Topic: General Cardiology

Abstract

Antiplatelet therapy in patients with atrial fibrillation: a systematic review and meta-analysis of randomized trials.

Benz AP, Johansson I, Dewilde WJM, Lopes RD, ... Eikelboom JW, Connolly SJ
Aims
The aim of this study was to systematically assess the effects of antiplatelets on clinical outcomes in patients with atrial fibrillation (AF), treated and not-treated with oral anticoagulation.
Methods and results
We searched MEDLINE, Embase, and CENTRAL from inception until September 2020. From 5446 citations, we selected randomized trials allocating patients with AF to antiplatelet therapy vs. control. We applied random-effects models for meta-analysis and assessed potential effect modification with background anticoagulation use. Eighteen trials including 21 518 participants met our prespecified eligibility criteria. In 10 studies without background anticoagulation, antiplatelets reduced all-cause stroke [486/6165 (events/patients) vs. 621/6061; risk ratio (RR) 0.77, 95% confidence interval (CI) 0.69-0.86, I2 = 0%]. In eight studies with background anticoagulation, there was a signal for an increase in all-cause stroke with antiplatelets (97/4608 vs. 72/4684; RR 1.33, 95% CI 0.98-1.79, I2 = 0%, P-value for interaction <0.001). A similar pattern emerged for ischaemic stroke. Irrespective of background anticoagulation use, antiplatelets increased major bleeding (509/10 402 vs. 328/10 496; RR 1.54, 95% CI 1.35-1.77, I2 = 0%) and intracranial haemorrhage (107/10 221 vs. 65/10 232; RR 1.64, 95% CI 1.20-2.24, I2 = 0%), and reduced myocardial infarction (201/9679 vs. 260/9751; RR 0.79, 95% CI 0.65-0.94, I2 = 0%, all P-values for interaction ≥0.36). Antiplatelets did not affect mortality (1221/10 299 vs. 1211/10 287; RR 1.02, 95% CI 0.89-1.17, I2 = 29%, P-value for interaction = 0.23).
Conclusions
In patients with AF not receiving oral anticoagulation, antiplatelet therapy modestly reduced stroke. There was a corresponding signal for harm when used on top of anticoagulation. Irrespective of background anticoagulation use, antiplatelet therapy significantly increased bleeding, moderately reduced myocardial infarction, and did not affect mortality.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Pharmacother: 29 Sep 2022; 8:648-659
Benz AP, Johansson I, Dewilde WJM, Lopes RD, ... Eikelboom JW, Connolly SJ
Eur Heart J Cardiovasc Pharmacother: 29 Sep 2022; 8:648-659 | PMID: 34142118
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Abstract

Diseases of the Aorta and Kidney Disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Sarafidis P, Martens S, Saratzis A, Kadian-Dodov D, ... Johansen K, for Conference Participants
Chronic kidney disease (CKD) is an independent risk factor for the development of abdominal aortic aneurysm (AAA), as well as for cardiovascular and renal events and all-cause mortality following surgery for AAA or thoracic aortic dissection. In addition, the incidence of acute kidney injury (AKI) after any aortic surgery is particularly high, and this AKI per se is independently associated with future cardiovascular events and mortality. On the other hand, both development of AKI after surgery and the long-term evolution of kidney function differ significantly depending on the type of AAA intervention (open surgery vs. the various subtypes of endovascular repair). Current knowledge regarding AAA in the general population may not be always applicable to CKD patients, as they have a high prevalence of co-morbid conditions and an elevated risk for periprocedural complications. This summary of a Kidney Disease: Improving Global Outcomes Controversies Conference group discussion reviews the epidemiology, pathophysiology, diagnosis, and treatment of Diseases of the Aorta in CKD and identifies knowledge gaps, areas of controversy, and priorities for future research.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Cardiovasc Res: 20 Sep 2022; 118:2582-2595
Sarafidis P, Martens S, Saratzis A, Kadian-Dodov D, ... Johansen K, for Conference Participants
Cardiovasc Res: 20 Sep 2022; 118:2582-2595 | PMID: 34469520
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Abstract

Left atrial appendage thrombus and cerebrovascular events post-transcatheter aortic valve implantation.

van Wiechen MP, Faure ME, Hokken TW, Ooms JF, ... Budde RPJ, Van Mieghem NM
Aims
To elucidate the frequency and clinical impact of left atrial appendage thrombus (LAAT) in patients set for transcatheter aortic valve implantation (TAVI).
Methods and results
All patients undergoing TAVI between January 2014 and June 2020 with analysable multislice computed tomography (MSCT) for LAAT were included. Baseline and procedural characteristics were collected, pre-procedural MSCT\'s were retrospectively analysed for LAAT presence. The primary endpoint was defined as the cumulative incidence of any cerebrovascular event (stroke or transient ischaemic attack) within the first year after TAVI. A Cox proportional hazards model was used to identify predictors.A total of 1050 cases had analysable MSCT. Median age was 80 [interquartile range (IQR) 74-84], median Society of Thoracic Surgeons\' Predicted Risk Of Mortality (STS-PROM) was 3.4% (IQR 2.3-5.5). Thirty-six percent were on oral anticoagulant therapy for atrial fibrillation (AF). LAAT was present in 48 (4.6%) of cases. Patients with LAAT were at higher operative risk [STS-PROM: 4.9% (2.9-7.1) vs. 3.4% (2.3-5.5), P = 0.01], had worse systolic left ventricular function [EF 52% (35-60) vs. 55% (45-65), P = 0.01] and more permanent pacemakers at baseline (35% vs. 10%, P < 0.01). All patients with LAAT had a history of AF and patients with LAAT were more often on vitamin K antagonist-treatment than patients without LAAT [43/47 (91%) vs. 232/329 (71%), P < 0.01]. LAAT [hazard ratio (HR) 2.94 (1.39-6.22), P < 0.01] and the implantation of more than one valve [HR 4.52 (1.79-11.25), P < 0.01] were independent predictors for cerebrovascular events.
Conclusion
Patients with MSCT-identified LAAT were at higher risk for cerebrovascular events during the first year after TAVI.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1345-1353
van Wiechen MP, Faure ME, Hokken TW, Ooms JF, ... Budde RPJ, Van Mieghem NM
Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1345-1353 | PMID: 34322706
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Abstract

Predicting future left anterior descending artery events from non-culprit lesions: insights from the Lipid-Rich Plaque study.

Kuku KO, Garcia-Garcia HM, Doros G, Mintz GS, ... Di Mario C, Waksman R
Aims
The left anterior descending (LAD) artery is the most frequently affected site by coronary artery disease. The prospective Lipid Rich Plaque (LRP) study, which enrolled patients undergoing imaging of non-culprits followed over 2 years, reported the successful identification of coronary segments at risk of future events based on near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) lipid signals. We aimed to characterize the plaque events involving the LAD vs. non-LAD segments.
Methods and results
LRP enrolled 1563 patients from 2014 to 2016. All adjudicated plaque events defined by the composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization by coronary bypass or percutaneous coronary intervention, and rehospitalization for angina with >20% stenosis progression and reported as non-culprit lesion-related major adverse cardiac events (NC-MACE) were classified by NIRS-IVUS maxLCBI4 mm (maximum 4-mm Lipid Core Burden Index) ≤400 or >400 and association with high-risk-plaque characteristics, plaque burden ≥70%, and minimum lumen area (MLA) ≤4 mm2. Fifty-seven events were recorded with more lipid-rich plaques in the LAD vs. left circumflex and right coronary artery; 12.5% vs. 10.4% vs. 11.3%, P = 0.097. Unequivocally, a maxLCBI4 mm >400 in the LAD was more predictive of NC-MACE [hazard ratio (HR) 4.32, 95% confidence interval (CI) (1.93-9.69); P = 0.0004] vs. [HR 2.56, 95% CI (1.06-6.17); P = 0.0354] in non-LAD segments. MLA ≤4 mm2 within the maxLCBI4 mm was significantly higher in the LAD (34.1% vs. 25.9% vs. 13.7%, P < 0.001).
Conclusion
Non-culprit lipid-rich segments in the LAD were more frequently associated with plaque-level events. LAD NIRS-IVUS screening may help identify patients requiring intensive surveillance and medical treatment.

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Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1365-1372
Kuku KO, Garcia-Garcia HM, Doros G, Mintz GS, ... Di Mario C, Waksman R
Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1365-1372 | PMID: 34410335
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Abstract

Left atrial strain is a predictor of left ventricular systolic and diastolic reverse remodelling in CRT candidates.

Galli E, Oger E, Aalen JM, Duchenne J, ... Smiseth OA, Donal E
Aims
The left atrium (LA) has a pivotal role in cardiac performance and LA deformation is a well-known prognostic predictor in several clinical conditions including heart failure with reduced ejection fraction. The aim of this study is to investigate the effect of cardiac resynchronization therapy (CRT) on both LA morphology and function and to assess the impact of LA reservoir strain (LARS) on left ventricular (LV) systolic and diastolic remodelling after CRT.
Methods and results
Two hundred and twenty-one CRT-candidates were prospectively included in the study in four tertiary centres and underwent echocardiography before CRT-implantation and at 6-month follow-up (FU). CRT-response was defined by a 15% reduction in LV end-systolic volume. LV systolic and diastolic remodelling were defined as the percent reduction in LV end-systolic and end-diastolic volume at FU. Indexed LA volume (LAVI) and LV-global longitudinal (GLS) strain were the main parameters correlated with LARS, with LV-GLS being the strongest determinant of LARS (r = -0.59, P < 0.0001). CRT induced a significant improvement in LAVI and LARS in responders (both P < 0.0001). LARS was an independent predictor of both LV systolic and diastolic remodelling at follow-up (r = -0.14, P = 0.049 and r = -0.17, P = 0.002, respectively).
Conclusion
CRT induces a significant improvement in LAVI and LARS in responders. In CRT candidates, the evaluation of LARS before CRT delivery is an independent predictor of LV systolic and diastolic remodelling at FU.

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Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1373-1382
Galli E, Oger E, Aalen JM, Duchenne J, ... Smiseth OA, Donal E
Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1373-1382 | PMID: 34432006
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Abstract

Adverse right ventricular remodelling, function, and stress responses in obesity: insights from cardiovascular magnetic resonance.

Lewis AJM, Abdesselam I, Rayner JJ, Byrne J, ... Neubauer S, Rider OJ
Aims
We aimed to determine the effect of increasing body weight upon right ventricular (RV) volumes, energetics, systolic function, and stress responses using cardiovascular magnetic resonance (CMR).
Methods and results
We first determined the effects of World Health Organization class III obesity [body mass index (BMI) > 40 kg/m2, n = 54] vs. healthy weight (BMI < 25 kg/m2, n = 49) upon RV volumes, energetics and systolic function using CMR. In less severe obesity (BMI 35 ± 5 kg/m2, n = 18) and healthy weight controls (BMI 21 ± 1 kg/m2, n = 9), we next performed CMR before and during dobutamine to evaluate RV stress response. A subgroup undergoing bariatric surgery (n = 37) were rescanned at median 1 year to determine the effects of weight loss. When compared with healthy weight, class III obesity was associated with adverse RV remodelling (17% RV end-diastolic volume increase, P < 0.0001), impaired cardiac energetics (19% phosphocreatine to adenosine triphosphate ratio reduction, P < 0.001), and reduction in RV ejection fraction (by 3%, P = 0.01), which was related to impaired energetics (R = 0.3, P = 0.04). Participants with less severe obesity had impaired RV diastolic filling at rest and blunted RV systolic and diastolic responses to dobutamine compared with healthy weight. Surgical weight loss (34 ± 15 kg weight loss) was associated with improvement in RV end-diastolic volume (by 8%, P = 0.006) and systolic function (by 2%, P = 0.03).
Conclusion
Increasing body weight is associated with significant alterations in RV volumes, energetic, systolic function, and stress responses. Adverse RV modelling is mitigated with weight loss. Randomized trials are needed to determine whether intentional weight loss improves symptoms and outcomes in patients with obesity and heart failure.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1383-1390
Lewis AJM, Abdesselam I, Rayner JJ, Byrne J, ... Neubauer S, Rider OJ
Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1383-1390 | PMID: 34453521
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Abstract

Clinical impact of left atrial appendage filling defects in patients undergoing transcatheter aortic valve implantation.

Okuno T, Lanz J, Stortecky S, Heg D, ... Windecker S, Pilgrim T
Aims
Incidental detection of left atrial appendage (LAA) filling defects is a common finding on multi-detector computed tomography in aortic stenosis patients under evaluation for transcatheter aortic valve implantation (TAVI). We aimed to investigate the incidence of LAA filling defects before TAVI and its impact on clinical outcomes.
Methods and results
In a prospective registry, LAA filling defects were retrospectively evaluated and categorized into one of four sub-types: thrombus-like, heterogeneous, horizontal, and Hounsfield Unit (HU)-run-off. The primary endpoint was the composite of cardiovascular death or disabling stroke up to 1-year follow-up. Among 1621 patients undergoing TAVI between August 2007 and June 2018, LAA filling defects were present in 177 patients (11%), and categorized as thrombus-like in 22 (1.4%), heterogeneous in 37 (2.3%), horizontal in 80 (4.9%), and HU-run-off in 38 (2.4%). Compared to patients with normal LAA filling, patients with LAA filling defects had greater prevalence of atrial fibrillation (84.7% vs. 26.4%, P < 0.001) and history of cerebrovascular events (16.4% vs. 10.9%, P = 0.045). The primary endpoint occurred in 131 patients (9.2%) with normal LAA filling and in 36 patients (21.2%) with LAA filling defects (P < 0.001). Subgroup analysis suggested that the risk of disabling stroke was greatest in the thrombus-like pattern (23.0%), followed by the HU-run-off (8.0%), the heterogeneous (6.2%), and the horizontal pattern (1.2%).
Conclusion
LAA filling defects were observed in 11% of aortic stenosis patients undergoing TAVI and associated with an increased risk of cardiovascular death and disabling stroke up to 1 year following TAVI.
Trial registration
https://www.clinicaltrials.gov. NCT01368250.

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Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1354-1364
Okuno T, Lanz J, Stortecky S, Heg D, ... Windecker S, Pilgrim T
Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1354-1364 | PMID: 34463717
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Abstract

Measurement of compensatory arterial remodelling over time with serial coronary computed tomography angiography and 3D metrics.

van den Hoogen IJ, van Rosendael AR, Lin FY, Gianni U, ... Shaw LJ, Bax JJ
Aims
The magnitude of alterations in which coronary arteries remodel and narrow over time is not well understood. We aimed to examine changes in coronary arterial remodelling and luminal narrowing by three-dimensional (3D) metrics from serial coronary computed tomography angiography (CCTA).
Methods and results
From a multicentre registry of patients with suspected coronary artery disease who underwent clinically indicated serial CCTA (median interscan interval = 3.3 years), we quantitatively measured coronary plaque, vessel, and lumen volumes on both scans. Primary outcome was the per-segment change in coronary vessel and lumen volume from a change in plaque volume, focusing on arterial remodelling. Multivariate generalized estimating equations including statins were calculated comparing associations between groups of baseline percent atheroma volume (PAV) and location within the coronary artery tree. From 1245 patients (mean age 61 ± 9 years, 39% women), a total of 5721 segments were analysed. For each 1.00 mm3 increase in plaque volume, the vessel volume increased by 0.71 mm3 [95% confidence interval (CI) 0.63 to 0.79 mm3, P < 0.001] with a corresponding reduction in lumen volume by 0.29 mm3 (95% CI -0.37 to -0.21 mm3, P < 0.001). Serial 3D arterial remodelling and luminal narrowing was similar in segments with low and high baseline PAV (P ≥ 0.496). No differences were observed between left main and non-left main segments, proximal and distal segments and side branch and non-side branch segments (P ≥ 0.281).
Conclusions
Over time, atherosclerotic coronary plaque reveals prominent outward arterial remodelling that co-occurs with modest luminal narrowing. These findings provide additional insight into the compensatory mechanisms involved in the progression of coronary atherosclerosis.

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Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1336-1344
van den Hoogen IJ, van Rosendael AR, Lin FY, Gianni U, ... Shaw LJ, Bax JJ
Eur Heart J Cardiovasc Imaging: 10 Sep 2022; 23:1336-1344 | PMID: 34468717
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Abstract

Cardiovascular outcomes with GLP-1 receptor agonists vs. SGLT-2 inhibitors in patients with type 2 diabetes.

Nørgaard CH, Starkopf L, Gerds TA, Vestergaard P, ... Torp-Pedersen C, Lee CJ
Aims
We examined cardiovascular outcomes associated with initiation of glucagon-like peptide-1 receptor agonist (GLP-1RA) vs. sodium-glucose co-transporter-2 inhibitor (SGLT-2i) treatment in a real-world setting among patients with type 2 diabetes.
Methods and results
This Danish nationwide registry-based cohort study included patients with type 2 diabetes with a first-ever prescription of either GLP-1RA or SGLT-2i from 2013 through 2015 with follow-up until end of 2018. All analyses were standardized with respect to age, sex, diabetes duration, comorbidity, and comedication. The main outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Furthermore, the components of the composite outcome and hospitalization for heart failure were evaluated. Standardized average 3-year risks of outcomes and differences thereof were estimated using doubly robust estimation combining cause-specific Cox regression with propensity score regression. We identified 8913 new users of GLP-1RA and 5275 new users of SGLT-2i. The standardized 3-year risk associated with initiating GLP-1RA and SGLT-2i, respectively, was as follows: composite cardiovascular outcome, 5.6% [95% confidence interval (CI): 5.2-6.1] vs. 5.6% (95% CI: 4.8-6.3); cardiovascular mortality, 1.6% (95% CI: 1.3-1.9) vs. 1.5% (95% CI: 1.1-1.8); hospitalization for heart failure, 1.7% (95% CI: 1.5-2.0) vs. 1.8% (95% CI: 1.2-2.5); myocardial infarction, 2.1% (95% CI: 1.8-2.4) vs. 2.1% (95% CI: 1.5-2.6); and stroke, 2.5% (95% CI: 2.2-2.9) vs. 2.6% (95% CI: 2.2-3.1).
Conclusion
In this nationwide study of patients with type 2 diabetes, initiating GLP-1RA vs. SGLT-2i was not found to be associated with significant differences in cardiovascular risk.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 03 Sep 2022; 8:549-556
Nørgaard CH, Starkopf L, Gerds TA, Vestergaard P, ... Torp-Pedersen C, Lee CJ
Eur Heart J Cardiovasc Pharmacother: 03 Sep 2022; 8:549-556 | PMID: 34215881
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Abstract

An international audit of the management of dyslipidaemia and hypertension in patients with rheumatoid arthritis: results from 19 countries.

Rollefstad S, Ikdahl E, Wibetoe G, Sexton J, ... Medková H, Semb AG
Aims
To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP).
Methods and results
The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014-19. The treatment goal for BP was <140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid-lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high risk groups, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two per cent had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three-drug combination.
Conclusion
We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 03 Sep 2022; 8:539-548
Rollefstad S, Ikdahl E, Wibetoe G, Sexton J, ... Medková H, Semb AG
Eur Heart J Cardiovasc Pharmacother: 03 Sep 2022; 8:539-548 | PMID: 34232315
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Abstract

Cardiovascular risks associated with calcium supplementation in patients with osteoporosis: a nationwide cohort study.

Kim KJ, Kim MS, Hong N, Bae JH, ... Lee J, Kim SG
Aims
This study aimed to evaluate the real effects of calcium supplementation on cardiovascular outcomes within a population-based cohort.
Methods and results
From a nationwide health screening database in South Korea, a total of 11 297 patients with osteoporosis who had taken calcium supplementation with or without vitamin D for at least 90 days [total calcium group; calcium supplementation only (CaO), n = 567; calcium supplementation in combination with vitamin D (CaD), n = 10 730] were matched at a 1:1 ratio to patients who had not taken calcium supplements (control group) by using propensity scores. The overall mean age was 59.9 ± 8.8 years and the percentage of women was 87.9% in our study population. Over a median follow-up of 54 months, the incidence rate of composite cardiovascular diseases (CVDs) per 1000 person-years was not different between the groups: 9.73 in the total calcium group and 8.97 in the control group [adjusted hazard ratio (HR): 1.12; 95% confidence interval (CI): 0.99-1.28; P = 0.08]. However, calcium supplementation without vitamin D was associated with an increased risk of composite CVD (HR: 1.54; 95% CI: 1.17-2.04; P < 0.01), especially non-fatal myocardial infarction (HR: 1.89; 95% CI: 1.23-2.91; P < 0.01), compared with no calcium supplementation.
Conclusion
Our population-based study supported that taking calcium supplementation combined with vitamin D did not appear to be harmful to cardiovascular health, but reminded that calcium supplementation without vitamin D should be used carefully even in populations with low dietary calcium intake.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 03 Sep 2022; 8:568-577
Kim KJ, Kim MS, Hong N, Bae JH, ... Lee J, Kim SG
Eur Heart J Cardiovasc Pharmacother: 03 Sep 2022; 8:568-577 | PMID: 34244740
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Abstract

Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose-response model.

Jadhav SB, Crass RL, Chapel S, Kerschnitzki M, ... Watts GF, Catapano AL
Aims
Many patients are unable to achieve guideline-recommended LDL cholesterol (LDL-C) targets, despite taking maximally tolerated lipid-lowering therapy. Bempedoic acid, a competitive inhibitor of ATP citrate lyase, significantly lowers LDL-C with or without background statin therapy in diverse populations. Because pharmacodynamic interaction between statins and bempedoic acid is complex, a dose-response model was developed to predict LDL-C pharmacodynamics following administration of statins combined with bempedoic acid.
Methods and results
Bempedoic acid and statin dosing and LDL-C data were pooled from 14 phase 1-3 clinical studies. Dose-response models were developed for bempedoic acid monotherapy and bempedoic acid-statin combinations using previously published statin parameters. Simulations were performed using these models to predict change in LDL-C levels following treatment with bempedoic acid combined with clinically relevant doses of atorvastatin, rosuvastatin, simvastatin, and pravastatin. Dose-response models predicted that combining bempedoic acid with the lowest statin dose of commonly used statins would achieve a similar degree of LDL-C lowering as quadrupling that statin dose; for example, the predicted LDL-C lowering was 54% with atorvastatin 80 mg compared with 54% with atorvastatin 20 mg + bempedoic acid 180 mg, and 42% with simvastatin 40 mg compared with 46% with simvastatin 10 mg + bempedoic acid 180 mg.
Conclusion
These findings suggest bempedoic acid combined with lower statin doses offers similar LDL-C lowering compared with statin monotherapy at higher doses, potentially sparing patients requiring additional lipid-lowering therapies from the adverse events associated with higher statin doses.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 03 Sep 2022; 8:578-586
Jadhav SB, Crass RL, Chapel S, Kerschnitzki M, ... Watts GF, Catapano AL
Eur Heart J Cardiovasc Pharmacother: 03 Sep 2022; 8:578-586 | PMID: 34448822
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Abstract

Long-term prognostic value of right ventricular dysfunction on cardiovascular magnetic resonance imaging in anthracycline-treated cancer survivors.

Chhikara S, Hooks M, Athwal PSS, Hughes A, ... Blaes AH, Shenoy C
Aims
We aimed to determine the prevalence of right ventricular (RV) systolic dysfunction on cardiovascular magnetic resonance imaging (CMR) and its impact on long-term adverse outcomes in a large cohort of cancer survivors treated with anthracycline-based chemotherapy.
Methods and results
Consecutive cancer survivors treated with anthracyclines who underwent clinical CMR for suspected anthracycline-related cardiomyopathy were studied. The primary endpoint was a composite of all-cause death or major adverse cardiac events (MACE): heart failure hospitalization, heart transplantation, ventricular assist device implantation, resuscitated cardiac arrest, or life-threatening ventricular arrhythmia. The secondary endpoints were all-cause death, and cardiac death or MACE. Among 249 survivors who underwent CMR at a median of 2.9 years after cancer treatment, RV systolic dysfunction was present in 54 (21.7%). Of these, 50 (92.6%) had an abnormal left ventricular ejection fraction (LVEF). At a median follow-up time after the CMR of 2.7 years, 105 survivors experienced the primary endpoint. On Kaplan-Meier analyses, the cumulative incidence of the primary endpoint was significantly higher in survivors with abnormal RVEF compared with those with normal RVEF (P = 0.002). However, on Cox multivariable analyses, RVEF was not associated with the primary endpoint (HR 1.04 per 5% decrease; 95% CI 0.93-1.17; P = 0.46) after adjustment for non-imaging variables and LVEF. RVEF was also not associated with the secondary endpoints.
Conclusion
Among anthracycline-treated cancer survivors undergoing CMR for suspected cardiotoxicity, RV systolic dysfunction was present in one in five cases, accompanied by LV systolic dysfunction in nearly all cases, and was not independently associated with long-term outcomes.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Imaging: 22 Aug 2022; 23:1222-1230
Chhikara S, Hooks M, Athwal PSS, Hughes A, ... Blaes AH, Shenoy C
Eur Heart J Cardiovasc Imaging: 22 Aug 2022; 23:1222-1230 | PMID: 34297807
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Abstract

Association of coronary artery calcium score with qualitatively and quantitatively assessed adverse plaque on coronary CT angiography in the SCOT-HEART trial.

Osborne-Grinter M, Kwiecinski J, Doris M, McElhinney P, ... Dey D, Williams MC
Aims
Coronary artery calcification is a marker of cardiovascular risk, but its association with qualitatively and quantitatively assessed plaque subtypes is unknown.
Methods and results
In this post-hoc analysis, computed tomography (CT) images and 5-year clinical outcomes were assessed in SCOT-HEART trial participants. Agatston coronary artery calcium score (CACS) was measured on non-contrast CT and was stratified as zero (0 Agatston units, AU), minimal (1-9 AU), low (10-99 AU), moderate (100-399 AU), high (400-999 AU), and very high (≥1000 AU). Adverse plaques were investigated by qualitative (visual categorization of positive remodelling, low-attenuation plaque, spotty calcification, and napkin ring sign) and quantitative (calcified, non-calcified, low-attenuation, and total plaque burden; Autoplaque) assessments. Of 1769 patients, 36% had a zero, 9% minimal, 20% low, 17% moderate, 10% high, and 8% very high CACS. Amongst patients with a zero CACS, 14% had non-obstructive disease, 2% had obstructive disease, 2% had visually assessed adverse plaques, and 13% had low-attenuation plaque burden >4%. Non-calcified and low-attenuation plaque burden increased between patients with zero, minimal, and low CACS (P < 0.001), but there was no statistically significant difference between those with medium, high, and very high CACS. Myocardial infarction occurred in 41 patients, 10% of whom had zero CACS. CACS >1000 AU and low-attenuation plaque burden were the only predictors of myocardial infarction, independent of obstructive disease, and 10-year cardiovascular risk score.
Conclusion
In patients with stable chest pain, zero CACS is associated with a good but not perfect prognosis, and CACS cannot rule out obstructive coronary artery disease, non-obstructive plaque, or adverse plaque phenotypes, including low-attenuation plaque.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Imaging: 22 Aug 2022; 23:1210-1221
Osborne-Grinter M, Kwiecinski J, Doris M, McElhinney P, ... Dey D, Williams MC
Eur Heart J Cardiovasc Imaging: 22 Aug 2022; 23:1210-1221 | PMID: 34529050
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Impact:
Abstract

Statin but not aspirin treatment is associated with reduced cardiovascular risk in patients with diabetes without obstructive coronary artery disease: a cohort study from the Western Denmark Heart Registry.

Olesen KKW, Heide-Jørgensen U, Thim T, Thomsen RW, ... Sørensen HT, Maeng M
Aims
Patients with diabetes and no obstructive coronary artery disease (CAD) as assessed by coronary angiography (CAG) are frequently treated with aspirin and statins. We examined the effectiveness of aspirin and statin treatment on cardiovascular and bleeding incidence in patients with diabetes and absent obstructive CAD.
Methods and results
The study included patients with diabetes and absent obstructive CAD as assessed by CAG from 2003 to 2016 in Western Denmark. We stratified patients by aspirin and statin treatment within 6 months after CAG in two separate analyses. Outcomes were MACE (major adverse cardiovascular events, a composite of myocardial infarction, ischaemic stroke, and death) and bleeding (aspirin only). To account for confounding, we used propensity score-based weights to estimate the inverse probability of treatment-weighted hazard ratios (HRIPTW). We included 4124 patients with diabetes but without CAD as assessed by CAG, among whom 2474 (60%) received aspirin and 2916 (71%) received statin treatment within 6 months following CAG. Median follow-up was 4.9 years. Aspirin did not reduce 10-year MACE [21.3% vs. 21.8%, HRIPTW 1.01, 95% confidence interval (CI) 0.82-1.25], all-cause death (HRIPTW 0.96, 95% CI 0.74-1.23), or bleeding (HRIPTW 0.95, 95% CI 0.73-1.23), compared to those not receiving aspirin treatment. Statin treatment reduced MACE (25% vs. 37%, HRIPTW 0.58, 95% CI 0.48-0.70) compared to those not receiving statin treatment.
Conclusion
Among patients with diabetes and no obstructive CAD, aspirin neither reduced MACE nor increased bleeding. In contrast, statin treatment was associated with a major reduction in risk of MACE.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:434-441
Olesen KKW, Heide-Jørgensen U, Thim T, Thomsen RW, ... Sørensen HT, Maeng M
Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:434-441 | PMID: 33989394
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Impact:
Abstract

Outcomes after delayed primary percutaneous coronary intervention vs. pharmaco-invasive strategy in ST-segment elevation myocardial infarction in Norway.

Jortveit J, Pripp AH, Halvorsen S
Aims
Primary percutaneous coronary intervention (pPCI) is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI) provided it can be performed within 120 min from diagnosis. However, it is unclear whether pPCI or a pharmaco-invasive (P-I) strategy is the best choice in patients who cannot receive timely pPCI. The aim of the present study was to compare outcomes after delayed and late pPCI vs. a P-I strategy in STEMI patients who did not receive timely pPCI.
Methods and results
All patients with STEMI registered in the Norwegian Myocardial Infarction Registry (NORMI) between 2013 and 2019, with ≤12 h from symptom onset to first medical contact and available timelines were included in the study. The primary outcome was all-cause mortality, and follow-up was through 2019. A total of 21 121 (27% of 78 368) STEMI patients were registered in the NORMI. Among patients who met the inclusion criteria, 7238 (54%) patients underwent timely pPCI, 1537 (11%) delayed pPCI (121-180 min), 1012 (7%) late pPCI (>180 min), and 2338 (17%) patients were treated with a P-I strategy. After a median follow-up time of 2.5 years, mortality was higher in the delayed pPCI [adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI) 1.0-1.5] and in the late pPCI group (adjusted HR 1.4, 95% CI 1.1-1.7) compared to the P-I strategy group, but bleeding complications were more frequent after P-I strategy.
Conclusions
In STEMI patients who did not receive timely percutaneous coronary intervention, a P-I strategy seemed to be associated with better long-term survival compared to delayed/late pPCI.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:442-451
Jortveit J, Pripp AH, Halvorsen S
Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:442-451 | PMID: 34038535
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Impact:
Abstract

Impact of chronic kidney disease on the pharmacodynamic and pharmacokinetic effects of ticagrelor in patients with diabetes mellitus and coronary artery disease.

Franchi F, Rollini F, Been L, Maaliki N, ... Bass TA, Angiolillo DJ
Aims
Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) are at increased risk of atherothrombotic events. Ticagrelor reduces ischaemic events compared to clopidogrel, with the greatest risk reduction in patients with both DM and CKD. How CKD status affects the pharmacodynamic (PD) and pharmacokinetic (PK) profiles of different ticagrelor maintenance dose regimens in patients with DM is unknown.
Methods and results
In this randomized, crossover study, patients with DM on treatment with dual antiplatelet therapy (aspirin and clopidogrel) were stratified according to CKD status and randomized to ticagrelor 90 or 60 mg bid. PK/PD assessments were performed at baseline, after 7-10 days of ticagrelor (peak and trough), and after 7-10 days of alternative ticagrelor regimen (peak and trough). PK assessments included plasma concentrations of ticagrelor and its major metabolite. PD assessments included vasodilator-stimulated phosphoprotein (VASP)-platelet reactivity index (PRI), VerifyNow P2Y12, and light transmittance aggregometry (LTA). A total of 92 patients with DM (CKD, n = 44; non-CKD, n = 48) were randomized. Levels of platelet reactivity were lower with the 90 mg compared with the 60 mg ticagrelor dose, which was statistically significant in non-CKD but not in CKD patients for most PD measures. There were no significant differences in the primary endpoint (trough levels of VASP-PRI following ticagrelor 90 mg dosing) between cohorts (31 ± 20 vs. 25 ± 14; P = 0.105). VerifyNow and LTA provided similar findings. PK assessments tracked PD profiles showing increased plasma concentrations of ticagrelor and its major metabolite in CKD compared to non-CKD patients.
Conclusion
In patients with DM, although ticagrelor maintenance dose regimens (60 and 90 mg) yield potent P2Y12 inhibition, levels of platelet reactivity tended to be higher and subject to broader variability in non-CKD compared with CKD patients.
Clinical trial registration
http://www.clinicaltrials.gov Unique Identifier: NCT02539160.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:452-461
Franchi F, Rollini F, Been L, Maaliki N, ... Bass TA, Angiolillo DJ
Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:452-461 | PMID: 34114623
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Impact:
Abstract

Efficacy and safety of dual-pathway inhibition in patients with cardiovascular disease: a meta-analysis of 49 802 patients from 7 randomized trials.

Galli M, Capodanno D, Benenati S, D\'Amario D, ... Andreotti F, Angiolillo DJ
Aims
Low-dose (LD) direct oral anticoagulants (DOACs) in adjunct to antiplatelet therapy, known as dual-pathway inhibition (DPI), have been tested to prevent ischaemic events in patients with cardiovascular disease (CVD). We conducted a systematic review and meta-analysis to determine the overall safety and efficacy of LD DOACs vs placebo on a background of antiplatelet therapy.
Methods and results
All randomized controlled trials (RCTs) comparing LD DOAC (defined as a dosage below the lowest approved for stroke prevention) vs placebo among patients with CVD receiving single or dual antiplatelet therapy (DAPT) in at least 50% of the population and followed for at least 6 months, were included. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were used to overcome different follow-up durations across trials. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint major bleeding. A pre-specified subgroup analysis was performed for different DOAC-dose regimens. A total of 49 802 patients from 7 RCTs were included. Low-dose DOACs vs placebo were associated with significant reductions in MACE (IRR 0.85, 95% CI 0.78-0.91, number needed to treat, NNT, 86) and myocardial infarction (IRR 0.86, 95% CI 0.78-0.95, NNT 355) and significant increases of major (IRR 2.05, 95% CI 1.50-2.80, number needed to harm, NNH, 89) or all bleeding (IRR 1.82, 95% CI 1.49-2.22, NNH 23). Cardiovascular death (IRR 0.90, 95% CI 0.79-1.03, NNT 784), intracranial (IRR 1.18, 95% CI 0.71-1.96, NNH 1810), and fatal bleeding (IRR 1.13, 95% CI 0.76-1.69, NNH 3170) did not differ significantly between strategies. Non-significant reductions of all-cause death (IRR 0.90, 95% CI 0.80-1.01, NNT 821) and stroke (IRR 0.73, 95% CI 0.53-1.01, NNT 315) favoured LD DOACs. Meta-regression analyses showed a significant interaction between percentage of DAPT use and increased risk of major bleeding (P = 0.04), intracranial haemorrhage (P = 0.035), and stroke (P = 0.0003). Subgroup analysis of very LD DOAC, defined as ≤1/3 of the lowest approved dose for stroke prevention (i.e. rivaroxaban 2.5 mg twice daily) seemed to mitigate the risk of bleeding without any trade-off in efficacy compared to other LD DOAC regimens.
Conclusions
In patients with CVD, LD DOAC vs placebo on a background of antiplatelet therapy, reduced ischaemic events at the expense of increased major and all bleeding, but without significantly increasing intracranial or fatal bleeds, while the reduction of cardiovascular or total mortality and stroke was not statistically significant. A DPI with very LD DOAC (i.e. rivaroxaban 2.5 mg twice daily) appeared particularly advantageous, especially when combined with a single antiplatelet agent and used among patients at high ischaemic and low bleeding risk.
Study registration
This study is registered in PROSPERO (CRD42021232744).

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:519-528
Galli M, Capodanno D, Benenati S, D'Amario D, ... Andreotti F, Angiolillo DJ
Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:519-528 | PMID: 34146091
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Impact:
Abstract

Low-dose rivaroxaban plus aspirin in patients with polypharmacy and multimorbidity: an analysis from the COMPASS trial.

Vanassche T, Verhamme P, Anand SS, Shestakovska O, ... Eikelboom JW, Bosch J
Aims
To analyse whether the benefits and risks of rivaroxaban plus aspirin vary in patients with comorbidities and receiving multiple drugs. In patients with coronary or peripheral artery disease, adding low-dose rivaroxaban to aspirin reduces cardiovascular events and mortality. Polypharmacy and multimorbidity are frequent in such patients.
Methods and results
We describe ischaemic events (cardiovascular death, stroke, or myocardial infarction) and major bleeding in participants from the randomized, double-blind COMPASS study by number of cardiovascular medications and concomitant medical conditions. We compared event rates and hazard ratios (HRs) for rivaroxaban plus aspirin vs. aspirin alone by the number of medications and concomitant conditions, and tested for interaction between polypharmacy or multimorbidity and the antithrombotic regimen. The risk of ischaemic events was higher in patients with more concomitant drugs (HR 1.7, 95% confidence interval 1.5-2.1 for >4 vs. 0-2) and with more comorbidities (HR 2.3, 1.8-2.1 for >3 vs. 0-1). Multimorbidity, but not polypharmacy, was associated with a higher risk of major bleeding. The relative efficacy, safety, and net clinical benefit of rivaroxaban were not affected by the number of drugs or comorbidities. Patients taking more concomitant medications derived the largest absolute reduction in the net clinical outcome with added rivaroxaban (1.1% vs. 0.4% reduction with >4 vs. 0-2 cardiovascular drugs, number needed to treat 91 vs. 250).
Conclusion
Adding low-dose rivaroxaban to aspirin resulted in benefits irrespective of the number of concomitant drugs or comorbidities. Multiple comorbidities and/or polypharmacy should not dissuade the addition of rivaroxaban to aspirin in otherwise eligible patients.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:462-473
Vanassche T, Verhamme P, Anand SS, Shestakovska O, ... Eikelboom JW, Bosch J
Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:462-473 | PMID: 34191011
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Impact:
Abstract

Concerns about the use of digoxin in acute coronary syndromes.

Bugiardini R, Cenko E, Yoon J, van der Schaar M, ... Badimon L, Manfrini O
Aims
The use of digitalis has been plagued by controversy since its initial use. We aimed to determine the relationship between digoxin use and outcomes in hospitalized patients with acute coronary syndromes (ACSs) complicated by heart failure (HF) accounting for sex difference and prior heart diseases.
Methods and results
Of the 25 187 patients presenting with acute HF (Killip class ≥2) in the International Survey of Acute Coronary Syndromes Archives (NCT04008173) registry, 4722 (18.7%) received digoxin on hospital admission. The main outcome measure was all-cause 30-day mortality. Estimates were evaluated by inverse probability of treatment weighting models. Women who received digoxin had a higher rate of death than women who did not receive it [33.8% vs. 29.2%; relative risk (RR) ratio: 1.24; 95% confidence interval (CI): 1.12-1.37]. Similar odds for mortality with digoxin were observed in men (28.5% vs. 24.9%; RR ratio: 1.20; 95% CI: 1.10-1.32). Comparable results were obtained in patients with no prior coronary heart disease (RR ratio: 1.26; 95% CI: 1.10-1.45 in women and RR ratio: 1.21; 95% CI: 1.06-1.39 in men) and those in sinus rhythm at admission (RR ratio: 1.34; 95% CI: 1.15-1.54 in women and RR ratio: 1.26; 95% CI: 1.10-1.45 in men).
Conclusion
Digoxin therapy is associated with an increased risk of early death among women and men with ACS complicated by HF. This finding highlights the need for re-examination of digoxin use in the clinical setting of ACS.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:474-482
Bugiardini R, Cenko E, Yoon J, van der Schaar M, ... Badimon L, Manfrini O
Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:474-482 | PMID: 34251454
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Impact:
Abstract

Incidence, associated outcomes, and predictors of upper gastrointestinal bleeding following acute myocardial infarction: a SWEDEHEART-based nationwide cohort study.

Sarajlic P, Simonsson M, Jernberg T, Bäck M, Hofmann R
Aims
Of all spontaneous bleeding complications in patients with acute myocardial infarction (MI), upper gastrointestinal bleeding (UGIB) is common and of specific interest since it could be prevented by several prophylactic measures. We aimed to determine the incidence, associated outcomes, and predictors of UGIB following acute MI.
Methods and results
All patients with acute MI enrolled in the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry from January 2007 to June 2016 and discharged alive on any antithrombotic therapy (n = 149 477) were followed regarding UGIB for 1 year. Associated outcomes were determined by Cox proportional hazards regression with UGIB as a time-dependent covariate, adjusting for baseline characteristics, invasive treatment, and medical treatment at discharge. Predictors of UGIB were determined by logistic regression and machine learning models.At 1 year, UGIB had occurred in 2230 patients (cumulative incidence 1.5%) and was significantly associated with an increased risk of all-cause death [hazard ratio (HR) 2.86, 95% confidence interval (CI) 2.58-3.16] and stroke (HR 1.80, 95% CI 1.32-2.45) but not with recurrent MI (HR 1.17, 95% CI 0.97-1.42). The most important predictors of UGIB were haemoglobin, age, systolic blood pressure, blood glucose, smoking status, previous upper gastrointestinal bleeding, and antithrombotic and gastroprotective treatment.
Conclusion
After acute MI, readmission because of UGIB is common and significantly associated with poor prognosis. By using machine learning in addition to traditional logistic regression, new predictors of UGIB, such as blood glucose and smoking status, were identified.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:483-491
Sarajlic P, Simonsson M, Jernberg T, Bäck M, Hofmann R
Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:483-491 | PMID: 34423350
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Impact:
Abstract

Guided and unguided de-escalation from potent P2Y12 inhibitors among patients with acute coronary syndrome: a meta-analysis.

Tavenier AH, Mehran R, Chiarito M, Cao D, ... Sharma SK, Dangas G
Aim
Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) intends to balance ischemic and bleeding risks. Various DAPT de-escalation strategies, defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. We aimed to compare DAPT de-escalation to standard DAPT with full-dose potent P2Y12 inhibitors in ACS patients who underwent PCI.
Methods and results
PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials. Aspirin monotherapy trials were excluded. Five randomized trials (n = 10 779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n = 1242; platelet function guided to clopidogrel n = 1304; unguided to clopidogrel n = 1672; unguided to lower dose n = 1170) vs. standard DAPT (control group n = 5391) were included in this analysis. DAPT de-escalation was associated with a significant reduction in Bleeding Academic Research Consortium ≥2 bleeding (HR 0.57, 95% CI 0.42-0.78; I2 = 77%) as well as major adverse cardiac events, represented in most trials by the composite of cardiovascular mortality, myocardial infarction, stent thrombosis, and stroke (HR 0.77, 95% CI 0.62-0.96; I2 = 0%). Notwithstanding the limited power, consistency was noted across various de-escalation strategies.
Conclusion
De-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing (PFT), was associated with lower rates of clinically relevant bleeding and ischemic events as compared to standard DAPT with potent P2Y12 inhibitors based on five open-label RCTs reviewed.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:492-502
Tavenier AH, Mehran R, Chiarito M, Cao D, ... Sharma SK, Dangas G
Eur Heart J Cardiovasc Pharmacother: 11 Aug 2022; 8:492-502 | PMID: 34459481
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Impact:
Abstract

Diagnostic accuracy of dynamic CZT-SPECT in coronary artery disease. A systematic review and meta-analysis.

Panjer M, Dobrolinska M, Wagenaar NRL, Slart RHJA
Background
With the appearance of cadmium-zinc-telluride (CZT) cameras, dynamic myocardial perfusion imaging (MPI) has been introduced, but comparable data to other MPI modalities, such as quantitative coronary angiography (CAG) with fractional flow reserve (FFR) and positron emission tomography (PET), are lacking. This study aimed to evaluate the diagnostic accuracy of dynamic CZT single-photon emission tomography (SPECT) in coronary artery disease compared to quantitative CAG, FFR, and PET as reference.
Materials and methods
Different databases were screened for eligible citations performing dynamic CZT-SPECT against CAG, FFR, or PET. PubMed, OvidSP (Medline), Web of Science, the Cochrane Library, and EMBASE were searched on the 5th of July 2020. Studies had to meet the following pre-established inclusion criteria: randomized controlled trials, retrospective trails or observational studies relevant for the diagnosis of coronary artery disease, and performing CZT-SPECT and within half a year the methodological references. Studies which considered coronary stenosis between 50% and 70% as significant based only on CAG were excluded. Data extracted were sensitivity, specificity, likelihood ratios, and diagnostic odds ratios. Quality was assessed with QUADAS-2 and statistical analysis was performed using a bivariate model.
Results
Based on our criteria, a total of 9 studies containing 421 patients were included. For the assessment of CZT-SPECT, the diagnostic value pooled analysis with a bivariate model was calculated and yielded a sensitivity of 0.79 (% CI 0.73 to 0.85) and a specificity of 0.85 (95% CI 0.74 to 0.92). Diagnostic odds ratio (DOR) was 17.82 (95% CI 8.80 to 36.08, P < 0.001). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 3.86 (95% CI 2.76 to 5.38, P < 0.001) and 0.21 (95% CI 0.13 to 0.33, P < 0.001), respectively.
Conclusion
Based on the results of the current systematic review and meta-analysis, dynamic CZT-SPECT MPI demonstrated a good sensitivity and specificity to diagnose CAD as compared to the gold standards. However, due to the heterogeneity of the methodologies between the CZT-SPECT MPI studies and the relatively small number of included studies, it warrants further well-defined study protocols.

© 2021. The Author(s).

J Nucl Cardiol: 01 Aug 2022; 29:1686-1697
Panjer M, Dobrolinska M, Wagenaar NRL, Slart RHJA
J Nucl Cardiol: 01 Aug 2022; 29:1686-1697 | PMID: 34350553
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Impact:
Abstract

Accuracy of Cardiac Magnetic Resonance Imaging in Diagnosing Pediatric Cardiac Masses: A Multicenter Study.

Beroukhim RS, Ghelani S, Ashwath R, Balasubramanian S, ... Valsangiacomo E, Geva T
Background
After diagnosis of a cardiac mass, clinicians must weigh the benefits and risks of ascertaining a tissue diagnosis. Limited data are available on the accuracy of previously developed noninvasive pediatric cardiac magnetic resonance (CMR)-based diagnostic criteria.
Objectives
The goals of this study were to: 1) evaluate the CMR characteristics of pediatric cardiac masses from a large international cohort; 2) test the accuracy of previously developed CMR-based diagnostic criteria; and 3) expand diagnostic criteria using new information.
Methods
CMR studies (children 0-18 years of age) with confirmatory histological and/or genetic diagnosis were analyzed by 2 reviewers, without knowledge of prior diagnosis. Diagnostic accuracy was graded as: 1) single correct diagnosis; 2) correct diagnosis among a differential; or 3) incorrect diagnosis.
Results
Of 213 cases, 174 (82%) had diagnoses that were represented in the previously published diagnostic criteria. In 70% of 174 cases, both reviewers achieved a single correct diagnosis (94% of fibromas, 71% of rhabdomyomas, and 50% of myxomas). When ≤2 differential diagnoses were included, both reviewers reached a correct diagnosis in 86% of cases. Of 29 malignant tumors, both reviewers indicated malignancy as a single diagnosis in 52% of cases. Including ≤2 differential diagnoses, both reviewers indicated malignancy in 83% of cases. Of 6 CMR sequences examined, acquisition of first-pass perfusion and late gadolinium enhancement were independently associated with a higher likelihood of a single correct diagnosis.
Conclusions
CMR of cardiac masses in children leads to an accurate diagnosis in most cases. A comprehensive imaging protocol is associated with higher diagnostic accuracy.

Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 01 Aug 2022; 15:1391-1405
Beroukhim RS, Ghelani S, Ashwath R, Balasubramanian S, ... Valsangiacomo E, Geva T
JACC Cardiovasc Imaging: 01 Aug 2022; 15:1391-1405 | PMID: 34419404
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Impact:
Abstract

Risk factors profile of young and older patients with myocardial infarction.

Sagris M, Antonopoulos AS, Theofilis P, Oikonomou E, ... Kaski JC, Tousoulis D
Myocardial infarction (MI) among young adults (<45 years) represents a considerable proportion of the total heart attack incidents. The underlying pathophysiologic characteristics, atherosclerotic plaque features, and risk factors profile differ between young and older patients with MI. This review article discusses the main differences between the younger and elderly MI patients as well as the different pathogenic mechanisms underlying the development of MI in the younger. Young patients with MI often have eccentric atherosclerotic plaques with inflammatory features but fewer lesions, and are more likely to be smokers, obese, and have poor lifestyle, such as inactivity and alcohol intake. Compared to older MI patients, younger are more likely to be men, have familial-combined hyperlipidaemia and increased levels of lipoprotein-a. In addition, MI in younger patients may be related to use of cannabis, cocaine use, and androgenic anabolic steroids. Genomic differences especially in the pathways of coagulation and lipid metabolism have also been identified between young and older patients with MI. Better understanding of the risk factors and the anatomic and pathophysiologic processes in young adults can improve MI prevention and treatment strategies in this patient group. Awareness could help identify young subjects at increased risk and guide primary prevention strategies. Additional studies focusing on gene pathways related to lipid metabolism, inflammation, and coagulation are needed.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Cardiovasc Res: 27 Jul 2022; 118:2281-2292
Sagris M, Antonopoulos AS, Theofilis P, Oikonomou E, ... Kaski JC, Tousoulis D
Cardiovasc Res: 27 Jul 2022; 118:2281-2292 | PMID: 34358302
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Impact:
Abstract

Left ventricular longitudinal strain alterations in asymptomatic or mildly symptomatic paediatric patients with SARS-CoV-2 infection.

Sirico D, Di Chiara C, Costenaro P, Bonfante F, ... Giaquinto C, Di Salvo G
Aims
Compared with adult patients, clinical manifestations of children\'s coronavirus disease-2019 (COVID-19) are generally perceived as less severe. The objective of this study was to evaluate cardiac involvement in previously healthy children with asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.
Methods and results
We analysed a cohort of 53 paediatric patients (29 males, 55%), mean age 7.5 ± 4.7 years, who had a confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or only mildly symptomatic for COVID-19. Patients underwent standard transthoracic echocardiogram and speckle tracking echocardiographic study at least 3 months after diagnosis. Thirty-two age, sex, and body surface area comparable healthy subjects were used as control group. Left ventricular ejection fraction was within normal limits but significantly lower in the cases group compared to controls (62.4 ± 4.1% vs. 65.2 ± 5.5%; P = 0.012). Tricuspid annular plane systolic excursion (20.1 ± 3 mm vs. 19.8 ± 3.4 mm; P = 0.822) and left ventricular (LV) global longitudinal strain (-21.9 ± 2.4% vs. -22.6 ± 2.5%; P = 0.208) were comparable between the two groups. Regional LV strain analysis showed a significant reduction of the LV mid-wall segments strain among cases compared to controls. Furthermore, in the cases group, there were 14 subjects (26%) with a regional peak systolic strain below -16% (-2.5 Z score in our healthy cohort) in at least two segments. These subjects did not show any difference regarding symptoms or serological findings.
Conclusion
SARS-CoV-2 infection may affect left ventricular deformation in 26% of children despite an asymptomatic or only mildly symptomatic acute illness. A follow-up is needed to verify the reversibility of these alterations and their impact on long-term outcomes.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Imaging: 21 Jul 2022; 23:1083-1089
Sirico D, Di Chiara C, Costenaro P, Bonfante F, ... Giaquinto C, Di Salvo G
Eur Heart J Cardiovasc Imaging: 21 Jul 2022; 23:1083-1089 | PMID: 34219155
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Impact:
Abstract

Cardiovascular events in patients with chronic myeloid leukaemia treated with tyrosine kinase inhibitors in Taiwan: a nationwide population-based study.

Yang YC, Huang RY, Tsai HJ, Li PC, Yang YH, Hsieh KP
Aims
New-generation breakpoint cluster region-Abelson tyrosine kinase inhibitors (TKIs) have a higher incidence of cardiovascular events than imatinib in patients with chronic myeloid leukaemia (CML). However, this knowledge is insufficiently proven. Hence, this study aimed to explore the association between cardiovascular events and TKIs in patients with CML.
Methods and results
This retrospective population-based cohort study enrolled first-time users of imatinib, dasatinib, and nilotinib between 1 January 2007 and 31 December 2016. Arterial thromboembolic events (ATEs) were the primary outcome, while other cardiovascular-related events were the secondary outcomes. The event rates were estimated using Kaplan-Meier estimates, and the hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. Additionally, the competing risk was adjusted using the Fine and Gray competing risk model. We included 1207 patients. Nilotinib had a significantly higher ATE risk (subdistribution HR = 4.92, 95% CI = 1.68-14.36) than imatinib. Conversely, no difference was found for other cardiovascular-related events. Risks of ATE and other cardiovascular-related events were similar between dasatinib and imatinib and between nilotinib and dasatinib. The risk of ATE hospitalization consistently increased throughout the main analyses and sensitivity analyses.
Conclusion
Nilotinib-treated patients had a significantly higher risk of developing ATE than imatinib-treated patients. However, the risks of ATE and other cardiovascular-related events were not significantly different between dasatinib and imatinib.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur J Prev Cardiol: 20 Jul 2022; 29:1312-1321
Yang YC, Huang RY, Tsai HJ, Li PC, Yang YH, Hsieh KP
Eur J Prev Cardiol: 20 Jul 2022; 29:1312-1321 | PMID: 34179961
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Impact:
Abstract

Cyclic GMP modulating drugs in cardiovascular diseases: mechanism-based network pharmacology.

Petraina A, Nogales C, Krahn T, Mucke H, ... Hobbs AJ, Schmidt HHHW
Mechanism-based therapy centred on the molecular understanding of disease-causing pathways in a given patient is still the exception rather than the rule in medicine, even in cardiology. However, recent successful drug developments centred around the second messenger cyclic guanosine-3\'-5\'-monophosphate (cGMP), which is regulating a number of cardiovascular disease modulating pathways, are about to provide novel targets for such a personalized cardiovascular therapy. Whether cGMP breakdown is inhibited or cGMP synthesis is stimulated via guanylyl cyclases or their upstream regulators in different cardiovascular disease phenotypes, the outcomes seem to be so far uniformly protective. Thus, a network of cGMP-modulating drugs has evolved that act in a mechanism-based, possibly causal manner in a number of cardiac conditions. What remains a challenge is the detection of cGMPopathy endotypes amongst cardiovascular disease phenotypes. Here, we review the growing clinical relevance of cGMP and provide a glimpse into the future on how drugs interfering with this pathway may change how we treat and diagnose cardiovascular diseases altogether.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Cardiovasc Res: 20 Jul 2022; 118:2085-2102
Petraina A, Nogales C, Krahn T, Mucke H, ... Hobbs AJ, Schmidt HHHW
Cardiovasc Res: 20 Jul 2022; 118:2085-2102 | PMID: 34270705
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Impact:
Abstract

Testosterone therapy and cardiovascular diseases.

Cittadini A, Isidori AM, Salzano A
Since it was first synthesized in 1935, testosterone (T) has been viewed as the mythical Fountain of Youth, promising rejuvenation, restoring sexual appetites, growing stronger muscles, and quicker thinking. T is endowed with direct effects on myocardial and vascular structure and function, as well as on risk factors for cardiovascular (CV) disease. Indeed, low serum T levels are a risk factor for diabetes, metabolic syndrome, inflammation, and dyslipidaemia. Moreover, many studies have shown that T deficiency per se is an independent risk factor of CV and all-cause mortality. On this background and due to direct-to-patient marketing by drug companies, we have witnessed to the widespread use of T replacement therapy without clear indications particularly in late-life onset hypogonadism. The current review will dwell upon current evidence and controversies surrounding the role of T in the pathophysiology of CV diseases, the link between circulating T levels and CV risk, and the use of replacing T as a possible adjuvant treatment in specific CV disorders. Specifically, recent findings suggest that heart failure and type 2 diabetes mellitus represent two potential targets of T therapy once that a state of hypogonadism is diagnosed. However, only if ongoing studies solve the CV safety issue the T orchid may eventually \'bloom\'.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Cardiovasc Res: 20 Jul 2022; 118:2039-2057
Cittadini A, Isidori AM, Salzano A
Cardiovasc Res: 20 Jul 2022; 118:2039-2057 | PMID: 34293112
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Impact:
Abstract

Using multimarker screening to identify biomarkers associated with cardiovascular death in patients with atrial fibrillation.

Pol T, Hijazi Z, Lindbäck J, Oldgren J, ... Siegbahn A, Wallentin L
Aims
Atrial fibrillation (AF) is associated with higher mortality. Biomarkers may improve the understanding of key pathophysiologic processes in AF that lead to death. Using a new multiplex analytic technique, we explored the association between 268 biomarkers and cardiovascular (CV) death in anticoagulated patients with AF.
Methods and results
A case-cohort design with 1.8- to 1.9-year follow-up. The identification cohort included 517 cases and 4057 randomly selected patients from ARISTOTLE. The validation cohort included 277 cases and 1042 randomly selected controls from RE-LY. Plasma collected at randomization was analysed with conventional immunoassays and the OLINK proximity extension assay panels: CVDII, CVDIII, and Inflammation. Association between biomarkers and CV death was evaluated using Random Survival Forest, Boruta, and adjusted Cox-regression analyses. The biomarkers most strongly and consistently associated with CV death were as follows (hazard ratio for inter-quartile comparison [95% CI]): N-terminal pro-B-type natriuretic peptide [NT-proBNP; 1.63 (1.37-1.93)], cardiac troponin T [cTnT-hs; 1.60 (1.35-1.88)], interleukin-6 [IL-6; 1.29 (1.13-1.47)], growth differentiation factor-15 [GDF-15; 1.30 (1.10-1.53)], fibroblast growth factor 23 [FGF-23; 1.21 (1.10-1.33)], urokinase receptor [uPAR; 1.38 (1.16-1.64)], trefoil factor 3 [TFF3; 1.27 (1.10-1.46)], tumour necrosis factor receptor 1 [TNFR1; 1.21 (1.01-1.45)], TNF-related apoptosis-inducing ligand receptor 2 [TRAILR2; 1.18 (1.04-1.34)], and cathepsin L1 [CTSL1; 1.22 (1.07-1.39)].
Conclusion
In this comprehensive screening of 268 biomarkers in anticoagulated patients with AF, the underlying mechanisms most strongly associated with CV death were cardiorenal dysfunction (NT-proBNP, cTnT-hs, CTSL1, TFF3), oxidative stress (GDF-15), inflammation (IL-6, GDF-15), calcium balance, vascular and renal dysfunction (FGF-23), fibrinolysis (suPAR), and apoptosis (TNFR1, TRAILR2). These findings provide novel insights into pathophysiologic aspects associated with CV death in AF.
Clinicaltrials.gov identifier
NCT00412984 and NCT00262600.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Cardiovasc Res: 20 Jul 2022; 118:2112-2123
Pol T, Hijazi Z, Lindbäck J, Oldgren J, ... Siegbahn A, Wallentin L
Cardiovasc Res: 20 Jul 2022; 118:2112-2123 | PMID: 34358298
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Impact:
Abstract

Left ventricular mass versus pulse wave velocity as predictors of coronary artery disease in hypertensive patients: data from a 6-year-follow-up study.

Andrikou I, Dimitriadis K, Konstantinidis D, Leontsinis I, ... Tousoulis D, Tsioufis C
In treated hypertensive patients, there is a substantial residual cardiovascular (CV) risk that cannot be assessed by the available prediction models. This risk can be associated with subclinical organ damage, such as increased left ventricular mass (LVM) and arterial stiffness. However, it remains unknown which of these two CV markers better predicts coronary artery disease (CAD). A prospective cohort study was used to answer the above question. The study sample consisted of 1033 patients with hypertension (mean age 55.6 years, 538 males) free of CAD at baseline, who were followed for a mean period of 6 years. At baseline, all subjects underwent a complete echocardiographic study and pulse wave velocity (PWV) measurement. Hypertensive individuals who developed CAD (2.8%) compared to those without CAD at follow-up, had a higher baseline LVM index (by 16.7 g/m2, p < 0.001), higher prevalence of left ventricular hypertrophy (LVH) (21% greater, p = 0.027) and greater prevalence of high PWV levels at baseline (21% greater, p = 0.019). Multivariate Cox regression analysis revealed that baseline age >65 years (HR = 2.067, p = 0.001), male gender (HR = 3.664, p = 0.001), baseline chronic kidney disease (HR = 2.020, p = 0.026), baseline diabetes mellitus (HR = 1.952, p = 0.015) and baseline LVH (HR = 2.124 p = 0.001) turned out to be independent predictors of CAD, whereas high PWV levels were not. LVH proved to be an independent prognosticator of CAD in contrast to arterial stiffness that was not related to CAD after accounting for established confounders. Therefore, LVM can reliably help physicians to identify high-risk hypertensives in whom an intensified therapeutic management is warranted.

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

J Hum Hypertens: 01 Jul 2022; 36:617-621
Andrikou I, Dimitriadis K, Konstantinidis D, Leontsinis I, ... Tousoulis D, Tsioufis C
J Hum Hypertens: 01 Jul 2022; 36:617-621 | PMID: 34326471
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Abstract

Coronary artery bypass grafting versus stent implantation in patients with chronic coronary syndrome and left main disease: insights from a register throughout Germany.

Stachon P, Kaier K, Hehn P, Peikert A, ... Bode C, von Zur Mühlen C
Background
Recent randomized controlled trials have sparked debate about the optimal treatment of patients suffering from left main coronary artery disease. The present study analyzes outcomes of left main stenting versus coronary bypass grafting (CABG) in a nationwide registry in patients with chronic coronary syndrome (CCS).
Methods
All cases suffering from CCS and left main coronary artery disease treated either with CABG or stent, were identified within the database of the German bureau of statistics. Logistic or linear regression models were used with 20 baseline patient characteristics as potential confounders to compare both regimens.
Results
In 2018, 1318 cases with left main stenosis were treated with CABG and 8,920 with stent. Patients assigned for stenting were older (72.58 ± 9.87 vs. 68.63 ± 9.40, p < 0.001) and at higher operative risk, as assessed by logistic EuroSCORE (8.77 ± 8.45 vs. 4.85 ± 4.65, p < 0.001). After risk adjustment, no marked differences in outcomes were found for in-hospital mortality and stroke (risk adjusted odds ratio (aOR) for stent instead of CABG: aOR mortality: 1.08 [95% CI 0.66; 1.78], p = 0.748; aOR stroke: 0.59 [0.27; 1.32], p = 0.199). Stent implantation was associated with a reduced risk of relevant bleeding (aOR 0.38 [0.24; 0.61], p < 0.001), reduced prolonged ventilation time (aOR 0.54 [0.37 0.79], p = 0.002), and postoperative delirium (aOR 0.16 [0.11; 0.22], p < 0.001). Furthermore, stent implantation was associated with shorter hospital stay (- 6.78 days [- 5.86; - 7.71], p < 0.001) and lower costs (- €10,035 [- €11,500; - €8570], p < 0.001).
Conclusion
Left main stenting is a safe and effective treatment option for CCS-patients suffering from left main coronary artery disease at reasonable economic cost. Coronary artery bypass grafting versus stent implantation in patients with chronic coronary syndrome and left main disease: insights from a register throughout Germany. All cases with chronic coronary syndrome and left main stenosis treated in 2018 in Germany either with left main stenting or coronary bypass grafting were extracted from a nation-wide database. In-hospital outcomes were compared after logistic regression analysis.

© 2021. The Author(s).

Clin Res Cardiol: 01 Jul 2022; 111:742-749
Stachon P, Kaier K, Hehn P, Peikert A, ... Bode C, von Zur Mühlen C
Clin Res Cardiol: 01 Jul 2022; 111:742-749 | PMID: 34453576
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Abstract

Prevalence of hypertension mediated organ damage in subjects with high-normal blood pressure without known hypertension as well as cardiovascular and kidney disease.

Maloberti A, Rebora P, Occhino G, Alloni M, ... Valsecchi MG, Giannattasio C
Purpose of our study was to assess the prevalence of hypertension mediated organ damage (HMOD) in healthy subjects with high-normal Blood Pressure (BP) comparing them with subjects with BP values that are considered normal (<130/85 mmHg) or indicative of hypertension (≥140/90 mmHg). Seven hundred fifty-five otherwise healthy subjects were included. HMOD was evaluated as pulse wave velocity (PWV), left ventricular mass index (LVMI), and carotid intima-media thickness (IMT) and plaque. When subjects were classified according to BP levels we found that the high-normal BP group showed intermediate values of PWV and higher values of IMT. This corresponds to intermediate prevalence of arterial stiffness, while there were no differences for increased IMT or carotid plaque. No subjects showed left ventricular hypertrophy. At multivariable analysis, the odds of having arterial stiffness or carotid HMOD in the high-normal group resulted not different to the normal group. In conclusion, in our otherwise healthy population, high-normal BP values were not related to aortic, carotid or cardiac HMOD.

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

J Hum Hypertens: 01 Jul 2022; 36:610-616
Maloberti A, Rebora P, Occhino G, Alloni M, ... Valsecchi MG, Giannattasio C
J Hum Hypertens: 01 Jul 2022; 36:610-616 | PMID: 34493835
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Abstract

Treatment of atrial fibrillation with doxapram: TASK-1 potassium channel inhibition as a novel pharmacological strategy.

Wiedmann F, Beyersdorf C, Zhou XB, Kraft M, ... Katus HA, Schmidt C
Aims
TASK-1 (K2P3.1) two-pore-domain potassium channels are atrial-specific and significantly up-regulated in atrial fibrillation (AF) patients, contributing to AF-related electrical remodelling. Inhibition of TASK-1 in cardiomyocytes of AF patients was shown to counteract AF-related action potential duration shortening. Doxapram was identified as a potent inhibitor of the TASK-1 channel. In this study, we investigated the antiarrhythmic efficacy of doxapram in a porcine model of AF.
Methods and results
Doxapram successfully cardioverted pigs with artificially induced episodes of AF. We established a porcine model of persistent AF in domestic pigs via intermittent atrial burst stimulation using implanted pacemakers. All pigs underwent catheter-based electrophysiological investigations prior to and after 14 days of doxapram treatment. Pigs in the treatment group received intravenous administration of doxapram once per day. In doxapram-treated AF pigs, the AF burden was significantly reduced. After 14 days of treatment with doxapram, TASK-1 currents were still similar to values of sinus rhythm animals. Doxapram significantly suppressed AF episodes and normalized cellular electrophysiology by inhibition of the TASK-1 channel. Patch-clamp experiments on human atrial cardiomyocytes, isolated from patients with and without AF could reproduce the TASK-1 inhibitory effect of doxapram.
Conclusion
Repurposing doxapram might yield a promising new antiarrhythmic drug to treat AF in patients.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Cardiovasc Res: 22 Jun 2022; 118:1728-1741
Wiedmann F, Beyersdorf C, Zhou XB, Kraft M, ... Katus HA, Schmidt C
Cardiovasc Res: 22 Jun 2022; 118:1728-1741 | PMID: 34028533
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Impact:
Abstract

Efficacy and safety of direct oral anticoagulant in morbidly obese patients with atrial fibrillation: systematic review and meta-analysis.

Thangjui S, Kewcharoen J, Yodsuwan R, Trongtorsak A, ... Winans ARM, Bischof E
Aims
We conducted a systematic review and meta-analysis on three outcomes. We assessed the efficacy and safety of direct oral anticoagulants (DOAC) compared to vitamin K antagonists (VKA) in morbidly obese patients with atrial fibrillation (AF). We compared the efficacy and safety of DOAC in obese patients and non-obese patients with AF. Finally, we updated the current knowledge of outcomes of AF patients with obesity compared with normal-weight patients regardless of anticoagulation type.
Methods and results
Using PubMed and Embase, we searched for literature published from inception to August 2020 for studies conducted in morbidly obese patients with AF who used DOACs and/or VKA for stroke or systemic embolism (stroke/SE) prevention that report efficacy and/or safety data. GRADE assessment was performed to determine the quality of the meta-analysis results. Direct oral anticoagulant was not statistically different from VKA in reducing stroke/SE with relative risk (RR) of 0.85 [95% confidence interval (CI): 0.56-1.29; very low certainty evidence]. Major bleeding risk was lower in the DOAC groups with RR of 0.62 (95% CI: 0.48-0.80; low certainty evidence). Obese patients with AF who used DOACs had lower risk of stroke/SE and similar major bleeding risk compared to non-obese patients with RR of 0.77 (95% CI: 0.70-0.84; low certainty evidence) and 1.02 (95% CI: 0.94-1.09; low certainty evidence), respectively. Obese patients with AF who used any type of anticoagulant had lower risk of stroke/SE compared to normal-weight patients with RR of 0.62 (95% CI: 0.57-0.69; low certainty evidence).
Conclusion
The use of DOACs in morbidly obese patients may be reasonable if needed, and more dedicated studies are needed to make a more robust recommendation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Pharmacother: 08 Jun 2022; 8:325-335
Thangjui S, Kewcharoen J, Yodsuwan R, Trongtorsak A, ... Winans ARM, Bischof E
Eur Heart J Cardiovasc Pharmacother: 08 Jun 2022; 8:325-335 | PMID: 33730164
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Impact:
Abstract

Anticoagulation in atrial fibrillation and liver disease: a pooled-analysis of >20 000 patients.

Chen S, Pürerfellner H, Meyer C, Sommer P, ... Chun JKR, Schmidt B
Aims
Anticoagulation for atrial fibrillation patients with liver disease represents a clinical dilemma. We sought to evaluate the efficacy/safety of different anticoagulation, i.e. vitamin K antagonist (VKA) and non-VKA oral anticoagulants (NOACs) in such patient group.
Methods and results
This was a pooled-analysis enrolling up-to-date clinical data. Two subsets: subset A (VKA vs. Non-Anticoagulation) and subset B (NOACs vs. VKA) were pre-specified. The study outcomes were ischaemic stroke (IS)/thromboembolism (TE), major bleeding (MB), intracranial bleeding (ICB), gastrointestinal bleeding (GIB), and all-cause mortality. A total of 20 042 patients\' data were analysed (subset A: N = 10 275, subset B: N = 9767). Overall mean age: 71 ± 11 years, mean CHA2DS2-VASc score: 4.0 ± 1.8, mean HAS-BLED score: 3.6 ± 1.2. The majority of the patients had Child-Pugh category (A-B). As compared with Non-Anticoagulation, VKA seemed to reduce the risk of IS/TE [odds ratio (OR): 0.60, P = 0.05], but heighten the risk of all-bleeding events including MB (OR: 2.81, P = 0.01), ICB (OR: 1.60, P = 0.01), and GIB (OR: 3.32, P = 0.01). When compared with VKA, NOACs had similar efficacy in reducing the risk of IS/TE (OR: 0.82, P = 0.64), significantly lower risk of MB (OR: 0.54, P = 0.0003) and ICB (OR: 0.35, P < 0.0001), and trend towards reduced risk of GIB (OR: 0.72, P = 0.12) and all-cause mortality (OR: 0.79, P = 0.35). The favourable effects were maintained in subgroups of individual NOAC.
Conclusions
VKA appears to reduce the risk of IS/TE but increase all-bleeding events. NOACs have similar effect in reducing the risk of IS/TE and have significantly lower risk of MB and ICB as compared with VKA. NOACs seem to be associated with better clinical outcome than VKA in patients with mild-moderate liver disease.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Pharmacother: 08 Jun 2022; 8:336-345
Chen S, Pürerfellner H, Meyer C, Sommer P, ... Chun JKR, Schmidt B
Eur Heart J Cardiovasc Pharmacother: 08 Jun 2022; 8:336-345 | PMID: 33871577
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Impact:
Abstract

Weekend vs. weekday admission and clinical outcomes in heart failure patients with and without atrial fibrillation in Taiwan.

Hu WS, Lin CL
Aims
We conducted this study to explore the associations of weekend and weekday admission with the clinical events among heart failure (HF) patients with and without comorbid atrial fibrillation (AF).
Methods and results
In this study, we recruited 57 919 HF patients without AF hospitalized on weekends and 57 919 HF patients without AF hospitalized on weekdays. There were 21407 and 21407 HF patients with AF hospitalized on weekends and weekdays, respectively. The outcomes of interest included all-cause mortality, cardiovascular (CV) death, and HF recurrence requiring admission. The Cox proportional hazard regression model was applied to estimate the hazard ratio. Variables found to be statistically significant in a univariable Cox proportional hazard regression model were further examined in a multivariable Cox proportional hazard regression model. The cumulative incidence curves were obtained by the Kaplan-Meier method and assessed by the log-rank test. HF patients with AF and hospitalized on weekends had the highest incidence rates of rehospitalization due to HF (233.8 per 1000 person-years) and CV death (23.9 per 1000 person-years) among four groups. The Kaplan-Meier method shows that HF patients with AF had the higher cumulative incidence of rehospitalization due to HF than the patients without AF.
Conclusion
HF patients with AF and hospitalized on weekends are at highest risk of HF recurrence requiring hospitalization among these four groups.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 08 Jun 2022; 8:346-352
Hu WS, Lin CL
Eur Heart J Cardiovasc Pharmacother: 08 Jun 2022; 8:346-352 | PMID: 34180528
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Impact:
Abstract

Oral antithrombotic therapy for the prevention of recurrent cerebrovascular events.

Capodanno D, Angiolillo DJ
Stroke is frequently a disabling and even life-threatening condition that has an ischaemic cause in most cases. Transient ischaemic attack (TIA) is a lower risk condition that still exposes to the risk of future major cardiovascular events. The causes of stroke can be classified as cardioembolic disease, large vessel disease, small vessel disease, undetermined, or others. Cardioembolic disease and atherothrombosis of large arteries are the most common underlying processes of ischaemic stroke and TIA. Therefore, antithrombotic therapy is a central strategy in the pharmacological management of these patients. However, because antithrombotic therapy provides ischaemic protection at the price of increased bleeding, defining the fine balance between efficacy and safety is a clinical challenge. Numerous trials have recently defined the current indications to the use of anticoagulant and antiplatelet therapy in patients with various subtypes of ischaemic stroke or TIA. In this review, we provide an updated appraisal of the currently available evidence on the use of various oral antithrombotic agents for prevention of recurrent events after an ischaemic stroke or TIA.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 08 Jun 2022; 8:383-391
Capodanno D, Angiolillo DJ
Eur Heart J Cardiovasc Pharmacother: 08 Jun 2022; 8:383-391 | PMID: 34374741
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Abstract

Discontinuation of direct oral anticoagulants among patients with atrial fibrillation according to gender and cohabitation status: a nationwide cohort study.

Binding C, Olesen JB, Lee CJ, Lip GYH, ... Gislason G, Bonde AN
Aims
The aim of this study was to evaluate the risk of discontinuing treatment with direct oral anticoagulants (DOACs) among patients with atrial fibrillation (AF) according to cohabitation status and gender.
Methods and results
Using the Danish national registers, we identified 32 364 patients with AF aged 40-90 years undergoing treatment with DOACs. The study period was from 2013 to 2017, and patients were followed for 2 years, or until death, outcome, or emigration. The main outcome was discontinuation of DOAC treatment for at least 30 days. The absolute 2-year risk of DOAC discontinuation was highest among men living alone [35.7%, 95% confidence interval (CI): 37.3-34.1%]. Men living alone had a 4.6% (95% CI: 6.4-2.8%) higher absolute risk of discontinuation and a 12% [hazard ratio (HR): 1.12, 95% CI: 1.04-1.20] higher relative risk of discontinuation compared with men living with a partner. Female patients living alone likewise had a higher absolute risk of DOAC discontinuation (2.6%, 95% CI: 4.4-0.09%) compared with female patients living with a partner, yet no statistically significant difference in relative risk. In an analysis evaluating gender, we found male gender to be associated with a significantly higher relative risk of DOAC discontinuation (HR: 1.33, 95% CI: 1.26-1.40) compared with female gender (P-value for interaction with cohabitant status = 0.5996).
Conclusion
In this nationwide population study, male gender and living alone were associated with a higher risk of DOAC discontinuation among patients with AF.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 08 Jun 2022; 8:353-362
Binding C, Olesen JB, Lee CJ, Lip GYH, ... Gislason G, Bonde AN
Eur Heart J Cardiovasc Pharmacother: 08 Jun 2022; 8:353-362 | PMID: 34415024
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Impact:
Abstract

Persistence of uncontrolled hypertension post-cardiac rehabilitation in stable coronary patients.

Denolle T, Pellen C, Serandour AL, Lebreton S, Revault d\'Allonnes F
In stable coronary heart disease, uncontrolled risk factors are strongly associated with incident myocardial infarction. We analysed the management of hypertension in 746 stable coronary patients recruited between 2005 and 2015 in a single-centre prospective study. Risk factors and pharmacological treatments were documented prior to and immediately after cardiac rehabilitation, and 1 year later. One year post-cardiac rehabilitation, all cardiovascular risk factors were significantly better controlled with the notable exception of hypertension: blood pressure (BP) <140/90 mmHg in 60% of the total population vs 49% (N = 450) of hypertensive patients (20% or 10%, according to the ACC/AHA 2017 or ESH/ESC guidelines, respectively). Of those who had achieved normotension by the end of cardiac rehabilitation, 42% had uncontrolled hypertension again 1 year later; in addition, body weight had increased, while physical activity and antihypertensive drug use had dropped (differences between controlled or uncontrolled hypertension at 1 year post-cardiac rehabilitation, NS). Three factors were correlated with BP elevations: discontinuation of betablockade: +7.9 mmHg; age >65 years: +6.2 mmHg; diabetes mellitus: +7.6 mmHg. Only 48% hypertensive patients were on guideline-recommended antihypertensive polytherapy. Although 28% were still hypertensive post-cardiac rehabilitation, and hypertension remained uncontrolled in 70% 1 year later, 61% antihypertensive prescriptions were not adjusted post-cardiac rehabilitation. One year post-cardiac rehabilitation, hypertension was the only cardiovascular risk factor that had not improved. This can be attributed to three main reasons, all associated with BP elevations: precipitous reduction in betablockade, physicians\' inertia when faced with uncontrolled hypertension and lack of adherence to international guidelines.

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

J Hum Hypertens: 01 Jun 2022; 36:537-543
Denolle T, Pellen C, Serandour AL, Lebreton S, Revault d'Allonnes F
J Hum Hypertens: 01 Jun 2022; 36:537-543 | PMID: 33963270
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Impact:
Abstract

Left atrial strain by speckle tracking predicts atrial fibrosis in patients undergoing heart transplantation.

Lisi M, Mandoli GE, Cameli M, Pastore MC, ... Mondillo S, Henein MY
Aims
In patients with heart failure (HF), chronically raised left ventricular (LV) filling pressures lead to progressive left atrial (LA) dysfunction and fibrosis. We aimed to assess the correlation of LA reservoir strain (peak atrial longitudinal strain, PALS) by speckle tracking echocardiography (STE) and LA fibrosis assessed by myocardial biopsy in patients undergoing heart transplantation (HTx).
Methods and results
Forty-eight patients with advanced HF [mean age 51.2 ± 8.1 years, 29% females; LV ejection fraction ≤25% and New York Heart Association (NYHA) class III-IV] referred for HTx were enrolled and underwent pre-operative echocardiographic evaluation, right heart catheterization, and cardiopulmonary exercise testing. Exclusion criteria were non-sinus rhythm, mechanical ventilation, severe mitral/tricuspid regurgitation, or other valvular disease and poor acoustic window. After HTx, LA bioptic samples were collected and analysed to determine the extent of myocardial fibrosis (%). LA fibrosis showed correlation with PALS (R = -0.88, P < 0.0001), VO2max (R = -0.68, P < 0.0001), NYHA class (R = 0.66, P < 0.0001), LA stiffness (R = 0.58, P = 0.0002), and E/e\' (R = 0.44, P = 0.005), while poorly correlated with E/A ratio (R = 0.23, P = 0.21). PALS had a good correlation with NYHA class (R = -0.64, P < 0.0001), PAoP (R = -0.61, P = 0.03) and VO2max (R = 0.57, P = 0.0001). Multivariate regression analysis identified PALS (beta = -0.91, P < 0.001) and LA Volume (beta = -0.19, P = 0.03) as predictors of LA Fibrosis, while E/e\' was not a significant predictor (beta = 0.15, P = 0.08).
Conclusion
Emerging as a possible index of myocardial fibrosis in patients with advanced HF, PALS could help to optimize the management and the selection of those patients with irreversible LA structural damage for advanced therapeutic strategies.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Imaging: 01 Jun 2022; 23:829-835
Lisi M, Mandoli GE, Cameli M, Pastore MC, ... Mondillo S, Henein MY
Eur Heart J Cardiovasc Imaging: 01 Jun 2022; 23:829-835 | PMID: 34118154
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Abstract

Risk predicting for acute coronary syndrome based on machine learning model with kinetic plaque features from serial coronary computed tomography angiography.

Wang Y, Chen H, Sun T, Li A, ... Wang X, Cao F
Aims
More patients with suspected coronary artery disease underwent coronary computed tomography angiography (CCTA) as gatekeeper. However, the prospective relation of plaque features to acute coronary syndrome (ACS) events has not been previously explored.
Methods and results
One hundred and one out of 452 patients with documented ACS event and received more than once CCTA during the past 12 years were recruited. Other 101 patients without ACS event were matched as case control. Baseline, follow-up, and changes of anatomical, compositional, and haemodynamic parameters [e.g. luminal stenosis, plaque volume, necrotic core, calcification, and CCTA-derived fractional flow reserve (CT-FFR)] were analysed by independent CCTA measurement core laboratories. Baseline anatomical, compositional, and haemodynamic parameters of lesions showed no significant difference between the two cohorts (P > 0.05). While the culprit lesions exhibited significant increase of luminal stenosis (10.18 ± 2.26% vs. 3.62 ± 1.41%, P = 0.018), remodelling index (0.15 ± 0.14 vs. 0.09 ± 0.01, P < 0.01), and necrotic core (4.79 ± 1.84% vs. 0.43 ± 1.09%, P = 0.019) while decrease of CT-FFR (-0.05 ± 0.005 vs. -0.01 ± 0.003, P < 0.01) and calcium ratio (-4.28 ± 2.48% vs. 4.48 ± 1.46%, P = 0.004) between follow-up CCTA and baseline scans in comparison to that of non-culprit lesion. The XGBoost model comprising the top five important plaque features revealed higher predictive ability (area under the curve 0.918, 95% confidence interval 0.861-0.968).
Conclusions
Dynamic changes of plaque features are highly relative with subsequent ACS events. The machine learning model of integrating these lesion characteristics (e.g. CT-FFR, necrotic core, remodelling index, plaque volume, and calcium) can improve the ability for predicting risks of ACS events.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Imaging: 01 Jun 2022; 23:800-810
Wang Y, Chen H, Sun T, Li A, ... Wang X, Cao F
Eur Heart J Cardiovasc Imaging: 01 Jun 2022; 23:800-810 | PMID: 34151931
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Abstract

Aortic enlargement and coronary artery calcification in a general population cohort.

Ballegaard CR, Pham MHC, Sigvardsen PE, Kühl JT, ... Køber LV, Kofoed KF
Aims
The role of atherosclerosis in the pathogenesis of aortic enlargement is uncertain. We aimed to evaluate the relationship between the diameters of the ascending, descending and abdominal aorta, and coronary artery calcification.
Methods and results
Individuals in the Copenhagen General Population Study underwent thoracic and abdominal computed tomography. Maximal aortic diameters were measured in each aortic segment and coronary artery calcium scores (CACS) were calculated. Participants were stratified into five predefined groups according to CACSs and compared to aortic dimensions. The relation between aortic diameter and CACS was adjusted for risk factors for aortic dilatation in a multivariable model. A total of 2678 eligible individuals were included. In all segments of the aorta, aortic diameter was associated to CACSs, with mean increases in aortic diameters ranging from 0.7 to 3.5 mm in individuals with calcified coronary arteries compared to non-calcified subjects (P-value < 0.001). After correction for risk factors, individuals with CACS above 400 had larger ascending, descending and abdominal aortic diameter than the non-calcified reference group (P-value < 0.01).
Conclusion
Enlarged thoracic and abdominal aortic vascular segments are associated with co-existing coronary artery calcification in the general population.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur Heart J Cardiovasc Imaging: 01 Jun 2022; 23:855-862
Ballegaard CR, Pham MHC, Sigvardsen PE, Kühl JT, ... Køber LV, Kofoed KF
Eur Heart J Cardiovasc Imaging: 01 Jun 2022; 23:855-862 | PMID: 34166489
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Abstract

2D high resolution vs. 3D whole heart myocardial perfusion cardiovascular magnetic resonance.

Nazir MS, Shome J, Villa ADM, Ryan M, ... Chiribiri A, Plein S
Aims
Developments in myocardial perfusion cardiovascular magnetic resonance (CMR) allow improvements in spatial resolution and/or myocardial coverage. Whole heart coverage may provide the most accurate assessment of myocardial ischaemic burden, while high spatial resolution is expected to improve detection of subendocardial ischaemia. The objective of this study was to compare myocardial ischaemic burden as depicted by 2D high resolution and 3D whole heart stress myocardial perfusion in patients with coronary artery disease.
Methods and results
Thirty-eight patients [age 61 ± 8 (21% female)] underwent 2D high resolution (spatial resolution 1.2 mm2) and 3D whole heart (in-plane spatial resolution 2.3 mm2) stress CMR at 3-T in randomized order. Myocardial ischaemic burden (%) was visually quantified as perfusion defect at peak stress perfusion subtracted from subendocardial myocardial scar and expressed as a percentage of the myocardium. Median myocardial ischaemic burden was significantly higher with 2D high resolution compared with 3D whole heart [16.1 (2.0-30.6) vs. 13.4 (5.2-23.2), P = 0.004]. There was excellent agreement between myocardial ischaemic burden (intraclass correlation coefficient 0.81; P < 0.0001), with mean ratio difference between 2D high resolution vs. 3D whole heart 1.28 ± 0.67 (95% limits of agreement -0.03 to 2.59). When using a 10% threshold for a dichotomous result for presence or absence of significant ischaemia, there was moderate agreement between the methods (κ = 0.58, P < 0.0001).
Conclusion
2D high resolution and 3D whole heart myocardial perfusion stress CMR are comparable for detection of ischaemia. 2D high resolution gives higher values for myocardial ischaemic burden compared with 3D whole heart, suggesting that 2D high resolution is more sensitive for detection of ischaemia.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Imaging: 01 Jun 2022; 23:811-819
Nazir MS, Shome J, Villa ADM, Ryan M, ... Chiribiri A, Plein S
Eur Heart J Cardiovasc Imaging: 01 Jun 2022; 23:811-819 | PMID: 34179941
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Abstract

The Impact of Persistent Smoking After Surgery on Long-term Outcomes After Stage I Non-small Cell Lung Cancer Resection.

Heiden BT, Eaton DB, Chang SH, Yan Y, ... Kozower BD, Puri V
Background
Smoking at the time of surgical treatment for lung cancer increases the risk for perioperative morbidity and mortality. The prevalence of persistent smoking in the postoperative period and its association with long-term oncologic outcomes are poorly described.
Research question
What is the relationship between persistent smoking and long-term outcomes in early-stage lung cancer after surgical treatment?
Study design and methods
We performed a retrospective cohort study using a uniquely compiled Veterans Health Administration dataset of patients with clinical stage I non-small cell lung cancer (NSCLC) undergoing surgical treatment between 2006 and 2016. We defined persistent smoking as individuals who continued smoking 1 year after surgery and characterized the relationship between persistent smoking and disease-free survival and overall survival.
Results
This study included 7,489 patients undergoing surgical treatment for clinical stage I NSCLC. Of 4,562 patients (60.9%) who were smoking at the time of surgery, 2,648 patients (58.0%) continued to smoke at 1 year after surgery. Among 2,927 patients (39.1%) who were not smoking at the time of surgical treatment, 573 (19.6%) relapsed and were smoking at 1 year after surgery. Persistent smoking at 1 year after surgery was associated with significantly shorter overall survival (adjusted hazard ration [aHR], 1.291; 95% CI, 1.197-1.392; P < .001). However, persistent smoking was not associated with inferior disease-free survival (aHR, 0.989; 95% CI, 0.884-1.106; P = .84).
Interpretation
Persistent smoking after surgery for stage I NSCLC is common and is associated with inferior overall survival. Providers should continue to assess smoking habits in the postoperative period given its disproportionate impact on long-term outcomes after potentially curative treatment for early-stage lung cancer.

Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Chest: 01 Jun 2022; 161:1687-1696
Heiden BT, Eaton DB, Chang SH, Yan Y, ... Kozower BD, Puri V
Chest: 01 Jun 2022; 161:1687-1696 | PMID: 34919892
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Abstract

Functional capacity assessment and Minimal Clinically Important Difference in post-acute cardiac patients: the role of Short Physical Performance Battery.

Rinaldo L, Caligari M, Acquati C, Nicolazzi S, ... Marcassa C, Corrà U
Background
The Short Physical Performance Battery (SPPB) test is a well-established tool to assess physical performance, and to identify frail patients. Assessment of the SPPB in a specific population of elder patients in cardiac rehabilitation phase after a cardiac event is missing.
Aim
The aim of this study was to correlate SPPB and the cardiac rehabilitation outcome in a group of elder patients after a cardiac event and to identify the Minimal Clinically Important Difference (MCID) of the SPPB.
Methods
Consecutive (n = 392) patients aged ≥75 years, in the rehabilitation phase after cardiac surgery (70.1%), congestive heart failure (7.4%), or acute coronary syndrome (22.5%), were enrolled. SPPB was performed twice: on admission and discharge. The MCID was assessed with the \'anchor method\', and the Patient Global Impression of Change was employed as the anchor.
Results
On admission, SPPB classified 56, 117, 116, and 94 patients as severe, moderate, mild, or minimal/no limitations, respectively. Patients with the lower SPPB had the longer length of stay, and the higher complications rate. At receiver operating characteristic analysis, an SPPB improvement >1 was identified as the MCID (area-under-curve 0.77, 95% CI 0.67-0.85). Overall, 285 patients (74.2%) had a \'clinically significant\' improvement in SPPB, with a rate of improvement higher in patients with severe/moderate limitations (83.0%) and lower in those with mild (78.9%) or minimal/no limitations (53.6%).
Conclusion
A lower SPPB score is associated with a higher complications rate in the post-acute phase. An improvement >1 point of SPPB was identified as the MCID; this reference value could serve as the goal for rehabilitation interventions.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur J Prev Cardiol: 25 May 2022; 29:1008-1014
Rinaldo L, Caligari M, Acquati C, Nicolazzi S, ... Marcassa C, Corrà U
Eur J Prev Cardiol: 25 May 2022; 29:1008-1014 | PMID: 33846721
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Abstract

Anxa1 in smooth muscle cells protects against acute aortic dissection.

Zhou C, Lin Z, Cao H, Chen Y, ... Pan B, Zheng L
Aims
Acute aortic dissection (AAD) is a life-threatening disease with high morbidity and mortality. Previous studies have showed that vascular smooth muscle cell (VSMC) phenotype switching modulates vascular function and AAD progression. However, whether an endogenous signalling system that protects AAD progression exists remains unknown. Our aim is to investigate the role of Anxa1 in VSMC phenotype switching and the pathogenesis of AAD.
Methods and results
We first assessed Anxa1 expression levels by immunohistochemical staining in control aorta and AAD tissue from mice. A strong increase of Anxa1 expression was seen in the mouse AAD tissues. In line with these findings, micro-CT scan results indicated that Anxa1 plays a role in the development of AAD in our murine model, with systemic deficiency of Anxa1 markedly progressing AAD. Conversely, administration of Anxa1 mimetic peptide, Ac2-26, rescued the AAD phenotype in Anxa1-/- mice. Transcriptomic studies revealed a novel role for Anxa1 in VSMC phenotype switching, with Anxa1 deficiency triggering the synthetic phenotype of VSMCs via down-regulation of the JunB/MYL9 pathway. The resultant VSMC synthetic phenotype rendered elevated inflammation and enhanced matrix metalloproteinases (MMPs) production, leading to augmented elastin degradation. VSMC-restricted deficiency of Anxa1 in mice phenocopied VSMC phenotype switching and the consequent exacerbation of AAD. Finally, our studies in human AAD aortic specimens recapitulated key findings in murine AAD, specifically that the decrease of Anxa1 is associated with VSMC phenotype switch, heightened inflammation, and enhanced MMP production in human aortas.
Conclusions
Our findings demonstrated that Anxa1 is a novel endogenous defender that prevents AAD by inhibiting VSMC phenotype switching, suggesting that Anxa1 signalling may be a potential target for AAD pharmacological therapy.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Cardiovasc Res: 06 May 2022; 118:1564-1582
Zhou C, Lin Z, Cao H, Chen Y, ... Pan B, Zheng L
Cardiovasc Res: 06 May 2022; 118:1564-1582 | PMID: 33757117
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Abstract

Role of oxidative stress in calcific aortic valve disease and its therapeutic implications.

Greenberg HZE, Zhao G, Shah AM, Zhang M
Calcific aortic valve disease (CAVD) is the end result of active cellular processes that lead to the progressive fibrosis and calcification of aortic valve leaflets. In western populations, CAVD is a significant cause of cardiovascular morbidity and mortality, and in the absence of effective drugs, it will likely represent an increasing disease burden as populations age. As there are currently no pharmacological therapies available for preventing, treating, or slowing the development of CAVD, understanding the mechanisms underlying the initiation and progression of the disease is important for identifying novel therapeutic targets. Recent evidence has emerged of an important causative role for reactive oxygen species (ROS)-mediated oxidative stress in the pathophysiology of CAVD, inducing the differentiation of valve interstitial cells into myofibroblasts and then osteoblasts. In this review, we focus on the roles and sources of ROS driving CAVD and consider their potential as novel therapeutic targets for this debilitating condition.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Cardiovasc Res: 06 May 2022; 118:1433-1451
Greenberg HZE, Zhao G, Shah AM, Zhang M
Cardiovasc Res: 06 May 2022; 118:1433-1451 | PMID: 33881501
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Abstract

Burden of cardiovascular risk factors and disease in five Asian groups in Catalonia: a disaggregated, population-based analysis of 121 000 first-generation Asian immigrants.

Satish P, Vela E, Bilal U, Cleries M, ... Mauri J, Cainzos-Achirica M
Aims
To evaluate the burden of cardiovascular risk factors and disease (CVD) among five Asian groups living in Catalonia (Spain): Indian, Pakistani, Bangladeshi, Filipino, and Chinese.
Methods and results
Retrospective cohort study using the Catalan Health Surveillance System database including 42 488 Pakistanis, 40 745 Chinese, 21 705 Indians, 9544 Filipinos, and 6907 Bangladeshis; and 5.3 million native individuals (\'locals\'). We estimated the age-adjusted prevalence (as of 31 December 2019) and incidence (during 2019) of diabetes, hypertension, hyperlipidaemia, obesity, tobacco use, coronary heart disease (CHD), cerebrovascular disease, atrial fibrillation, and heart failure (HF). Bangladeshis had the highest prevalence of diabetes (17.4% men, 22.6% women) followed by Pakistanis. Bangladeshis also had the highest prevalence of hyperlipidaemia (23.6% men, 18.3% women), hypertension among women (24%), and incident tobacco use among men. Pakistani women had the highest prevalence of obesity (28%). For CHD, Bangladeshi men had the highest prevalence (7.3%), followed by Pakistanis (6.3%); and Pakistanis had the highest prevalence among women (3.2%). For HF, the prevalence in Pakistani and Bangladeshi women was more than twice that of locals. Indians had the lowest prevalence of diabetes across South Asians, and of CHD across South Asian men, while the prevalence of CHD among Indian women was twice that of local women (2.6% vs. 1.3%). Filipinos had the highest prevalence of hypertension among men (21.8%). Chinese men and women had the lowest prevalence of risk factors and CVD.
Conclusions
In Catalonia, preventive interventions adapted to the risk profile of different Asian immigrant groups are needed, particularly for Bangladeshis and Pakistanis.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur J Prev Cardiol: 06 May 2022; 29:916-924
Satish P, Vela E, Bilal U, Cleries M, ... Mauri J, Cainzos-Achirica M
Eur J Prev Cardiol: 06 May 2022; 29:916-924 | PMID: 33969397
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Abstract

Effects of intensive urate lowering therapy with febuxostat in comparison with allopurinol on pulse wave velocity in patients with gout and increased cardiovascular risk: the FORWARD study.

Desideri G, Rajzer M, Gerritsen M, Nurmohamed MT, ... Tausche AK, Borghi C
Aims
Hyperuricaemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. This study aimed to assess whether febuxostat and allopurinol could differently influence carotid-femoral pulse wave velocity (cfPWV) in patients with gout and elevated serum uric acid (SUA) levels.
Methods and results
A multi-centre, multinational, phase IV, randomized, parallel-group, active-controlled, open-label trial with blind endpoints evaluation. One hundred and ninety-seven adults with gout and SUA levels ≥8 mg/dL were randomized to febuxostat or allopurinol in a 1:1 ratio for 36 weeks. The primary outcome was the comparison of the effects of febuxostat and allopurinol on changes in cfPWV. The mean cfPWV values at randomization and Week 36 were 8.69 and 9.00 m/s, respectively for subjects randomized to febuxostat and 9.02 and 9.05 m/s for subjects randomized to allopurinol. No statistically significant changes in cfPWV by treatment assignment were observed at any time point for any of the assessed parameters. More subjects who received febuxostat had serum urate concentrations ≤6 mg/dL following treatment (78.3% vs. 61.1% at Week 36, P = 0.0137). Treatment-emergent adverse events were reported by 51 (52.0%) patients randomized to febuxostat and 63 (62.5%) patients randomized to allopurinol. The majority of events were mild in both treatment groups and included gout flares and arthralgia.
Conclusion
In patients with gout and elevated SUA levels the arterial stiffness remained stable both with febuxostat and allopurinol. Febuxostat was more effective and faster than allopurinol in achieving the SUA target. Both treatments were safe and well tolerated.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021.

Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:236-242
Desideri G, Rajzer M, Gerritsen M, Nurmohamed MT, ... Tausche AK, Borghi C
Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:236-242 | PMID: 33410912
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