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BACKGROUND: We aimed to study the effect of social containment mandates on ACS presentation during COVID-19 pandemic using location activity and mobility data from mobile phone map services. METHODS: We conducted a cross-sectional study using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) including all ACS presentations during the pandemic until May 07, 2020. Using a count regression model, we adjusted for day of the week, daily weather, and incidence of COVID-19. RESULTS: A 10% increase in activity around areas of residence was associated with 38% lower rates of ACS hospitalisations whereas increased activity relating to retail and recreation, grocery stores and pharmacies, workplaces as well as mode of mobility was associated with 10-20% higher rates of ACS hospitalisations. CONCLUSION: Government policy regarding social containment mandates has important public health implications for medical emergencies like ACS and may explain the decline in ACS presentations observed during COVID-19 pandemic.

Objective Patients with rheumatoid arthritis (RA) are at increased risk of coronary artery disease (CAD) and seem to develop more severe acute coronary syndromes (ACS) than the general population. Because few studies have investigated the CAD distribution in the context of acute or stable CAD in RA, the objective was to investigate whether this risk is due to a different distribution and severity of coronary stenoses (versus non-RA), resulting in clinical manifestation of CAD. Methods We performed a population-based study using linkages of nationwide clinical, health, and demographics registers. We compared 1 cohort of patients with RA, and 1 matched cohort of patients without RA, undergoing a first coronary angiography from 2006 through 2015. Cardiovascular (CV) characteristics and the presence and distribution of clinically significant stenoses were compared (through odds ratios [ORs]), stratified by indication (stable CAD, ST-elevation myocardial infarction [STEMI], and non–ST-elevation ACS [NSTACS]), using logistic regression. Results We identified 2,985 patients with RA and 10,290 patients without RA who underwent a first coronary angiography. A higher proportion of patients with RA (75% versus 69%) had STEMI and NSTACS as indication for angiography. We found no difference in the presence and distribution of clinically significant coronary stenoses in RA compared with the patients without RA, regardless of the CAD type (for having any significant stenosis in stable CAD OR 0.9, STEMI OR 0.8, and NSTACS OR 1.1), stratification by RA duration, sex, or burden of concomitant CV risk factors. Conclusion Although RA may accelerate the development of clinical CAD events, the underlying angiographic characteristics are similar to those in patients without RA.

BACKGROUND: Potent antithrombotic therapy has significantly improved prognosis for patients with acute myocardial infarction (AMI), however, at a price of increased bleeding risk. Chronic gastric infection with Helicobacter pylori (Hp) commonly causes upper gastrointestinal bleeding and is proposed as a risk factor for subsequent bleeding post AMI. The prevalence of active Hp in a current AMI population and the feasibility of Hp screening as part of routine clinical care are unclear. OBJECTIVE: To determine the prevalence of active Hp infection in a contemporary AMI cohort and to establish the feasibility of Hp diagnosis as part of routine clinical MI care. DESIGN: Multicenter, prospective cohort study. SETTING: Two university hospitals in Stockholm, Sweden. PARTICIPANTS: Patients admitted for AMI between November 6, 2019 and April 4, 2020. After written informed consent, Hp diagnostics was performed with a bedside urea breath test (Diabact, Mayoly Spindler) incorporated into routine care during the hospitalization period. EXPOSURE: Positive test for Hp infection. MAIN OUTCOMES AND MEASURES: The primary outcome was the prevalence of Hp infection. Secondary aims included predictive factors in patient characteristics and outcomes which were obtained from linkage with national registries. Predefined subgroup analyses included stratification for proton pump inhibitor use and infarct type. RESULTS: Three hundred and ten consecutive AMI patients (median age 67; 23% female; 41% ST-elevation MI [STEMI]) were enrolled. Overall, the Hp prevalence was 20% (95%CI, 15.5-24.7). Hp positive status was significantly more common in smokers compared with nonsmokers (36% vs 21%, respectively; P < .05) and in patients presenting with STEMI compared with Non-STEMI (26% vs 15%, respectively; P = .02). The latter observation remained significant after multivariable adjustment. After exclusion of 97 subjects with current proton pump inhibitor use, the Hp prevalence was 24% (95%CI, 18.9

AIMS: To assess the real-world clinical performance of a sirolimus-eluting ultrathin-strut drug-eluting stent (DES) [Orsiro, Biotronik AG] in a large nationwide cohort of patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: From the Swedish Coronary Angiography and Angioplasty Registry, the 2-year outcomes of 4,561 patients implanted with Orsiro (Orsiro group) and 69,570 receiving other newer generation DES (n-DES group) were analyzed. The rate of definite stent thrombosis was low in both groups (0.67% and 0.83% for Orsiro and n-DES, respectively; adjusted hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.55-1.46, p-value 0.66). Restenosis was also infrequent (1.5% versus 2.0% with Orsiro and n-DES, adjusted HR 0.81, 95% CI 0.63-1.03, p-value=0.09). The risk of target lesion revascularization by PCI was lower in the Orsiro group (1.6% versus 2.3%, adjusted HR 0.75, 95% CI 0.60-0.94, p-value=0.013). All-cause mortality and myocardial infarction did not show a statistically significant difference between the two groups (mortality of 7.5% in both groups, adjusted HR 0.99, 95% CI 0.72-1.35, p-value=0.94; 6.0% versus 5.2% for myocardial infarction, adjusted HR 1.19, 95% CI 1.00-1.43, p-value=0.06). CONCLUSIONS: In a nationwide scenario, the use of a sirolimus-eluting ultrathin-strut DES portended favorable clinical outcomes.

AIMS: Clinical trials have demonstrated that a reduction in low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular (CV) events. This has, however, not yet been shown in a real-world setting. We aimed to investigate the association between LDL-C changes and statin intensity with prognosis after a myocardial infarction (MI). METHODS AND RESULTS: Patients admitted with MI were followed for mortality and major CV events. Changes in LDL-C between the MI and a 6- to 10-week follow-up visit were analysed. The associations between quartiles of LDL-C change and statin intensity with outcomes were assessed using adjusted Cox regression analyses. A total of 40 607 patients were followed for a median of 3.78 years. The median change in LDL-C was a 1.20 mmol/L reduction. Patients with larger LDL-C reduction (1.85 mmol/L, 75th percentile) compared with a smaller reduction (0.36 mmol/L, 25th percentile) had lower hazard ratios (HR) for all outcomes (95% confidence interval): composite of CV mortality, MI, and ischaemic stroke 0.77 (0.70-0.84); all-cause mortality 0.71 (0.63-0.80); CV mortality 0.68 (0.57-0.81); MI 0.81 (0.73-0.91); ischaemic stroke 0.76 (0.62-0.93); heart failure hospitalization 0.73 (0.63-0.85), and coronary artery revascularization 0.86 (0.79-0.94). Patients with ≥50% LDL-C reduction using high-intensity statins at discharge had a lower incidence of all outcomes compared with those using a lower intensity statin. CONCLUSIONS: Larger early LDL-C reduction and more intensive statin therapy after MI were associated with a reduced hazard of all CV outcomes and all-cause mortality. This supports clinical trial data suggesting that earlier lowering of LDL-C after an MI confers the greatest benefit.

Objectives To analyze the clinical outcome of percutaneous coronary intervention (PCI) using the Xience drug eluting stent (DES) versus other modern DES. Methods This retrospective study based on the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) analyzed the outcome of PCI using Xience versus other commonly used modern DES, 2007 to 2017. The primary outcome measure was a combination of all-cause death, myocardial infarction (MI) and revascularisation with PCI. Angiographical outcome measures were in-stent restenosis (ISR) and stent thrombosis (ST). Results Rates of the primary outcome measure for Xience and other DES were 31.9% and 28.2% respectively, adjusted hazard ratio (HR) 0.99 (95% CI 0.95-1.03). Crude rates of ISR were 2.9% versus 2.1% over 4.3 and 2.9 years respectively, adjusted HR 0.93 (95% CI 0.81-1.06). Crude rates of ST were 0.9% versus 0.7%, adjusted HR 1.07 (95% CI 0.82-1.39). Results were consistent in all sensitivity analyses. Conclusions This nationally complete, real-world study confirms that Xience is a safe and effective DES with low-event rates of ISR and ST. Compared with a control group containing a large proportion of thinner strut stents and absorbable polymers, Xience exhibits similar results in all important clinical endpoint

Background Health checks can detect risk factors and initiate prevention of cardiovascular diseases but there is no consensus on how to communicate the results. The aim of this study was to investigate the preferences of the general population for communicating health check results. Methods A randomly selected sample of the Swedish population aged 40-70 years completed a discrete choice experiment survey that included questions on sociodemographics, lifestyle and health and 15 choice questions consisting of six attributes (written results, notification method, consultation time, waiting time, lifestyle recommendation and cost). Data were analyzed with a latent class analysis (LCA). Relative importance of the attributes and predicted uptake for several scenarios were estimated. Results In the analysis, 432 individuals were included (response rate 29.6%). A three-class LCA model best fit the data. Cost was the most important attribute in all classes. Preferences heterogeneity was found for the other attributes; in Class 1, receiving consultation time and the written results were important, respondents in Class 2 dominated on costs and respondents in Class 3 found consultation time, waiting time and lifestyle recommendations to be important. Health literate respondents were more likely to belong to Class 3. The predicted uptake rates ranged from 7 to 88% for different health checks with large differences across the classes. Conclusion Cost was most important when deciding whether to participate in a health check. Although cost was the most important factor, it is not sufficient to offer health checks free-of-charge if other requirements regarding how the test results are communicated are not in place; participants need to be able to understand their results.

Aims Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown. Methods and results We explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality. Conclusion The NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.

BACKGROUND: Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y12-inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy-Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry). METHODS: In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days. RESULTS: Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment-elevation MI were randomized to receive bivalirudin or heparin. The mean age was 66.8 years. According to protocol recommendations, 87% were treated with potent oral P2Y12-inhibitors before start of angiography and radial access was used in 90%. GPI was used in 51 (3.4%) and 74 (4.9%) of patients randomized to receive bivalirudin and heparin, respectively. The primary end point occurred in 12.5% (187 of 1501) and 13.0% (196 of 1504; hazard ratio [HR], 0.95 [95% CI, 0.78-1.17], P=0.64) with consistent results in all major subgroups. All-cause death occurred in 3.9% versus 3.9% (HR, 1.00 [0.70-1.45], P=0.98), MI in 1.7% versus 2.2% (HR, 0.76 [0.45-1.28], P=0.30), major bleeding in 8.3% versus 8.0% (HR, 1.04 [0.81-1.33], P=0.78), and definite stent thrombosis in 0.5% versus 1.3% (HR, 0.42 [0.18-0.96], P=0.04). CONCLUSIONS: In patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with radial access and receiving current recommended treatments with potent P2Y12-inhibitors rate of the composite of all-caus

Background The purpose of this study is to investigate the impact of oxygen therapy on cardiovascular outcomes in relation to sex in patients with confirmed myocardial infarction (MI). Methods The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction trial randomized 6,629 patients to oxygen at 6 L/min for 6-12 hours or ambient air. In the present subgroup analysis including 5,010 patients (1,388 women and 3,622 men) with confirmed MI, we report the effect of supplemental oxygen on the composite of all-cause death, rehospitalization with MI, or heart failure at long-term follow-up, stratified according to sex. Results Event rate for the composite endpoint was 18.1% in women allocated to oxygen, compared to 21.4% in women allocated to ambient air (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.65-1.05). In men, the incidence was 13.6% in patients allocated to oxygen compared to 13.3% in patients allocated to ambient air (HR 1.03, 95% CI 0.86-1.23). No significant interaction in relation to sex was found ( P = .16). Irrespective of allocated treatment, the composite endpoint occurred more often in women compared to men (19.7 vs 13.4%, HR 1.51; 95% CI, 1.30-1.75). After adjustment for age alone, there was no difference between the sexes (HR 1.06, 95% CI 0.91-1.24), which remained consistent after multivariate adjustment. Conclusion Oxygen therapy in normoxemic MI patients did not significantly affect all-cause mortality or rehospitalization for MI or heart failure in women or men. The observed worse outcome in women was explained by differences in baseline characteristics, especially age. (Am Heart J 2021;237:13 & ndash;24.), Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [VR20130307]; Swedish HeartLung FoundationSwedish Heart-Lung Foundation [HLF 2018-0187]; Region Stockholm [K 2017-4577]

Background: The clinical importance of intraprocedural stent thrombosis (IPST) during percutaneous coronary intervention in the contemporary era of potent oral P2Y12 inhibitors is not established. The aim of this study was to assess IPST and its association with clinical outcome in patients with myocardial infarction undergoing percutaneous coronary intervention with contemporary antithromboticmedications. Methods and Results: The VALIDATE-SWEDEHEART study (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) included 6006 patients with myocardial infarction, treated with potent P2Y12 inhibitors during percutaneous coronary intervention. IPST, defined as a new or worsening thrombus related to a stent deployed during the procedure, was reported by the interventional cardiologist in 55 patients (0.9%) and was significantly associated with ST-segment elevation myocardial infarction presentation, longer stents, bailout glycoprotein IIb/IIIa inhibitors, and final Thrombolysis in Myocardial Infarction flow <3. The primary composite end point included cardiovascular death, myocardial infarction, out-of-laboratory definite stent thrombosis and target vessel revascularization within 30 days. Secondary end points were major bleeding and the individual components of the primary composite end point. Patients with versus without IPST had significantly higher rates of the primary composite end point (20.0% versus 4.4%), including higher rates of cardiovascular death, target vessel revascularization, and definite stent thrombosis, but not myocardial infarction or major bleeding. By multivariable analysis, IPST was independently associated with the primary composite end point (hazard ratio, 3.82; 95% CI, 2.05-7.12; P<0.001). Conclusions: I, Funding agencies:Thorsten Westerstrom's Research FoundationSixten Gemzeus Research FoundationUlla Ekdahl's Research Foundation

Part of "Debate: Prasugrel rather than ticagrelor is the preferred treatment for NSTE-ACS patients who proceed to PCI and pretreatment should not be performed in patients planned for an early invasive strategy: Introduction"

Previous studies have demonstrated superior patency of no-touch as compared to conventional saphenous vein grafts in coronary artery bypass grafting. We aimed to compare mid-term clinical outcomes of both techniques in a large cohort of routine patients. We identified all patients undergoing nonemergent primary coronary artery bypass grafting with either no-touch or conventional saphenous vein grafts at our institution between 2000 and 2020. Propensity score matching was used to create adjusted cohorts based on 5288 eligible patients. The primary outcome was the combined endpoint of all-cause mortality and repeat revascularization. Secondary outcomes were individual rates of all-cause mortality and repeat revascularization, surgical complications, and short-term mortality. Propensity score matching resulted in cohorts of no-touch (n = 923) and conventional (n = 923) saphenous vein grafted patients with comparable baseline characteristics. Mean follow-up time was significantly shorter for the no-touch compared to the conventional cohort (4.9 ± 2.3 vs 8.3 ± 2.6 years, P < 0.001). Up to 7-year follow-up, neither the rate of the primary composite endpoint nor death differed significantly between the cohorts. The rate of repeat revascularization was significantly higher in patients in the no-touch cohort (12.9% vs 9.3% at 7-year follow-up, P = 0.022. Post-hoc analysis of percutaneous coronary intervention during follow-up revealed comparable rates of saphenous vein graft failure (no-touch 42/923 (4.6%) vs conventional 32/923 (3.5%), P = 0.286). In this large propensity score matched registry study, coronary artery bypass with no-touch compared to conventional saphenous vein grafting did neither enhance mid-term survival nor reduce the rate of repeat revascularization.

Prior trials of dual antiplatelet therapy excluded patients with moderate ischemic stroke. These patients were included in the Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial, but results have not been reported separately, raising concerns about safety and efficacy in this subgroup. To evaluate the efficacy and safety of ticagrelor plus aspirin in patients with moderate ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 4 to 5). The THALES trial was a randomized trial conducted at 414 hospitals in 28 countries in January 2018 and December 2019. This exploratory analysis compared patients with moderate stroke (baseline NIHSS score of 4 to 5) with patients with less severe stroke (NIHSS score of 0 to 3). A total of 9983 patients with stroke were included in the present analysis, after excluding 2 patients with NIHSS scores greater than 5 and 1031 patients with transient ischemic attack. Data were analyzed from March to April 2021. Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily on days 2 to 30) or placebo within 24 hours after symptom onset. All patients received aspirin, 300 to 325 mg, on day 1 followed by aspirin, 75 to 100 mg, daily on days 2 to 30. Patients were observed for 30 additional days. The primary outcome was time to stroke or death within 30 days. The primary safety outcome was time to severe bleeding. In total, 3312 patients presented with moderate stroke and 6671 presented with less severe stroke. Of those in the moderate stroke group, 1293 (39.0%) were female, and the mean (SD) age was 64.5 (10.8) years; of those in the less severe stroke group, 2518 (37.7%) were female, and the mean (SD) age was 64.8 (11.2) years. The observed primary outcome event rate in patients with moderate stroke was 7.6% (129 of 1671) for those in the ticagrelor group and 9.1% (150 of 1641) for those in the placebo group (hazard ratio, 0.84; 95% CI, 0.6

During four decades, the ECG limb lead display has differed between Sweden and the rest of the world. In the classical, or international, display, the limb leads are presented in two groups in non-contiguous order: I, II, III, and aVR, aVL, aVF. When ECG recording and presentation was standardized in Sweden, a joint decision between several medical specialty associations was made to use the so-called Cabrera presentation, in which limb leads are presented in contiguous order: aVL, I, -aVR, II, aVF and III. This presentation is logical and easily understood., Original article in Swedish

BACKGROUND: Left ventricular ejection fraction (LVEF) affects outcome of valve replacement (AVR) in aortic stenosis (AS). The study aim was to investigate the prognostic importance of concomitant cardiovascular disease in relation to preoperative LVEF. METHODS AND RESULTS: All adult patients undergoing AVR due to AS 2008-2014 in a national register for heart diseases were included. All-cause mortality and hospitalization for heart failure during follow-up after AVR, stratified by preserved or reduced LVEF (=50%), was derived from national patient registers and analyzed by Cox regression.During the study period 10,406 patients, median age 73 years, a median follow-up of 35 months were identified. Preserved LVEF was present in 7,512 (72.2%). Among them 647 (8.6%) had a history of heart failure (HF) and 1,099 (14.6%) atrial fibrillation (AF) before intervention. Preoperative HF was associated with higher mortality irrespective of preserved or reduced LVEF: Hazard Ratio (HR) 1.64 (95% C.I. 1.35 -1.99) and 1.58 (95% C.I. 1.30 -1.92). Prior AF was associated with a higher risk of mortality in patients with preserved but not in those with reduced LVEF: HR 1.62 (95% C.I. 1.36 -1.92) and 1.05 (95% C.I. 0.86 -1.28). Irrespective of LVEF preoperative HF and AF were associated with an increased risk of postoperative heart failure hospitalization. CONCLUSION: In patients planned for AVR, a history of HF or AF, irrespective of LVEF, worsens the postoperative prognosis. HF and AF can be seen as markers of myocardial fibrosis not necessarily discovered by LVEF and the merely use of it, besides symptoms, for timing of AVR seems suboptimal.

BACKGROUND: The Second Primary Angioplasty in Myocardial Infarction (PAMI-II) risk score is recommended by guidelines to identify low-risk patients with ST-elevation myocardial infarction (STEMI) for an early discharge strategy. AIMS: We aimed to assess the safety of early discharge (≤2 days) for low-risk STEMI treated with primary percutaneous coronary intervention (PCI). METHODS: Using nationwide data from the SWEDEHEART registry we identified patients with STEMI treated with primary PCI during 2009-2017 of whom 8092 (26.4%) were identified as low risk with the PAMI-II score. Low risk patients were stratified according to their length of hospital stay (≤2 days vs. >2 days) The main endpoint was major adverse cardiovascular events (MACE) including death, reinfarction treated with PCI, stroke or heart failure hospitalization) at one year using a Cox proportional hazard model with propensity score as well as an inverse probability weighting propensity score of average treatment effect to adjust for confounders. RESULTS: There were 1449 (17.9%) patients discharged ≤2 days of admission. After adjustment, the 1-year MACE rate were not higher for patients discharged at >2 days from admission than patients discharged ≤2 days (4.3% vs. 3.2%; adjusted HR, 1.31 [95% CI, 0.92-1.87, p=0.14]) and no difference were observed regarding any of the individual components of the main outcome. Results were consistent across all subgroups with no difference in MACE between early and late discharge patients. CONCLUSIONS: Nationwide observational data suggests that early discharge of low-risk patients with STEMI treated with PCI is not associated with an increase in 1-year MACE.

Background and Purpose: In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack, the THALES trial (Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo. The primary efficacy outcome of THALES included hemorrhagic stroke and death, events also counted in the primary safety outcome. We sought to disentangle risk and benefit, assess their relative impact, and attempt to identify subgroups with disproportionate risk or benefit. Methods: In a randomized, placebo-controlled, double-blind trial of patients with mild-to-moderate acute noncardioembolic ischemic stroke or high-risk transient ischemic attack, patients were randomized within 24 hours after symptom onset to a 30-day regimen of either ticagrelor plus aspirin or matching placebo plus aspirin. For the present analyses, we defined the efficacy outcome, major ischemic events, as the composite of ischemic stroke or nonhemorrhagic death, and defined the safety outcome, major hemorrhage, as intracranial hemorrhage or hemorrhagic death. Net clinical impact was defined as the combination of these 2 end points. Results: In 11 016 patients (5523 ticagrelor-aspirin and 5493 aspirin), a major ischemic event occurred in 294 patients (5.3%) in the ticagrelor-aspirin group and in 359 patients (6.5%) in the aspirin group (absolute risk reduction 1.19% [95% CI, 0.31%-2.07%]). Major hemorrhage occurred in 22 patients (0.4%) in the ticagrelor-aspirin group and 6 patients (0.1%) in the aspirin group (absolute risk increase 0.29% [95% CI, 0.10%-0.48%]). Net clinical impact favored ticagrelor-aspirin (absolute risk reduction 0.97% [95% CI, 0.08%-1.87%]). Findings were similar when different thresholds for disability were applied and over a range of predefined subgroups. Conclusions: In patients with mild

Importance: Prior trials of dual antiplatelet therapy excluded patients with moderate ischemic stroke. These patients were included in the Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial, but results have not been reported separately, raising concerns about safety and efficacy in this subgroup. Objective: To evaluate the efficacy and safety of ticagrelor plus aspirin in patients with moderate ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 4 to 5). Design, Setting, and Participants: The THALES trial was a randomized trial conducted at 414 hospitals in 28 countries in January 2018 and December 2019. This exploratory analysis compared patients with moderate stroke (baseline NIHSS score of 4 to 5) with patients with less severe stroke (NIHSS score of 0 to 3). A total of 9983 patients with stroke were included in the present analysis, after excluding 2 patients with NIHSS scores greater than 5 and 1031 patients with transient ischemic attack. Data were analyzed from March to April 2021. Interventions: Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily on days 2 to 30) or placebo within 24 hours after symptom onset. All patients received aspirin, 300 to 325 mg, on day 1 followed by aspirin, 75 to 100 mg, daily on days 2 to 30. Patients were observed for 30 additional days. Main Outcomes and Measures: The primary outcome was time to stroke or death within 30 days. The primary safety outcome was time to severe bleeding. Results: In total, 3312 patients presented with moderate stroke and 6671 presented with less severe stroke. Of those in the moderate stroke group, 1293 (39.0%) were female, and the mean (SD) age was 64.5 (10.8) years; of those in the less severe stroke group, 2518 (37.7%) were female, and the mean (SD) age was 64.8 (11.2) years. The observed primary outcome event rate in patients with moderate stroke was 7.6% (129 of 1671) for those

AIMS: The aim of this article was to compare rates of all-cause death at 10 years following coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in patients with or without diabetes. METHODS AND RESULTS: The SYNTAXES study evaluated up to 10-year survival of 1800 patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) randomized to receive either PCI or CABG in the SYNTAX trial. Ten-year all-cause death according to diabetic status and revascularization strategy was examined. In diabetics (n = 452), the risk of mortality was numerically higher with PCI compared with CABG at 5 years [19.6% vs. 13.3%, hazard ratio (HR): 1.53, 95% confidence interval (CI): 0.96, 2.43, P = 0.075], with the opposite seen between 5 and 10 years (PCI vs. CABG: 20.8% vs. 24.4%, HR: 0.82, 95% CI: 0.52, 1.27, P = 0.366). Irrespective of diabetic status, there was no significant difference in all-cause death at 10 years between patients receiving PCI or CABG, the absolute treatment difference was 1.9% in diabetics (PCI vs. CABG: 36.4% vs. 34.5%, difference: 1.9%, 95% CI: -7.6%, 11.1%, P = 0.551). Among insulin-treated patients (n = 182), all-cause death at 10 years was numerically higher with PCI (47.9% vs. 39.6%, difference: 8.2%, 95% CI: -6.5%, 22.5%, P = 0.227). CONCLUSIONS: The treatment effects of PCI vs. CABG on all-cause death at 10 years in patients with 3VD and/or LMCAD were similar irrespective of the presence of diabetes. There may, however, be a survival benefit with CABG in patients with insulin-treated diabetes. The association between revascularization strategy and very long-term ischaemic and safety outcomes for patients with diabetes needs further investigation in dedicated trials. TRIAL REGISTRATION: SYNTAX: ClinicalTrials.gov reference: NCT00114972 and SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.

Physical activity may prevent anxiety, but the importance of exercise intensity, sex-specific mechanisms, and duration of the effects remains largely unknown. We used an observational study design to follow 395,369 individuals for up to 21 years to investigate if participation in an ultralong-distance cross-country ski race (Vasaloppet, up to 90 km) was associated with a lower risk of developing anxiety. Skiers in the race and matched non-skiers from the general population were studied after participation in the race using the Swedish population and patient registries. Skiers (n = 197,685, median age 36 years, 38% women) had a significantly lower risk of developing anxiety during the follow-up compared to non-skiers (adjusted hazard ratio, HR 0.42). However, among women, higher physical performance (measured as the finishing time to complete the race, a proxy for higher exercise dose) was associated with an increased risk of anxiety compared to slower skiing women (HR 2.00). For men, the finishing time of the race did not significantly impact the risk of anxiety. Our results support the recommendations of engaging in physical activity to decrease the risk of anxiety in both men and women. The impact of physical performance level on the risk of anxiety requires further investigations among women.

Purpose of Review We assessed the differences in the 2020 European Society of Cardiology (ESC) versus 2015 ESC and 2014 American College of Cardiology (ACC) guidelines on the management of non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Recent Findings The recent publication of the 2020 ESC has provided a comprehensive series of recommendations on diagnosis and management of patients presenting with NSTE-ACS. However, there are discrepancies between the 2020 ESC versus 2015 ESC and 2014 ACC guidelines, creating uncertainty among clinicians in routine practices. Our investigation provides insights into several domains, including diagnosis, risk stratification, pharmacological treatments, invasive treatment, and special populations. Summary Overall, it seems that the 2020 version of the ESC guideline for the management of NSTE-ACS provides the most evidence-based recommendations for clinicians; although due to the lack of validated investigation across some of the proposed recommendations, further longitudinal multicenter studies are warranted to address the current questions.

Background Complete revascularization in ST elevation myocardial infarction (STEMI) patients with multivessel disease has resulted in reduction in composite clinical endpoints in medium sized trials. Only one trial showed an effect on hard clinical endpoints, but the revascularization procedure was guided by angiographic evaluation of stenosis severity. Consequently, it is not clear how Fractional Flow Reserve (FFR)-guided percutaneous coronary intervention (PCI) affects hard clinical endpoints in STEMI. Methods and Results The Ffr-gUidance for compLete non-cuLprit REVASCularization (FULL REVASC) - is a pragmatic, multicenter, international, registry-based randomized clinical trial designed to evaluate whether a strategy of FFR-guided complete revascularization of non-culprit lesions, reduces the combined primary endpoint of total mortality, non-fatal MI and unplanned revascularization. 1,545 patients were randomized to receive FFR-guided PCI during the index hospitalization or initial conservative management of non-culprit lesions. We found that in angiographically severe non-culprit lesions of 90-99% severity, 1 in 5 of these lesions were re-classified as non-flow limiting by FFR. Considering lesions of intermediate severity (70%-89%), half were re-classified as non-flow limiting by FFR. The study is event driven for an estimated follow-up of at least 2.75 years to detect a 9.9%/year >7.425%/year difference (HR = 0.74 at 80% power (alpha = .05)) for the combined primary endpoint. Conclusion This large randomized clinical trial is designed and powered to evaluate the effect of complete revascularization with FFR-guided PCI during index hospitalization on total mortality, non-fatal MI and unplanned revascularization following primary PCI in STEMI patients with multivessel disease. Enrollment completed in September 2019 and follow-up is ongoing.

Background: Whether factor V Leiden is associated with lower bleeding risk in patients with acute coronary syndromes using (dual) antiplatelet therapy has yet to be investigated. Methods and Results: We pooled data from 3 randomized clinical trials, conducted in patients with acute coronary syndromes, with adjudicated bleeding outcomes. Cox regression models were used to obtain overall and cause-specific hazard ratios (HRs) to account for competing risk of atherothrombotic outcomes (ie, composite of ischemic stroke, myocardial infarction, and cardiovascular death) in each study. Estimates from the individual studies were pooled using fixed effect meta-analysis. The 3 studies combined included 17 623 patients of whom 969 (5.5%) were either heterozygous or homozygous (n=23) carriers of factor V Leiden. During 1 year of follow-up, a total of 1289 (7.3%) patients developed major (n=559) or minor bleeding. Factor V Leiden was associated with a lower risk of combined major and minor bleeding (adjusted cause-specific HR, 0.75; 95% CI, 0.56-1.00; P=0.046; I-2=0%) but a comparable risk of major bleeding (adjusted cause-specific HR, 0.93; 95% CI, 0.62-1.39; P=0.73; I-2=0%). Adjusted pooled cause-specific HRs for the association of factor V Leiden with atherothrombotic events alone and in combination with bleeding events were 0.75 (95% CI, 0.55-1.02; P=0.06; I-2=0%) and 0.75 (95% CI, 0.61-0.92; P=0.007; I-2=0%), respectively. Conclusions: Given that the lower risk of bleeding conferred by factor V Leiden was not counterbalanced by a higher risk of atherothrombotic events, these findings warrant future assessment for personalized medicine such as selecting patients for extended or intensive antiplatelet therapy.

Background: Takotsubo syndrome (TS) is a potentially life-threatening acute cardiac syndrome with a clinical presentation similar to myocardial infarction and for which the natural history, management, and outcome remain incompletely understood. Our aim was to assess the relative short-term mortality risk of TS, ST-segment-elevation myocardial infarction (STEMI), and non-STEMI (NSTEMI) and to identify predictors of in-hospital complications and poor prognosis in patients with TS. Methods and Results: This is an observational cohort study based on the data from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry). We included all patients (n=117 720) who underwent coronary angiography in Sweden attributed to TS (N=2898 [2.5%]), STEMI (N=48 493 [41.2%]), or NSTEMI (N=66 329 [56.3%]) between January 2009 and February 2018. We compared patients with TS to those with NSTEMI or STEMI. The primary end point was all-cause mortality at 30 days. Secondary outcomes were acute heart failure (Killip Class >= 2) and cardiogenic shock (Killip Class 4) at the time of angiography. Patients with TS were more often women compared with patients with STEMI or NSTEMI. TS was associated with unadjusted and adjusted 30-day mortality risks lower than STEMI (adjusted hazard ratio [adjHR], 0.60; 95% CI, 0.48-0.76; P<0.001), but higher than NSTEMI (adjHR, 2.70; 95% CI, 2.14-3.41; P<0.001). Compared with STEMI, TS was associated with a similar risk of acute heart failure (adjHR, 1.26; 95% CI, 0.91-1.76; P=0.16) but a lower risk of cardiogenic shock (adjHR, 0.55; 95% CI, 0.34-0.89; P=0.02). The relative 30-day mortality risk for TS versus STEMI and NSTEMI was higher for smokers than nonsmokers (adjusted P interaction STEMI=0.01 and P interaction NSTEMI=0.01). Conclusions: The 30-day mortality rate in TS was higher than in NSTEMI but lower than STEMI despite a similar risk of acute heart failure in TS and STEMI. Among patients with TS, smoking was an independent predictor of

Aims To evaluate the impact of chronic obstructive pulmonary disease (COPD) on 10-year all-cause death and the treatment effect of CABG versus PCI on 10-year all-cause death in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) and COPD. Methods Patients were stratified according to COPD status and compared with regard to clinical outcomes. Ten-year all-cause death was examined according to the presence of COPD and the revascularization strategy. Results COPD status was available for all randomized 1800 patients, of whom, 154 had COPD (8.6%) at the time of randomization. Regardless of the revascularization strategy, patients with COPD had a higher risk of 10-year all-cause death, compared with those without COPD (43.1% vs. 24.9%; hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.56–2.64; p < 0.001). Among patients with COPD, CABG appeared to have a slightly lower risk of 10-year all-cause death compared with PCI (42.3% vs. 43.9%; HR: 0.96; 95% CI: 0.59–1.56, p = 0.858), whereas among those without COPD, CABG had a significantly lower risk of 10-year all-cause death (22.7% vs. 27.1%; HR: 0.81; 95% CI: 0.67–0.99, p = 0.041). There was no significant differential treatment effect of CABG versus PCI on 10-year all-cause death between patients with and without COPD (p interaction = 0.544). Conclusions COPD was associated with a higher risk of 10-year all-cause death after revascularization for complex coronary artery disease. The presence of COPD did not significantly modify the beneficial effect of CABG versus PCI on 10-year all-cause death. Trial registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050

Background Characteristics and prognosis of patients admitted with strong suspicion of myocardial infarction (MI) but discharged without an MI diagnosis are not well-described. Objectives To compare background characteristics and cardiovascular outcomes in patients discharged with or without MI diagnosis. Methods The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial compared 6629 patients with strong suspicion of MI randomized to oxygen or ambient air. The main composite end-point of this subgroup analysis was the incidence of all-cause death, rehospitalization with MI, heart failure (HF) or stroke during a follow-up of 2.1 years (median; range: 1-3.7 years) irrespective of randomized treatment. Results 1619 (24%) received a non-MI discharge diagnosis, and 5010 patients (76%) were diagnosed with MI. Groups were similar in age, but non-MI patients were more commonly female and had more comorbidities. At thirty days, the incidence of the composite end-point was 2.8% (45 of 1619) in non-MI patients, compared to 5.0% (250 of 5010) in MI patients with lower incidences in all individual end-points. However, for the long-term follow-up, the incidence of the composite end-point increased in the non-MI patients to 17.7% (286 of 1619) as compared to 16.0% (804 of 5010) in MI patients, mainly driven by a higher incidence of all-cause death, stroke and HF. Conclusions Patients admitted with a strong suspicion of MI but discharged with another diagnosis had more favourable outcomes in the short-term perspective, but from one year onwards, cardiovascular outcomes and death deteriorated to a worse long-term prognosis.

Aims: The VALIDATE-SWEDEHEART trial was a registry-based randomized trial comparing bivalirudin and heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention. It showed no differences in mortality at 30 or 180 days. This study examines how well the trial population results may generalize to the population of all screened patients with fulfilled inclusion criteria in regard to mortality at 30 and 180 days. Methods: The standardized difference in the mean propensity score for trial inclusion between trial population and the screened not-enrolled with fulfilled inclusion criteria was calculated as a metric of similarity. Propensity scores were then used in an inverse-probability weighted Cox regression analysis using the trial population only to estimate the difference in mortality as it would have been had the trial included all screened patients with fulfilled inclusion criteria. Patients who were very likely to be included were weighted down and those who had a very low probability of being in the trial were weighted up. Results: The propensity score difference was 0.61. There were no significant differences in mortality between bivalirudin and heparin in the inverse-probability weighted analysis (hazard ratio 1.11, 95% confidence interval (0.73, 1.68)) at 30 days or 180 days (hazard ratio 0.98, 95% confidence interval (0.70, 1.36)). Conclusion: The propensity score difference demonstrated that the screened not-enrolled with fulfilled inclusion criteria and trial population were not similar. The inverse-probability weighted analysis showed no significant differences in mortality. From this, we conclude that the VALIDATE results may be generalized to the screened not-enrolled with fulfilled inclusion criteria.

BACKGROUND: The prothrombotic defect factor V Leiden (FVL) may confer higher risk of ST-segment-elevation myocardial infarction (STEMI), compared with non-ST-segment-elevation acute coronary syndrome, and may be associated with more myocardial necrosis caused by higher thrombotic burden. METHODS AND RESULTS: Patients without history of cardiovascular disease were selected from 2 clinical trials conducted in patients with acute coronary syndrome. FVL was defined as G-to-A substitution at nucleotide 1691 in the factor V (factor V R506Q) gene. Odds ratios were calculated for the association of FVL with STEMI adjusted for age and sex in the overall population and in the subgroups including sex, age (>= 70 versus <70 years), and traditional cardiovascular risk factors. The peak biomarker levels (ie, creatine kinase-myocardial band and high-sensitivity troponin I or T) after STEMI were contrasted between FVL carriers and noncarriers. Because of differences in troponin assays, peak high-sensitivity troponin levels were converted to a ratio scale. The prevalence of FVL mutation was comparable in patients with STEMI (6.0%) and non-ST-segment-elevation acute coronary syndrome (5.8%). The corresponding sex-and age-adjusted odds ratio was 1.06 (95% CI, 0.86-1.30; P=0.59) for the association of FVL with STEMI. Subgroup analysis did not show any differences. In patients with STEMI, neither the median peak creatine kinase-myocardial band nor the peak high-sensitivity troponin ratio showed any differences between wild-type and FVL carriers (P for difference: creatine kinase-myocardial band=0.33; high sensitivity troponin ratio=0.54). CONCLUSIONS: In a general population with acute coronary syndrome, FVL did not discriminate between a STEMI or non-ST-segment-elevation acute coronary syndrome presentation and was unrelated to peak cardiac necrosis markers in patients with STEMI.

Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients with chronic coronary syndrome and acute coronary syndrome undergoing percutaneous coronary intervention, but choosing the optimal treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from either shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y(12) inhibitor monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk scores, platelet function testing, and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint on the use of different risk stratification methods alongside clinical judgement in current clinical practice. [GRAPHICS]

Background: Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs). Methods: PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065. Findings: Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2%, 95% CI 11.0-15.6) of 898 patients, with 66 (8.0%, 95% CI 6.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9% [SD 15.9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adj