Journal: Eur Heart J

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<div><h4>Long-term outcomes of perioperative myocardial infarction/injury after non-cardiac surgery.</h4><i>Puelacher C, Gualandro DM, Glarner N, Lurati Buse G, ... Mueller C, BASEL-PMI Investigators </i><br /><b>Aims</b><br />Perioperative myocardial infarction/injury (PMI) following non-cardiac surgery is a frequent cardiac complication. Better understanding of the underlying aetiologies and outcomes is urgently needed.<br /><b>Methods and results</b><br />Aetiologies of PMIs detected within an active surveillance and response programme were centrally adjudicated by two independent physicians based on all information obtained during clinically indicated PMI work-up including cardiac imaging among consecutive high-risk patients undergoing major non-cardiac surgery in a prospective multicentre study. PMI aetiologies were hierarchically classified into \'extra-cardiac\' if caused by a primarily extra-cardiac disease such as severe sepsis or pulmonary embolism; and \'cardiac\', further subtyped into type 1 myocardial infarction (T1MI), tachyarrhythmia, acute heart failure (AHF), or likely type 2 myocardial infarction (lT2MI). Major adverse cardiac events (MACEs) including acute myocardial infarction, AHF (both only from day 3 to avoid inclusion bias), life-threatening arrhythmia, and cardiovascular death as well as all-cause death were assessed during 1-year follow-up. Among 7754 patients (age 45-98 years, 45% women), PMI occurred in 1016 (13.1%). At least one MACE occurred in 684/7754 patients (8.8%) and 818/7754 patients died (10.5%) within 1 year. Outcomes differed starkly according to aetiology: in patients with extra-cardiac PMI, T1MI, tachyarrhythmia, AHF, and lT2MI 51%, 41%, 57%, 64%, and 25% had MACE, and 38%, 27%, 40%, 49%, and 17% patients died within 1 year, respectively, compared to 7% and 9% in patients without PMI. These associations persisted in multivariable analysis.<br /><b>Conclusion</b><br />At 1 year, most PMI aetiologies have unacceptably high rates of MACE and all-cause death, highlighting the urgent need for more intensive treatments.<br /><b>Study registration</b><br />https://clinicaltrials.gov/ct2/show/NCT02573532.<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: 27 Jan 2023; epub ahead of print</small></div>
Puelacher C, Gualandro DM, Glarner N, Lurati Buse G, ... Mueller C, BASEL-PMI Investigators
Eur Heart J: 27 Jan 2023; epub ahead of print | PMID: 36705050
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<div><h4>Factors influencing post-surgical survival in degenerative mitral regurgitation.</h4><i>Butcher SC, Essayagh B, Steyerberg EW, Benfari G, ... Bax JJ, Enriquez-Sarano M</i><br /><b>Aims</b><br />Indications for surgery in patients with degenerative mitral regurgitation (DMR) are increasingly liberal in all clinical guidelines but the role of secondary outcome determinants (left atrial volume index ≥60 mL/m2, atrial fibrillation, pulmonary artery systolic pressure ≥50 mmHg and moderate to severe tricuspid regurgitation) and their impact on post-operative outcome remain disputed. Whether these secondary outcome markers are just reflective of the DMR severity or intrinsically affect survival after DMR surgery is uncertain and may have critical importance in the management of patients with DMR. To address these gaps of knowledge the present study gathered a large cohort of patients with quantified DMR, accounted for the number of secondary outcome markers and examined their independent impact on survival after surgical correction of the DMR.<br /><b>Methods and results</b><br />The Mitral Regurgitation International DAtabase-Quantitative registry includes patients with isolated DMR from centres across North America, Europe, and the Middle East. Patient enrolment extended from January 2003 to January 2020. All patients undergoing mitral valve surgery within 1 year of registry enrolment were selected. A total of 2276 patients [65 (55-73) years, 32% male] across five centres met study eligibility criteria. Over a median follow-up of 5.6 (3.6 to 8.7) years, 278 patients (12.2%) died. In a comprehensive multivariable Cox regression model adjusted for age, EuroSCORE II, symptoms, left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LV ESD) and DMR severity, the number of secondary outcome determinants was independently associated with post-operative all-cause mortality, with adjusted hazard ratios of 1.56 [95% confidence interval (CI): 1.11-2.20, P = 0.011], 1.78 (95% CI: 1.23-2.58, P = 0.002) and 2.58 (95% CI: 1.73-3.83, P < 0.0001) for patients with one, two, and three or four secondary outcome determinants, respectively. A model incorporating the number of secondary outcome determinants demonstrated a higher C-index and was significantly more concordant with post-operative mortality than models incorporating traditional Class I indications alone [the presence of symptoms (P = 0.0003), or LVEF ≤60% (P = 0.006), or LV ESD ≥40 mm (P = 0.014)], while there was no significant difference in concordance observed compared with a model that incorporated the number of Class I indications for surgery combined (P = 0.71).<br /><b>Conclusion</b><br />In this large cohort of patients treated surgically for DMR, the presence and number of secondary outcome determinants was independently associated with post-surgical survival and demonstrated better outcome discrimination than traditional Class I indications for surgery. Randomised controlled trials are needed to determine if patients with severe DMR who demonstrate a cardiac phenotype with an increasing number of secondary outcome determinants would benefit from earlier surgery.<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 Jan 2023; epub ahead of print</small></div>
Butcher SC, Essayagh B, Steyerberg EW, Benfari G, ... Bax JJ, Enriquez-Sarano M
Eur Heart J: 26 Jan 2023; epub ahead of print | PMID: 36702625
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<div><h4>Improving representativeness in trials: a call to action from the Global Cardiovascular Clinical Trialists Forum.</h4><i>Filbey L, Zhu JW, D\'Angelo F, Thabane L, ... Zannad F, Van Spall HGC</i><br /><AbstractText>Participants enrolled in cardiovascular disease (CVD) randomized controlled trials are not often representative of the population living with the disease. Older adults, children, women, Black, Indigenous and People of Color, and people living in low- and middle-income countries are typically under-enrolled in trials relative to disease distribution. Treatment effect estimates of CVD therapies have been largely derived from trial evidence generated in White men without complex comorbidities, limiting the generalizability of evidence. This review highlights barriers and facilitators of trial enrollment, temporal trends, and the rationale for representativeness. It proposes strategies to increase representativeness in CVD trials, including trial designs that minimize the research burden on participants, inclusive recruitment practices and eligibility criteria, diversification of clinical trial leadership, and research capacity-building in under-represented regions. Implementation of such strategies could generate better and more generalizable evidence to reduce knowledge gaps and position the cardiovascular trial enterprise as a vehicle to counter existing healthcare inequalities.</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: 25 Jan 2023; epub ahead of print</small></div>
Filbey L, Zhu JW, D'Angelo F, Thabane L, ... Zannad F, Van Spall HGC
Eur Heart J: 25 Jan 2023; epub ahead of print | PMID: 36702610
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<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>
Bruhn J, Malmborg M, Garred CH, Ravn P, ... Kober L, Schou M
Eur Heart J: 24 Jan 2023; epub ahead of print | PMID: 36691953
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<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>
Mark PB, Carrero JJ, Matsushita K, Sang Y, ... Visseren FLJ, Stengel B
Eur Heart J: 24 Jan 2023; epub ahead of print | PMID: 36691956
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<div><h4>Lifestyle habits associated with cardiac conduction disease.</h4><i>Frimodt-Møller EK, Soliman EZ, Kizer JR, Vittinghoff E, ... Gottdiener JS, Marcus GM</i><br /><b>Aims</b><br />Cardiac conduction disease can lead to syncope, heart failure, and death. The only available therapy is pacemaker implantation, with no established prevention strategies. Research to identify modifiable risk factors has been scant.<br /><b>Methods and results</b><br />Data from the Cardiovascular Health Study, a population-based cohort study of adults ≥ 65 years with annual 12-lead electrocardiograms obtained over 10 years, were utilized to examine relationships between baseline characteristics, including lifestyle habits, and conduction disease. Of 5050 participants (mean age 73 ± 6 years; 52% women), prevalent conduction disease included 257 with first-degree atrioventricular block, 99 with left anterior fascicular block, 9 with left posterior fascicular block, 193 with right bundle branch block (BBB), 76 with left BBB, and 102 with intraventricular block at baseline. After multivariable adjustment, older age, male sex, a larger body mass index, hypertension, and coronary heart disease were associated with a higher prevalence of conduction disease, whereas White race and more physical activity were associated with a lower prevalence. Over a median follow-up on 7 (interquartile range 1-9) years, 1036 developed incident conduction disease. Older age, male sex, a larger BMI, and diabetes were each associated with incident conduction disease. Of lifestyle habits, more physical activity (hazard ratio 0.91, 95% confidence interval 0.84-0.98, P = 0.017) was associated with a reduced risk, while smoking and alcohol did not exhibit a significant association.<br /><b>Conclusion</b><br />While some difficult to control comorbidities were associated with conduction disease as expected, a readily modifiable lifestyle factor, physical activity, was associated with a lower risk.<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: 20 Jan 2023; epub ahead of print</small></div>
Frimodt-Møller EK, Soliman EZ, Kizer JR, Vittinghoff E, ... Gottdiener JS, Marcus GM
Eur Heart J: 20 Jan 2023; epub ahead of print | PMID: 36660815
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<div><h4>Transcatheter versus surgical aortic valve replacement in lower-risk and higher-risk patients: a meta-analysis of randomized trials.</h4><i>Ahmad Y, Howard JP, Arnold AD, Madhavan MV, ... Forrest JK, Leon MB</i><br /><b>Aims</b><br />Additional randomized clinical trial (RCT) data comparing transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) is available, including longer term follow-up. A meta-analysis comparing TAVI to SAVR was performed. A pragmatic risk classification was applied, partitioning lower-risk and higher-risk patients.<br /><b>Methods and results</b><br />The main endpoints were death, strokes, and the composite of death or disabling stroke, occurring at 1 year (early) or after 1 year (later). A random-effects meta-analysis was performed. Eight RCTs with 8698 patients were included. In lower-risk patients, at 1 year, the risk of death was lower after TAVI compared with SAVR [relative risk (RR) 0.67; 95% confidence interval (CI) 0.47 to 0.96, P = 0.031], as was death or disabling stroke (RR 0.68; 95% CI 0.50 to 0.92, P = 0.014). There were no differences in strokes. After 1 year, in lower-risk patients, there were no significant differences in all main outcomes. In higher-risk patients, there were no significant differences in main outcomes. New-onset atrial fibrillation, major bleeding, and acute kidney injury occurred less after TAVI; new pacemakers, vascular complications, and paravalvular leak occurred more after TAVI.<br /><b>Conclusion</b><br />In lower-risk patients, there was an early mortality reduction with TAVI, but no differences after later follow-up. There was also an early reduction in the composite of death or disabling stroke, with no difference at later follow-up. There were no significant differences for higher-risk patients. Informed therapy decisions may be more dependent on the temporality of events or secondary endpoints than the long-term occurrence of main clinical outcomes.<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: 20 Jan 2023; epub ahead of print</small></div>
Ahmad Y, Howard JP, Arnold AD, Madhavan MV, ... Forrest JK, Leon MB
Eur Heart J: 20 Jan 2023; epub ahead of print | PMID: 36660821
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<div><h4>Sortilin enhances fibrosis and calcification in aortic valve disease by inducing interstitial cell heterogeneity.</h4><i>Iqbal F, Schlotter F, Becker-Greene D, Lupieri A, ... Sonawane AR, Aikawa E</i><br /><b>Aims</b><br />Calcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored.<br /><b>Methods and results</b><br />An aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification. In vitro experiments employed human primary VICs cultured in osteogenic conditions for 7, 14, and 21 days; and processed for imaging, proteomics, and transcriptomics including single-cell RNA-sequencing (scRNA-seq). The AVWI mouse model showed reduced AV fibrosis, calcification, and stenosis in sortilin-deficient mice vs. littermate controls. Protein studies identified the transition of human VICs into a myofibroblast-like phenotype mediated by sortilin. Sortilin loss-of-function decreased in vitro VIC calcification. ScRNA-seq identified 12 differentially expressed cell clusters in human VIC samples, where a novel combined inflammatory myofibroblastic-osteogenic VIC (IMO-VIC) phenotype was detected with increased expression of SORT1, COL1A1, WNT5A, IL-6, and serum amyloid A1. VICs sequenced with sortilin deficiency showed decreased IMO-VIC phenotype.<br /><b>Conclusion</b><br />Sortilin promotes CAVD by mediating valvular fibrosis and calcification, and a newly identified phenotype (IMO-VIC). This is the first study to examine the role of sortilin in valvular calcification and it may render it a therapeutic target to inhibit IMO-VIC emergence by simultaneously reducing inflammation, fibrosis, and calcification, the three key pathological processes underlying CAVD.<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 Jan 2023; epub ahead of print</small></div>
Iqbal F, Schlotter F, Becker-Greene D, Lupieri A, ... Sonawane AR, Aikawa E
Eur Heart J: 20 Jan 2023; epub ahead of print | PMID: 36660854
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<div><h4>Cognitive-behavioural therapy reduces psychological distress in younger patients with cardiac disease: a randomized trial.</h4><i>Holdgaard A, Eckhardt-Hansen C, Lassen CF, Kjesbu IE, ... Prescott E, Rasmusen HK</i><br /><b>Aims</b><br />To test whether usual outpatient cardiac rehabilitation (CR) supplemented by a cognitive-behavioural therapy (CBT) intervention may reduce anxiety and depression compared with usual CR.<br /><b>Methods and results</b><br />In this multicentre randomized controlled trial, 147 cardiac patients (67% men, mean age 54 years, 92% with coronary artery disease) with psychological distress defined as a hospital anxiety and depression scale (HADS) anxiety or depression score ≥8 were randomized to five sessions of group CBT plus usual CR (intervention, n = 74) or CR alone (control, n = 73). Patients with severe distress or a psychiatric diagnosis were excluded. The intervention was delivered by cardiac nurses with CBT training and supervised by a psychologist. A reference, non-randomized group (background, n = 41) of consecutive patients without psychological distress receiving usual CR was included to explore the effect of time on HADS score. The primary outcome, total HADS score after 3 months, improved more in the intervention than in the control group [the mean total HADS score improved by 8.0 (standard deviation 5.6) vs. 4.1 (standard deviation 7.8), P < 0.001]. Significant between-group differences were maintained after 6 months. Compared with the control group, the intervention group also had greater adherence to CR (P = 0.003), more improvement in the heart-related quality of life (HeartQoL) at 6 months (P < 0.01), and a significant reduction in cardiac readmissions at 12 months (P < 0.01). The background group had no significant change in HADS score over time.<br /><b>Conclusion</b><br />Brief CBT provided by cardiac nurses in relation to CR reduced anxiety and depression scores, improved HeartQoL and adherence to CR, and reduced cardiovascular readmissions. The programme is simple and may be implemented by CR nurses.<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 Jan 2023; epub ahead of print</small></div>
Holdgaard A, Eckhardt-Hansen C, Lassen CF, Kjesbu IE, ... Prescott E, Rasmusen HK
Eur Heart J: 18 Jan 2023; epub ahead of print | PMID: 36649937
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<div><h4>Recurrent venous thromboembolism and bleeding with extended anticoagulation: the VTE-PREDICT risk score.</h4><i>de Winter MA, Büller HR, Carrier M, Cohen AT, ... Nijkeuter M, VTE-PREDICT study group </i><br /><b>Aims</b><br />Deciding to stop or continue anticoagulation for venous thromboembolism (VTE) after initial treatment is challenging, as individual risks of recurrence and bleeding are heterogeneous. The present study aimed to develop and externally validate models for predicting 5-year risks of recurrence and bleeding in patients with VTE without cancer who completed at least 3 months of initial treatment, which can be used to estimate individual absolute benefits and harms of extended anticoagulation.<br /><b>Methods and results</b><br />Competing risk-adjusted models were derived to predict recurrent VTE and clinically relevant bleeding (non-major and major) using 14 readily available patient characteristics. The models were derived from combined individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15,141, 220 recurrences, 189 bleeding events). External validity was assessed in the Danish VTE cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257, 2283 recurrences, 3335 bleeding events). Absolute treatment effects were estimated by combining the models with hazard ratios from trials and meta-analyses. External validation in different settings showed agreement between predicted and observed risks up to 5 years, with C-statistics ranging from 0.48-0.71 (recurrence) and 0.61-0.68 (bleeding). In the Danish VTE cohort, 5-year risks ranged from 4% to 19% for recurrent VTE and 1% -19% for bleeding.<br /><b>Conclusion</b><br />The VTE-PREDICT risk score can be applied to estimate the effect of extended anticoagulant treatment for individual patients with VTE and to support shared decision-making.<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: 17 Jan 2023; epub ahead of print</small></div>
de Winter MA, Büller HR, Carrier M, Cohen AT, ... Nijkeuter M, VTE-PREDICT study group
Eur Heart J: 17 Jan 2023; epub ahead of print | PMID: 36648242
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<div><h4>Targeting endothelial tight junctions to predict and protect thoracic aortic aneurysm and dissection.</h4><i>Yang X, Xu C, Yao F, Ding Q, ... Cong X, Kong W</i><br /><b>Aims</b><br />Whether changes in endothelial tight junctions (TJs) lead to the formation of thoracic aortic aneurysm and dissection (TAAD) and serve as an early indicator and therapeutic target remains elusive.<br /><b>Methods and results</b><br />Single-cell RNA sequencing analysis showed aberrant endothelial TJ expressions in the thoracic aortas of patients with TAAD. In a β-aminopropionitrile (BAPN)-induced TAAD mouse model, endothelial TJ function was disrupted in the thoracic aortas at an early stage (5 and 10 days) as observed by a vascular permeability assay, while the intercellular distribution of crucial TJ components was significantly decreased by en face staining. For the non-invasive detection of endothelial TJ function, two dextrans of molecular weights 4 and 70 kDa were conjugated with the magnetic resonance imaging (MRI) contrast agent Gd-DOTA to synthesize FITC-dextran-DOTA-Gd and rhodamine B-dextran-DOTA-Gd. MRI images showed that both probes accumulated in the thoracic aortas of the BAPN-fed mice. Particularly, the mice with increased accumulated signals from 5 to 10 days developed TAAD at 14 days, whereas the mice with similar signals between the two time points did not. Furthermore, the protease-activated receptor 2 inhibitor AT-1001, which seals TJs, alleviated the BAPN-induced impairment of endothelial TJ function and expression and subsequently reduced TAAD incidence. Notably, endothelial-targeted ZO-1 conditional knockout increased TAAD incidence. Mechanistically, vascular inflammation and edema were observed in the thoracic aortas of the BAPN-fed mice, whereas these phenomena were attenuated by AT-1001.<br /><b>Conclusion</b><br />The disruption of endothelial TJ function is an early event prior to TAAD formation, herein serving as a potential indicator and a promising target for TAAD.<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 Jan 2023; epub ahead of print</small></div>
Yang X, Xu C, Yao F, Ding Q, ... Cong X, Kong W
Eur Heart J: 14 Jan 2023; epub ahead of print | PMID: 36638776
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<div><h4>ESC/EACTS vs. ACC/AHA guidelines for the management of severe aortic stenosis.</h4><i>Lee G, Chikwe J, Milojevic M, Wijeysundera HC, ... Fremes SE, Tam DY</i><br /><AbstractText>Aortic stenosis (AS) is a serious and complex condition, for which optimal management continues to evolve rapidly. An understanding of current clinical practice guidelines is critical to effective patient care and shared decision-making. This state of the art review of the 2021 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines and 2020 American College of Cardiology/American Heart Association Guidelines compares their recommendations for AS based on the evidence to date. The European and American guidelines were generally congruent with the exception of three key distinctions. First, the European guidelines recommend intervening at a left ventricular ejection fraction of 55%, compared with 60% over serial imaging by the American guidelines for asymptomatic patients. Second, the European guidelines recommend a threshold of ≥65 years for surgical bioprosthesis, whereas the American guidelines employ multiple age categories, providing latitude for patient factors and preferences. Third, the guidelines endorse different age cut-offs for transcatheter vs. surgical aortic valve replacement, despite limited evidence. This review also discusses trends indicating a decreasing proportion of mechanical valve replacements. Finally, the review identifies gaps in the literature for areas including transcatheter aortic valve implantation in asymptomatic patients, the appropriateness of Ross procedures, concomitant coronary revascularization with aortic valve replacement, and bicuspid AS. To summarize, this state of the art review compares the latest European and American guidelines on the management of AS to highlight three areas of divergence: timing of intervention, valve selection, and surgical vs. transcatheter aortic valve replacement criteria.</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: 12 Jan 2023; epub ahead of print</small></div>
Lee G, Chikwe J, Milojevic M, Wijeysundera HC, ... Fremes SE, Tam DY
Eur Heart J: 12 Jan 2023; epub ahead of print | PMID: 36632841
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<div><h4>Elevated remnant cholesterol, plasma triglycerides, and cardiovascular and non-cardiovascular mortality.</h4><i>Wadström BN, Pedersen KM, Wulff AB, Nordestgaard BG</i><br /><b>Aims</b><br />Cholesterol carried in triglyceride-rich lipoproteins, also called remnant cholesterol, is being increasingly acknowledged as an important causal risk factor for atherosclerosis. Elevated remnant cholesterol, marked by elevated plasma triglycerides, is associated causally with an increased risk of atherosclerotic cardiovascular disease. The association with cause-specific mortality is, however, unclear. The aim of this study was to test the hypothesis that elevated remnant cholesterol and plasma triglycerides are associated with increased mortality from cardiovascular disease, cancer, and other causes.<br /><b>Methods and results</b><br />Using a contemporary population-based cohort, 87 192 individuals from the Copenhagen General Population Study aged 20-69 years at baseline in 2003-2015 were included. During up to 13 years of follow-up, 687 individuals died from cardiovascular disease, 1594 from cancer, and 856 from other causes, according to the National Danish Causes of Death Registry. In individuals with remnant cholesterol ≥1.0 mmol/L (≥39 mg/dL; 22% of the population) compared with those with levels <0.5 mmol/L (<19 mg/dL), multivariable-adjusted mortality hazard ratios were 2.2 (95% confidence interval 1.3-3.5) for cardiovascular disease, 1.0 (0.7-1.3) for cancer, and 2.1 (1.4-3.3) for other causes. Exploratory analysis of the cause of death subcategories showed corresponding hazard ratios of 4.4 (1.6-11) for ischemic heart disease, 8.4 (2.0-34) for infectious diseases, and 9.1 (1.9-43) for endocrinological diseases. Results for plasma triglycerides >2 vs. <1 mmol/L (>177 vs. <89 mg/dL) were similar.<br /><b>Conclusion</b><br />Remnant cholesterol of ≥1 mmol/L (39 mg/dL), present in 22% of the population, and plasma triglycerides of ≥2 mmol/L (177 mg/dL), present in 28% of the population, were associated with two-fold mortality from cardiovascular and other causes, but not from cancer. This novel finding should be confirmed in other cohorts.<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: 12 Jan 2023; epub ahead of print</small></div>
Wadström BN, Pedersen KM, Wulff AB, Nordestgaard BG
Eur Heart J: 12 Jan 2023; epub ahead of print | PMID: 36631967
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<div><h4>Investigator-reported ventricular arrhythmias and mortality in heart failure with mildly reduced or preserved ejection fraction.</h4><i>Curtain JP, Adamson C, Kondo T, Butt J, ... Jhund PS, McMurray JJV</i><br /><b>Aims</b><br />Few reports have examined the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) or their relationship with mortality in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF).<br /><b>Methods and results</b><br />Data from the PARAGON-HF, TOPCAT, I-Preserve, and CHARM-Preserved trials were merged. VT/VF, reported as adverse events, were identified. Patients who experienced VT/VF were compared with patients who did not. The relationship between VT/VF and mortality was examined in time-updated Cox proportional hazard regression models. Variables associated with VT/VF were examined in Cox proportional hazard regression models. The rate of VT/VF in patients with HFmrEF compared with patients with HFpEF was examined in a Cox proportional hazards regression model. Of 13 609 patients, over a median follow-up of 1170 days (interquartile range: 966-1451), 146 (1.1%) experienced an investigator-reported VT/VF (incidence rate 0.3 per 100 person-years). Patients who experienced VT/VF were more likely to be male, have had a myocardial infarction, poorer renal function, more adverse left ventricular remodelling, and higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) than patients who did not. Occurrence of VT/VF was associated with NT-proBNP, history of atrial fibrillation/flutter, male sex, lower ejection fraction, and history of hypertension. VT/VF was associated with all-cause death [adjusted hazard ratio (HR): 3.95, 95% confidence interval (CI): 2.80-5.57; P < 0.001] and cardiovascular death, driven by death from heart failure and not sudden death. Patients with HFmrEF had a higher rate of VT/VF than patients with HFpEF (adjusted HR: 2.19, 95% CI: 1.77-2.71).<br /><b>Conclusion</b><br />VT/VF was uncommon in patients with HFmrEF and HFpEF. However, such events were strongly associated with mortality and appear to be a marker of disease severity rather than risk of sudden death.<br /><b>Clinical trial registration</b><br />ClinicalTrials.gov unique identifier: NCT01920711(PARAGON-HF); NCT00094302 (TOPCAT); NCT00095238 (I-Preserve); NCT00634712 (CHARM-Preserved).<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: 12 Jan 2023; epub ahead of print</small></div>
Curtain JP, Adamson C, Kondo T, Butt J, ... Jhund PS, McMurray JJV
Eur Heart J: 12 Jan 2023; epub ahead of print | PMID: 36632831
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<div><h4>Artificial intelligence to enhance clinical value across the spectrum of cardiovascular healthcare.</h4><i>Gill SK, Karwath A, Uh HW, Cardoso VR, ... Kotecha D, BigData@Heart Consortium and the cardAIc group </i><br /><AbstractText>Artificial intelligence (AI) is increasingly being utilized in healthcare. This article provides clinicians and researchers with a step-wise foundation for high-value AI that can be applied to a variety of different data modalities. The aim is to improve the transparency and application of AI methods, with the potential to benefit patients in routine cardiovascular care. Following a clear research hypothesis, an AI-based workflow begins with data selection and pre-processing prior to analysis, with the type of data (structured, semi-structured, or unstructured) determining what type of pre-processing steps and machine-learning algorithms are required. Algorithmic and data validation should be performed to ensure the robustness of the chosen methodology, followed by an objective evaluation of performance. Seven case studies are provided to highlight the wide variety of data modalities and clinical questions that can benefit from modern AI techniques, with a focus on applying them to cardiovascular disease management. Despite the growing use of AI, further education for healthcare workers, researchers, and the public are needed to aid understanding of how AI works and to close the existing gap in knowledge. In addition, issues regarding data access, sharing, and security must be addressed to ensure full engagement by patients and the public. The application of AI within healthcare provides an opportunity for clinicians to deliver a more personalized approach to medical care by accounting for confounders, interactions, and the rising prevalence of multi-morbidity.</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: 11 Jan 2023; epub ahead of print</small></div>
Gill SK, Karwath A, Uh HW, Cardoso VR, ... Kotecha D, BigData@Heart Consortium and the cardAIc group
Eur Heart J: 11 Jan 2023; epub ahead of print | PMID: 36629285
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<div><h4>Genetic causes of heart failure with preserved ejection fraction: emerging pharmacological treatments.</h4><i>Olivotto I, Udelson JE, Pieroni M, Rapezzi C</i><br /><AbstractText>Heart failure with preserved ejection fraction (HFpEF) is a major driver of cardiac morbidity and mortality in developed countries, due to ageing populations and the increasing prevalence of comorbidities. While heart failure with reduced ejection fraction is dominated by left ventricular impairment, HFpEF results from a complex interplay of cardiac remodelling, peripheral circulation, and concomitant features including age, hypertension, obesity, and diabetes. In an important subset, however, HFpEF is subtended by specific diseases of the myocardium that are genetically determined, have distinct pathophysiology, and are increasingly amenable to targeted, innovative treatments. While each of these conditions is rare, they collectively represent a relevant subset within HFpEF cohorts, and their prompt recognition has major consequences for clinical practice, as access to dedicated, disease-specific treatments may radically change the quality of life and outcome. Furthermore, response to standard heart failure treatment will generally be modest for these individuals, whose inclusion in registries and trials may dilute the perceived efficacy of treatments targeting mainstream HFpEF. Finally, a better understanding of the molecular underpinnings of monogenic myocardial disease may help identify therapeutic targets and develop innovative treatments for selected HFpEF phenotypes of broader epidemiological relevance. The field of genetic cardiomyopathies is undergoing rapid transformation due to recent, groundbreaking advances in drug development, and deserves greater awareness within the heart failure community. The present review addressed existing and developing therapies for genetic causes of HFpEF, including hypertrophic cardiomyopathy, cardiac amyloidosis, and storage diseases, discussing their potential impact on management and their broader implications for our understanding of HFpEF at large.</AbstractText><br /><br />© The Author(s) 2022. 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 Dec 2022; epub ahead of print</small></div>
Olivotto I, Udelson JE, Pieroni M, Rapezzi C
Eur Heart J: 30 Dec 2022; epub ahead of print | PMID: 36582184
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<div><h4>Endocrine functions of the heart: from bench to bedside.</h4><i>Volpe M, Gallo G, Rubattu S</i><br /><AbstractText>Heart has a recognized endocrine function as it produces several biologically active substances with hormonal properties. Among these hormones, the natriuretic peptide (NP) system has been extensively characterized and represents a prominent expression of the endocrine function of the heart. Over the years, knowledge about the mechanisms governing their synthesis, secretion, processing, and receptors interaction of NPs has been intensively investigated. Their main physiological endocrine and paracrine effects on cardiovascular and renal systems are mostly mediated through guanylate cyclase-A coupled receptors. The potential role of NPs in the pathophysiology of heart failure and particularly their counterbalancing action opposing the overactivation of renin-angiotensin-aldosterone and sympathetic nervous systems has been described. In addition, NPs are used today as key biomarkers in cardiovascular diseases with both diagnostic and prognostic significance. On these premises, multiple therapeutic strategies based on the biological properties of NPs have been attempted to develop new cardiovascular therapies. Apart from the introduction of the class of angiotensin receptor/neprilysin inhibitors in the current management of heart failure, novel promising molecules, including M-atrial natriuretic peptide (a novel atrial NP-based compound), have been tested for the treatment of human hypertension. The development of new drugs is currently underway, and we are probably only at the dawn of novel NPs-based therapeutic strategies. The present article also provides an updated overview of the regulation of NPs synthesis and secretion by microRNAs and epigenetics as well as interactions of cardiac hormones with other endocrine systems.</AbstractText><br /><br />© The Author(s) 2022. 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 Dec 2022; epub ahead of print</small></div>
Volpe M, Gallo G, Rubattu S
Eur Heart J: 30 Dec 2022; epub ahead of print | PMID: 36582126
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<div><h4>Cardiometabolic multimorbidity and incident dementia: the Swedish twin registry.</h4><i>Dove A, Guo J, Marseglia A, Fastbom J, ... Pedersen NL, Xu W</i><br /><b>Aims</b><br />Cardiometabolic diseases (CMDs), including diabetes, heart disease, and stroke, are established risk factors for dementia, but their combined impact has been investigated only recently. This study aimed to examine the association between mid- and late-life cardiometabolic multimorbidity and dementia and explore the role of genetic background in this association.<br /><b>Methods and results</b><br />Within the Swedish Twin Registry, 17 913 dementia-free individuals aged ≥60 were followed for 18 years. CMDs [including age of onset in mid (60) or late (≥60) life] and dementia were ascertained from medical records. Cardiometabolic multimorbidity was defined as having ≥2 CMDs. Cox regression was used to estimate the CMD-dementia association in (i) a classical cohort study design and (ii) a co-twin study design involving 356 monozygotic and dizygotic pairs. By comparing the strength of the association in the two designs, the contribution of genetic background was estimated. At baseline, 3,312 (18.5%) participants had 1 CMD and 839 (4.7%) had ≥2 CMDs. Over the follow-up period, 3,020 participants developed dementia. In the classic cohort design, the hazard ratio (95% confidence interval) of dementia was 1.42 (1.27-1.58) for 1 CMD and 2.10 (1.73-2.57) for ≥2 CMDs. Dementia risk was stronger with mid-life as opposed to late-life CMDs. In the co-twin design, the CMD-dementia association was attenuated among monozygotic [0.99 (0.50-1.98)] but not dizygotic [1.55 (1.15-2.09)] twins, suggesting that the association was in part due to genetic factors common to both CMDs and dementia.<br /><b>Conclusion</b><br />Cardiometabolic multimorbidity, particularly in mid-life, is associated with an increased risk of dementia. Genetic background may underpin this association.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 29 Dec 2022; epub ahead of print</small></div>
Dove A, Guo J, Marseglia A, Fastbom J, ... Pedersen NL, Xu W
Eur Heart J: 29 Dec 2022; epub ahead of print | PMID: 36577740
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<div><h4>Prevalence, patterns and outcomes of cardiac involvement in Erdheim-Chester disease.</h4><i>Azoulay LD, Bravetti M, Cohen-Aubart F, Emile JF, ... Cluzel P, Haroche J</i><br /><b>Aims</b><br />Cardiac involvement of Erdheim-Chester disease (ECD), a rare L group histiocytosis, has been reported to be associated with poor outcomes, but systematic studies are lacking. The present study aimed to investigate the prevalence, clinical features, imaging features, and prognosis of cardiac involvement in ECD in a large series.<br /><b>Methods and results</b><br />All patients with ECD who underwent cardiac magnetic resonance (CMR) imaging between 2003 and 2019 at a French tertiary center were retrospectively included. Primary outcome was all-cause mortality. Secondary outcomes were pericarditis, cardiac tamponade, conduction disorders, device implantation and coronary artery disease (CAD). A total of 200 patients were included [63 (54-71) years, 30% female, 58% BRAFV600E mutated]. Median follow-up was 5.5 years (3.3-9 years). On CMR, right atrioventricular sulcus infiltration was observed in 37% of patients, and pericardial effusion was seen in 24% of patients. In total, 8 patients (4%) had pericarditis (7 acute, 1 constrictive), 10 patients (5%) had cardiac tamponade, 5 patients (2.5%) had ECD-related high-degree conduction disorders, and 45 patients (23%) had CAD. Overall, cardiac involvement was present in 96 patients (48%) and was associated with BRAFV600E mutation [Odds ratio (OR) = 7.4, 95% confidence interval (CI) (3.5-16.8), P < 0.001] and ECD-related clinical events [OR = 5, 95%CI (1.5-21.2), P = 0.004] but not with lower survival in multivariate analysis [adjusted hazard ratio (HR) = 1.4, 95% CI (0.8-2.5), P = 0.2].<br /><b>Conclusion</b><br />Cardiac involvement is present in nearly half of ECD patients and is associated with BRAFV600E mutation and complications (pericarditis, cardiac tamponade, and conduction disorders) but not with lower survival.<br /><br />© The Author(s) 2022. 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: 21 Dec 2022; epub ahead of print</small></div>
Azoulay LD, Bravetti M, Cohen-Aubart F, Emile JF, ... Cluzel P, Haroche J
Eur Heart J: 21 Dec 2022; epub ahead of print | PMID: 36545799
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<div><h4>Primary prevention of acute cardiovascular events by influenza vaccination: an observational study.</h4><i>Davidson JA, Banerjee A, Douglas I, Leyrat C, ... Smeeth L, Warren-Gash C</i><br /><b>Aims</b><br />Previous studies show a reduced incidence of first myocardial infarction and stroke 1-3 months after influenza vaccination, but it is unclear how underlying cardiovascular risk impacts the association.<br /><b>Methods and results</b><br />The study used linked Clinical Practice Research Datalink, Hospital Episode Statistics Admitted Patient Care and Office for National Statistics mortality data from England between 1 September 2008 and 31 August 2019. From the data, individuals aged 40-84 years with a first acute cardiovascular event and influenza vaccination occurring within 12 months of each September were selected. Using a self-controlled case series analysis, season-adjusted cardiovascular risk stratified incidence ratios (IRs) for cardiovascular events after vaccination compared with baseline time before and >120 days after vaccination were generated. 193 900 individuals with a first acute cardiovascular event and influenza vaccine were included. 105 539 had hypertension and 172 050 had a QRISK2 score ≥10%. In main analysis, acute cardiovascular event risk was reduced in the 15-28 days after vaccination [IR 0.72 (95% CI 0.70-0.74)] and, while the effect size tapered, remained reduced to 91-120 days after vaccination [0.83 (0.81-0.88)]. Reduced cardiovascular events were seen after vaccination among individuals of all age groups and with raised and low cardiovascular risk.<br /><b>Conclusions</b><br />Influenza vaccine may offer cardiovascular benefit among individuals at varying cardiovascular risk. Further studies are needed to characterize the populations who could derive the most cardiovascular benefits from vaccination.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 20 Dec 2022; epub ahead of print</small></div>
Davidson JA, Banerjee A, Douglas I, Leyrat C, ... Smeeth L, Warren-Gash C
Eur Heart J: 20 Dec 2022; epub ahead of print | PMID: 36537199
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<div><h4>Fractional flow reserve versus angiography-guided strategy in acute myocardial infarction with multivessel disease: a randomized trial.</h4><i>Lee JM, Kim HK, Park KH, Choo EH, ... Hahn JY, FRAME-AMI Investigators</i><br /><b>Aims</b><br />In patients with acute myocardial infarction (MI) and multivessel coronary artery disease, percutaneous coronary intervention (PCI) of non-infarct-related artery reduces death or MI. However, whether selective PCI guided by fractional flow reserve (FFR) is superior to routine PCI guided by angiography alone is unclear. The current trial sought to compare FFR-guided PCI with angiography-guided PCI for non-infarct-related artery lesions among patients with acute MI and multivessel disease.<br /><b>Methods and results</b><br />Patients with acute MI and multivessel coronary artery disease who had undergone successful PCI of the infarct-related artery were randomly assigned to either FFR-guided PCI (FFR ≤0.80) or angiography-guided PCI (diameter stenosis of >50%) for non-infarct-related artery lesions. The primary end point was a composite of time to death, MI, or repeat revascularization. A total of 562 patients underwent randomization. Among them, 60.0% underwent immediate PCI for non-infarct-related artery lesions and 40.0% were treated by a staged procedure during the same hospitalization. PCI was performed for non-infarct-related artery in 64.1% in the FFR-guided PCI group and 97.1% in the angiography-guided PCI group, and resulted in significantly fewer stent used in the FFR-guided PCI group (2.2 ± 1.1 vs. 2.5 ± 0.9, P < 0.001). At a median follow-up of 3.5 years (interquartile range: 2.7-4.1 years), the primary end point occurred in 18 patients of 284 patients in the FFR-guided PCI group and in 40 of 278 patients in the angiography-guided PCI group (7.4% vs. 19.7%; hazard ratio, 0.43; 95% confidence interval, 0.25-0.75; P = 0.003). The death occurred in five patients (2.1%) in the FFR-guided PCI group and in 16 patients (8.5%) in the angiography-guided PCI group; MI in seven (2.5%) and 21 (8.9%), respectively; and unplanned revascularization in 10 (4.3%) and 16 (9.0%), respectively.<br /><b>Conclusion</b><br />In patients with acute MI and multivessel coronary artery disease, a strategy of selective PCI using FFR-guided decision-making was superior to a strategy of routine PCI based on angiographic diameter stenosis for treatment of non-infarct-related artery lesions regarding the risk of death, MI, or repeat revascularization.<br /><br />© The Author(s) 2022. 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: 20 Dec 2022; epub ahead of print</small></div>
Lee JM, Kim HK, Park KH, Choo EH, ... Hahn JY, FRAME-AMI Investigators
Eur Heart J: 20 Dec 2022; epub ahead of print | PMID: 36540034
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<div><h4>Acute aortic dissection: evidence, uncertainties, and future therapies.</h4><i>Rylski B, Schilling O, Czerny M</i><br /><AbstractText>Remarkable progress has become especially apparent in aortic medicine in the last few decades, leading to essential changes in how thoracic aortic dissection is understood and treated. This state-of-the-art review article addresses the mechanisms of acute aortic dissection, explaining the role of its primary entry location, proximal, and distal dissection extension in their clinical presentation and impact on the decision-making process towards the best treatment approach. The latest evidence on novel treatment methods for acute aortic syndromes is presented, and the diverse dissection classification systems that remain uncertain are discussed, which reveals the need for shared terminology and more clarity. Finally, future aspects are discussed in treating acute aortic dissection, such as the endovascular treatment of aortic dissection Type A and biomarkers for acute aortic syndromes.</AbstractText><br /><br />© The Author(s) 2022. 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: 20 Dec 2022; epub ahead of print</small></div>
Rylski B, Schilling O, Czerny M
Eur Heart J: 20 Dec 2022; epub ahead of print | PMID: 36540036
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<div><h4>Moderate-intensity statin with ezetimibe vs. high-intensity statin in patients with diabetes and atherosclerotic cardiovascular disease in the RACING trial.</h4><i>Lee YJ, Cho JY, You SC, Lee YH, ... Jang Y, Kim JS</i><br /><b>Aims</b><br />This study evaluated the effect of moderate-intensity statin with ezetimibe combination therapy vs. high-intensity statin monotherapy among patients with diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD).<br /><b>Methods and results</b><br />This was a pre-specified, stratified subgroup analysis of the DM cohort in the RACING trial. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. Among total patients, 1398 (37.0%) had DM at baseline. The incidence of the primary outcome was 10.0% and 11.3% among patients with DM randomized to ezetimibe combination therapy vs. high-intensity statin monotherapy (hazard ratio: 0.89; 95% confidence interval: 0.64-1.22; P = 0.460). Intolerance-related discontinuation or dose reduction of the study drug was observed in 5.2% and 8.7% of patients in each group, respectively (P = 0.014). LDL cholesterol levels <70 mg/dL at 1, 2, and 3 years were observed in 81.0%, 83.1%, and 79.9% of patients in the ezetimibe combination therapy group, and 64.1%, 70.2%, and 66.8% of patients in the high-intensity statin monotherapy group (all P < 0.001). In the total population, no significant interactions were found between DM status and therapy regarding primary outcome, intolerance-related discontinuation or dose reduction, and the proportion of patients with LDL cholesterol levels <70 mg/dL.<br /><b>Conclusion</b><br />Ezetimibe combination therapy effects observed in the RACING trial population are preserved among patients with DM. This study supports moderate-intensity statin with ezetimibe combination therapy as a suitable alternative to high-intensity statins if the latter cannot be tolerated, or further reduction in LDL cholesterol is required among patients with DM and ASCVD.<br /><b>Clinical trial registration</b><br />ClinicalTrials.gov, Identifier:NCT03044665.<br /><br />© The Author(s) 2022. 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 Dec 2022; epub ahead of print</small></div>
Lee YJ, Cho JY, You SC, Lee YH, ... Jang Y, Kim JS
Eur Heart J: 19 Dec 2022; epub ahead of print | PMID: 36529993
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<div><h4>Common diagnostic errors in adults with congenital heart disease.</h4><i>Celermajer DS, Baker DW, Cordina RL, Gatzoulis M, Broberg CS</i><br /><AbstractText>Owing to the great advances in the care for children with congenital heart disease by paediatric cardiac surgeons and cardiologists, there are ever increasing numbers of patients with congenital heart disease who reach adult life. At some stage during the late teenage years or soon after, these patients \'transition\' from paediatric cardiac care to surveillance by cardiologists who look after adults. Many such specialists, however, are more familiar with commoner acquired heart problems such as coronary disease, heart failure, and arrhythmia in structurally normal hearts and less familiar with congenital heart disease. For this reason, international guidelines have suggested that the care of young adults with congenital heart disease take place in designated specialist adult congenital heart disease centres. It remains very important, however, for general cardiologists to have a good understanding of many aspects of adult congenital heart disease, including common pitfalls to avoid and, importantly, when to refer on, to a specialist centre. To help healthcare providers across the spectrum of cardiology practice to address common themes in adult congenital heart disease, this state-of-the-art review provides a series of case vignettes to illustrate frequent diagnostic problems that we have seen in our tertiary-level adult congenital heart disease centres, which are sometimes encountered in general cardiology settings. These include commonly \'missed\' diagnoses, or errors with diagnosis or management, in these often very complex patients.</AbstractText><br /><br />© The Author(s) 2022. 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: 17 Dec 2022; epub ahead of print</small></div>
Celermajer DS, Baker DW, Cordina RL, Gatzoulis M, Broberg CS
Eur Heart J: 17 Dec 2022; epub ahead of print | PMID: 36527303
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<div><h4>Empagliflozin, irrespective of blood pressure, improves outcomes in heart failure with preserved ejection fraction: the EMPEROR-Preserved trial.</h4><i>Böhm M, Anker S, Mahfoud F, Lauder L, ... Packer M, Butler J</i><br /><b>Aims</b><br />Empagliflozin reduces the risk of cardiovascular death or heart failure (HF) hospitalization in patients with HF and preserved ejection fraction. This study aims to evaluate if systolic blood pressure (SBP) moderates these effects.<br /><b>Methods and results</b><br />The association of SBP and the treatment effects of empagliflozin in EMPEROR-Preserved (empagliflozin outcome trial in patients with chronic heart failure with preserved ejection fraction) was evaluated. Randomized patients (n = 5988) were grouped according to SBP at baseline (<110 mmHg, n = 455; 110-130 mmHg, n = 2415; > 130 mmHg, n = 3118). The effect of empagliflozin on blood pressure, cardiovascular death or HF hospitalization (primary outcome), total HF hospitalizations, and rate of decline in estimated glomerular filtration rate was studied. Over a median of 26.2 months, the placebo-corrected decline was small and not significantly different across baseline SBP. On placebo, the risk of cardiovascular death or hospitalization for HF was 8.58 at >130 mmHg, 8.26 at 110-130 mmHg, and 11.59 events per 100 patient-years at <110 mmHg (P = 0.12 vs. > 130 mmHg, P = 0.08 vs. 110-130 mmHg). There was no evidence for baseline SBP moderating the effect of empagliflozin on risk of HF events (primary endpoint interaction P = 0.69, recurrent HF hospitalizations interaction P = 0.55). When comparing empagliflozin with placebo, SBP did not meaningfully associate with adverse events such as hypotension, volume depletion, and acute renal failure.<br /><b>Conclusion</b><br />In EMPEROR-Preserved, empagliflozin was effective and safe without SBP meaningfully moderating empagliflozin\'s treatment effects. This analysis of EMPEROR-Preserved shows that empagliflozin can be used safely and effectively without blood pressure being a meaningful moderator of the drug benefit.<br /><b>Clinical trial registration</b><br />URL: https://www.clinicaltrials.gov Unique identifier: NCT03057951.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 07 Dec 2022; epub ahead of print</small></div>
Böhm M, Anker S, Mahfoud F, Lauder L, ... Packer M, Butler J
Eur Heart J: 07 Dec 2022; epub ahead of print | PMID: 36478225
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<div><h4>Acute ischaemic stroke: recent advances in reperfusion treatment.</h4><i>Widimsky P, Snyder K, Sulzenko J, Hopkins LN, Stetkarova I</i><br /><AbstractText>During the last 5-7 years, tremendous progress was achieved in the reperfusion treatment of acute ischaemic stroke during its first few hours from symptom onset. This review summarizes the latest evidence from randomized clinical trials and prospective registries with a focus on endovascular treatment using stent retrievers, aspiration catheters, thrombolytics, and (in selected patients) carotid stenting. Novel approaches in prehospital (mobile interventional stroke teams) and early hospital (direct transfer to angiography) management are described, and future perspectives (\'all-in-one\' laboratories with angiography and computed tomography integrated) are discussed. There is reasonable chance for patients with moderate-to-severe acute ischaemic stroke to survive without permanent sequelae when the large-vessel occlusion is removed by means of modern pharmaco-mechanic approach. Catheter thrombectomy is now the golden standard of acute stroke treatment. The role of cardiologists in stroke is expanding from diagnostic help (to reveal the cause of stroke) to acute therapy in those regions where such up-to-date Class I. A treatment is not yet available.</AbstractText><br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 07 Dec 2022; epub ahead of print</small></div>
Widimsky P, Snyder K, Sulzenko J, Hopkins LN, Stetkarova I
Eur Heart J: 07 Dec 2022; epub ahead of print | PMID: 36477996
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<div><h4>Polygenic risk scores for the prediction of cardiometabolic disease.</h4><i>O\'Sullivan JW, Ashley EA, Elliott PM</i><br /><AbstractText>Cardiometabolic diseases contribute more to global morbidity and mortality than any other group of disorders. Polygenic risk scores (PRSs), the weighted summation of individually small-effect genetic variants, represent an advance in our ability to predict the development and complications of cardiometabolic diseases. This article reviews the evidence supporting the use of PRS in seven common cardiometabolic diseases: coronary artery disease (CAD), stroke, hypertension, heart failure and cardiomyopathies, obesity, atrial fibrillation (AF), and type 2 diabetes mellitus (T2DM). Data suggest that PRS for CAD, AF, and T2DM consistently improves prediction when incorporated into existing clinical risk tools. In other areas such as ischaemic stroke and hypertension, clinical application appears premature but emerging evidence suggests that the study of larger and more diverse populations coupled with more granular phenotyping will propel the translation of PRS into practical clinical prediction tools.</AbstractText><br /><br />© The Author(s) 2022. 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 Dec 2022; epub ahead of print</small></div>
O'Sullivan JW, Ashley EA, Elliott PM
Eur Heart J: 07 Dec 2022; epub ahead of print | PMID: 36478054
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<div><h4>Translational opportunities of single-cell biology in atherosclerosis.</h4><i>de Winther MPJ, Bäck M, Evans P, Gomez D, ... Bochaton-Piallat ML, Monaco C</i><br /><AbstractText>The advent of single-cell biology opens a new chapter for understanding human biological processes and for diagnosing, monitoring, and treating disease. This revolution now reaches the field of cardiovascular disease (CVD). New technologies to interrogate CVD samples at single-cell resolution are allowing the identification of novel cell communities that are important in shaping disease development and direct towards new therapeutic strategies. These approaches have begun to revolutionize atherosclerosis pathology and redraw our understanding of disease development. This review discusses the state-of-the-art of single-cell analysis of atherosclerotic plaques, with a particular focus on human lesions, and presents the current resolution of cellular subpopulations and their heterogeneity and plasticity in relation to clinically relevant features. Opportunities and pitfalls of current technologies as well as the clinical impact of single-cell technologies in CVD patient care are highlighted, advocating for multidisciplinary and international collaborative efforts to join the cellular dots of CVD.</AbstractText><br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 07 Dec 2022; epub ahead of print</small></div>
de Winther MPJ, Bäck M, Evans P, Gomez D, ... Bochaton-Piallat ML, Monaco C
Eur Heart J: 07 Dec 2022; epub ahead of print | PMID: 36478058
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<div><h4>Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials.</h4><i>Costa F, Montalto C, Branca M, Hong SJ, ... Mehran R, Valgimigli M</i><br /><b>Aims</b><br />The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients.<br /><b>Methods and results</b><br />A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation.<br /><b>Conclusion</b><br />In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen.<br /><b>Study registration</b><br />PROSPERO registration number CRD42021284004.<br /><br />© The Author(s) 2022. 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 Dec 2022; epub ahead of print</small></div>
Costa F, Montalto C, Branca M, Hong SJ, ... Mehran R, Valgimigli M
Eur Heart J: 07 Dec 2022; epub ahead of print | PMID: 36477292
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<div><h4>Lifetime risk of comorbidity in patients with simple congenital heart disease: a Danish nationwide study.</h4><i>El-Chouli M, Meddis A, Christensen DM, Gerds TA, ... Idorn L, Gislason G</i><br /><b>Aims</b><br />In a continuously ageing population of patients with congenital heart disease (CHD), understanding the long-term risk of morbidity is crucial. The aim of this study was to compare the lifetime risks of developing comorbidities in patients with simple CHD and matched controls.<br /><b>Methods and results</b><br />Using the Danish nationwide registers spanning from 1977 to 2018, simple CHD cases were defined as isolated atrial septal defect (ASD), ventricular septal defect (VSD), pulmonary stenosis, or patent ductus arteriosus in patients surviving until at least 5 years of age. There were 10 controls identified per case. Reported were absolute lifetime risks and lifetime risk differences (between patients with simple CHD and controls) of incident comorbidities stratified by groups and specific cardiovascular comorbidities. Of the included 17 157 individuals with simple CHD, the largest subgroups were ASD (37.7%) and VSD (33.9%), and 52% were females. The median follow-up time for patients with CHD was 21.2 years (interquartile range: 9.4-39.0) and for controls, 19.8 years (9.0-37.0). The lifetime risks for the investigated comorbidities were higher and appeared overall at younger ages for simple CHD compared with controls, except for neoplasms and chronic kidney disease. The lifetime risk difference among the comorbidity groups was highest for neurological disease (male: 15.2%, female: 11.3%), pulmonary disease (male: 9.1%, female: 11.7%), and among the specific comorbidities for stroke (male: 18.9%, female: 11.4%). The overall risk of stroke in patients with simple CHD was mainly driven by ASD (male: 28.9%, female: 17.5%), while the risks of myocardial infarction and heart failure were driven by VSD. The associated lifetime risks of stroke, myocardial infarction, and heart failure in both sexes were smaller in invasively treated patients compared with untreated patients with simple CHD.<br /><b>Conclusion</b><br />Patients with simple CHD had increased lifetime risks of all comorbidities compared with matched controls, except for neoplasms and chronic kidney disease. These findings highlight the need for increased attention towards early management of comorbidity risk factors.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 07 Dec 2022; epub ahead of print</small></div>
El-Chouli M, Meddis A, Christensen DM, Gerds TA, ... Idorn L, Gislason G
Eur Heart J: 07 Dec 2022; epub ahead of print | PMID: 36477305
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<div><h4>Economic, ethical, and environmental sustainability of cardiac imaging.</h4><i>Picano E</i><br /><AbstractText>Current cardiology guidelines assign a class of recommendation 1 for the diagnosis of chest pain to five imaging techniques based on either anatomic (coronary computed tomography angiography) or functional approaches, such as stress single-photon emission tomography, stress positron emission tomography, stress cardiovascular magnetic resonance, and stress echocardiography. The choice is left to the prescribing physician, based on local availability and expertise. However, the five techniques differ substantially in their cost, applicability based on patient characteristics, long-term risk, and environmental impact. The average European immediate cost ranges from 50 to 1000 euros. The radiation exposure ranges from 0 to 500 chest x-rays. The environmental footprint ranges from 3 to 300 kg of carbon dioxide emissions equivalent. The ethical code of the World Medical Association 2021 recommends the responsible use of healthcare money by doctors, with the minimization of potential damage to patients and the environment. The Euratom law 2013/directive 59 reinforces the justification principle and the optimization principle for medical radiation exposures, with the legal responsibility of both the referrer and the practitioner. A small cost, a minimal long-term risk, and a modest carbon emission per examination multiplied by billions of tests per year become an unaffordable economic burden in the short-term, significant population damage to public health over the years, and impacts on climate change in decades. The cardiology community may wish to adopt a more sustainable practice with affordable, radiation-optimized, and carbon-neutral practices for the benefit of patients, physicians, payers, and the planet.</AbstractText><br /><br />© The Author(s) 2022. 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 Dec 2022; epub ahead of print</small></div>
Picano E
Eur Heart J: 07 Dec 2022; epub ahead of print | PMID: 36477859
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<div><h4>Prevention of cardiorenal damage: importance of albuminuria.</h4><i>Ruilope LM, Ortiz A, Lucia A, Miranda B, ... Ruiz-Hurtado G, Pitt B</i><br /><AbstractText>Chronic kidney disease (CKD) is projected to become a leading global cause of death by 2040, and its early detection is critical for effective and timely management. The current definition of CKD identifies only advanced stages, when kidney injury has already destroyed >50% of functioning kidney mass as reflected by an estimated glomerular filtration rate <60 mL/min/1.73 m2 or a urinary albumin/creatinine ratio >six-fold higher than physiological levels (i.e. > 30 mg/g). An elevated urinary albumin-excretion rate is a known early predictor of future cardiovascular events. There is thus a \'blind spot\' in the detection of CKD, when kidney injury is present but is undetectable by current diagnostic criteria, and no intervention is made before renal and cardiovascular damage occurs. The present review discusses the CKD \'blind spot\' concept and how it may facilitate a holistic approach to CKD and cardiovascular disease prevention and implement the call for albuminuria screening implicit in current guidelines. Cardiorenal risk associated with albuminuria in the high-normal range, novel genetic and biochemical markers of elevated cardiorenal risk, and the role of heart and kidney protective drugs evaluated in recent clinical trials are also discussed. As albuminuria is a major risk factor for cardiovascular and renal disease, starting from levels not yet considered in the definition of CKD, the implementation of opportunistic or systematic albuminuria screening and therapy, possibly complemented with novel early biomarkers, has the potential to improve cardiorenal outcomes and mitigate the dismal 2040 projections for CKD and related cardiovascular burden.</AbstractText><br /><br />© The Author(s) 2022. 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 Dec 2022; epub ahead of print</small></div>
Ruilope LM, Ortiz A, Lucia A, Miranda B, ... Ruiz-Hurtado G, Pitt B
Eur Heart J: 07 Dec 2022; epub ahead of print | PMID: 36477861
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<div><h4>Acute, periprocedural and longterm antithrombotic therapy in older adults.</h4><i>Andreotti F, Geisler T, Collet JP, Gigante B, ... Verheugt FWA, Vilahur G</i><br /><AbstractText>The first international guidance on antithrombotic therapy in the elderly came from the European Society of Cardiology Working Group on Thrombosis in 2015. This same group has updated its previous report on antiplatelet and anticoagulant drugs for older patients with acute or chronic coronary syndromes, atrial fibrillation, or undergoing surgery or procedures typical of the elderly (transcatheter aortic valve implantation and left atrial appendage closure). The aim is to provide a succinct but comprehensive tool for readers to understand the bases of antithrombotic therapy in older patients, despite the complexities of comorbidities, comedications and uncertain ischaemic- vs. bleeding-risk balance. Fourteen updated consensus statements integrate recent trial data and other evidence, with a focus on high bleeding risk. Guideline recommendations, when present, are highlighted, as well as gaps in evidence. Key consensus points include efforts to improve medical adherence through deprescribing and polypill use; adoption of universal risk definitions for bleeding, myocardial infarction, stroke and cause-specific death; multiple bleeding-avoidance strategies, ranging from gastroprotection with aspirin use to selection of antithrombotic-drug composition, dosing and duration tailored to multiple variables (setting, history, overall risk, age, weight, renal function, comedications, procedures) that need special consideration when managing older adults.</AbstractText><br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 07 Dec 2022; epub ahead of print</small></div>
Andreotti F, Geisler T, Collet JP, Gigante B, ... Verheugt FWA, Vilahur G
Eur Heart J: 07 Dec 2022; epub ahead of print | PMID: 36477865
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<div><h4>JCAD promotes arterial thrombosis through PI3K/Akt modulation: a translational study.</h4><i>Liberale L, Puspitasari YM, Ministrini S, Akhmedov A, ... Lüscher TF, Camici GG</i><br /><b>Aims</b><br />Variants of the junctional cadherin 5 associated (JCAD) locus associate with acute coronary syndromes. JCAD promotes experimental atherosclerosis through the large tumor suppressor kinase 2 (LATS2)/Hippo pathway. This study investigates the role of JCAD in arterial thrombosis.<br /><b>Methods and results</b><br />JCAD knockout (Jcad-/-) mice underwent photochemically induced endothelial injury to trigger arterial thrombosis. Primary human aortic endothelial cells (HAECs) treated with JCAD small interfering RNA (siJCAD), LATS2 small interfering RNA (siLATS2) or control siRNA (siSCR) were employed for in vitro assays. Plasma JCAD was measured in patients with chronic coronary syndrome or ST-elevation myocardial infarction (STEMI). Jcad-/- mice displayed reduced thrombogenicity as reflected by delayed time to carotid occlusion. Mechanisms include reduced activation of the coagulation cascade [reduced tissue factor (TF) expression and activity] and increased fibrinolysis [higher thrombus embolization episodes and D-dimer levels, reduced vascular plasminogen activator inhibitor (PAI)-1 expression]. In vitro, JCAD silencing inhibited TF and PAI-1 expression in HAECs. JCAD-silenced HAECs (siJCAD) displayed increased levels of LATS2 kinase. Yet, double JCAD and LATS2 silencing did not restore the control phenotype. si-JCAD HAECs showed increased levels of phosphoinositide 3-kinases (PI3K)/ proteinkinase B (Akt) activation, known to downregulate procoagulant expression. The PI3K/Akt pathway inhibitor-wortmannin-prevented the effect of JCAD silencing on TF and PAI-1, indicating a causative role. Also, co-immunoprecipitation unveiled a direct interaction between JCAD and Akt. Confirming in vitro findings, PI3K/Akt and P-yes-associated protein levels were higher in Jcad-/- animals. Lastly, as compared with chronic coronary syndrome, STEMI patients showed higher plasma JCAD, which notably correlated positively with both TF and PAI-1 levels.<br /><b>Conclusions</b><br />JCAD promotes arterial thrombosis by modulating coagulation and fibrinolysis. Herein, reported translational data suggest JCAD as a potential therapeutic target for atherothrombosis.<br /><br />© The Author(s) 2022. 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 Dec 2022; epub ahead of print</small></div>
Liberale L, Puspitasari YM, Ministrini S, Akhmedov A, ... Lüscher TF, Camici GG
Eur Heart J: 05 Dec 2022; epub ahead of print | PMID: 36469488
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<div><h4>Healthcare utilization and quality of life for atrial fibrillation burden: the CIRCA-DOSE study.</h4><i>Andrade JG, Deyell MW, Macle L, Steinberg JS, ... Khairy P, Aguilar M</i><br /><b>Aims</b><br />Atrial tachyarrhythmia recurrence ≥30 s remains the primary endpoint of clinical trials; however, this definition has not been correlated with clinical outcomes or pathophysiological processes. This study sought to determine the atrial tachyarrhythmia duration and burden associated with meaningful clinical outcomes.<br /><b>Methods and results</b><br />The time and duration of every atrial tachyarrhythmia episode recorded on implantable cardiac monitor were evaluated. Healthcare utilization and quality of life in the year following ablation were prospectively collected. Three hundred and forty-six patients provided 126 110 monitoring days. One-year freedom from recurrence increased with arrhythmia duration thresholds, from 52.6 (182/346) to 93.3% (323/346; P < 0.0001). Patients with atrial fibrillation (AF) recurrence limited to durations ≤1 h had rates of healthcare utilization comparable with patients free of recurrence, while patients with AF recurrences lasting >1 h had a relative risk for emergency department consultation of 3.2 [95% confidence interval (CI) 2.0-5.3], hospitalization of 5.3 (95% CI 2.9-9.6), and repeat ablation of 27.1 (95% CI 10.5-71.0). Patients with AF burden of ≤0.1% had rates of healthcare utilization comparable with patients free of recurrence, while patients with AF burden of >0.1% had a relative risk for emergency department consultation of 2.4 (95% CI 1.9-3.9), hospitalization of 6.8 (95% CI 3.6-13.0), cardioversion of 9.1 (95% CI 3.3-25.6), and repeat ablation of 21.8 (95% CI 9.2-52.2). Compared with patients free of recurrence, the disease-specific quality of life was significantly impaired with AF episode durations >24 h, or AF burdens >0.1%.<br /><b>Conclusion</b><br />AF recurrence, as defined by 30 s of arrhythmia, lacks clinical relevance. AF episode durations >1 h or burdens >0.1% were associated with increased rates of healthcare utilization.<br /><br />© The Author(s) 2022. 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 Dec 2022; epub ahead of print</small></div>
Andrade JG, Deyell MW, Macle L, Steinberg JS, ... Khairy P, Aguilar M
Eur Heart J: 02 Dec 2022; epub ahead of print | PMID: 36459112
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<div><h4>Late outcomes of ST-elevation myocardial infarction treated by pharmaco-invasive or primary percutaneous coronary intervention.</h4><i>Jamal J, Idris H, Faour A, Yang W, ... Lo S, French JK</i><br /><b>Aims</b><br />Pharmaco-invasive percutaneous coronary intervention (PI-PCI) is recommended for patients with ST-elevation myocardial infarction (STEMI)who are unable to undergo timely primary PCI (pPCI). The present study examined late outcomes after PI-PCI (successful reperfusion followed by scheduled PCI or failed reperfusion and rescue PCI)compared with timely and late pPCI (>120 min from first medical contact).<br /><b>Methods and results</b><br />All patients with STEMI presenting within 12 h of symptom onset, who underwent PCI during their initial hospitalization at Liverpool Hospital (Sydney), from October 2003 to March 2014, were included. Amongst 2091 STEMI patients (80% male), 1077 (52%)underwent pPCI (68% timely, 32% late), and 1014 (48%)received PI-PCI (33% rescue, 67% scheduled). Mortality at 3 years was 11.1% after pPCI (6.7% timely, 20.2% late) and 6.2% after PI-PCI (9.4% rescue, 4.8% scheduled); P < 0.01. After propensity matching, the adjusted mortality hazard ratio (HR) for timely pPCI compared with scheduled PCI was 0.9 (95% CIs 0.4-2.0) and compared with rescue PCI was 0.5 (95% CIs 0.2-0.9). The adjusted mortality HR for late pPCI, compared with scheduled PCI was 2.2 (95% CIs 1.2-3.1)and compared with rescue PCI, it was 1.5 (95% CIs 0.7-2.0).<br /><b>Conclusion</b><br />Patients who underwent late pPCI had higher mortality rates than those undergoing a pharmaco-invasive strategy. Despite rescue PCI being required in a third of patients, a pharmaco-invasive approach should be considered when delays to PCI are anticipated, as it achieves better outcomes than late pPCI.<br /><br />© The Author(s) 2022. 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 Dec 2022; epub ahead of print</small></div>
Jamal J, Idris H, Faour A, Yang W, ... Lo S, French JK
Eur Heart J: 02 Dec 2022; epub ahead of print | PMID: 36459120
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<div><h4>Transfemoral aortic valve implantation: procedural hospital volume and mortality in Germany.</h4><i>Bestehorn K, Bestehorn M, Zahn R, Perings C, Stellbrink C, Schächinger V</i><br /><b>Aims</b><br />Studies assessing transfemoral transcatheter aortic valve implantation (TF-TAVI) showed lower rates of in-hospital mortality at high-volume hospitals and minimum caseloads were recommended to assure quality standards.<br /><b>Methods and results</b><br />All patients in the German mandatory quality assurance registry with elective or urgent TF-TAVI procedures in 2018 and 2019 at 81 and 82 hospitals, respectively, were analysed. Observed in-hospital mortality was adjusted to expected mortality by the German AKL-KATH score (O/E) as well as by the EuroScore II (O/E2). Hospital volume and O/E were correlated by regression analyses and volume quartiles. 18 763 patients (age: 81.1 ± 1.0 years, mean EuroSCORE II: 6.9 ± 1.8%) and 22 137 patients (mean age: 80.7 ± 3.5 years, mean EuroSCORE II: 6.5 ± 1.6%) were analysed in 2018 and 2019, respectively. The average observed in-hospital mortality was 2.57 ± 1.83% and 2.36 ± 1.60%, respectively. Unadjusted in-hospital mortality was significantly inversely related to hospital volume by linear regression in both years. After risk adjustment, the association between hospital volume and O/E was statistically significant in 2019 (R2 = 0.049; P = 0.046), but not in 2018 (R2 = 0.027; P = 0.14). The variance of O/E explained by the number of cases in 2019 was low (4.9%). Differences in O/E outcome between the first and the fourth quartile were not statistically significant in both years (1.10 ± 1.02 vs. 0.82 ± 0.46; P = 0.26 in 2018; 1.16 0 .97 vs. 0.74 ± 0.39; P = 0.084 in 2019). Any chosen volume cut-off could not precisely differentiate between hospitals with not acceptable quality (>95th percentile O/E of all hospitals) and those with acceptable (O/E ≤95th percentile) or above-average (O/E < 1) quality. For example, in 2019 a cut-off value of 150 would only exclude one of two hospitals with not acceptable quality, while 20 hospitals with acceptable or above-average quality (25% of all hospitals) would be excluded.<br /><b>Conclusion</b><br />The association between hospital volume and in-hospital mortality in patients undergoing elective TF-TAVI in Germany in 2018 and 2019 was weak and not consistent throughout various analytical approaches, indicating no clinical relevance of hospital volume for the outcome. However, these data were derived from a healthcare system with restricted access to hospitals to perform TAVI and overall high TAVI volumes. Instead of the unprecise surrogate hospital volume, the quality of hospitals performing TF-TAVI should be directly assessed by real achieved risk-adjusted mortality.<br /><br />© The Author(s) 2022. 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 Dec 2022; epub ahead of print</small></div>
Bestehorn K, Bestehorn M, Zahn R, Perings C, Stellbrink C, Schächinger V
Eur Heart J: 02 Dec 2022; epub ahead of print | PMID: 36459131
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<div><h4>Use of cardiac imaging in chronic coronary syndromes: the EURECA Imaging registry.</h4><i>Neglia D, Liga R, Gimelli A, Podlesnikar T, ... Delgado V, EURECA Investigators </i><br /><b>Background</b><br />The prospective, multicentre EURECA registry assessed the use of imaging and adoption of the European Society of Cardiology (ESC) Guidelines (GL) in patients with chronic coronary syndromes (CCS).<br /><b>Methods</b><br />Between May 2019 and March 2020, 5156 patients were recruited in 73 centres from 24 ESC member countries. The adoption of GL recommendations was evaluated according to clinical presentation and pre-test probability (PTP) of obstructive coronary artery disease (CAD).<br /><b>Results</b><br />The mean age of the population was 64 ± 11 years, 60% of patients were males, 42% had PTP >15%, 27% had previous CAD, and ejection fraction was <50% in 5%. Exercise ECG was performed in 32% of patients, stress imaging as the first choice in 40%, and computed tomography coronary angiography (CTCA) in 22%. Invasive coronary angiography (ICA) was the first or downstream test in 17% and 11%, respectively. Obstructive CAD was documented in 24% of patients, inducible ischaemia in 19%, and 13% of patients underwent revascularization. In 44% of patients, the overall diagnostic process did not adopt the GL. In these patients, referral to stress imaging (21% vs. 58%; P < 0.001) or CTCA (17% vs. 30%; P < 0.001) was less frequent, while exercise ECG (43% vs. 22%; P < 0.001) and ICA (48% vs. 15%; P < 0.001) were more frequently performed. The adoption of GL was associated with fewer ICA, higher proportion of diagnosis of obstructive CAD (60% vs. 39%, P < 0.001) and revascularization (54% vs. 37%, P < 0.001), higher quality of life, fewer additional testing, and longer times to late revascularization.<br /><b>Conclusions</b><br />In patients with CCS, current clinical practice does not adopt GL recommendations on the use of diagnostic tests in a significant proportion of patients. When the diagnostic approach adopts GL recommendations, invasive procedures are less frequently used and the diagnostic yield and therapeutic utility are superior.<br /><br />© The Author(s) 2022. 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 Dec 2022; epub ahead of print</small></div>
Neglia D, Liga R, Gimelli A, Podlesnikar T, ... Delgado V, EURECA Investigators
Eur Heart J: 01 Dec 2022; epub ahead of print | PMID: 36452988
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<div><h4>Epidemiology of heart failure in young adults: a French nationwide cohort study.</h4><i>Lecoeur E, Domengé O, Fayol A, Jannot AS, Hulot JS</i><br /><b>Aims</b><br />Heart failure (HF) in young adults is uncommon, and changes in its incidence and prognosis in recent years are poorly described.<br /><b>Methods and results</b><br />The incidence and prognosis of HF in young adults (18-50 years) were characterized using nationwide medico-administrative data from the French National Hospitalization Database (period 2013-2018). A total of 1,486 877 patients hospitalized for incident HF were identified, including 70 075 (4.7%) patients aged 18-50 years (estimated incidence of 0.44‰ for this age group). During the study period, the overall incidence of HF tended to decrease in the overall population but significantly increased by ∼0.041‰ in young adults (P < 0.001). This increase was notably observed among young men (from 0.51‰ to 0.59‰, P < 0.001), particularly those aged 36-50 years. In these young men, ischaemic heart disease (IHD) was the most frequently reported cause of HF, whereas non-ischaemic HF was mainly observed in patients ≤ 35 years old. In contrast to non-ischaemic HF, the incidence of IHD increased over the study period, which suggests that IHD-related HF is progressively affecting younger patients. Concordantly, young HF patients presented with high rates of traditional IHD risk factors, including obesity, smoking, hypertension, dyslipidaemia, or diabetes. Lastly, the rates of re-hospitalization (for HF or for any cause) within two years after the first HF event and in-hospital mortality were high in all groups, indicating a poor-prognosis population.<br /><b>Conclusion</b><br />Strategies for the prevention of HF risk factors should be strongly considered for patients under 50 years old.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 01 Dec 2022; epub ahead of print</small></div>
Lecoeur E, Domengé O, Fayol A, Jannot AS, Hulot JS
Eur Heart J: 01 Dec 2022; epub ahead of print | PMID: 36452998
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<div><h4>Sex-Related Characteristics and Short-Term Outcomes of Patients Undergoing Transcatheter Tricuspid Valve Intervention for Tricuspid Regurgitation.</h4><i>Scotti A, Coisne A, Taramasso M, Granada JF, ... Hahn RT, Latib A</i><br /><b>Background:</b><br/>and aims</b><br />The impact of sex in patients with significant tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI) is unknown. The aim of this study was to investigate sex-specific outcomes in patients with significant TR treated with TTVI versus medical therapy alone.<br /><b>Methods</b><br />The TriValve (Transcatheter Tricuspid Valve Therapies) registry collected patients with significant TR from 24 centers who underwent TTVI from 2016 to 2021. A control cohort was formed by medically managed patients with ≥ severe isolated TR diagnosed in 2015-2018. Primary endpoint was freedom from all-cause mortality. Secondary endpoints were heart failure (HF) hospitalization, New York Heart Association (NYHA) functional status, and TR severity. One-year outcomes were assessed for the TriValve cohort and compared with the control cohort with the inverse probability of treatment weighting (IPTW).<br /><b>Results</b><br />A total of 556 and 2072 patients were included from the TriValve and control groups, respectively. After TTVI, there was no difference between women and men in 1-year freedom from all-cause mortality (80.9% vs. 77.9%, p = 0.56, nor in HF hospitalization (p = 0.36), NYHA functional class III-IV (p = 0.17), and TR severity >2 + at last follow-up (p = 0.42). Multivariable Cox-regression weighted by IPTW showed an improved 1-year survival after TTVI compared to medical therapy alone in both women (adjusted hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.23-0.83, p = 0.01) and men (adjusted HR 0.42, 95% CI 0.18-0.89, p = 0.03).<br /><b>Conclusions</b><br />After TTVI in high-risk patients, there were no sex-related differences in terms of survival, HF hospitalization, functional status, and TR reduction up to 1 year. The IPTW analysis shows a survival benefit of TTVI over medical therapy alone in both women and men.<br /><br />© The Author(s) 2022. 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: 29 Nov 2022; epub ahead of print</small></div>
Scotti A, Coisne A, Taramasso M, Granada JF, ... Hahn RT, Latib A
Eur Heart J: 29 Nov 2022; epub ahead of print | PMID: 36445158
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<div><h4>Type 2 diabetes mellitus and higher rate of complete atrioventricular block: a Danish Nationwide Registry.</h4><i>Haxha S, Halili A, Malmborg M, Pedersen-Bjergaard U, ... Torp-Pedersen C, Bang CN</i><br /><b>Aims</b><br />The present study aimed to determine the association between Type 2 diabetes mellitus (T2DM) and third-degree (complete) atrioventricular block.<br /><b>Methods and results</b><br />This nationwide nested case-control study included patients older than 18 years, diagnosed with third-degree atrioventricular block between 1 July 1995 and 31 December 2018. Data on medication, comorbidity, and outcomes were collected from Danish registries. Five controls, from the risk set of each case of third-degree atrioventricular block, were matched on age and sex to fit a Cox regression model with time-dependent exposure and time-dependent covariates. Subgroup analysis was conducted with Cox regression models for each subgroup. We located 25 995 cases with third-degree atrioventricular block that were matched with 130 004 controls. The mean age was 76 years and 62% were male. Cases had more T2DM (21% vs. 11%), hypertension (69% vs. 50%), atrial fibrillation (25% vs. 10%), heart failure (20% vs. 6.3%), and myocardial infarction (19% vs. 9.2%), compared with the control group. In Cox regression analysis, adjusting for comorbidities and atrioventricular nodal blocking agents, T2DM was significantly associated with third-degree atrioventricular block (hazard ratio: 1.63, 95% confidence interval: 1.57-1.69). The association remained in several subgroup analyses of diseases also suspected to be associated with third-degree atrioventricular block. There was a significant interaction with comorbidities of interest including hypertension, atrial fibrillation, heart failure, and myocardial infarction.<br /><b>Conclusion</b><br />In this nationwide study, T2DM was associated with a higher rate of third-degree atrioventricular block compared with matched controls. The association remained independent of atrioventricular nodal blocking agents and other comorbidities known to be associated with third-degree atrioventricular block.<br /><br />© The Author(s) 2022. 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 Nov 2022; epub ahead of print</small></div>
Haxha S, Halili A, Malmborg M, Pedersen-Bjergaard U, ... Torp-Pedersen C, Bang CN
Eur Heart J: 26 Nov 2022; epub ahead of print | PMID: 36433808
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<div><h4>Long-term mortality, cardiovascular events, and bleeding in stable patients 1 year after myocardial infarction: a Danish nationwide study.</h4><i>Christensen DM, Schjerning AM, Smedegaard L, Charlot MG, ... Gislason G, Sehested TSG</i><br /><b>Aims</b><br />Outcomes after myocardial infarction (MI) improved during recent decades alongside better risk factor management and implementation of guideline-recommended treatments. However, it is unknown whether this applies to stable patients who are event-free 1 year after MI.<br /><b>Methods and results</b><br />Using nationwide Danish registries, we included all patients with first-time MI during 2000-17 who survived 1 year free from bleeding and cardiovascular events (n = 82 108, median age 64 years, 68.2% male). Follow-up started 1 year after MI and continued through January 2022. Crude risks of mortality, cardiovascular events, and bleeding were estimated in consecutive 3-year periods. Standardized risks were calculated with respect to the distribution of age, sex, comorbidities, and treatments in the latter period. Guideline-recommended treatment use increased during the study period: e.g. statins (68.6-92.5%) and percutaneous coronary intervention (23.9-68.2%). The crude 5-year risks of outcomes decreased (all P-trend <0.001): Mortality, 18.6% (95% confidence interval [CI]: 17.9-19.2) to 12.5% (CI: 11.9-13.1); Recurrent MI, 7.5% (CI: 7.1-8.0) to 5.5% (CI: 5.1-6.0); Bleeding, 3.9% (CI: 3.6-4.3) to 2.7% (CI: 2.4-3.0). Crude 5-year risk of mortality in 2015-17 was as low as 2.6% for patients aged <60 years. Use of guideline-recommended treatments was associated with improved outcomes: After standardization for changes in treatments, 5-year risk of mortality in 2000-02 was 15.5% (CI: 14.9-16.2).<br /><b>Conclusions</b><br />For patients who were event-free 1 year after MI, the long-term risks of mortality, cardiovascular events, and bleeding decreased significantly, along with an improved use of guideline-recommended treatments between 2000 and 2017. In the most recent period, 1 year after MI, the risk of additional events was lower than previously reported.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 26 Nov 2022; epub ahead of print</small></div>
Christensen DM, Schjerning AM, Smedegaard L, Charlot MG, ... Gislason G, Sehested TSG
Eur Heart J: 26 Nov 2022; epub ahead of print | PMID: 36433809
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<div><h4>Dietary metabolic signatures and cardiometabolic risk.</h4><i>Shah RV, Steffen LM, Nayor M, Reis JP, ... Clish CB, Murthy VL</i><br /><b>Aims</b><br />Observational studies of diet in cardiometabolic-cardiovascular disease (CM-CVD) focus on self-reported consumption of food or dietary pattern, with limited information on individual metabolic responses to dietary intake linked to CM-CVD. Here, machine learning approaches were used to identify individual metabolic patterns related to diet and relation to long-term CM-CVD in early adulthood.<br /><b>Methods and results</b><br />In 2259 White and Black adults (age 32.1 ± 3.6 years, 45% women, 44% Black) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, multivariate models were employed to identify metabolite signatures of food group and composite dietary intake across 17 food groups, 2 nutrient groups, and healthy eating index-2015 (HEI2015) diet quality score. A broad array of metabolites associated with diet were uncovered, reflecting food-related components/catabolites (e.g. fish and long-chain unsaturated triacylglycerols), interactions with host features (microbiome), or pathways broadly implicated in CM-CVD (e.g. ceramide/sphingomyelin lipid metabolism). To integrate diet with metabolism, penalized machine learning models were used to define a metabolite signature linked to a putative CM-CVD-adverse diet (e.g. high in red/processed meat, refined grains), which was subsequently associated with long-term diabetes and CVD risk numerically more strongly than HEI2015 in CARDIA [e.g. diabetes: standardized hazard ratio (HR): 1.62, 95% confidence interval (CI): 1.32-1.97, P < 0.0001; CVD: HR: 1.55, 95% CI: 1.12-2.14, P = 0.008], with associations replicated for diabetes (P < 0.0001) in the Framingham Heart Study.<br /><b>Conclusion</b><br />Metabolic signatures of diet are associated with long-term CM-CVD independent of lifestyle and traditional risk factors. Metabolomics improves precision to identify adverse consequences and pathways of diet-related CM-CVD.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 25 Nov 2022; epub ahead of print</small></div>
Shah RV, Steffen LM, Nayor M, Reis JP, ... Clish CB, Murthy VL
Eur Heart J: 25 Nov 2022; epub ahead of print | PMID: 36424694
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<div><h4>Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial.</h4><i>Trullàs JC, Morales-Rull JL, Casado J, Carrera-Izquierdo M, ... Manzano L, CLOROTIC trial investigators </i><br /><b>Aims</b><br />To evaluate whether the addition of hydrochlorothiazide (HCTZ) to intravenous furosemide is a safe and effective strategy for improving diuretic response in acute heart failure (AHF).<br /><b>Methods and results</b><br />A prospective, double-blind, placebo-controlled trial, including patients with AHF randomized to receive HCTZ or placebo in addition to an intravenous furosemide regimen. The coprimary endpoints were changes in body weight and patient-reported dyspnoea 72 h after randomization. Secondary outcomes included metrics of diuretic response and mortality/rehospitalizations at 30 and 90 days. Safety outcomes (changes in renal function and/or electrolytes) were also assessed. Two hundred and thirty patients (48% women, 83 years) were randomized. Patients assigned to HCTZ were more likely to lose weight at 72 h than those assigned to placebo [-2.3 vs. -1.5 kg; adjusted estimated difference (notionally 95% confidence interval) -1.14 (-1.84 to -0.42); P = 0.002], but there were no significant differences in patient-reported dyspnoea (area under the curve for visual analogue scale: 960 vs. 720; P = 0.497). These results were similar 96 h after randomization. Patients allocated to HCTZ showed greater 24 h diuresis (1775 vs. 1400 mL; P = 0.05) and weight loss for each 40 mg of furosemide (at 72 and at 96 h) (P < 0.001). Patients assigned to HCTZ more frequently presented impaired renal function (increase in creatinine >26.5 μmoL/L or decrease in eGFR >50%; 46.5 vs. 17.2%; P < 0.001), but hypokalaemia and hypokalaemia were similar between groups. There were no differences in mortality or rehospitalizations.<br /><b>Conclusion</b><br />The addition of HCTZ to loop diuretic therapy improved diuretic response in patients with AHF.<br /><br />© The Author(s) 2022. 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 Nov 2022; epub ahead of print</small></div>
Trullàs JC, Morales-Rull JL, Casado J, Carrera-Izquierdo M, ... Manzano L, CLOROTIC trial investigators
Eur Heart J: 24 Nov 2022; epub ahead of print | PMID: 36423214
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<div><h4>Survival of patients with congenital ventricular septal defect.</h4><i>Eckerström F, Nyboe C, Maagaard M, Redington A, Hjortdal VE</i><br /><b>Aims</b><br />The long-term survival of patients with isolated congenital ventricular septal defect (VSD) is not well described. The aim of this study was to describe the survival of a national cohort of patients with VSD compared with the general population.<br /><b>Methods and results</b><br />Using Danish nationwide medical registries, all patients diagnosed with congenital VSD (n = 9,136) in the period 1977-2018 were included. Patients with chromosomal abnormalities and concomitant congenital cardiac malformations other than atrial septal defect were excluded. Each patient was matched by birthyear and sex with ten controls from the general Danish population. Kaplan-Meier survival function and Cox proportional hazard regression were used to compute survival and mortality risk. Median follow-up was 22 years (interquartile range: 11-37). VSD patients displayed lower survival (P<0.001) yielding a hazard ratio (HR) for mortality of 2.7 [95% confidence interval (CI): 2.4-3.0] compared with matched controls. The adjusted HR for mortality among patients with unrepaired VSD was 2.7 (95% CI: 2.4-3.0) and 2.8 (95% CI: 2.1-3.7) for patients with surgically closed VSD. Stratified by era of VSD diagnosis, the HR for mortality was 3.2 (95% CI: 2.8-3.7) for unrepaired patients diagnosed before 1990 and 2.4 (95% CI: 2.0-2.7) for patients diagnosed later. Cardiac-related death was the commonest cause of death among unrepaired (30%) and surgically closed (65%) patients.<br /><b>Conclusion</b><br />Patients with VSD had lower survival compared with the general population. The HR for mortality was increased over 2.5-fold in patients with unrepaired defect (Eisenmenger syndrome excluded) and over 1.5-fold in patients with surgically closed defect (excluding surgical mortality).<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 24 Nov 2022; epub ahead of print</small></div>
Eckerström F, Nyboe C, Maagaard M, Redington A, Hjortdal VE
Eur Heart J: 24 Nov 2022; epub ahead of print | PMID: 36418929
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<div><h4>Applicability of European Society of Cardiology guidelines according to gross national income.</h4><i>van Dijk WB, Schuit E, van der Graaf R, Groenwold RHH, ... de Vries MC, Grobbee DE</i><br /><b>Aims</b><br />To assess the feasibility to comply with the recommended actions of ESC guidelines on general cardiology areas in 102 countries and assess how compliance relates to the country\'s income level.<br /><b>Methods and results</b><br />All recommendations from seven ESC guidelines on general cardiology areas were extracted and labelled on recommended actions. A survey was sent to all 102 ESC national and affiliated cardiac societies (NCSs). Respondents were asked to score recommended actions on their availability in clinical practice on a four-point Likert scale (fully available, mostly/often available, mostly/often unavailable, fully unavailable), and select the top three barriers perceived as being responsible for limiting their national availability. Applicability was assessed overall, per World Bank gross national income (GNI) level, and per guideline.A total of 875 guideline recommendations on general cardiology was extracted. Responses were received from 64 of 102 (62.7%) NCSs. On average, 71·6% [95% confidence interval (CI): 68.6-74.6] of the actions were fully available, 9.9% (95% CI: 8.7-11.1) mostly/often available, 6.7% (95% CI: 5.4-8.0) mostly/often unavailable, and 11·8% (95% CI: 9.5-14.1) fully unavailable. In low-income countries (LICs), substantially more actions were fully unavailable [29·4% (95% CI: 22.6-36.3)] compared with high-income countries [HICs, countries 2.4% (95% CI: 1.2-3.7); P < 0.05]. Nevertheless, a proportion of actions with the lowest availability scores were often fully or mostly unavailable independent of GNIs. Actions were most often not available due to lack of reimbursement and other financial barriers.<br /><b>Conclusion</b><br />Local implementation of ESC guidelines on general cardiology is high in HICs and low in LICs , being inversely correlated with country gross national incomes.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 18 Nov 2022; epub ahead of print</small></div>
van Dijk WB, Schuit E, van der Graaf R, Groenwold RHH, ... de Vries MC, Grobbee DE
Eur Heart J: 18 Nov 2022; epub ahead of print | PMID: 36396400
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<div><h4>Bone morphogenetic protein 10: a novel risk marker of ischaemic stroke in patients with atrial fibrillation.</h4><i>Hijazi Z, Benz AP, Lindbäck J, Alexander JH, ... Siegbahn A, Wallentin L</i><br /><b>Aims</b><br />Biomarkers specifically related to atrial tissue may increase the understanding of the pathophysiology of atrial fibrillation (AF) and further improve risk prediction in this setting. Bone morphogenetic protein 10 (BMP10) is a protein expressed in the atrial myocardium. We evaluated the association between BMP10 and the risk of ischaemic stroke and other cardiovascular events in large cohorts of patients with AF, treated with and without oral anticoagulation (OAC).<br /><b>Methods and results</b><br />BMP10 was measured in plasma samples collected at randomisation in patients with AF without OAC in the ACTIVE A and AVERROES trials (n = 2974), and with OAC in the ARISTOTLE trial (n = 13 079). BMP10 was analysed with a prototype Elecsys immunoassay. Associations with outcomes were evaluated by Cox-regression models adjusted for clinical characteristics, kidney function, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Median concentrations of BMP10 were 2.47 and 2.44 ng/mL, in the non-OAC and OAC cohort, respectively. Increasing BMP10 was associated with lower body mass index, older age, female sex, kidney dysfunction, and AF rhythm. BMP10 was consistently associated with ischaemic stroke. In the non-OAC cohort, BMP10 increased the concordance index of the multivariable model from 0.713 to 0.733 (P = 0.004) and in the OAC cohort from 0.673 to 0.694 (P < 0.001). Additionally, BMP10 maintained a significant prognostic value after additionally adjusting for NT-proBNP. BMP10 was not independently associated with bleeding or with death.<br /><b>Conclusion</b><br />The novel atrial biomarker BMP10 was independently associated with ischaemic stroke in patients with AF irrespective of OAC treatment. BMP10 seems to be more specifically related to the risk of ischaemic stroke in AF.<br /><b>One-sentence summary</b><br />In this study, BMP10 may be a novel specific biomarker of ischaemic stroke in patients with atrial fibrillation, irrespective of oral anticoagulation.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 16 Nov 2022; epub ahead of print</small></div>
Hijazi Z, Benz AP, Lindbäck J, Alexander JH, ... Siegbahn A, Wallentin L
Eur Heart J: 16 Nov 2022; epub ahead of print | PMID: 36380569
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<div><h4>Lipoprotein(a) levels in children with suspected familial hypercholesterolaemia: a cross-sectional study.</h4><i>de Boer LM, Hutten BA, Zwinderman AH, Wiegman A</i><br /><b>Aims</b><br />Familial hypercholesterolaemia (FH) predisposes children to the early initiation of atherosclerosis and is preferably diagnosed by DNA analysis. Yet, in many children with a clinical presentation of FH, no mutation is found. Adult data show that high levels of lipoprotein(a) [Lp(a)] may underlie a clinical presentation of FH, as the cholesterol content of Lp(a) is included in conventional LDL cholesterol measurements. As this is limited to adult data, Lp(a) levels in children with and without (clinical) FH were evaluated.<br /><b>Methods and results</b><br />Children were eligible if they visited the paediatric lipid clinic (1989-2020) and if Lp(a) measurement and DNA analysis were performed. In total, 2721 children (mean age: 10.3 years) were included and divided into four groups: 1931 children with definite FH (mutation detected), 290 unaffected siblings/normolipidaemic controls (mutation excluded), 108 children with probable FH (clinical presentation, mutation not detected), and 392 children with probable non-FH (no clinical presentation, mutation not excluded). In children with probable FH, 32% were found to have high Lp(a) [geometric mean (95% confidence interval) of 15.9 (12.3-20.6) mg/dL] compared with 10 and 10% [geometric means (95% confidence interval) of 11.5 (10.9-12.1) mg/dL and 9.8 (8.4-11.3) mg/dL] in children with definite FH (P = 0.017) and unaffected siblings (P = 0.002), respectively.<br /><b>Conclusion</b><br />Lp(a) was significantly higher and more frequently elevated in children with probable FH compared with children with definite FH and unaffected siblings, suggesting that high Lp(a) may underlie the clinical presentation of FH when no FH-causing mutation is found. Performing both DNA analysis and measuring Lp(a) in all children suspected of FH is recommended to assess possible LDL cholesterol overestimation related to increased Lp(a).<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 16 Nov 2022; epub ahead of print</small></div>
de Boer LM, Hutten BA, Zwinderman AH, Wiegman A
Eur Heart J: 16 Nov 2022; epub ahead of print | PMID: 36382390
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<div><h4>Vinculin phosphorylation impairs vascular endothelial junctions promoting atherosclerosis.</h4><i>Shih YT, Wei SY, Chen JH, Wang WL, ... Chien S, Chiu JJ</i><br /><b>Background:</b><br/>and aims</b><br />Atherosclerosis preferentially develops in arterial branches and curvatures where vascular endothelium is exposed to disturbed flow. In this study, the effects of disturbed flow on the regulation of vascular endothelial phosphoproteins and their contribution to therapeutic application in atherogenesis were elucidated.<br /><b>Methods</b><br />Porcine models, large-scale phosphoproteomics, transgenic mice, and clinical specimens were used to discover novel site-specific phosphorylation alterations induced by disturbed flow in endothelial cells (ECs).<br /><b>Results</b><br />A large-scale phosphoproteomics analysis of native endothelium from disturbed (athero-susceptible) vs. pulsatile flow (athero-resistant) regions of porcine aortas led to the identification of a novel atherosclerosis-related phosphoprotein vinculin (VCL) with disturbed flow-induced phosphorylation at serine 721 (VCLS721p). The induction of VCLS721p was mediated by G-protein-coupled receptor kinase 2 (GRK2)S29p and resulted in an inactive form of VCL with a closed conformation, leading to the VE-cadherin/catenin complex disruption to enhance endothelial permeability and atherogenesis. The generation of novel apolipoprotein E-deficient (ApoE-/-) mice overexpressing S721-non-phosphorylatable VCL mutant in ECs confirmed the critical role of VCLS721p in promoting atherosclerosis. The administration of a GRK2 inhibitor to ApoE-/- mice suppressed plaque formation by inhibiting endothelial VCLS721p. Studies on clinical specimens from patients with coronary artery disease (CAD) revealed that endothelial VCLS721p is a critical clinicopathological biomarker for atherosclerosis progression and that serum VCLS721p level is a promising biomarker for CAD diagnosis.<br /><b>Conclusions</b><br />The findings of this study indicate that endothelial VCLS721p is a valuable hemodynamic-based target for clinical assessment and treatment of vascular disorders resulting from atherosclerosis.<br /><br />© The Author(s) 2022. 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: 16 Nov 2022; epub ahead of print</small></div>
Shih YT, Wei SY, Chen JH, Wang WL, ... Chien S, Chiu JJ
Eur Heart J: 16 Nov 2022; epub ahead of print | PMID: 36380599
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<div><h4>Childhood adversity and cardiovascular disease in early adulthood: a Danish cohort study.</h4><i>Bengtsson J, Elsenburg LK, Andersen GS, Larsen ML, Rieckmann A, Rod NH</i><br /><b>Aims</b><br />To examine the effect of childhood adversity on the development of cardiovascular disease (CVD) between ages 16 and 38, specifically focusing on ischaemic heart disease and cerebrovascular disease.<br /><b>Methods and results</b><br />Register data on all children born in Denmark between 1 January 1980 and 31 December 2001, who were alive and resident in Denmark without a diagnosis of CVD or congenital heart disease until age 16 were used, totalling 1 263 013 individuals. Cox proportional hazards and Aalen additive hazards models were used to estimate adjusted hazard ratios (HRs) and adjusted hazard differences of CVD from ages 16 to 38 in five trajectory groups of adversity experienced between ages 0 and 15. In total, 4118 individuals developed CVD between their 16th birthday and 31 December 2018. Compared with those who experienced low levels of adversity, those who experienced severe somatic illness and death in the family (men: adjusted HR: 1.6, 95% confidence interval: 1.4-1.8, women: 1.4, 1.2-1.6) and those who experienced very high rates of adversity across childhood and adolescence (men: 1.6, 1.3-2.0, women: 1.6, 1.3-2.0) had a higher risk of developing CVD, corresponding to 10-18 extra cases of CVD per 100 000 person-years in these groups.<br /><b>Conclusions</b><br />Individuals who have been exposed to childhood adversity are at higher risk of developing CVD in young adulthood compared to individuals with low adversity exposure. These findings suggest that interventions targeting the social origins of adversity and providing support for affected families may have long-term cardio-protective effects.<br /><br />© The Author(s) 2022. 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: 15 Nov 2022; epub ahead of print</small></div>
Bengtsson J, Elsenburg LK, Andersen GS, Larsen ML, Rieckmann A, Rod NH
Eur Heart J: 15 Nov 2022; epub ahead of print | PMID: 36375818
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<div><h4>Patient selection for long-term secondary prevention with ticagrelor: insights from PEGASUS-TIMI 54.</h4><i>Bonaca MP, Im K, Magnani G, Bansilal S, ... Braunwald E, Sabatine MS</i><br /><b>Aim</b><br />In patients with prior myocardial infarction (MI) on aspirin, the addition of ticagrelor reduces ischaemic risk but increases bleeding risk. The simultaneous assessment of baseline ischaemic and bleeding risk may assist clinicians in selecting patients who are most likely to have a favourable risk/benefit profile with long-term ticagrelor.<br /><b>Methods and results</b><br />PEGASUS-TIMI 54 randomized 21 162 prior MI patients, 13 956 of which to the approved 60 mg dose or placebo and who had all necessary data. The primary efficacy endpoint was cardiovascular death, MI, or stroke, and the primary safety outcome was TIMI major bleeding; differences in Kaplan-Meier event rates at 3 years are presented. Post-hoc subgroups based on predictors of bleeding and ischaemic risk were merged into a selection algorithm. Patients were divided into four groups: those with a bleeding predictor (n = 2721, 19%) and then those without a bleeding predictor and either 0-1 ischaemic risk factor (IRF; n = 3004, 22%), 2 IRF (n = 4903, 35%), or ≥3 IRF (n = 3328, 24%). In patients at high bleeding risk, ticagrelor increased bleeding [absolute risk difference (ARD) +2.3%, 95% confidence interval (CI) 0.6, 3.9] and did not reduce the primary efficacy endpoint (ARD +0.08%, 95% CI -2.4 to 2.5). In patients at low bleeding risk, the ARDs in the primary efficacy endpoint with ticagrelor were -0.5% (-2.2, 1.3), -1.5% (-3.1, 0.02), and -2.6% (-5.0, -0.24, P = 0.03) in those with ≤1, 2, and 3 risk factors, respectively (P = 0.076 for trend across groups). There were significant trends for greater absolute risk reductions for cardiovascular death (P-trend 0.018), all-cause mortality (P-trend 0.027), and net outcomes (P-trend 0.037) with ticagrelor across these risk groups.<br /><b>Conclusion</b><br />In a post-hoc exploratory analysis of patients with prior MI, long-term ticagrelor therapy appears to be best suited for those with prior MI with multiple IRFs at low bleeding risk.<br /><b>Clinical trial registration</b><br />NCT01225562 ClinicalTrials.gov.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 11 Nov 2022; epub ahead of print</small></div>
Bonaca MP, Im K, Magnani G, Bansilal S, ... Braunwald E, Sabatine MS
Eur Heart J: 11 Nov 2022; epub ahead of print | PMID: 36367709
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<div><h4>Surgical or Percutaneous Coronary Revascularisation for Heart Failure: An In Silico Model using Routinely Collected Health Data to Emulate a Clinical Trial.</h4><i>Pathak S, Lai FY, Miksza J, Petrie MC, ... Perera D, Murphy GJ</i><br /><b>Background</b><br />The choice of revascularization with coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in people with ischaemic left ventricular dysfunction is not guided by high-quality evidence.<br /><b>Methods</b><br />A trial of CABG versus PCI in people with heart failure was modelled in-silico using routinely collected healthcare data. The in-silico trial cohort was selected by matching the target trial cohort, identified from Hospital Episode Statistics in England, with individual patient data from the STICH trial. Allocation to CABG versus complex PCI demonstrated random variation across administrative regions in England and was a valid statistical instrument. The primary outcome was 5-year all-cause mortality or cardiovascular hospitalization. Instrumental variable analysis (IVA) was used for the primary analysis. Results were expressed as average treatment effects (ATEs) with 95% confidence intervals (CI).<br /><b>Results</b><br />The target population included 13,519 heart failure patients undergoing CABG or complex PCI between April 2009 and March 2015. After matching, the emulated trial cohort included 2046 patients. The unadjusted primary outcome rate was 51.1% in the CABG group and 70.0% in the PCI group. IVA of the emulated cohort showed that CABG was associated with a lower risk of the primary outcome (ATE -16.2%, 95% CI -20.6% to -11.8%), with comparable estimates in the unmatched target population (ATE -15.5%, 95% CI -17.5% to -13.5%).<br /><b>Conclusions</b><br />In people with heart failure, in-silico modelling suggests that CABG is associated with fewer deaths or cardiovascular hospitalizations at 5 years versus complex PCI. A pragmatic clinical trial is needed to test this hypothesis and this trial would be feasible.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 09 Nov 2022; epub ahead of print</small></div>
Pathak S, Lai FY, Miksza J, Petrie MC, ... Perera D, Murphy GJ
Eur Heart J: 09 Nov 2022; epub ahead of print | PMID: 36350978
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<div><h4>Cost-effectiveness of population screening for atrial fibrillation: the STROKESTOP study.</h4><i>Lyth J, Svennberg E, Bernfort L, Aronsson M, ... Engdahl J, Levin LÅ</i><br /><b>Aims</b><br />Previous studies on the cost-effectiveness of screening for atrial fibrillation (AF) are based on assumptions of long-term clinical effects. The STROKESTOP study, which randomised 27 975 persons aged 75/76 years into a screening invitation group and a control group, has a median follow-up time of 6.9 years. The aim of this study was to estimate the cost-effectiveness of population-based screening for AF using clinical outcomes.<br /><b>Methods and results</b><br />The analysis is based on a Markov cohort model. The prevalence of AF, the use of oral anticoagulation, clinical event data, and all-cause mortality were taken from the STROKESTOP study. The cost for clinical events, age-specific utilities, utility decrement due to stroke, and stroke death was taken from the literature. Uncertainty in the model was considered in a probabilistic sensitivity analysis. Per 1000 individuals invited to the screening, there were 77 gained life years and 65 gained quality-adjusted life years. The incremental cost was €1.77 million lower in the screening invitation group. Gained quality-adjusted life years to a lower cost means that the screening strategy was dominant. The result from 10 000 Monte Carlo simulations showed that the AF screening strategy was cost-effective in 99.2% and cost-saving in 92.7% of the simulations. In the base-case scenario, screening of 1000 individuals resulted in 10.6 [95% confidence interval (CI): -22.5 to 1.4] fewer strokes (8.4 ischaemic and 2.2 haemorrhagic strokes), 1.0 (95% CI: -1.9 to 4.1) more cases of systemic embolism, and 2.9 (95% CI: -18.2 to 13.1) fewer bleedings associated with hospitalization.<br /><b>Conclusion</b><br />Based on the STROKESTOP study, this analysis shows that a broad AF screening strategy in an elderly population is cost-effective. Efforts should be made to increase screening participation.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.<br /><br /><small>Eur Heart J: 09 Nov 2022; epub ahead of print</small></div>
Lyth J, Svennberg E, Bernfort L, Aronsson M, ... Engdahl J, Levin LÅ
Eur Heart J: 09 Nov 2022; epub ahead of print | PMID: 36349968
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<div><h4>Electrocardiogram-based deep learning improves outcome prediction following cardiac resynchronization therapy.</h4><i>Wouters PC, van de Leur RR, Vessies MB, van Stipdonk AMW, ... Meine M, van Es R</i><br /><b>Aims</b><br />This study aims to identify and visualize electrocardiogram (ECG) features using an explainable deep learning-based algorithm to predict cardiac resynchronization therapy (CRT) outcome. Its performance is compared with current guideline ECG criteria and QRSAREA.<br /><b>Methods and results</b><br />A deep learning algorithm, trained on 1.1 million ECGs from 251 473 patients, was used to compress the median beat ECG, thereby summarizing most ECG features into only 21 explainable factors (FactorECG). Pre-implantation ECGs of 1306 CRT patients from three academic centres were converted into their respective FactorECG. FactorECG predicted the combined clinical endpoint of death, left ventricular assist device, or heart transplantation [c-statistic 0.69, 95% confidence interval (CI) 0.66-0.72], significantly outperforming QRSAREA and guideline ECG criteria [c-statistic 0.61 (95% CI 0.58-0.64) and 0.57 (95% CI 0.54-0.60), P < 0.001 for both]. The addition of 13 clinical variables was of limited added value for the FactorECG model when compared with QRSAREA (Δ c-statistic 0.03 vs. 0.10). FactorECG identified inferolateral T-wave inversion, smaller right precordial S- and T-wave amplitude, ventricular rate, and increased PR interval and P-wave duration to be important predictors for poor outcome. An online visualization tool was created to provide interactive visualizations (https://crt.ecgx.ai).<br /><b>Conclusion</b><br />Requiring only a standard 12-lead ECG, FactorECG held superior discriminative ability for the prediction of clinical outcome when compared with guideline criteria and QRSAREA, without requiring additional clinical variables. End-to-end automated visualization of ECG features allows for an explainable algorithm, which may facilitate rapid uptake of this personalized decision-making tool in CRT.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 07 Nov 2022; epub ahead of print</small></div>
Wouters PC, van de Leur RR, Vessies MB, van Stipdonk AMW, ... Meine M, van Es R
Eur Heart J: 07 Nov 2022; epub ahead of print | PMID: 36342291
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<div><h4>High-density lipoprotein revisited: biological functions and clinical relevance.</h4><i>von Eckardstein A, Nordestgaard BG, Remaley AT, Catapano AL</i><br /><AbstractText>Previous interest in high-density lipoproteins (HDLs) focused on their possible protective role in atherosclerotic cardiovascular disease (ASCVD). Evidence from genetic studies and randomized trials, however, questioned that the inverse association of HDL-cholesterol (HDL-C) is causal. This review aims to provide an update on the role of HDL in health and disease, also beyond ASCVD. Through evolution from invertebrates, HDLs are the principal lipoproteins, while apolipoprotein B-containing lipoproteins first developed in vertebrates. HDLs transport cholesterol and other lipids between different cells like a reusable ferry, but serve many other functions including communication with cells and the inactivation of biohazards like bacterial lipopolysaccharides. These functions are exerted by entire HDL particles or distinct proteins or lipids carried by HDL rather than by its cholesterol cargo measured as HDL-C. Neither does HDL-C measurement reflect the efficiency of reverse cholesterol transport. Recent studies indicate that functional measures of HDL, notably cholesterol efflux capacity, numbers of HDL particles, or distinct HDL proteins are better predictors of ASCVD events than HDL-C. Low HDL-C levels are related observationally, but also genetically, to increased risks of infectious diseases, death during sepsis, diabetes mellitus, and chronic kidney disease. Additional, but only observational, data indicate associations of low HDL-C with various autoimmune diseases, and cancers, as well as all-cause mortality. Conversely, extremely high HDL-C levels are associated with an increased risk of age-related macular degeneration (also genetically), infectious disease, and all-cause mortality. HDL encompasses dynamic multimolecular and multifunctional lipoproteins that likely emerged during evolution to serve several physiological roles and prevent or heal pathologies beyond ASCVD. For any clinical exploitation of HDL, the indirect marker HDL-C must be replaced by direct biomarkers reflecting the causal role of HDL in the respective disease.</AbstractText><br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 07 Nov 2022; epub ahead of print</small></div>
von Eckardstein A, Nordestgaard BG, Remaley AT, Catapano AL
Eur Heart J: 07 Nov 2022; epub ahead of print | PMID: 36337032
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<div><h4>Cardiac troponin release following coronary artery bypass grafting: mechanisms and clinical implications.</h4><i>Heuts S, Gollmann-Tepeköylü C, Denessen EJS, Olsthoorn JR, ... Thielmann M, Mingels AMA</i><br /><AbstractText>The use of biomarkers is undisputed in the diagnosis of primary myocardial infarction (MI), but their value for identifying MI is less well studied in the postoperative phase following coronary artery bypass grafting (CABG). To identify patients with periprocedural MI (PMI), several conflicting definitions of PMI have been proposed, relying either on cardiac troponin (cTn) or the MB isoenzyme of creatine kinase, with or without supporting evidence of ischaemia. However, CABG inherently induces the release of cardiac biomarkers, as reflected by significant cTn concentrations in patients with uncomplicated postoperative courses. Still, the underlying (patho)physiological release mechanisms of cTn are incompletely understood, complicating adequate interpretation of postoperative increases in cTn concentrations. Therefore, the aim of the current review is to present these potential underlying mechanisms of cTn release in general, and following CABG in particular (Graphical Abstract). Based on these mechanisms, dissimilarities in the release of cTnI and cTnT are discussed, with potentially important implications for clinical practice. Consequently, currently proposed cTn biomarker cut-offs by the prevailing definitions of PMI might warrant re-assessment, with differentiation in cut-offs for the separate available assays and surgical strategies. To resolve these issues, future prospective studies are warranted to determine the prognostic influence of biomarker release in general and PMI in particular.</AbstractText><br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 07 Nov 2022; epub ahead of print</small></div>
Heuts S, Gollmann-Tepeköylü C, Denessen EJS, Olsthoorn JR, ... Thielmann M, Mingels AMA
Eur Heart J: 07 Nov 2022; epub ahead of print | PMID: 36337034
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<div><h4>Coronary microvascular dysfunction is associated with impaired cognitive function: the cerebral-coronary connection study (C3 study).</h4><i>Mejia-Renteria H, Travieso A, Matías-Guiu JA, Yus M, ... Matías-Guiu J, Escaned J</i><br /><b>Background</b><br />It remains unknown whether the presence of coronary microcirculatory dysfunction (CMD) correlates with its equivalent condition in the brain, cerebral small vessel disease (CSVD). The cerebral-coronary connection (C3), a prospective blinded study, investigated the prevalence of CMD in patients with coronary artery disease (CAD) and its association with CSVD and cognitive function.<br /><b>Methods and results</b><br />Patients with documented CAD fulfilling inclusion criteria underwent physiological assessment of epicardial vessels and the microcirculation using intracoronary pressure and Doppler. Coronary microcirculation-related indices included coronary flow reserve (CFR) and hyperaemic microvascular resistance. Brain magnetic resonance imaging, transcranial Doppler (TCD), and neurocognitive examination were performed. Overall, 67 patients were included in the study (mean age 66 years, 73% female). Patients with abnormal CFR (<2.0) (55.2%) showed higher burden of white-matter hyperintensities: 43.2 vs. 20.0% (P = 0.044). After statistical adjustment, low CFR was associated with lower grey matter volume (P = 0.024) and with parameters of white-matter microstructural damage in diffusion-tensor imaging (lower fractional anisotropy and higher mean diffusivity, P = 0.029 and P = 0.032, respectively). Low CFR was associated with higher resistive (P = 0.027) and pulsatility (P = 0.043) values on TCD, and worse neurocognitive test scores (lower mini mental state examination, P = 0.025, and slower Trail Making Test A, P = 0.034).<br /><b>Conclusions</b><br />Coronary microcirculatory dysfunction is frequent in patients with CAD and correlates with CSVD, abnormal cerebral flow haemodynamics, and significant cognitive impairment. These findings support the hypothesis that microvascular dysfunction in the heart and the brain are part of a single pathological process affecting microcirculation in patients with CAD.<br /><b>Clinical trial registration</b><br />ClinicalTrials.gov NCT04131075.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 07 Nov 2022; epub ahead of print</small></div>
Mejia-Renteria H, Travieso A, Matías-Guiu JA, Yus M, ... Matías-Guiu J, Escaned J
Eur Heart J: 07 Nov 2022; epub ahead of print | PMID: 36337036
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<div><h4>Prevalence, Trends and Outcomes of Cardiovascular Diseases in Pregnant Patients in the United States: 2010 to 2019.</h4><i>Majmundar M, Doshi R, Patel KN, Zala H, Kumar A, Kalra A</i><br /><b>Background:</b><br/>and aims</b><br />Contemporary data on the prevalence, trends, and outcomes of cardiovascular, diseases (CVD) in pregnant patients are limited. This study aimed to analyze the, prevalence, trends, and outcomes of CVD and their subtypes in hospitalized pregnant, patients in the United States (U.S.).<br /><b>Methods</b><br />This retrospective population-based cohort study used the Nationwide Readmission Database to identify all hospitalized pregnant patients from January 1, 2010, to, December 31, 2019. Data analyses were conducted from January-February 2022., Pregnancy-associated hospitalizations were identified. Main outcomes were, prevalence and trend of CVD in pregnant patients.<br /><b>Results</b><br />39,212,104 hospitalized pregnant patients were identified: 4,409,924 with CVD (11.3%), and 34,802,180 without CVD (88.8%). The annual age adjusted CVD prevalence, increased from 9.2% in 2010 to 14.8% in 2019 (p < 0.001). Hypertensive disorder of, pregnancy (1069/10,000) was the most common, and aortic dissection (0.1/10,000), was the least common CVD. Trends of all CVD subtypes increased; however, the trend, of valvular heart disease decreased. Age adjusted in-hospital all-cause mortality was, 8.2/10,000 in CVD but its trend decreased from 8.1/10,000 in 2010 to 6.5/10,000 in, 2019 (p < 0.001). CVD was associated with 15.51 times higher odds of in-hospital allcause, mortality compared with non-CVD patients (odds ratio (OR): 15.51, 95% CI, 13.22-18.20, p < 0.001). CVD was associated with higher 6-week postpartum readmission (OR: 1.97, 95% CI: 1.95-1.99), myocardial infarction (OR: 3.04, 95% CI:, 2.57-3.59), and stroke (OR: 2.66, 95% CI: 2.41-2.94) (p < 0.001 for all).<br /><b>Conclusion</b><br />There is an increasing age adjusted trend in overall CVD and its subtypes among, pregnant patients in the U.S. from 2010 to 2019. Pregnant patients with CVD had, higher odds of in-hospital mortality than those without CVD. However, in-hospital allcause, mortality among patients with and without CVD decreased over the past 10, years. CVD was associated with higher 6-week postpartum all-cause readmission, myocardial infarction, and stroke.<br /><br />© The Author(s) 2022. 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 Nov 2022; epub ahead of print</small></div>
Majmundar M, Doshi R, Patel KN, Zala H, Kumar A, Kalra A
Eur Heart J: 07 Nov 2022; epub ahead of print | PMID: 36342471
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<div><h4>Hypertension management in patients with cardiovascular comorbidities.</h4><i>Lauder L, Mahfoud F, Azizi M, Bhatt DL, ... Weber T, Böhm M</i><br /><AbstractText>Arterial hypertension is a leading cause of death globally. Due to ageing, the rising incidence of obesity, and socioeconomic and environmental changes, its incidence increases worldwide. Hypertension commonly coexists with Type 2 diabetes, obesity, dyslipidaemia, sedentary lifestyle, and smoking leading to risk amplification. Blood pressure lowering by lifestyle modifications and antihypertensive drugs reduce cardiovascular (CV) morbidity and mortality. Guidelines recommend dual- and triple-combination therapies using renin-angiotensin system blockers, calcium channel blockers, and/or a diuretic. Comorbidities often complicate management. New drugs such as angiotensin receptor-neprilysin inhibitors, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists improve CV and renal outcomes. Catheter-based renal denervation could offer an alternative treatment option in comorbid hypertension associated with increased sympathetic nerve activity. This review summarises the latest clinical evidence for managing hypertension with CV comorbidities.</AbstractText><br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 07 Nov 2022; epub ahead of print</small></div>
Lauder L, Mahfoud F, Azizi M, Bhatt DL, ... Weber T, Böhm M
Eur Heart J: 07 Nov 2022; epub ahead of print | PMID: 36342266
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<div><h4>Effect of inclisiran on lipids in primary prevention: the ORION-11 trial.</h4><i>Ray KK, Kallend D, Leiter LA, Raal FJ, ... Wright RS, ORION-11 Investigators</i><br /><b>Aims</b><br />Patients often require combination therapies to achieve LDL cholesterol (LDL-C) targets for the primary prevention of atherosclerotic cardiovascular disease. This study investigates the effect of inclisiran, a small interfering ribonucleic acid targeting hepatic proprotein convertase subtilisin/kexin type 9 production, in primary prevention patients with elevated LDL-C despite statins.<br /><b>Methods and results</b><br />This pre-specified analysis of the placebo-controlled, randomized ORION-11 trial included 203 individuals at risk of, but without prior, cardiovascular events and LDL-C ≥2.6 mmol/L, despite maximally tolerated statins. Inclisiran 284 mg or placebo was administered on Days 1, 90, and thereafter every 6 months up to 540 days. Co-primary endpoints were percentage LDL-C change from baseline to Day 510 and time-adjusted change from baseline after Day 90 and up to Day 540. Key secondary endpoints included percentage and absolute changes in atherogenic lipoproteins. Safety was assessed over 540 days. The mean baseline (SD) LDL-C was 3.6 (1.5) mmol/L. At Day 510, the placebo-corrected LDL-C change with inclisiran was -43.7% [95% confidence interval (CI): -52.8 to -34.6] with a corresponding time-adjusted change of -41.0% (95% CI: -47.8 to -34.2); (P < 0.0001). The placebo-corrected absolute change in LDL-C at Day 510 with inclisiran was -1.5 mmol/L (95% CI: -1.8 to -1.2), with a respective time-adjusted change of -1.3 mmol/L (95% CI: -1.6 to -1.1). Inclisiran significantly lowered non-HDL cholesterol and apolipoprotein B (apoB) at Day 510 vs. placebo (P < 0.0001 for both), with a greater likelihood of attaining lipoprotein and apoB goals, and was well-tolerated except for mainly mild, treatment-emergent adverse events at the injection site.<br /><b>Conclusion</b><br />Inclisiran was generally well-tolerated in primary prevention patients with elevated LDL-C, who derived significant reductions in atherogenic lipoprotein levels with twice-yearly maintenance dosing.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 04 Nov 2022; epub ahead of print</small></div>
Ray KK, Kallend D, Leiter LA, Raal FJ, ... Wright RS, ORION-11 Investigators
Eur Heart J: 04 Nov 2022; epub ahead of print | PMID: 36331315
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<div><h4>Inclisiran and cardiovascular events: a patient-level analysis of phase III trials.</h4><i>Ray KK, Raal FJ, Kallend DG, Jaros MJ, ... Wright RS, ORION Phase III investigators</i><br /><b>Background</b><br />Inclisiran, an siRNA administered twice-yearly, significantly reduced LDL cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a lower risk of cardiovascular (CV) events is not yet established.<br /><b>Methods and results</b><br />Patient-level, pooled analysis of ORION-9, -10 and -11, included patients with heterozygous familial hypercholesterolaemia, atherosclerotic CV disease (ASCVD), or ASCVD risk equivalent on maximally tolerated statin-therapy, randomized 1:1 to receive 284 mg inclisiran or placebo on Days 1, 90, and 6-monthly thereafter for 18 months. Prespecified exploratory endpoint of major cardiovascular events (MACEs) included non-adjudicated CV death, cardiac arrest, non-fatal myocardial infarction (MI), and fatal and non-fatal stroke, evaluated as part of safety assessments using a standard Medical Dictionary for Regulatory Activities basket. Although not prespecified, total fatal and non-fatal MI, and stroke were also evaluated. Mean LDL-C at baseline was 2.88 mmol/L. At Day 90, the placebo-corrected percentage reduction in LDL-C with inclisiran was 50.6%, corresponding to an absolute reduction of 1.37 mmol/L (both P < 0.0001). Among 3655 patients over 18 months, 303 (8.3%) experienced MACE, including 74 (2.0%) fatal and non-fatal MIs, and 28 (0.8%) fatal and non-fatal strokes. Inclisiran significantly reduced composite MACE [OR (95% CI): 0.74 (0.58-0.94)], but not fatal and non-fatal MIs [OR (95% CI): 0.80 (0.50-1.27)] or fatal and non-fatal stroke [OR (95% CI): 0.86 (0.41-1.81)].<br /><b>Conclusion</b><br />This analysis offers early insights into the potential CV benefits of lowering LDL-C with inclisiran and suggests potential benefits for MACE reduction. These findings await confirmation in the larger CV outcomes trials of longer duration.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 04 Nov 2022; epub ahead of print</small></div>
Ray KK, Raal FJ, Kallend DG, Jaros MJ, ... Wright RS, ORION Phase III investigators
Eur Heart J: 04 Nov 2022; epub ahead of print | PMID: 36331326
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<div><h4>Serial troponin-T and long-term outcomes in suspected acute coronary syndrome.</h4><i>Pareek M, Kragholm KH, Kristensen AMD, Vaduganathan M, ... Bhatt DL, Torp-Pedersen C</i><br /><b>Background</b><br />Long-term prognostic implications of serial high-sensitivity troponin concentrations in subjects with suspected acute coronary syndrome are unknown.<br /><b>Methods and results</b><br />Individuals with a first diagnosis of myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019 who underwent two high-sensitivity troponin-T (hsTnT) measurements 1-7 h apart were identified through Danish national registries. Absolute and relative risks for death at days 0-30 and 31-365, stratified for whether subjects had normal or elevated hsTnT concentrations, and whether these concentrations changed by <20%, > 20 to 50%, or >50% in either direction from first to second measurement, were calculated through multivariable logistic regression with average treatment effect modeling. Of the 28 902 individuals included, 2.8% had died at 30 days, whereas 4.9% of those who had survived the first 30 days died between days 31-365. The standardized risk of death was highest among subjects with two elevated hsTnT concentrations (0-30 days: 4.3%, 31-365 days: 7.2%). In this group, mortality was significantly higher in those with a > 20 to 50% or >50% rise from first to second measurement, though only at 30 days. The risk of death was very low in subjects with two normal hsTnT concentrations (0-30 days: 0.1%, 31-365 days: 0.9%) and did not depend on relative or absolute changes between measurements.<br /><b>Conclusions</b><br />Individuals with suspected acute coronary syndrome and two consecutively elevated hsTnT concentrations consistently had the highest risk of death. Mortality was very low in subjects with two normal hsTnT concentrations, irrespective of changes between measurements.<br /><br />© The Author(s) 2022. 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: 04 Nov 2022; epub ahead of print</small></div>
Pareek M, Kragholm KH, Kristensen AMD, Vaduganathan M, ... Bhatt DL, Torp-Pedersen C
Eur Heart J: 04 Nov 2022; epub ahead of print | PMID: 36329643
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<div><h4>Cost effectiveness of population screening vs. no screening for cardiovascular disease: the Danish Cardiovascular Screening trial (DANCAVAS).</h4><i>Søgaard R, Diederichsen ACP, Rasmussen LM, Lambrechtsen J, ... Busk M, Lindholt JS</i><br /><b>Aims</b><br />A recent trial has shown that screening of men for cardiovascular disease (CVD) may reduce all-cause mortality. This study assesses the cost effectiveness of such screening vs. no screening from the perspective of European healthcare systems.<br /><b>Methods and results</b><br />Randomized controlled trial-based cost-effectiveness evaluation with a mean 5.7 years of follow-up. Screening was based on low-dose computed tomography to detect coronary artery calcification and aortic/iliac aneurysms, limb blood pressure measurement to detect peripheral artery disease and hypertension, telemetric assessment of the heart rhythm to detect atrial fibrillation, and measurements of the cholesterol and HgbA1c levels. Censoring-adjusted incremental costs, life years (LY), and quality-adjusted LY (QALY) were estimated and used for cost-effectiveness analysis. The incremental cost of screening for the entire health care sector was €207 [95% confidence interval (CI) -24; 438, P = 0.078] per invitee for which gains of 0.019 LY (95% CI -0.007; 0.045, P = 0.145) and 0.023 QALY (95% CI -0.001; 0.046, P = 0.051) were achieved. The corresponding incremental cost-effectiveness ratios were of €10 812 per LY and €9075 per QALY, which would be cost effective at probabilities of 0.73 and 0.83 for a willingness to pay of €20 000. Assessment of population heterogeneity showed that cost effectiveness could be more attractive for younger men without CVD at baseline.<br /><b>Conclusions</b><br />Comprehensive screening for CVD is overall cost effective at conventional thresholds for willingness to pay and also competitive to the cost effectiveness of common cancer screening programmes. The screening target group, however, needs to be settled.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 01 Nov 2022; 43:4392-4402</small></div>
Søgaard R, Diederichsen ACP, Rasmussen LM, Lambrechtsen J, ... Busk M, Lindholt JS
Eur Heart J: 01 Nov 2022; 43:4392-4402 | PMID: 36029019
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<div><h4>Influenza vaccination strategy in acute coronary syndromes: the VIP-ACS trial.</h4><i>Fonseca HAR, Furtado RHM, Zimerman A, Lemos PA, ... Nicolau JC, Berwanger O</i><br /><b>Aims</b><br />To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events.<br /><b>Methods and results</b><br />Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79-1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66-1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75-1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups.<br /><b>Conclusion</b><br />Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting.<br /><b>Clinical trial registration</b><br />ClinicalTrials.gov number: NCT04001504.<br /><br />© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 01 Nov 2022; 43:4378-4388</small></div>
Fonseca HAR, Furtado RHM, Zimerman A, Lemos PA, ... Nicolau JC, Berwanger O
Eur Heart J: 01 Nov 2022; 43:4378-4388 | PMID: 36030400
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This program is still in alpha version.