<div><h4>Nonthrombogenic Roles of the Left Atrial Appendage: JACC Review Topic of the Week.</h4><i>Alkhouli M, Di Biase L, Natale A, Rihal CS, ... Lakkireddy D, Friedman PA</i><br /><AbstractText>The atrial appendage (LAA) is a well-established source of cardioembolism in patients with atrial fibrillation. Therefore, research involving the LAA has largely focused on its thrombogenic attribute and the utility of its exclusion in stroke prevention. However, recent studies have highlighted several novel functions of the LAA that may have important therapeutic implications. In this paper, we provide a concise overview of the LAA anatomy and summarize the emerging data on its nonthrombogenic roles.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Mar 2023; 81:1063-1075</small></div>

<div><h4>Intrapericardial long non-coding RNA-Tcf21 antisense RNA inducing demethylation administration promotes cardiac repair.</h4><i>Zhu D, Liu S, Huang K, Li J, ... Li Z, Cheng K</i><br /><b>Aims</b><br />Epicardium and epicardium-derived cells are critical players in myocardial fibrosis. Mesenchymal stem cell-derived extracellular vesicles (EVs) have been studied for cardiac repair to improve cardiac remodelling, but the actual mechanisms remain elusive. The aim of this study is to investigate the mechanisms of EV therapy for improving cardiac remodelling and develop a promising treatment addressing myocardial fibrosis.<br /><b>Methods and results</b><br />Extracellular vesicles were intrapericardially injected for mice myocardial infarction treatment. RNA-seq, in vitro gain- and loss-of-function experiments, and in vivo studies were performed to identify targets that can be used for myocardial fibrosis treatment. Afterward, a lipid nanoparticle-based long non-coding RNA (lncRNA) therapy was prepared for mouse and porcine models of myocardial infarction treatment. Intrapericardial injection of EVs improved adverse myocardial remodelling in mouse models of myocardial infarction. Mechanistically, Tcf21 was identified as a potential target to improve cardiac remodelling. Loss of Tcf21 function in epicardium-derived cells caused increased myofibroblast differentiation, whereas forced Tcf21 overexpression suppressed transforming growth factor-β signalling and myofibroblast differentiation. LncRNA-Tcf21 antisense RNA inducing demethylation (TARID) that enriched in EVs was identified to up-regulate Tcf21 expression. Formulated lncRNA-TARID-laden lipid nanoparticles up-regulated Tcf21 expression in epicardium-derived cells and improved cardiac function and histology in mouse and porcine models of myocardial infarction.<br /><b>Conclusion</b><br />This study identified Tcf21 as a critical target for improving cardiac fibrosis. Up-regulating Tcf21 by using lncRNA-TARID-laden lipid nanoparticles could be a promising way to treat myocardial fibrosis. This study established novel mechanisms underlying EV therapy for improving adverse remodelling and proposed a lncRNA therapy for cardiac fibrosis.<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 Mar 2023; epub ahead of print</small></div>

<div><h4>Sex Differences in Extensive Mitral Annular Calcification With Associated Mitral Valve Dysfunction.</h4><i>Churchill TW, Yucel E, Bernard S, Namasivayam M, ... Hung J, Bertrand PB</i><br /><AbstractText>Mitral annular calcification (MAC)-related mitral valve (MV) dysfunction is an increasingly recognized entity, which confers a high burden of morbidity and mortality. Although more common among women, there is a paucity of data regarding how the phenotype of MAC and the associated adverse clinical implications may differ between women and men. A total of 3,524 patients with extensive MAC and significant MAC-related MV dysfunction (i.e., transmitral gradient ≥3 mm Hg) were retrospectively analyzed from a large institutional database, with the goal of defining gender differences in clinical and echocardiographic characteristics and the prognostic importance of MAC-related MV dysfunction. We stratified patients into low- (3 to 5 mm Hg), moderate- (5 to 10 mm Hg), and high- (≥10 mm Hg) gradient groups and analyzed the gender differences in phenotype and outcome. The primary outcome was all-cause mortality, assessed using adjusted Cox regression models. Women represented the majority (67%) of subjects, were older (79.3 ± 10.4 vs 75.5 ± 10.9 years, p <0.001) and had a lower burden of cardiovascular co-morbidities than men. Women had higher transmitral gradients (5.7 ± 2.7 vs 5.3 ± 2.6 mm Hg, p <0.001), more concentric hypertrophy (49% vs 33%), and more mitral regurgitation. The median survival was 3.4 years (95% confidence interval 3.0 to 3.6) among women and 3.0 years (95% confidence interval 2.6 to 4.5) among men. The adjusted survival was worse among men, and the prognostic impact of the transmitral gradient did not differ overall by gender. In conclusion, we describe important gender differences among patients with MAC-related MV dysfunction and show worse adjusted survival among men; although, the adverse prognostic impact of the transmitral gradient was similar between men and women.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 05 Mar 2023; 193:83-90</small></div>

<div><h4>Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients.</h4><i>Nissen SE, Lincoff AM, Brennan D, Ray KK, ... Nicholls SJ, CLEAR Outcomes Investigators</i><br /><b>Background</b><br />Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain.<br /><b>Methods</b><br />We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects (\"statin-intolerant\" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo. The primary end point was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization.<br /><b>Results</b><br />A total of 13,970 patients underwent randomization; 6992 were assigned to the bempedoic acid group and 6978 to the placebo group. The median duration of follow-up was 40.6 months. The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = 0.004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 [8.2%] vs. 663 [9.5%]; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = 0.006); fatal or nonfatal myocardial infarction (261 [3.7%] vs. 334 [4.8%]; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P = 0.002); and coronary revascularization (435 [6.2%] vs. 529 [7.6%]; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = 0.001). Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels.<br /><b>Conclusions</b><br />Among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization). (Funded by Esperion Therapeutics; CLEAR Outcomes ClinicalTrials.gov number, NCT02993406.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 04 Mar 2023; epub ahead of print</small></div>

<div><h4>Association of Cardiac Remodeling with Aortic Regurgitation Outcomes: The AR Consortium of the SCMR Registry.</h4><i>Malahfji M, Crudo V, Kaolawanich Y, Nguyen DT, ... Kim R, Shah DJ</i><br /><b>Background</b><br />Quantitative cardiac magnetic resonance (CMR) outcome studies in aortic regurgitation (AR) are few. It is unclear if volume measurements are beneficial over diameters.<br /><b>Objectives</b><br />To evaluate the association of CMR quantitative thresholds and outcomes in AR patients.<br /><b>Methods</b><br />in a multicenter study, asymptomatic patients with moderate or severe AR on CMR with preserved LV ejection fraction (LVEF) were evaluated. Primary outcome was development of symptoms or decrease in LVEF to <50%, guideline indications for surgery based on LV dimensions, or death under medical management. Secondary outcome was the same excluding surgery for remodeling indications. We excluded patients who underwent surgery within 30 days of CMR. ROC analyses for the association with outcome were performed.<br /><b>Results</b><br />We studied 458 patients, median age 60 (IQR 46-70) years. During a median follow-up of 2.4 years (IQR 0.9, 5.3), 133 events occurred. Optimal thresholds were regurgitant volume of 47 ml and regurgitant fraction of 43%, indexed LV end-systolic (iLVES) volume of 43 ml/m<sup>2,</sup> iLVED volume of 109 ml/m<sup>2</sup>, and iLVES diameter of 2 cm/m<sup>2</sup>. In multivariable regression analysis, iLVES volume ≥43 ml/m<sup>2</sup> (HR 2.53 (1.75, 3.66), P<0.001) and and iLVED volume ≥ 109 ml/m<sup>2</sup> were independently associated with the outcomes and provided additional discrimination improvement over iLVES diameter, whereas iLVES diameter was independently associated with the primary outcome but not the secondary outcome.<br /><b>Conclusion</b><br />In asymptomatic AR patients with preserved LVEF, CMR findings can be used to guide management. CMR based LV end-systolic volume assessment performed favorably compared to LV diameters.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 03 Mar 2023; epub ahead of print</small></div>

<div><h4>TAVR in 2023: Who Should Not Get It?</h4><i>Bhogal S, Rogers T, Aladin A, Ben-Dor I, ... Yakubov SJ, Waksman R</i><br /><AbstractText>Since the first transcatheter delivery of an aortic valve prosthesis was performed by Cribier et al in 2002, the picture of aortic stenosis (AS) therapeutics has changed dramatically. Initiated from an indication of inoperable to high surgical risk, extending to intermediate and low risk, transcatheter aortic valve replacement (TAVR) is now an approved treatment for patients with severe, symptomatic AS across all the risk categories. The current evidence supports TAVR as a frontline therapy for treating severe AS. The crucial question remains concerning the subset of patients who still are not ideal candidates for TAVR because of certain inherent anatomic, nonmodifiable, and procedure-specific factors. Therefore, in this study, we focus on these scenarios and reasons for referring selected patients for surgical aortic valve replacement in 2023.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 27 Feb 2023; 193:1-18</small></div>

<div><h4>Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson\'s Disease.</h4><i>Krishna V, Fishman PS, Eisenberg HM, Kaplitt M, ... Dalvi A, Elias WJ</i><br /><b>Background</b><br />Unilateral focused ultrasound ablation of the internal segment of globus pallidus has reduced motor symptoms of Parkinson\'s disease in open-label studies.<br /><b>Methods</b><br />We randomly assigned, in a 3:1 ratio, patients with Parkinson\'s disease and dyskinesias or motor fluctuations and motor impairment in the off-medication state to undergo either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary outcome was a response at 3 months, defined as a decrease of at least 3 points from baseline either in the score on the Movement Disorders Society-Unified Parkinson\'s Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state. Secondary outcomes included changes from baseline to month 3 in the scores on various parts of the MDS-UPDRS. After the 3-month blinded phase, an open-label phase lasted until 12 months.<br /><b>Results</b><br />Of 94 patients, 69 were assigned to undergo ultrasound ablation (active treatment) and 25 to undergo the sham procedure (control); 65 patients and 22 patients, respectively, completed the primary-outcome assessment. In the active-treatment group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group (difference, 37 percentage points; 95% confidence interval, 15 to 60; P = 0.003). Of the patients in the active-treatment group who had a response, 19 met the MDS-UPDRS III criterion only, 8 met the UDysRS criterion only, and 18 met both criteria. Results for secondary outcomes were generally in the same direction as those for the primary outcome. Of the 39 patients in the active-treatment group who had had a response at 3 months and who were assessed at 12 months, 30 continued to have a response. Pallidotomy-related adverse events in the active-treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness.<br /><b>Conclusions</b><br />Unilateral pallidal ultrasound ablation resulted in a higher percentage of patients who had improved motor function or reduced dyskinesia than a sham procedure over a period of 3 months but was associated with adverse events. Longer and larger trials are required to determine the effect and safety of this technique in persons with Parkinson\'s disease. (Funded by Insightec; ClinicalTrials.gov number, NCT03319485.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 23 Feb 2023; 388:683-693</small></div>

<div><h4>Prognostic Impact of Right Ventricular Strain in Isolated Severe Tricuspid Regurgitation.</h4><i>Hinojar R, Zamorano JL, González Gómez A, García-Martin A, ... Sanchez Recalde A, Fernández-Golfín C</i><br /><b>Background</b><br />Right ventricular (RV) systolic function is an established marker of outcomes in patients with severe tricuspid regurgitation (TR). Timely detection of RV dysfunction with conventional 2D echocardiography is challenging. RV strain has emerged as an accurate and sensitive tool for evaluation of RV function with the capability of detecting subclinical RV dysfunction. This study aimed to evaluate the prognostic value of RV strain parameters in early stages of severe TR.<br /><b>Methods</b><br />Consecutive patients with at least (≥) severe TR (severe, massive or torrential TR) and absence of a formal indication for tricuspid valve intervention in secondary TR evaluated in the Heart Valve Clinic were prospectively included. RV systolic function was measured with conventional echocardiographic indices (RV fractional area change [FAC], tricuspid annular plane systolic excursion [TAPSE], DTI S wave [`S]) and with Speckle-tracking echocardiography (STE) derived automatic peak global and free wall longitudinal strain (RV-GLS and RV-FWLS respectively) using an automated 2D strain analytical software. A combined endpoint of hospital admission due to heart failure (HF) or all-cause mortality was defined.<br /><b>Results</b><br />A total of 266 patients were enrolled in the study and 151 were finally included. Strain parameters detected a higher percentage of abnormal RV values compared to conventional indices. During a median follow up of 26 months (IQR: 13-42 months), 35% of the patients reached the combined endpoint. Cumulative event-free survival was significantly worse in patients with impaired RV-GLS and RV-FWLS. Conventional indices of RV systolic function were not associated with outcomes (p>0.05 for all). On multivariate analysis, RV-FWLS was independently associated with mortality and HF (adjusted HR for abnormal RV-FWLS: 5.90 (3.17-10.99), <0.001).<br /><b>Conclusion</b><br />In early stages of severe TR, RV-FWLS is more frequently impaired compared to conventional indices of RV function. Among all parameters, RV-FWLS is the strongest predictor of mortality and HF independently of additional prognostic markers.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Soc Echocardiogr: 22 Feb 2023; epub ahead of print</small></div>

<div><h4>Left Ventricular Filling Pressure in Chronic Thromboembolic Pulmonary Hypertension.</h4><i>Gerges C, Pistritto AM, Gerges M, Friewald R, ... Klepetko W, Lang IM</i><br /><b>Background</b><br />Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of major pulmonary arteries with organized thrombi. Clinical risk factors for pulmonary hypertension due to left heart disease including metabolic syndrome, left-sided valvular heart disease, and ischemic heart disease are common in CTEPH patients.<br /><b>Objectives</b><br />The authors sought to investigate prevalence and prognostic implications of elevated left ventricular filling pressures (LVFP) in CTEPH.<br /><b>Methods</b><br />A total of 593 consecutive CTEPH patients undergoing a first diagnostic right and left heart catheterization were included in this study. Mean pulmonary arterial wedge pressure (mPAWP) and left ventricular end-diastolic pressure (LVEDP) were utilized for assessment of LVFP. Two cutoffs were applied to identify patients with elevated LVFP: 1) for the primary analysis mPAWP and/or LVEDP >15 mm Hg, as recommended by the current pulmonary hypertension guidelines; and 2) for the secondary analysis mPAWP and/or LVEDP >11 mm Hg, representing the upper limit of normal. Clinical and echocardiographic features, and long-term mortality were assessed.<br /><b>Results</b><br />LVFP was >15 mm Hg in 63 (10.6%) and >11 mm Hg in 222 patients (37.4%). Univariable logistic regression analysis identified age, systemic hypertension, diabetes, atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume as significant predictors of elevated LVFP. Atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume remained independent determinants of LVFP in adjusted analysis. At follow-up, higher LVFPs were measured in patients who had meanwhile undergone pulmonary endarterectomy (P = 0.002). LVFP >15 mm Hg (P = 0.021) and >11 mm Hg (P = 0.006) were both associated with worse long-term survival.<br /><b>Conclusions</b><br />Elevated LVFP is common, appears to be due to comorbid left heart disease, and predicts prognosis in CTEPH.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Feb 2023; 81:653-664</small></div>

<div><h4>Intravascular Imaging During Percutaneous Coronary Intervention: JACC State-of-the-Art Review.</h4><i>Truesdell AG, Alasnag MA, Kaul P, Rab ST, ... Kirtane AJ, ACC Interventional Council</i><br /><AbstractText>Coronary angiography has historically served as the gold standard for diagnosis of coronary artery disease and guidance of percutaneous coronary intervention (PCI). Adjunctive use of contemporary intravascular imaging (IVI) technologies has emerged as a complement to conventional angiography-to further characterize plaque morphology and optimize the performance of PCI. IVI has utility for preintervention lesion and vessel assessment, periprocedural guidance of lesion preparation and stent deployment, and postintervention assessment of optimal endpoints and exclusion of complications. The role of IVI in reducing major adverse cardiac events in complex lesion subsets is emerging, and further studies evaluating broader use are underway or in development. This paper provides an overview of currently available IVI technologies, reviews data supporting their utilization for PCI guidance and optimization across a variety of lesion subsets, proposes best practices, and advocates for broader use of these technologies as a part of contemporary practice.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 14 Feb 2023; 81:590-605</small></div>

<div><h4>Comparative Effectiveness of Left Atrial Appendage Occlusion Versus Oral Anticoagulation by Sex.</h4><i>Zeitler EP, Kearing S, Coylewright M, Nair D, ... Russo AM, Al-Khatib SM</i><br /><b>Background</b><br />The comparative real-world outcomes of older patients with atrial fibrillation (AF) treated with anticoagulation compared with left atrial appendage occlusion (LAAO) may be different from those in clinical trials because of differences in anticoagulation strategies and patient demographics, including a greater proportion of women. We sought to compare real-world outcomes between older patients with AF treated with anticoagulation and those treated with LAAO by sex.<br /><b>Methods</b><br />Using Medicare claims data from 2015 to 2019, we identified LAAO-eligible beneficiaries and divided them into sex subgroups. Patients receiving LAAO were matched 1:1 to those receiving anticoagulation alone through propensity score matching. The risks of mortality, stroke or systemic embolism, and bleeding were compared between matched groups with adjustment for potential confounding characteristics in Cox proportional hazards models.<br /><b>Results</b><br />Among women, 4085 LAAO recipients were matched 1:1 to those receiving anticoagulation; among men, 5378 LAAO recipients were similarly matched. LAAO was associated with a significant reduction in the risk of mortality for women and men (hazard ratio [HR], 0.509 [95% CI, 0.447-0.580]; and HR, 0.541 [95% CI, 0.487-0.601], respectively; <i>P</i><0.0001), with a similar finding for stroke or systemic embolism (HR, 0.655 [95% CI, 0.555-0.772]; and HR, 0.649 [95% CI, 0.552-0.762], respectively; <i>P</i><0.0001). Bleeding risk was significantly greater in LAAO recipients early after implantation but lower after the 6-week periprocedural period for women and men (HR, 0.772 [95% CI, 0.676-0.882]; and HR, 0.881 [95% CI, 0.784-0.989], respectively; <i>P</i><0.05).<br /><b>Conclusions</b><br />In a real-world population of older Medicare beneficiaries with AF, compared with anticoagulation, LAAO was associated with a reduction in the risk of death, stroke, and long-term bleeding among women and men. These findings should be incorporated into shared decision-making with patients considering strategies for reduction in AF-related stroke.<br /><br /><br /><br /><small>Circulation: 14 Feb 2023; 147:586-596</small></div>

<div><h4>Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.</h4><i>Huo X, Ma G, Tong X, Zhang X, ... Miao Z, ANGEL-ASPECT Investigators</i><br /><b>Background</b><br />The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations.<br /><b>Methods</b><br />We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization.<br /><b>Results</b><br />A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis.<br /><b>Conclusions</b><br />In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 10 Feb 2023; epub ahead of print</small></div>

<div><h4>Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth.</h4><i>Tita ATN, Carlo WA, McClure EM, Mwenechanya M, ... Koso-Thomas M, A-PLUS Trial Group</i><br /><b>Background</b><br />The use of azithromycin reduces maternal infection in women during planned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death.<br /><b>Methods</b><br />In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks\' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit.<br /><b>Results</b><br />A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events.<br /><b>Conclusions</b><br />Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 09 Feb 2023; epub ahead of print</small></div>

<div><h4>Rule-out of non-ST-segment elevation acute coronary syndrome by a single, pre-hospital troponin measurement: a randomized trial.</h4><i>Camaro C, Aarts GWA, Adang EMM, van Hout R, ... Gomes MER, van Royen N</i><br /><b>Aims</b><br />Patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are routinely transferred to the emergency department (ED). A clinical risk score with point-of-care (POC) troponin measurement might enable ambulance paramedics to identify low-risk patients in whom ED evaluation is unnecessary. The aim was to assess safety and healthcare costs of a pre-hospital rule-out strategy using a POC troponin measurement in low-risk suspected NSTE-ACS patients.<br /><b>Methods and results</b><br />This investigator-initiated, randomized clinical trial was conducted in five ambulance regions in the Netherlands. Suspected NSTE-ACS patients with HEAR (History, ECG, Age, Risk factors) score ≤3 were randomized to pre-hospital rule-out with POC troponin measurement or direct transfer to the ED. The sample size calculation was based on the primary outcome of 30-day healthcare costs. Secondary outcome was safety, defined as 30-day major adverse cardiac events (MACE), consisting of ACS, unplanned revascularization or all-cause death. : A total of 863 participants were randomized. Healthcare costs were significantly lower in the pre-hospital strategy (€1349 ± €2051 vs. €1960 ± €1808) with a mean difference of €611 [95% confidence interval (CI): 353-869; P < 0.001]. In the total population, MACE were comparable between groups [3.9% (17/434) in pre-hospital strategy vs. 3.7% (16/429) in ED strategy; P = 0.89]. In the ruled-out ACS population, MACE were very low [0.5% (2/419) vs. 1.0% (4/417)], with a risk difference of -0.5% (95% CI -1.6%-0.7%; P = 0.41) in favour of the pre-hospital strategy.<br /><b>Conclusion</b><br />Pre-hospital rule-out of ACS with a POC troponin measurement in low-risk patients significantly reduces healthcare costs while incidence of MACE was low in both strategies.<br /><b>Trial registration</b><br />Clinicaltrials.gov identifier NCT05466591 and International Clinical Trials Registry Platform id NTR 7346.<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 Feb 2023; epub ahead of print</small></div>

<div><h4>Right Ventricular Systolic Dysfunction in Adults With Anatomic Repair of d-Transposition of Great Arteries.</h4><i>Egbe AC, Miranda WR, Stephens EH, Anderson JH, ... Ramachandran D, Connolly HM</i><br /><AbstractText>The purpose of this study was to assess the prevalence of right ventricular (RV) systolic dysfunction in adults with anatomic repair of dextro-transposition of great arteries (d-TGAs), and to determine its relation to clinical outcomes across multiple domains (functional status, peak oxygen consumption, N-terminal pro-brain natriuretic peptide, and heart failure hospitalization). Adults with anatomic repair for d-TGA and with echocardiographic images for strain analysis were divided into 2 groups: (1) d-TGA status after an arterial switch operation (d-TGA-ASO group) and (2) d-TGA status after a Rastelli operation (d-TGA-Rastelli group). RV systolic function was assessed using RV global longitudinal strain (RVGLS), and RV systolic dysfunction was defined as RVGLS >-18%. We identified 151 patients (median age 21 years [19 to 28]; d-TGA-ASO group 89 [59%], and d-TGA-Rastelli group 62 [41%]). The mean RVGLS was -22 ± 4%, and 47 patients (31%) had RV systolic dysfunction. The d-TGA-Rastelli group had lower (less negative) RVGLS than that of the d-TGA-ASO group (-19 ± 3% vs -25 ± 3%, p <0.001) and higher prevalence of RV systolic dysfunction (48% vs 19%, p <0.001). RVGLS (absolute value) was associated with peak oxygen consumption (r = 0.58, p <0.001; adjusted R<sup>2</sup> = 0.28), log-N-terminal pro-brain natriuretic peptide (r = -0.41, p = 0.004; adjusted R<sup>2</sup> = 0.21), New York Heart Association class III/IV (odds ratio 2.29, 1.56 to 3.19, p = 0.01), and heart failure hospitalization (hazard ratio 0.93, 0.88 to 0.98, p = 0.009). RV systolic dysfunction was common in adults with d-TGA and anatomic repair and was associated with clinical outcomes. Longitudinal studies are required to determine the risk factors for progressive RV systolic dysfunction and to identify strategies for preventing RV systolic dysfunction in this population.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 08 Feb 2023; 192:101-108</small></div>

<div><h4>Acute Coronary Occlusion in Patients With Non-ST-Segment Elevation Out-of-Hospital Cardiac Arrest.</h4><i>Spirito A, Vaisnora L, Papadis A, Iacovelli F, ... Windecker S, Räber L</i><br /><b>Background</b><br />According to current guidelines, hemodynamic status should guide the decision between immediate and delayed coronary angiography (CAG) in out-of-hospital cardiac arrest (OHCA) patients without ST-segment elevation. A delayed strategy is advised in hemodynamically stable patients, and an immediate approach is recommended in unstable patients.<br /><b>Objectives</b><br />This study sought to assess the frequency, predictors, and clinical impact of acute coronary occlusion in hemodynamically stable and unstable OHCA patients without ST-segment elevation.<br /><b>Methods</b><br />Consecutive unconscious OHCA patients without ST-segment elevation who were undergoing CAG at Bern University Hospital (Bern, Switzerland) between 2011 and 2019 were included. Frequency and predictors of acute coronary artery occlusions and their impact on all-cause and cardiovascular mortality at 1 year were assessed.<br /><b>Results</b><br />Among the 386 patients, 169 (43.8%) were hemodynamically stable. Acute coronary occlusions were found in 19.5% of stable and 24.0% of unstable OHCA patients (P = 0.407), and the presence of these occlusions was predicted by initial chest pain and shockable rhythm, but not by hemodynamic status. Acute coronary occlusion was associated with an increased risk of cardiovascular death (adjusted HR: 2.74; 95% CI: 1.22-6.15) but not of all-cause death (adjusted HR: 0.72; 95% CI: 0.44-1.18). Hemodynamic instability was not predictive of fatal outcomes.<br /><b>Conclusions</b><br />Acute coronary artery occlusions were found in 1 in 5 OHCA patients without ST-segment elevation. The frequency of these occlusions did not differ between stable and unstable patients, and the occlusions were associated with a higher risk of cardiovascular death. In OHCA patients without ST-segment elevation, chest pain or shockable rhythm rather than hemodynamic status identifies patients with acute coronary occlusion.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Feb 2023; 81:446-456</small></div>

<div><h4>Infective Endocarditis After Transcatheter Aortic Valve Replacement: JACC State-of-the-Art Review.</h4><i>Del Val D, Panagides V, Mestres CA, Miró JM, Rodés-Cabau J</i><br /><AbstractText>Infective endocarditis (IE) is a rare but serious complication following transcatheter aortic valve replacement (TAVR). Despite substantial improvements in the TAVR procedure (less invasive) and its expansion to younger and healthier patients, the incidence of IE after TAVR remains stable, with incidence rates similar to those reported after surgical aortic valve replacement. Although IE after TAVR is recognized as a subtype of prosthetic valve endocarditis, this condition represents a particularly challenging scenario given its unique clinical and microbiological profile, the high incidence of IE-related complications, the uncertain role of cardiac surgery, and the dismal prognosis in most patients with TAVR-IE. The number of TAVR procedures is expected to grow exponentially in the coming years, increasing the number of patients at risk of developing this life-threatening complication. Therefore, a detailed understanding of this disease and its complications will be essential to improve clinical outcomes.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 31 Jan 2023; 81:394-412</small></div>

<div><h4>Purine synthesis suppression reduces the development and progression of pulmonary hypertension in rodent models.</h4><i>Ma Q, Yang Q, Xu J, Sellers HG, ... Fulton DJR, Huo Y</i><br /><b>Aims</b><br />Proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of pulmonary hypertension (PH). Proliferative cells utilize purine bases from the de novo purine synthesis (DNPS) pathways for nucleotide synthesis; however, it is unclear whether DNPS plays a critical role in VSMC proliferation during development of PH. The last two steps of DNPS are catalysed by the enzyme 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC). This study investigated whether ATIC-driven DNPS affects the proliferation of pulmonary artery smooth muscle cells (PASMCs) and the development of PH.<br /><b>Methods and results</b><br />Metabolites of DNPS in proliferative PASMCs were measured by liquid chromatography-tandem mass spectrometry. ATIC expression was assessed in platelet-derived growth factor-treated PASMCs and in the lungs of PH rodents and patients with pulmonary arterial hypertension. Mice with global and VSMC-specific knockout of Atic were utilized to investigate the role of ATIC in both hypoxia- and lung interleukin-6/hypoxia-induced murine PH. ATIC-mediated DNPS at the mRNA, protein, and enzymatic activity levels were increased in platelet-derived growth factor-treated PASMCs or PASMCs from PH rodents and patients with pulmonary arterial hypertension. In cultured PASMCs, ATIC knockdown decreased DNPS and nucleic acid DNA/RNA synthesis, and reduced cell proliferation. Global or VSMC-specific knockout of Atic attenuated vascular remodelling and inhibited the development and progression of both hypoxia- and lung IL-6/hypoxia-induced PH in mice.<br /><b>Conclusion</b><br />Targeting ATIC-mediated DNPS compromises the availability of purine nucleotides for incorporation into DNA/RNA, reducing PASMC proliferation and pulmonary vascular remodelling and ameliorating the development and progression of PH.<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 Jan 2023; epub ahead of print</small></div>

<div><h4>Substance Use Disorders Are Prevalent in Adults With Congenital Heart Disease and Are Associated With Increased Healthcare Use.</h4><i>Shalen EF, McGrath LB, Bhamidipati CM, Garcia IC, ... Broberg CS, Khan AM</i><br /><AbstractText>Adults with congenital heart disease (CHD) represent a heterogeneous group with significant long-term health risks. Previous studies have demonstrated a high prevalence of psychiatric disorders among adults with CHD; however, little is known about the frequency of co-morbid substance use disorders (SUDs) in patients with CHD. The Oregon All Payer All Claims (APAC) database for the years 2014 to 2017 was queried for adults aged 18 to 65 years with International Classification of Diseases, Ninth or Tenth Revision codes consistent with CHD. Alcohol and substance use were identified by International Classification of Diseases codes for use or dependence and classified in mutually exclusive categories of none, alcohol only, and other drugs (with or without alcohol). Descriptive statistics were used to characterize prevalence and chi-square tests were used to test for associations between variables. A total of 12,366 adults with CHD were identified. The prevalence of substance use was 15.7%. The prevalence of isolated alcohol use was 3.9%. A total of 19% of patients used tobacco. Insurance type, presence of a concurrent mental health diagnosis, and age were associated with substance use, whereas CHD complexity was not. Cardiovascular co-morbidities were more common in patients with reported substance use. Inpatient and emergency care use were higher in those with SUD. In conclusion, this study of substance and alcohol use among adults with CHD demonstrates high rates of co-morbid SUD, particularly among patients with mental health disorders and Medicaid insurance, associated with increased healthcare utilization. We identify a population in need of targeted interventions to improve long-term health.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 27 Jan 2023; 192:24-30</small></div>

<div><h4>In Vivo Dissection of Chamber-Selective Enhancers Reveals Estrogen-Related Receptor as a Regulator of Ventricular Cardiomyocyte Identity.</h4><i>Cao Y, Zhang X, Akerberg BN, Yuan H, ... Kelly DP, Pu WT</i><br /><b>Background</b><br />Cardiac chamber-selective transcriptional programs underpin the structural and functional differences between atrial and ventricular cardiomyocytes (aCMs and vCMs). The mechanisms responsible for these chamber-selective transcriptional programs remain largely undefined.<br /><b>Methods</b><br />We nominated candidate chamber-selective enhancers (CSEs) by determining the genome-wide occupancy of 7 key cardiac transcription factors (GATA4, MEF2A, MEF2C, NKX2-5, SRF, TBX5, TEAD1) and transcriptional coactivator P300 in atria and ventricles. Candidate enhancers were tested using an adeno-associated virus-mediated massively parallel reporter assay. Chromatin features of CSEs were evaluated by performing assay of transposase accessible chromatin sequencing and acetylation of histone H3 at lysine 27-highly integrative chromatin immunoprecipitation on aCMs and vCMs. CSE sequence requirements were determined by systematic tiling mutagenesis of 29 CSEs at 5 bp resolution. Estrogen-related receptor (ERR) function in cardiomyocytes was evaluated by Cre-loxP-mediated inactivation of ERRα and ERRγ in cardiomyocytes.<br /><b>Results</b><br />We identified 152 832 and 54 824 regions reproducibly occupied by at least 1 transcription factor or P300, in atria or ventricles, respectively. Enhancer activities of 2639 regions bound by transcription factors or P300 were tested in aCMs and vCMs by adeno-associated virus-mediated massively parallel reporter assay. This identified 1092 active enhancers in aCMs or vCMs. Several overlapped loci associated with cardiovascular disease through genome-wide association studies, and 229 exhibited chamber-selective activity in aCMs or vCMs. Many CSEs exhibited differential chromatin accessibility between aCMs and vCMs, and CSEs were enriched for aCM- or vCM-selective acetylation of histone H3 at lysine 27-anchored loops. Tiling mutagenesis of 29 CSEs identified the binding motif of ERRα/γ as important for ventricular enhancer activity. The requirement of ERRα/γ to activate ventricular CSEs and promote vCM identity was confirmed by loss of the vCM gene profile in ERRα/γ knockout vCMs.<br /><b>Conclusions</b><br />We identified 229 CSEs that could be useful research tools or direct therapeutic gene expression. We showed that chamber-selective multi-transcription factor, P300 occupancy, open chromatin, and chromatin looping are predictive features of CSEs. We found that ERRα/γ are essential for maintenance of ventricular identity. Finally, our gene expression, epigenetic, 3-dimensional genome, and enhancer activity atlas provide key resources for future studies of chamber-selective gene regulation.<br /><br /><br /><br /><small>Circulation: 27 Jan 2023; epub ahead of print</small></div>

<div><h4>Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest.</h4><i>Suverein MM, Delnoij TSR, Lorusso R, Brandon Bravo Bruinsma GJ, ... Maessen JG, van de Poll MCG</i><br /><b>Background</b><br />Extracorporeal cardiopulmonary resuscitation (CPR) restores perfusion and oxygenation in a patient who does not have spontaneous circulation. The evidence with regard to the effect of extracorporeal CPR on survival with a favorable neurologic outcome in refractory out-of-hospital cardiac arrest is inconclusive.<br /><b>Methods</b><br />In this multicenter, randomized, controlled trial conducted in the Netherlands, we assigned patients with an out-of-hospital cardiac arrest to receive extracorporeal CPR or conventional CPR (standard advanced cardiac life support). Eligible patients were between 18 and 70 years of age, had received bystander CPR, had an initial ventricular arrhythmia, and did not have a return of spontaneous circulation within 15 minutes after CPR had been initiated. The primary outcome was survival with a favorable neurologic outcome, defined as a Cerebral Performance Category score of 1 or 2 (range, 1 to 5, with higher scores indicating more severe disability) at 30 days. Analyses were performed on an intention-to-treat basis.<br /><b>Results</b><br />Of the 160 patients who underwent randomization, 70 were assigned to receive extracorporeal CPR and 64 to receive conventional CPR; 26 patients who did not meet the inclusion criteria at hospital admission were excluded. At 30 days, 14 patients (20%) in the extracorporeal-CPR group were alive with a favorable neurologic outcome, as compared with 10 patients (16%) in the conventional-CPR group (odds ratio, 1.4; 95% confidence interval, 0.5 to 3.5; P = 0.52). The number of serious adverse events per patient was similar in the two groups.<br /><b>Conclusions</b><br />In patients with refractory out-of-hospital cardiac arrest, extracorporeal CPR and conventional CPR had similar effects on survival with a favorable neurologic outcome. (Funded by the Netherlands Organization for Health Research and Development and Maquet Cardiopulmonary [Getinge]; INCEPTION ClinicalTrials.gov number, NCT03101787.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 26 Jan 2023; 388:299-309</small></div>

<div><h4>Major cardiovascular events and subsequent risk of kidney failure with replacement therapy: a CKD Prognosis Consortium study.</h4><i>Mark PB, Carrero JJ, Matsushita K, Sang Y, ... Visseren FLJ, Stengel B</i><br /><b>Aims</b><br />Chronic kidney disease (CKD) increases risk of cardiovascular disease (CVD). Less is known about how CVD associates with future risk of kidney failure with replacement therapy (KFRT).<br /><b>Methods and results</b><br />The study included 25 903 761 individuals from the CKD Prognosis Consortium with known baseline estimated glomerular filtration rate (eGFR) and evaluated the impact of prevalent and incident coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) events as time-varying exposures on KFRT outcomes. Mean age was 53 (standard deviation 17) years and mean eGFR was 89 mL/min/1.73 m2, 15% had diabetes and 8.4% had urinary albumin-to-creatinine ratio (ACR) available (median 13 mg/g); 9.5% had prevalent CHD, 3.2% prior stroke, 3.3% HF, and 4.4% prior AF. During follow-up, there were 269 142 CHD, 311 021 stroke, 712 556 HF, and 605 596 AF incident events and 101 044 (0.4%) patients experienced KFRT. Both prevalent and incident CVD were associated with subsequent KFRT with adjusted hazard ratios (HRs) of 3.1 [95% confidence interval (CI): 2.9-3.3], 2.0 (1.9-2.1), 4.5 (4.2-4.9), 2.8 (2.7-3.1) after incident CHD, stroke, HF and AF, respectively. HRs were highest in first 3 months post-CVD incidence declining to baseline after 3 years. Incident HF hospitalizations showed the strongest association with KFRT [HR 46 (95% CI: 43-50) within 3 months] after adjustment for other CVD subtype incidence.<br /><b>Conclusion</b><br />Incident CVD events strongly and independently associate with future KFRT risk, most notably after HF, then CHD, stroke, and AF. Optimal strategies for addressing the dramatic risk of KFRT following CVD events are needed.<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 Jan 2023; epub ahead of print</small></div>

<div><h4>Albuminuria and Heart Failure: JACC State-of-the-Art Review.</h4><i>Khan MS, Shahid I, Anker SD, Fonarow GC, ... Bakris GL, Butler J</i><br /><AbstractText>Although chronic kidney disease is characterized by low glomerular filtration rate (GFR) or albuminuria, estimated GFR (eGFR) is more widely utilized as a marker of risk profile in cardiovascular diseases, including heart failure (HF). The presence and magnitude of albuminuria confers a strong prognostic association in forecasting risk of incident HF as well as its progression, irrespective of eGFR. Despite the high prevalence of albuminuria in HF, whether it adds incremental prognostic information in clinical practice and serves as an independent risk marker, and whether there are any therapeutic implications of assessing albuminuria in patients with HF is less well-established. In this narrative review, we assess the potential role of albuminuria in risk profiling for development and progression of HF, strengths and limitations of utilizing albuminuria as a risk marker, its ability to serve in HF risk prediction models, and the implications of adopting albuminuria as an effective parameter in cardiovascular trials and practice.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 24 Jan 2023; 81:270-282</small></div>

<div><h4>Temporal trends in the incidence of malignancy in heart failure: a nationwide Danish study.</h4><i>Bruhn J, Malmborg M, Garred CH, Ravn P, ... Kober L, Schou M</i><br /><b>Aims</b><br />Cancer and heart failure (HF) share risk factors, pathophysiological mechanisms, and possibly genetics. Improved HF survival may increase the risk of cancer due to a competing risk. Whether the incidence of cancer has increased over time in patients with HF as survival has improved is unclear. Therefore, temporal trends of new onset cancer in HF patients between 1997 and 2016 were investigated.<br /><b>Methods and results</b><br />Using Danish nationwide registers, 103 711 individuals alive, free of cancer, and aged 30-80 years 1 year after HF diagnosis (index date) were included between 1 January 1997 and 31 December 2016. A five-year incidence rate of cancer for each year after index date was calculated. The median age and proportion of women at the index date decreased with advancing calendar time [1997-2001: 70.3 interquartile range (Q1-Q3 62.5-75.7), 60.9% men; 2012-16: 67.6 (59.2-73.8), 67.5% men]. The five-year incidence rate of cancer was 20.9 and 20.2 per 1,000 person-years in 1997 and 2016, respectively. In a multivariable Cox regression model, the hazard rates between index years 1997 (reference) and 2016 were not significantly different [hazard ratio 1.09 (0.97-1.23)]. The five-year absolute risk of cancer did not change with advancing calendar year, going from 9.0% (1997-2001) to 9.0% (2012-16). Five-year cumulative incidence of survival for HF patients increased with advancing calendar year, going from 55.9% (1997-2001) to 74.3% (2012-2016).<br /><b>Conclusion</b><br />Although cancer rates during 1997-2016 have remained stable within 1-6 years after the HF diagnosis, long-term survival following a HF diagnosis has increased significantly.<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 Jan 2023; epub ahead of print</small></div>