USA and Europe: clinical implications.</h4><i>Wayda B, Angleitner P, Smits JM, van Kins A, ... Khush KK, Zuckermann AO</i><br /><b>Background:</b><br/>and aims</b><br />Given limited evidence and lack of consensus on donor acceptance for heart transplant (HT), selection practices vary widely across HT centres in the USA. Similar variation likely exists on a broader scale-across countries and HT systems-but remains largely unexplored. This study characterized differences in heart donor populations and selection practices between the USA and Eurotransplant-a consortium of eight European countries-and their implications for system-wide outcomes.<br /><b>Methods</b><br />Characteristics of adult reported heart donors and their utilization (the percentage of reported donors accepted for HT) were compared between Eurotransplant (n = 8714) and the USA (n = 60 882) from 2010 to 2020. Predictors of donor acceptance were identified using multivariable logistic regression. Additional analyses estimated the impact of achieving Eurotransplant-level utilization in the USA amongst donors of matched quality, using probability of acceptance as a marker of quality.<br /><b>Results</b><br />Eurotransplant reported donors were older with more cardiovascular risk factors but with higher utilization than in the USA (70% vs. 44%). Donor age, smoking history, and diabetes mellitus predicted non-acceptance in the USA and, by a lesser magnitude, in Eurotransplant; donor obesity and hypertension predicted non-acceptance in the USA only. Achieving Eurotransplant-level utilization amongst the top 30%-50% of donors (by quality) would produce an additional 506-930 US HTs annually.<br /><b>Conclusions</b><br />Eurotransplant countries exhibit more liberal donor heart acceptance practices than the USA. Adopting similar acceptance practices could help alleviate the scarcity of donor hearts and reduce waitlist morbidity in the USA.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 03 Nov 2023; epub ahead of print</small></div>

<div><h4>Potassium intake: the Cinderella electrolyte.</h4><i>O\'Donnell M, Yusuf S, Vogt L, Mente A, Messerli FH</i><br /><AbstractText>Dietary guidelines recommend intake targets for some essential minerals, based on observational and experimental evidence relating mineral intake levels to health outcomes. For prevention of cardiovascular disease, reducing sodium intake and increasing potassium intake are the principal tools. While reducing sodium intake has received greatest public health priority, emerging evidence suggests that increasing potassium intake may be a more important target for cardiovascular prevention. Increased potassium intake reduces blood pressure and mitigates the hypertensive effects of excess sodium intake, and the recent large Phase III SSaSS trial reported that increasing potassium intake (and reducing sodium intake) in populations with low potassium intake and high sodium intake, through salt substitution (25% KCl, 75%NaCl), reduces the risk of stroke in patients at increased cardiovascular risk. As key sources of potassium intake include fruit, vegetables, nuts, and legumes, higher potassium intake may be associated with healthy dietary patterns. The current review makes the case that increasing potassium intake might represent a more advantageous dietary strategy for prevention of cardiovascular disease. Future research should focus on addressing the independent effect of potassium supplementation in populations with low or moderate potassium intake, and determine effective strategies to increase potassium intake from diet.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 03 Nov 2023; epub ahead of print</small></div>

<div><h4>Endpoint adjudication in cardiovascular clinical trials.</h4><i>Khan MS, Usman MS, Van Spall HGC, Greene SJ, ... Januzzi JL, Butler J</i><br /><AbstractText>Endpoint adjudication (EA) is a common feature of contemporary randomized controlled trials (RCTs) in cardiovascular medicine. Endpoint adjudication refers to a process wherein a group of expert reviewers, known as the clinical endpoint committee (CEC), verify potential endpoints identified by site investigators. Events that are determined by the CEC to meet pre-specified trial definitions are then utilized for analysis. The rationale behind the use of EA is that it may lessen the potential misclassification of clinical events, thereby reducing statistical noise and bias. However, it has been questioned whether this is universally true, especially given that EA significantly increases the time, effort, and resources required to conduct a trial. Herein, we compare the summary estimates obtained using adjudicated vs. non-adjudicated site designated endpoints in major cardiovascular RCTs in which both were reported. Based on these data, we lay out a framework to determine which trials may warrant EA and where it may be redundant. The value of EA is likely greater when cardiovascular trials have nuanced primary endpoints, endpoint definitions that align poorly with practice, sub-optimal data completeness, greater operator variability, and lack of blinding. EA may not be needed if the primary endpoint is all-cause death or all-cause hospitalization. In contrast, EA is likely merited for more nuanced endpoints such as myocardial infarction, bleeding, worsening heart failure as an outpatient, unstable angina, or transient ischaemic attack. A risk-based approach to adjudication can potentially allow compromise between costs and accuracy. This would involve adjudication of a small proportion of events, with further adjudication done if inconsistencies are detected.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 02 Nov 2023; epub ahead of print</small></div>

<div><h4>Mendelian randomization for cardiovascular diseases: principles and applications.</h4><i>Larsson SC, Butterworth AS, Burgess S</i><br /><AbstractText>Large-scale genome-wide association studies conducted over the last decade have uncovered numerous genetic variants associated with cardiometabolic traits and risk factors. These discoveries have enabled the Mendelian randomization (MR) design, which uses genetic variation as a natural experiment to improve causal inferences from observational data. By analogy with the random assignment of treatment in randomized controlled trials, the random segregation of genetic alleles when DNA is transmitted from parents to offspring at gamete formation is expected to reduce confounding in genetic associations. Mendelian randomization analyses make a set of assumptions that must hold for valid results. Provided that the assumptions are well justified for the genetic variants that are employed as instrumental variables, MR studies can inform on whether a putative risk factor likely has a causal effect on the disease or not. Mendelian randomization has been increasingly applied over recent years to predict the efficacy and safety of existing and novel drugs targeting cardiovascular risk factors and to explore the repurposing potential of available drugs. This review article describes the principles of the MR design and some applications in cardiovascular epidemiology.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 02 Nov 2023; epub ahead of print</small></div>

<div><h4>Routine stress testing in diabetic patients after percutaneous coronary intervention: the POST-PCI trial.</h4><i>Kim H, Kang DY, Lee J, Choi Y, ... Park SJ, Park DW</i><br /><b>Background:</b><br/>and aims</b><br />The optimal follow-up surveillance strategy for high-risk diabetic patients with had undergone percutaneous coronary intervention (PCI) remains unknown.<br /><b>Methods</b><br />The POST-PCI (Pragmatic Trial Comparing Symptom-Oriented versus Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention) study was a randomized trial comparing a follow-up strategy of routine functional testing at 1 year vs. standard care alone after high-risk PCI. Randomization was stratified according to diabetes status. The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years.<br /><b>Results</b><br />Among 1706 randomized patients, participants with diabetes (n = 660, 38.7%) had more frequent comorbidities and a higher prevalence of complex anatomical or procedural characteristics than those without diabetes (n = 1046, 61.3%). Patients with diabetes had a 52% greater risk of primary composite events [hazard ratio (HR) 1.52; 95% confidence interval (CI) 1.02-2.27; P = .039]. The 2-year incidences of the primary composite outcome were similar between strategies of routine functional testing or standard care alone in diabetic patients (7.1% vs. 7.5%; HR 0.94; 95% CI 0.53-1.66; P = .82) and non-diabetic patients (4.6% vs. 5.1%; HR 0.89; 95% CI 0.51-1.55; P = .68) (interaction term for diabetes: P = .91). The incidences of invasive coronary angiography and repeat revascularization after 1 year were higher in the routine functional-testing group than the standard-care group irrespective of diabetes status.<br /><b>Conclusions</b><br />Despite being at higher risk for adverse clinical events, patients with diabetes who had undergone high-risk PCI did not derive incremental benefit from routine surveillance stress testing compared with standard care alone during follow-up.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 02 Nov 2023; epub ahead of print</small></div>

<div><h4>Transfemoral tricuspid valve replacement and one-year outcomes: the TRISCEND study.</h4><i>Kodali S, Hahn RT, Makkar R, Makar M, ... Windecker S, TRISCEND study investigators </i><br /><b>Background:</b><br/>and aims</b><br />For patients with symptomatic, severe tricuspid regurgitation (TR), early results of transcatheter tricuspid valve (TV) intervention studies have shown significant improvements in functional status and quality of life associated with right-heart reverse remodelling. Longer-term follow-up is needed to confirm sustained improvements in these outcomes.<br /><b>Methods</b><br />The prospective, single-arm, multicentre TRISCEND study enrolled 176 patients to evaluate the safety and performance of transcatheter TV replacement in patients with ≥moderate, symptomatic TR despite medical therapy. Major adverse events, reduction in TR grade and haemodynamic outcomes by echocardiography, and clinical, functional, and quality-of-life parameters are reported to one year.<br /><b>Results</b><br />Enrolled patients were 71.0% female, mean age 78.7 years, 88.0% ≥ severe TR, and 75.4% New York Heart Association classes III-IV. Tricuspid regurgitation was reduced to ≤mild in 97.6% (P < .001), with increases in stroke volume (10.5 ± 16.8 mL, P < .001) and cardiac output (0.6 ± 1.2 L/min, P < .001). New York Heart Association class I or II was achieved in 93.3% (P < .001), Kansas City Cardiomyopathy Questionnaire score increased by 25.7 points (P < .001), and six-minute walk distance increased by 56.2 m (P < .001). All-cause mortality was 9.1%, and 10.2% of patients were hospitalized for heart failure.<br /><b>Conclusions</b><br />In an elderly, highly comorbid population with ≥moderate TR, patients receiving transfemoral EVOQUE transcatheter TV replacement had sustained TR reduction, significant increases in stroke volume and cardiac output, and high survival and low hospitalization rates with improved clinical, functional, and quality-of-life outcomes to one year. Funded by Edwards Lifesciences, TRISCEND ClinicalTrials.gov number, NCT04221490.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 01 Nov 2023; epub ahead of print</small></div>

<div><h4>Five critical quality criteria for artificial intelligence-based prediction models.</h4><i>van Royen FS, Asselbergs FW, Alfonso F, Vardas P, van Smeden M</i><br /><AbstractText>To raise the quality of clinical artificial intelligence (AI) prediction modelling studies in the cardiovascular health domain and thereby improve their impact and relevancy, the editors for digital health, innovation, and quality standards of the European Heart Journal propose five minimal quality criteria for AI-based prediction model development and validation studies: complete reporting, carefully defined intended use of the model, rigorous validation, large enough sample size, and openness of code and software.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 28 Oct 2023; epub ahead of print</small></div>

<div><h4>Clinical implementation of partial oral treatment in infective endocarditis: the Danish POETry study.</h4><i>Pries-Heje MM, Hjulmand JG, Lenz IT, Hasselbalch RB, ... Iversen KK, Bundgaard H</i><br /><b>Background:</b><br/>and aims</b><br />In the Partial Oral Treatment of Endocarditis (POET) trial, stabilized patients with left-sided infective endocarditis (IE) were randomized to oral step-down antibiotic therapy (PO) or conventional continued intravenous antibiotic treatment (IV), showing non-inferiority after 6 months. In this study, the first guideline-driven clinical implementation of the oral step-down POET regimen was examined.<br /><b>Methods</b><br />Patients with IE, caused by Staphylococcus aureus, Enterococcus faecalis, Streptococcus spp. or coagulase-negative staphylococci diagnosed between May 2019 and December 2020 were possible candidates for initiation of oral step-down antibiotic therapy, at the discretion of the treating physician. The composite primary outcome in patients finalizing antibiotic treatment consisted of embolic events, unplanned cardiac surgery, relapse of bacteraemia and all-cause mortality within 6 months.<br /><b>Results</b><br />A total of 562 patients [median age 74 years (IQR, interquartile range, 65-80), 70% males] with IE were possible candidates; PO was given to 240 (43%) patients and IV to 322 (57%) patients. More patients in the IV group had IE caused by S. aureus, or had an intra-cardiac abscess, or a pacemaker and more were surgically treated. The primary outcome occurred in 30 (13%) patients in the PO group and in 59 (18%) patients in the IV group (P = .051); in the PO group, 20 (8%) patients died vs. 46 (14%) patients in the IV group (P = .024). PO-treated patients had a shorter median length of stay [PO 24 days (IQR 17-36) vs. IV 43 days (IQR 32-51), P < .001].<br /><b>Conclusions</b><br />After clinical implementation of the POET regimen almost half of the possible candidates with IE received oral step-down antibiotic therapy. Patients in the IV group had more serious risk factors for negative outcomes. At 6-month follow-up, there was a numerically but not statistically significant difference towards a lower incidence of the primary outcome, a lower incidence of all-cause mortality and a reduced length of stay in the PO group. Due to the observational design of the study, the lower mortality may to some extent reflect selection bias and unmeasured confounding. Clinical implementation of PO regimens seemed feasible and safe.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 25 Oct 2023; epub ahead of print</small></div>

<div><h4>Outcomes of transcatheter pulmonary SAPIEN 3 valve implantation: an international registry.</h4><i>Hascoët S, Bentham JR, Giugno L, Betrián-Blasco P, ... Fraisse A, EUROPULMS3 investigators</i><br /><b>Background:</b><br/>and aims</b><br />Transcatheter pulmonary valve implantation (TPVI) is indicated to treat right-ventricular outflow tract (RVOT) dysfunction related to congenital heart disease (CHD). Outcomes of TPVI with the SAPIEN 3 valve that are insufficiently documented were investigated in the EUROPULMS3 registry of SAPIEN 3-TPVI.<br /><b>Methods</b><br />Patient-related, procedural, and follow-up outcome data were retrospectively assessed in this observational cohort from 35 centres in 15 countries.<br /><b>Results</b><br />Data for 840 consecutive patients treated in 2014-2021 at a median age of 29.2 (19.0-41.6) years were obtained. The most common diagnosis was conotruncal defect (70.5%), with a native or patched RVOT in 50.7% of all patients. Valve sizes were 20, 23, 26, and 29 mm in 0.4%, 25.5%, 32.1%, and 42.0% of patients, respectively. Valve implantation was successful in 98.5% [95% confidence interval (CI), 97.4%-99.2%] of patients. Median follow-up was 20.3 (7.1-38.4) months. Eight patients experienced infective endocarditis; 11 required pulmonary valve replacement, with a lower incidence for larger valves (P = .009), and four experienced pulmonary valve thrombosis, including one who died and three who recovered with anticoagulation. Cumulative incidences (95%CI) 1, 3, and 6 years after TPVI were as follows: infective endocarditis, 0.5% (0.0%-1.0%), 0.9% (0.2%-1.6%), and 3.8% (0.0%-8.4%); pulmonary valve replacement, 0.4% (0.0%-0.8%), 1.3% (0.2%-2.4%), and 8.0% (1.2%-14.8%); and pulmonary valve thrombosis, 0.4% (0.0%-0.9%), 0.7% (0.0%-1.3%), and 0.7% (0.0%-1.3%), respectively.<br /><b>Conclusions</b><br />Outcomes of SAPIEN 3 TPVI were favourable in patients with CHD, half of whom had native or patched RVOTs.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 24 Oct 2023; epub ahead of print</small></div>

<div><h4>Healthy sleep score changes and incident cardiovascular disease in European prospective community-based cohorts.</h4><i>Nambiema A, Lisan Q, Vaucher J, Perier MC, ... Marques-Vidal P, Empana JP</i><br /><b>Background:</b><br/>and aims</b><br />Evidence on the link between sleep patterns and cardiovascular diseases (CVDs) in the community essentially relies on studies that investigated one single sleep pattern at one point in time. This study examined the joint effect of five sleep patterns at two time points with incident CVD events.<br /><b>Methods</b><br />By combining the data from two prospective studies, the Paris Prospective Study III (Paris, France) and the CoLaus|PsyCoLaus study (Lausanne, Switzerland), a healthy sleep score (HSS, range 0-5) combining five sleep patterns (early chronotype, sleep duration of 7-8 h/day, never/rarely insomnia, no sleep apnoea, and no excessive daytime sleepiness) was calculated at baseline and follow-up.<br /><b>Results</b><br />The study sample included 11 347 CVD-free participants aged 53-64 years (44.6% women). During a median follow-up of 8.9 years [interquartile range (IQR): 8.0-10.0], 499 first CVD events occurred (339 coronary heart disease (CHD) and 175 stroke). In multivariate Cox analysis, the risk of CVD decreased by 18% [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.76-0.89] per one-point increment in the HSS. After a median follow-up of 6.0 years (IQR: 4.0-8.0) after the second follow-up, 262 first CVD events occurred including 194 CHD and 72 stroke. After adjusting for baseline HSS and covariates, the risk of CVD decreased by 16% (HR 0.84, 95% CI 0.73-0.97) per unit higher in the follow-up HSS over 2-5 years.<br /><b>Conclusions</b><br />Higher HSS and HSS improvement over time are associated with a lower risk of CHD and stroke in the community.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 20 Oct 2023; epub ahead of print</small></div>

<div><h4>Acute heart failure: current pharmacological treatment and perspectives.</h4><i>Deniau B, Costanzo MR, Sliwa K, Asakage A, Mullens W, Mebazaa A</i><br /><AbstractText>Acute heart failure (AHF) represents the most frequent cause of unplanned hospital admission in patients older than 65 years. Symptoms and clinical signs of AHF (e.g. dyspnoea, orthopnoea, oedema, jugular vein distension, and variation of body weight) are mostly related to systemic venous congestion secondary to various mechanisms including extracellular fluids, increased ventricular filling pressures, and/or auto-transfusion of blood from the splanchnic into the pulmonary circulation. Thus, the initial management of AHF patients should be mostly based on decongestive therapies on admission followed, before discharge, by rapid implementation of guideline-directed oral medical therapies for heart failure. The therapeutic management of AHF requires the identification and rapid diagnosis of the disease, the diagnosis of the cause (or triggering factor), the evaluation of severity, the presence of comorbidities, and, finally, the initiation of a rapid treatment. The most recent guidelines from ESC and ACC/AHA/HFSA have provided updated recommendations on AHF management. Recommended pharmacological treatment for AHF includes diuretic therapy aiming to relieve congestion and achieve optimal fluid status, early and rapid initiation of oral therapies before discharge combined with a close follow-up. Non-pharmacological AHF management requires risk stratification in the emergency department and non-invasive ventilation in case of respiratory failure. Vasodilators should be considered as initial therapy in AHF precipitated by hypertension. On the background of recent large randomized clinical trials and international guidelines, this state-of-the-art review describes current pharmacological treatments and potential directions for future research in AHF.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 18 Oct 2023; epub ahead of print</small></div>

<div><h4>Intra-pocket ultrasound-guided axillary vein puncture vs. cephalic vein cutdown for cardiac electronic device implantation: the ACCESS trial.</h4><i>Charles P, Ditac G, Montoy M, Thenard T, ... Harbaoui B, Fareh S</i><br /><b>Background:</b><br/>and aims</b><br />Intra-pocket ultrasound-guided axillary vein puncture (IPUS-AVP) for venous access in implantation of transvenous cardiac implantable electronic devices (CIED) is uncommon due to the lack of clinical evidence supporting this technique. This study investigated the efficacy and early complications of IPUS-AVP compared to the standard method using cephalic vein cutdown (CVC) for CIED implantation.<br /><b>Methods</b><br />ACCESS was an investigator-led, interventional, randomized (1:1 ratio), monocentric, controlled superiority trial. A total of 200 patients undergoing CIED implantation were randomized to IPUS-AVP (n = 101) or CVC (n = 99) as a first assigned route. The primary endpoint was the success rate of insertion of all leads using the first assigned venous access technique. The secondary endpoints were time to venous access, total procedure duration, fluoroscopy time, X-ray exposure, and complications. Complications were monitored during a follow-up period of three months after procedure.<br /><b>Results</b><br />IPUS-AVP was significantly superior to CVC for the primary endpoint with 100 (99.0%) vs. 86 (86.9%) procedural successes (P = .001). Cephalic vein cutdown followed by subclavian vein puncture was successful in a total of 95 (96.0%) patients, P = .21 vs. IPUS-AVP. All secondary endpoints were also significantly improved in the IPUS-AVP group with reduction in time to venous access [3.4 vs. 10.6 min, geometric mean ratio (GMR) 0.32 (95% confidence interval, CI, 0.28-0.36), P < .001], total procedure duration [33.8 vs. 46.9 min, GMR 0.72 (95% CI 0.67-0.78), P < .001], fluoroscopy time [2.4 vs. 3.3 min, GMR 0.74 (95% CI 0.63-0.86), P < .001], and X-ray exposure [1083 vs. 1423 mGy.cm², GMR 0.76 (95% CI 0.62-0.93), P = .009]. There was no significant difference in complication rates between groups (P = .68).<br /><b>Conclusions</b><br />IPUS-AVP is superior to CVC in terms of success rate, time to venous access, procedure duration, and radiation exposure. Complication rates were similar between the two groups. Intra-pocket ultrasound-guided axillary vein puncture should be a recommended venous access technique for CIED implantation.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 13 Oct 2023; epub ahead of print</small></div>

<div><h4>A 20-year population study of peripartum cardiomyopathy.</h4><i>Jackson AM, Macartney M, Brooksbank K, Brown C, ... Jhund PS, Petrie MC</i><br /><b>Background:</b><br/>and aims</b><br />The epidemiology of peripartum cardiomyopathy (PPCM) in Europe is poorly understood and data on long-term outcomes are lacking. A retrospective, observational, population-level study of validated cases of PPCM in Scotland from 1998 to 2017 was conducted.<br /><b>Methods</b><br />Women hospitalized with presumed de novo left ventricular systolic dysfunction around the time of pregnancy and no clear alternative cause were included. Each case was matched to 10 controls. Incidence and risk factors were identified. Morbidity and mortality were examined in mothers and children.<br /><b>Results</b><br />The incidence of PPCM was 1 in 4950 deliveries. Among 225 women with PPCM, obesity, gestational hypertensive disorders, and multi-gestation were found to be associated with having the condition. Over a median of 8.3 years (9.7 years for echocardiographic outcomes), 8% of women with PPCM died and 75% were rehospitalized for any cause at least once. Mortality and rehospitalization rates in women with PPCM were ∼12- and ∼3-times that of controls, respectively. The composite of all-cause death, mechanical circulatory support, or cardiac transplantation occurred in 14%. LV recovery occurred in 76% and, of those who recovered, 13% went on to have a decline in LV systolic function despite initial recovery. The mortality rate for children born to women with PPCM was ∼5-times that of children born to controls and they had an ∼3-times greater incidence of cardiovascular disease over a median of 8.8 years.<br /><b>Conclusions</b><br />PPCM affected 1 in 4950 women around the time of pregnancy. The condition is associated with considerable morbidity and mortality for the mother and child. There should be a low threshold for investigating at-risk women. Long term follow-up, despite apparent recovery, should be considered.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 07 Oct 2023; epub ahead of print</small></div>

<div><h4>Mavacamten: a first-in-class myosin inhibitor for obstructive hypertrophic cardiomyopathy.</h4><i>Braunwald E, Saberi S, Abraham TP, Elliott PM, Olivotto I</i><br /><AbstractText>Mavacamten is a first-in-class, targeted, cardiac-specific myosin inhibitor approved by the US Food and Drug Administration for the treatment of adults with symptomatic New York Heart Association Classes II and III obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten was developed to target the hyper-contractile phenotype, which plays a critical role in the pathophysiology of the disease. In Phase 2 and 3 clinical trials, mavacamten was well tolerated, reduced left ventricular outflow tract gradients, improved exercise capacity and symptoms, and was associated with improvements in other clinically relevant parameters, such as patient-reported outcomes and circulating biomarkers. In addition, treatment with mavacamten was associated with evidence of favourable cardiac remodelling in multi-modality imaging studies. Mavacamten substantially reduced guideline eligibility for septal reduction therapy candidates with oHCM and drug-refractory symptoms. In this article, the available efficacy and safety data from completed and ongoing clinical studies of mavacamten in patients with symptomatic oHCM are reviewed. Longer term extension studies may help address questions related to the positioning of mavacamten in current oHCM management algorithms, interactions with background therapy, as well as the potential for disease modification beyond symptomatic relief of left ventricular outflow tract obstruction.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 07 Oct 2023; epub ahead of print</small></div>

<div><h4>Assessment of late gadolinium enhancement in hypertrophic cardiomyopathy improves risk stratification based on current guidelines.</h4><i>Wang J, Yang S, Ma X, Zhao K, ... Chen X, Zhao S</i><br /><b>Background:</b><br/>and aims</b><br />Identifying patients with hypertrophic cardiomyopathy (HCM) who are candidates for implantable cardioverter defibrillator (ICD) implantation in primary prevention for sudden cardiac death (SCD) is crucial. The aim of this study was to externally validate the 2022 European Society of Cardiology (ESC) model and other guideline-based ICD class of recommendation (ICD-COR) models and explore the utility of late gadolinium enhancement (LGE) in further risk stratification.<br /><b>Methods</b><br />Seven hundred and seventy-four consecutive patients who underwent cardiac magnetic resonance imaging were retrospectively enrolled.<br /><b>Results</b><br />Forty-six (5.9%) patients reached the SCD-related endpoint during 7.4 ± 2.5 years of follow-up. Patients suffering from SCD had higher ESC Risk-SCD score (4.3 ± 2.4% vs. 2.8 ± 2.1%, P < .001) and LGE extent (13.7 ± 9.4% vs. 4.9 ± 6.6%, P < .001). Compared with the 2014 ESC model, the 2022 ESC model showed increased area under the curve (.76 vs. .63), sensitivity (76.1% vs. 43.5%), positive predictive value (16.8% vs. 13.6%), and negative predictive value (98.1% vs. 95.9%). The C-statistics for SCD prediction of 2011 American College of Cardiology (ACC)/American Heart Association (AHA), 2014 ESC, 2020 AHA/ACC, and 2022 ESC models were .68, .64, .76 and .78, respectively. Furthermore, in patients without extensive LGE, LGE ≥5% was responsible for seven-fold SCD risk after multivariable adjustment. Whether in ICD-COR II or ICD-COR III, patients with LGE ≥5% and <15% showed significantly worse prognosis than those with LGE <5% (all P < .001).<br /><b>Conclusions</b><br />The 2022 ESC model performed better than the 2014 ESC model with especially improved sensitivity. LGE enabled further risk stratification based on current guidelines.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 05 Oct 2023; epub ahead of print</small></div>

<div><h4>Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.</h4><i>Hahn RT, Lawlor MK, Davidson CJ, Badhwar V, ... Leon MB, Hausleiter J</i><br /><AbstractText>Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.</AbstractText><br /><br />© 2023 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 04 Oct 2023; epub ahead of print</small></div>

<div><h4>The Vienna Prediction Model for identifying patients at low risk of recurrent venous thromboembolism: a prospective cohort study.</h4><i>Kyrle PA, Eischer L, Šinkovec H, Gressenberger P, ... Heinze G, Eichinger S</i><br /><b>Background:</b><br/>and aims</b><br />Patients with unprovoked venous thromboembolism (VTE) have a high recurrence risk, and guidelines suggest extended-phase anticoagulation. Many patients never experience recurrence but are exposed to bleeding. The aim of this study was to assess the performance of the Vienna Prediction Model (VPM) and to evaluate if the VPM accurately identifies these patients.<br /><b>Methods</b><br />In patients with unprovoked VTE, the VPM was performed 3 weeks after anticoagulation withdrawal. Those with a predicted 1-year recurrence risk of ≤5.5% were prospectively followed. Study endpoint was recurrent VTE over 2 years.<br /><b>Results</b><br />A total of 818 patients received anticoagulation for a median of 3.9 months. 520 patients (65%) had a predicted annual recurrence risk of ≤5.5%. During a median time of 23.9 months, 52 patients had non-fatal recurrence. The recurrence risk was 5.2% [95% confidence interval (CI) 3.2-7.2] at 1 year and 11.2% (95% CI 8.3-14) at 2 years. Model calibration was adequate after 1 year. The VPM underestimated the recurrence risk of patients with a 2-year recurrence rate of >5%. In a post-hoc analysis, the VPM\'s baseline hazard was recalibrated. Bootstrap validation confirmed an ideal ratio of observed and expected recurrence events. The recurrence risk was highest in men with proximal deep-vein thrombosis or pulmonary embolism and lower in women regardless of the site of incident VTE.<br /><b>Conclusions</b><br />In this prospective evaluation of the performance of the VPM, the 1-year rate of recurrence in patients with unprovoked VTE was 5.2%. Recalibration improved identification of patients at low recurrence risk and stratification into distinct low-risk categories.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 28 Sep 2023; epub ahead of print</small></div>

<div><h4>Acquired cardiovascular disease in adults with congenital heart disease.</h4><i>Brida M, De Rosa S, Legendre A, Ladouceur M, ... Diller G, Gatzoulis MA</i><br /><AbstractText>Rates of successful surgical repair and life expectancy for patients with congenital heart disease have increased dramatically in recent decades. Thanks to advances in diagnosis, treatment, and follow-up care, an ever-increasing number of individuals with congenital heart disease are reaching advanced age. The exposure to cardiovascular risk factors during their lifetime is modifying the outlook and late clinical trajectory of adult congenital heart disease (ACHD). Their disease burden is shifting from congenital to acquired, primarily atherosclerotic cardiovascular disease (ASCVD) with worrisome consequences. In addition, the complex background of ACHD often curbs appropriate preventive strategies by general practitioners or adult cardiologists. Comprehensive guidance for the prevention and management of acquired heart disease in ACHD patients is currently not available, as this topic has not been covered by the European Society of Cardiology (ESC) guidelines on cardiovascular disease prevention or the ESC guidelines for the management of ACHD. In this document, a state-of-the-art overview of acquired heart disease in ACHD patients and guidance on ASCVD prevention for both ACHD specialists and non-ACHD cardiologists are provided. The aim is to provide a clinical consensus statement to foster the development of a sustainable strategy for the prevention of ASCVD in a practical and simple-to-follow way in this ever-growing cardiovascular cohort, thus reducing their cardiovascular burden.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 27 Sep 2023; epub ahead of print</small></div>

<div><h4>Smoking and cardiovascular outcomes after percutaneous coronary intervention: a Korean study.</h4><i>Ki YJ, Han K, Kim HS, Han JK</i><br /><b>Background:</b><br/>and aims</b><br />The authors investigated the impact of smoking and its cessation after percutaneous coronary intervention (PCI) on cardiovascular outcomes.<br /><b>Methods</b><br />Using a nationwide database from the Korean National Health Insurance System, 74 471 patients undergoing PCI between 2009 and 2016 were classified as non-, ex-, or current smokers, depending on smoking status at the first health check-up within 1 year after PCI. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of all-cause death, myocardial infarction, coronary revascularization, and stroke.<br /><b>Results</b><br />During 4.0 years of follow-up, current smokers had a 19.8% higher rate of MACCE than non-smokers [adjusted hazard ratio (aHR) 1.198; 95% confidence interval (CI) 1.137-1.263], and ex-smokers tended to have a comparable rate with that of non-smokers (aHR 1.036; 95% CI .992-1.081). For 31 887 patients with both pre- and post-PCI health check-up data, the effects of smoking cessation were analysed. Among quitters who stopped smoking after PCI, quitters with cumulative smoking exposure of <20 pack-years (PYs) tended to have a comparable rate of MACCE with that of persistent non-smokers. However, the rate in quitters with cumulative exposure of ≥20 PYs was comparable with that of persistent smokers [aHR (95% CI) for <10 PY, 1.182 (.971-1.438); 10-20 PYs 1.114 (.963-1.290); 20-30 PYs 1.206 (1.054-1.380); ≥ 30 PYs 1.227 (1.113-1.352); persistent smokers 1.223 (1.126-1.328), compared with persistent non-smokers, respectively, P for interaction <.001].<br /><b>Conclusions</b><br />Smoking is associated with a higher risk of adverse outcomes in patients undergoing PCI. Quitters after PCI with <20 PYs were associated with a risk comparable with that of non-smokers.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 26 Sep 2023; epub ahead of print</small></div>

<div><h4>Birth weight influences cardiac structure, function, and disease risk: evidence of a causal association.</h4><i>Ardissino M, Morley AP, Slob EAW, Schuermans A, ... Honigberg MC, Ng FS</i><br /><b>Background:</b><br/>and aims</b><br />Low birth weight is a common pregnancy complication, which has been associated with higher risk of cardiometabolic disease in later life. Prior Mendelian randomization (MR) studies exploring this question do not distinguish the mechanistic contributions of variants that directly influence birth weight through the foetal genome (direct foetal effects), vs. variants influencing birth weight indirectly by causing an adverse intrauterine environment (indirect maternal effects). In this study, MR was used to assess whether birth weight, independent of intrauterine influences, is associated with cardiovascular disease risk and measures of adverse cardiac structure and function.<br /><b>Methods</b><br />Uncorrelated (r2 < .001), genome-wide significant (P < 5 × 10-8) single nucleotide polymorphisms were extracted from genome-wide association studies summary statistics for birth weight overall, and after isolating direct foetal effects only. Inverse-variance weighted MR was utilized for analyses on outcomes of atrial fibrillation, coronary artery disease, heart failure, ischaemic stroke, and 16 measures of cardiac structure and function. Multiple comparisons were accounted for by Benjamini-Hochberg correction.<br /><b>Results</b><br />Lower genetically-predicted birth weight, isolating direct foetal effects only, was associated with an increased risk of coronary artery disease (odds ratio 1.21, 95% confidence interval 1.06-1.37; P = .031), smaller chamber volumes, and lower stroke volume, but higher contractility.<br /><b>Conclusions</b><br />The results of this study support a causal role of low birth weight in cardiovascular disease, even after accounting for the influence of the intrauterine environment. This suggests that individuals with a low birth weight may benefit from early targeted cardiovascular disease prevention strategies, independent of whether this was linked to an adverse intrauterine environment during gestation.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 20 Sep 2023; epub ahead of print</small></div>

<div><h4>Acquired risk factors and incident atrial fibrillation according to age and genetic predisposition.</h4><i>Wang N, Yu Y, Sun Y, Zhang H, ... Wang B, Lu Y</i><br /><b>Background:</b><br/>and aims</b><br />Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. Investigations of risk factor profiles for AF according to age and genetic risk groups are essential to promote individualized strategies for the prevention and control of AF.<br /><b>Methods</b><br />A total of 409 661 participants (mean age, 56 years; 46% men) free of AF at baseline and with complete information about risk factors were included from the UK Biobank cohort. The hazard ratios and population-attributable risk (PAR) percentages of incident AF associated with 23 risk factors were examined, including 3 social factors, 7 health behaviours, 6 cardiometabolic factors, 6 clinical comorbidities, and the genetic risk score (GRS), across 3 age groups (40-49, 50-59, and 60-69 years) and 3 genetic risk groups (low, moderate, and high GRS).<br /><b>Results</b><br />After a follow-up of 5 027 587 person-years, 23 847 participants developed AF. Most cardiometabolic factors and clinical comorbidities showed a significant interaction with age, whereby the associations were generally strengthened in younger groups (Pinteraction < .002). However, only low LDL cholesterol, renal dysfunction, and cardiovascular disease showed a significant interaction with genetic risk, and the associations with these factors were stronger in lower genetic risk groups (Pinteraction < .002). Cardiometabolic factors consistently accounted for the largest number of incident AF cases across all age groups (PAR: 36.2%-38.9%) and genetic risk groups (34.0%-41.9%), with hypertension and overweight/obesity being the two leading modifiable factors. Health behaviours (PAR: 11.5% vs. 8.7%) and genetic risk factors (19.1% vs. 14.3%) contributed to more AF cases in the 40-49 years group than in the 60-69 years group, while the contribution of clinical comorbidities remained relatively stable across different age groups. The AF risk attributable to overall cardiometabolic factors (PAR: 41.9% in the low genetic risk group and 34.0% in the high genetic risk group) and clinical comorbidities (24.7% and 15.9%) decreased with increasing genetic risk. The impact of social factors on AF was relatively low across the groups by age and genetic risk.<br /><b>Conclusions</b><br />This study provided comprehensive information about age- and genetic predisposition-related risk factor profiles for AF in a cohort of UK adults. Prioritizing risk factors according to age and genetic risk stratifications may help to achieve precise and efficient prevention of AF.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 19 Sep 2023; epub ahead of print</small></div>

<div><h4>Lack of association between fluoroquinolone and aortic aneurysm or dissection.</h4><i>Huh K, Kang M, Jung J</i><br /><b>Background:</b><br/>and aims</b><br />An increased risk of aortic aneurysm and aortic dissection (AA/AD) has been reported with fluoroquinolone (FQ) use. However, recent studies suggested confounding factors by indication. This study aimed to investigate the risk of AA/AD associated with FQ use.<br /><b>Methods</b><br />This nationwide population-based study included adults aged ≥20 years who received a prescription of oral FQ or third-generation cephalosporins (3GC) during outpatient visits from 2005 to 2016. Data source was the National Health Insurance Service reimbursement database. The primary outcome was hospitalization or in-hospital death with a primary diagnosis of AA/AD. A self-controlled case series (SCCS) and Cox proportional hazards model were used. Self-controlled case series compared the incidence of the primary outcome in the risk period vs. the control periods.<br /><b>Results</b><br />A total of 954 308 patients (777 109 with FQ and 177 199 with 3GC use) were included. The incidence rate ratios for AA/AD between the risk period and the pre-risk period were higher in the 3GC group [11.000; 95% confidence interval (CI) 1.420-85.200] compared to the FQ group (2.000; 95% CI 0.970-4.124). The overall incidence of AA/AD among the patients who received FQ and 3GC was 5.40 and 8.47 per 100 000 person-years. There was no significant difference in the risk between the two groups (adjusted hazard ratio 0.752; 95% CI 0.515-1.100) in the inverse probability of treatment-weighted Cox proportional hazards model. Subgroup and sensitivity analysis showed consistent results.<br /><b>Conclusions</b><br />There was no significant difference in the risk of AA/AD in patients who were administered oral FQ compared to those administered 3GC. The study findings suggest that the use of FQ should not be deterred when clinically indicated.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 19 Sep 2023; epub ahead of print</small></div>

<div><h4>Cardiac magnetic resonance biomarkers as surrogate endpoints in cardiovascular trials for myocardial diseases.</h4><i>Benz DC, Gräni C, Antiochos P, Heydari B, ... Dorbala S, Kwong RY</i><br /><AbstractText>Cardiac magnetic resonance offers multiple facets in the diagnosis, risk stratification, and management of patients with myocardial diseases. Particularly, its feature to precisely monitor disease activity lends itself to quantify response to novel therapeutics. This review critically appraises the value of cardiac magnetic resonance imaging biomarkers as surrogate endpoints for prospective clinical trials. The primary focus is to comprehensively outline the value of established cardiac magnetic resonance parameters in myocardial diseases. These include heart failure, cardiac amyloidosis, iron overload cardiomyopathy, hypertrophic cardiomyopathy, cardio-oncology, and inflammatory cardiomyopathies like myocarditis and sarcoidosis.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 13 Sep 2023; epub ahead of print</small></div>

<div><h4>Mechanisms of benefits of sodium-glucose cotransporter 2 inhibitors in heart failure with preserved ejection fraction.</h4><i>Pandey AK, Bhatt DL, Pandey A, Marx N, ... Pandey A, Verma S</i><br /><AbstractText>For decades, heart failure with preserved ejection fraction (HFpEF) proved an elusive entity to treat. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently been shown to reduce the composite of heart failure hospitalization or cardiovascular death in patients with HFpEF in the landmark DELIVER and EMPEROR-Preserved trials. While improvements in blood sugar, blood pressure, and attenuation of kidney disease progression all may play some role, preclinical and translational research have identified additional mechanisms of these agents. The SGLT2 inhibitors have intriguingly been shown to induce a nutrient-deprivation and hypoxic-like transcriptional paradigm, with increased ketosis, erythropoietin, and autophagic flux in addition to altering iron homeostasis, which may contribute to improved cardiac energetics and function. These agents also reduce epicardial adipose tissue and alter adipokine signalling, which may play a role in the reductions in inflammation and oxidative stress observed with SGLT2 inhibition. Emerging evidence also indicates that these drugs impact cardiomyocyte ionic homeostasis although whether this is through indirect mechanisms or via direct, off-target effects on other ion channels has yet to be clearly characterized. Finally, SGLT2 inhibitors have been shown to reduce myofilament stiffness as well as extracellular matrix remodelling/fibrosis in the heart, improving diastolic function. The SGLT2 inhibitors have established themselves as robust, disease-modifying therapies and as recent trial results are incorporated into clinical guidelines, will likely become foundational in the therapy of HFpEF.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 07 Sep 2023; epub ahead of print</small></div>

<div><h4>Electronic health record alerts for management of heart failure with reduced ejection fraction in hospitalized patients: the PROMPT-AHF trial.</h4><i>Ghazi L, Yamamoto Y, Fuery M, O\'Connor K, ... Desai NR, Ahmad T</i><br /><b>Background:</b><br/>and aims</b><br />Patients hospitalized for acute heart failure (AHF) continue to be discharged on an inadequate number of guideline-directed medical therapies (GDMT) despite evidence that inpatient initiation is beneficial. This study aimed to examine whether a tailored electronic health record (EHR) alert increased rates of GDMT prescription at discharge in eligible patients hospitalized for AHF.<br /><b>Methods</b><br />Pragmatic trial of messaging to providers about treatment of acute heart failure (PROMPT-AHF) was a pragmatic, multicenter, EHR-based, and randomized clinical trial. Patients were automatically enrolled 48 h after admission if they met pre-specified criteria for an AHF hospitalization. Providers of patients in the intervention arm received an alert during order entry with relevant patient characteristics along with individualized GDMT recommendations with links to an order set. The primary outcome was an increase in the number of GDMT prescriptions at discharge.<br /><b>Results</b><br />Thousand and twelve patients were enrolled between May 2021 and November 2022. The median age was 74 years; 26% were female, and 24% were Black. At the time of the alert, 85% of patients were on β-blockers, 55% on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, 20% on mineralocorticoid receptor antagonist (MRA) and 17% on sodium-glucose cotransporter 2 inhibitor. The primary outcome occurred in 34% of both the alert and no alert groups [adjusted risk ratio (RR): 0.95 (0.81, 1.12), P = .99]. Patients randomized to the alert arm were more likely to have an increase in MRA [adjusted RR: 1.54 (1.10, 2.16), P = .01]. At the time of discharge, 11.2% of patients were on all four pillars of GDMT.<br /><b>Conclusions</b><br />A real-time, targeted, and tailored EHR-based alert system for AHF did not lead to a higher number of overall GDMT prescriptions at discharge. Further refinement and improvement of such alerts and changes to clinician incentives are needed to overcome barriers to the implementation of GDMT during hospitalizations for AHF. GDMT remains suboptimal in this setting, with only one in nine patients being discharged on a comprehensive evidence-based regimen for heart failure.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 31 Aug 2023; epub ahead of print</small></div>

<div><h4>Stroke risk in women with atrial fibrillation.</h4><i>Buhari H, Fang J, Han L, Austin PC, ... Lee DS, Abdel-Qadir H</i><br /><b>Background:</b><br/>and aims</b><br />Female sex is associated with higher rates of stroke in atrial fibrillation (AF) after adjustment for other CHA2DS2-VASc factors. This study aimed to describe sex differences in age and cardiovascular care to examine their relationship with stroke hazard in AF.<br /><b>Methods</b><br />Population-based cohort study using administrative datasets of people aged ≥66 years diagnosed with AF in Ontario between 2007 and 2019. Cause-specific hazard regression was used to estimate the adjusted hazard ratio (HR) for stroke associated with female sex over a 2-year follow-up. Model 1 included CHA2DS2-VASc factors, with age modelled as 66-74 vs. ≥ 75 years. Model 2 treated age as a continuous variable and included an age-sex interaction term. Model 3 further accounted for multimorbidity and markers of cardiovascular care.<br /><b>Results</b><br />The cohort consisted of 354 254 individuals with AF (median age 78 years, 49.2% female). Females were more likely to be diagnosed in emergency departments and less likely to receive cardiologist assessments, statins, or LDL-C testing, with higher LDL-C levels among females than males. In Model 1, the adjusted HR for stroke associated with female sex was 1.27 (95% confidence interval 1.21-1.32). Model 2 revealed a significant age-sex interaction, such that female sex was only associated with increased stroke hazard at age >70 years. Adjusting for markers of cardiovascular care and multimorbidity further decreased the HR, so that female sex was not associated with increased stroke hazard at age ≤80 years.<br /><b>Conclusion</b><br />Older age and inequities in cardiovascular care may partly explain higher stroke rates in females with AF.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 30 Aug 2023; epub ahead of print</small></div>