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Left ventricular thrombus (LVT) is a recognized complication of acute myocardial infarction which is associated with stroke. There has yet to be a published systematic review that focuses on outcomes for patients with LVT. We conducted a systematic review on treatments, adverse events and thrombus resolution in patients with LVT. Meta-analysis and numerical pooling were used to evaluate the difference in outcomes based on treatment and the presence or absence of LVT. A total of 39 studies were included (5475 patients with LVT and 356 589 patients with no LVT). The use of direct oral anticoagulants (DOACs) was associated with reduced mortality [RR, 0.66; 95% confidence interval (CI), 0.45-0.97; I2 = 9%] and bleeding (RR, 0.64; 95% CI, 0.48-0.85; I2 = 0%) compared to warfarin but there was a nonsignificant reduction in stroke/embolic events (RR, 0.95; 95% CI, 0.76-1.19; I2 = 3%). For patients with any treatment, the rate of stroke/embolic events, bleeding and mortality at follow-up of up to 12 months was 6.4, 3.7 and 7.9%, respectively. Pooled results from six studies that evaluated resolution at 6 months suggest that 80% of LVT were resolved. Apixaban was associated with the highest rate of (93.3%) whereas warfarin exhibited the lowest rate of resolution 73.1%. LVT is best managed with DOAC compared to warfarin therapy. An individualized approach to antithrombotic therapy is warranted as there appears to be no duration of therapy that clearly results in the resolution of all cases of LVT so follow-up imaging after discontinuation of anticoagulant is needed. Left ventricular thrombus (LVT) is a recognized complication of acute myocardial infarction which is associated with stroke. There has yet to be a published systematic review that focuses on outcomes for patients with LVT. We conducted a systematic review on treatments, adverse events and thrombus resolution in patients with LVT. Meta-analysis and numerical pooling were used to evaluate the difference in outcomes based on treatment and the presence or absence of LVT. A total of 39 studies were included (5475 patients with LVT and 356 589 patients with no LVT). The use of direct oral anticoagulants (DOACs) was associated with reduced mortality [RR, 0.66; 95% confidence interval (CI), 0.45-0.97; I2 = 9%] and bleeding (RR, 0.64; 95% CI, 0.48-0.85; I2 = 0%) compared to warfarin but there was a nonsignificant reduction in stroke/embolic events (RR, 0.95; 95% CI, 0.76-1.19; I2 = 3%). For patients with any treatment, the rate of stroke/embolic events, bleeding and mortality at follow-up of up to 12 months was 6.4, 3.7 and 7.9%, respectively. Pooled results from six studies that evaluated resolution at 6 months suggest that 80% of LVT were resolved. Apixaban was associated with the highest rate of (93.3%) whereas warfarin exhibited the lowest rate of resolution 73.1%. LVT is best managed with DOAC compared to warfarin therapy. An individualized approach to antithrombotic therapy is warranted as there appears to be no duration of therapy that clearly results in the resolution of all cases of LVT so follow-up imaging after discontinuation of anticoagulant is needed.

Background and ObjectivesIn patients with ischemic stroke (IS) or transient ischemic attack (TIA) and cortical superficial siderosis (cSS), there are few data regarding the risk of future cerebrovascular events and also about the benefits and safety of antithrombotic drugs for secondary prevention. We investigated the associations of cSS and stroke risk in patients with recent IS or TIA.MethodsWe retrospectively analyzed the Microbleeds International Collaborative Network (MICON) database. We selected patients with IS or TIA from cohorts who had MRI-assessed cSS, available data on antithrombotic treatments, recurrent cerebrovascular events (intracranial hemorrhage [ICrH], IS, or any stroke [ICrH or IS]), and mortality. We calculated incidence rates (IRs) and performed univariable and multivariable Cox regression analyses.ResultsOf 12,669 patients (mean age 70.4 ± 12.3 years, 57.3% men), cSS was detected in 273 (2.2%) patients. During a mean follow-up of 24 ± 17 months, IS was more frequent than ICrH in both cSS (IR 57.1 vs 14.6 per 1,000 patient-years) and non-cSS (33.7 vs 6.3 per 1,000 patient-years) groups. Compared with the non-cSS group, cSS was associated with any stroke on multivariable analysis {IR 83 vs 42 per 1,000 patient-years, adjusted hazard ratio [HR] for cSS 1.62 (95% CI: 1.14–2.28;p= 0.006)}. This association was not significant in subgroups of patients treated with antiplatelet drugs (n = 6,554) or with anticoagulants (n = 4,044). Patients with cSS who were treated with both antiplatelet drugs and anticoagulants (n = 1,569) had a higher incidence of ICrH (IR 107.5 vs 4.9 per 1,000 patient-years, adjusted HR 13.26; 95% CI: 2.90–60.63;p= 0.001) and of any stroke (IR 198.8 vs 34.7 per 1,000 patient-years, adjusted HR 5.03; 95% CI: 2.03–12.44;p< 0.001) compared with the non-cSS group.DiscussionPatients with IS or TIA with cSS are at increased risk of stroke (ICrH or IS) during follow-up; the risk of IS exceeds that of ICrH for patients receiving antiplatelet or anticoagulant treatment alone, but the risk of ICrH exceeds that of IS in patients receiving both treatments. The findings suggest that either antiplatelet or anticoagulant treatment alone should not be avoided in patients with cSS, but combined antithrombotic therapy might be hazardous. Our findings need to be confirmed by randomized clinical trials.

Background: Further studies are needed to expand the evidence for the association of rivaroxaban with a lower risk of adverse renal outcomes in patients with atrial fibrillation (AF) as compared with warfarin, especially in Asians.Objectives: To determine whether there are differences in adverse renal outcomes between rivaroxaban and warfarin-treated AF patients.Methods: Using the Korean nationwide claims database partly linked to laboratory results, patients with AF who initiated warfarin or rivaroxaban from 1 January 2014 to 31 December 2017 were identified. Inverse probability of treatment weighting (IPTW) was used to balance the baseline characteristics of the two groups. The primary outcome (kidney failure) was defined as the need for maintenance dialysis or having kidney transplantation. For the exploratory analysis in a subset of patients with baseline and follow-up laboratory results, the composite of renal outcomes, including estimated glomerular filtration rate (eGFR) lower than 15 ml/min/1.73 m2 at follow-up measurement, starting dialysis, or having kidney transplantation, ≥ 30% decline in eGFR, doubling of serum creatinine level, and acute kidney injury (AKI) were evaluated. The two groups were compared using Cox proportional hazards regression in the weighted population.Results: We identified 30,933 warfarin users and 17,013 rivaroxaban users (51% of low dose rivaroxaban). After IPTW, the mean age was 70 years, and the mean CHA2DS2-VASc score was 3.9 in both groups. During a median follow-up of 0.93 (interquartile ranges 0.23-2.10) years, weighted incidence rates of kidney failure for warfarin and rivaroxaban were 0.83 and 0.32 per 100 person-years, respectively. Compared with the warfarin group, the rivaroxaban group was associated with a lower risk of kidney failure (hazard ratio [HR] 0.389, 95% confidence interval [CI] 0.300-0.499, p < 0.001). In patients with preexisting chronic kidney disease or eGFR ≤ 60 ml/min/1.73 m2, rivaroxaban was more beneficial than warfarin in reducing the risk of kidney failure. For the composite of five renal outcomes in the exploratory analysis, the rivaroxaban group showed a lower risk than warfarin (HR 0.798, 95% CI 0.713-0.892, p < 0.001).Conclusion: Rivaroxaban was associated with lower risks of renal adverse outcomes than warfarin in Korean patients with AF. Background: Further studies are needed to expand the evidence for the association of rivaroxaban with a lower risk of adverse renal outcomes in patients with atrial fibrillation (AF) as compared with warfarin, especially in Asians. Objectives: To determine whether there are differences in adverse renal outcomes between rivaroxaban and warfarin-treated AF patients. Methods: Using the Korean nationwide claims database partly linked to laboratory results, patients with AF who initiated warfarin or rivaroxaban from 1 January 2014 to 31 December 2017 were identified. Inverse probability of treatment weighting (IPTW) was used to balance the baseline characteristics of the two groups. The primary outcome (kidney failure) was defined as the need for maintenance dialysis or having kidney transplantation. For the exploratory analysis in a subset of patients with baseline and follow-up laboratory results, the composite of renal outcomes, including estimated glomerular filtration rate (eGFR) lower than 15 ml/min/1.73 m 2 at follow-up measurement, starting dialysis, or having kidney transplantation, ≥ 30% decline in eGFR, doubling of serum creatinine level, and acute kidney injury (AKI) were evaluated. The two groups were compared using Cox proportional hazards regression in the weighted population. Results: We identified 30,933 warfarin users and 17,013 rivaroxaban users (51% of low dose rivaroxaban). After IPTW, the mean age was 70 years, and the mean CHA 2DS 2-VASc score was 3.9 in both groups. During a median follow-up of 0.93 (interquartile ranges 0.23–2.10) years, weighted incidence rates of kidney failure for warfarin and rivaroxaban were 0.83 and 0.32 per 100 person-years, respectively. Compared with the warfarin group, the rivaroxaban group was associated with a lower risk of kidney failure (hazard ratio [HR] 0.389, 95% confidence interval [CI] 0.300–0.499, p < 0.001). In patients with preexisting chronic kidney disease or eGFR ≤ 60 ml/min/1.73 m 2, rivaroxaban was more beneficial than warfarin in reducing the risk of kidney failure. For the composite of five renal outcomes in the exploratory analysis, the rivaroxaban group showed a lower risk than warfarin (HR 0.798, 95% CI 0.713–0.892, p < 0.001). Conclusion: Rivaroxaban was associated with lower risks of renal adverse outcomes than warfarin in Korean patients with AF.

Additional file 3. Questionnaire responses from healthcare professionals regarding the care and management for AF.

Additional file 2. Demographic characteristics of included participants.

Conventional dual antiplatelet therapy (DAPT) for patients with acute coronary syndromes undergoing percutaneous coronary intervention comprises aspirin with a potent P2Y purinoceptor 12 (P2Y12) inhibitor (prasugrel or ticagrelor) for 12 months. Although this approach reduces ischaemic risk, patients are exposed to a substantial risk of bleeding. Strategies to reduce bleeding include de-escalation of DAPT intensity (downgrading from potent P2Y12 inhibitor at conventional doses to either clopidogrel or reduced-dose prasugrel) or abbreviation of DAPT duration. Either strategy requires assessment of the ischaemic and bleeding risks of each individual. De-escalation of DAPT intensity can reduce bleeding without increasing ischaemic events and can be guided by platelet function testing or genotyping. Abbreviation of DAPT duration after 1-6 months, followed by monotherapy with aspirin or a P2Y12 inhibitor, reduces bleeding without an increase in ischaemic events in patients at high bleeding risk, particularly those without high ischaemic risk. However, these two strategies have not yet been compared in a head-to-head clinical trial. In this Consensus Statement, we summarize the evidence base for these treatment approaches, provide guidance on the assessment of ischaemic and bleeding risks, and provide consensus statements from an international panel of experts to help clinicians to optimize these DAPT approaches for individual patients to improve outcomes.

Additional file 5. Supporting quotes from healthcare professional’s response to the open-ended questions.

Additional file 1. Quantitative questionnaire for healthcare professionals.

Additional file 4. Questionnaire responses from healthcare professionals regarding the treatment and monitoring for AFa.

There are limited studies on the prevalence and incidence of clinically diagnosed hypertrophic myocardiopathy (HCM) and its mortality in the Chinese population, and the projected population burden of HCM over the next decades. We collected data on HCM and its mortality from the Beijing Municipal Health Commission Information Center (BMHCIC) database and estimated the prevalence and incidence based on the whole Beijing population. Calculation of population trends was performed using annual percentage change (APC) and average annual percentage change (AAPC). Finally, future HCM incidence was built by modelling projection of HCM to the next decades using Poisson regression analysis and Gray Model 1,1(GM [1,1]). The prevalence of HCM was 0.0069% (95%CI, 0.0065–0.0072%; N = 1343) in 2010, rising to 0.076% (95% CI, 0.074–0.077%; N = 16,616) in 2019, and the incidence of HCM was 6.85 per 100 000 person-year in 2010, rising to 11.76 per 100 000 person-year in 2019. Males had higher prevalence and incidence of HCM than females. The APPC for the rising incidence of HCM was 5.8% and the expected numbers will double increase in 2029 by assuming the same increase trend as the last decades. HCM had increased annual incidence of HF (APPC: 8.4, 4.4–12.6, p p > 0.05) during the studied period. Males had lower mortality (2.70% vs. 4.20%, p

Importance: Guidelines recommend that all risk factors for early-onset atrial fibrillation, including lifestyle factors, be proactively managed, considering the poor prognosis of the disease. Not much is known about the association of cumulative alcohol intake with the risk of atrial fibrillation in young adults aged 20 to 39 years, especially among heavy drinkers. Objective: To explore the association of alcohol consumption with the risk of incident atrial fibrillation in young adults. Design, Setting, and Participants: Using the National Health Insurance Service database, a nationwide population-based cohort study of adults aged 20 to 39 years without prior atrial fibrillation who underwent 4 serial annual health examinations between 2009 and 2012 was conducted. The cumulative alcohol consumption burden over 4 years was calculated by assigning 1 point to more than moderate drinking (≥105 g of alcohol per week) each year. Additionally, a semiquantitative cumulative burden was calculated by assigning 0, 1, 2, and 3 points to non, mild (

BackgroundLittle is known regarding the risk of clinical outcomes depending on the clustering of lifestyle behaviors after atrial fibrillation (AF) diagnosis. This study evaluated the association between a cluster of healthy lifestyle behaviors and the risk of adverse outcomes in patients with AF.MethodsUsing the Korean National Insurance Service database, patients who were newly diagnosed with AF between 2009 and 2016 were included. A healthy lifestyle behavior score (HLS) was calculated by assigning 1 point each for non-current smoking, for non-drinking, and for performing regular exercise from the self-reported questionnaire in health examinations. The primary outcome was defined as major adverse cardiovascular event (MACE), including ischemic stroke, myocardial infarction, and hospitalization for heart failure.ResultsA total of 208,662 patients were included; 7.1% in HLS 0, 22.7% in HLS 1, 58.6% in HLS 2, and 11.6% in HLS 3 groups. Patients with HLS 1, 2, and 3 were associated with a lower risk of MACE than those with HLS 0 (adjusted hazard ratio [95% confidence interval (CI)]: 0.788 [0.762–0.855], 0.654 [0.604–0.708], and 0.579 [0.527–0.636], respectively). After propensity score weighting, consistent results were observed. The risk reduction of healthy lifestyle combinations was consistently observed in various subgroups, regardless of the CHA2DS2-VASc score and oral anticoagulant use.ConclusionIncreased number of healthy lifestyle behaviors was significantly associated with lower MACE risk in patients with new-onset AF. These findings support the promotion of a healthy lifestyle to reduce the risk of adverse events in patients with AF.

Importance: Incident atrial fibrillation (AF) is associated with an increased risk of dementia. However, data on the association between smoking cessation after AF diagnosis and dementia risk are limited.Objective: To evaluate the association between changes in smoking status after AF diagnosis and dementia risk.Design, Setting, and Participants: This nationwide cohort study with 126 252 patients used data from the Korean National Health Insurance Service database, including patients who had a national health checkup examination within 2 years before and after AF diagnosis between January 1, 2010, and December 31, 2016. Based on their smoking status, participants were classified as never smokers, ex-smokers, quit smokers, and current smokers. Ex-smokers were defined as those who had quit smoking before the first examination and remained quit until the second examination. Patients who were current smokers at the first health examination but had quit smoking before the second examination were classed as quit smokers. The index date was the second health examination. Patients were followed up until dementia, death, or the study period ended (December 31, 2017), whichever occurred first. Data were analyzed from January 13, 2020, to March 29, 2022.Exposures: Smoking cessation after newly diagnosed AF.Main Outcomes and Measures: Dementia, including Alzheimer disease and vascular dementia, was the primary outcome. Cox proportional hazards regression model was used to estimate hazard ratios.Results: A total of 126 252 patients (mean [SD] age, 62.6 [12.0] years; 61.9% men) were included in the analysis. The mean (SD) CHA2DS2-VASc score, which measures the risk of ischemic stroke, was 2.7 (1.7). Smoking status of the total study population was as follows: 65 579 never smokers (51.9%), 34 670 ex-smokers (27.5%), 8919 quit smokers (7.1%), and 17 084 current smokers (13.5%). During a median of 3 years of follow-up, dementia occurred in 5925 patients (1.11 per 1000 person-years). After multivariable adjustment, the risk of quit smokers was significantly lower than that of current smokers (hazard ratio, 0.83 [95% CI, 0.72-0.95]).Conclusions and Relevance: The findings of this cohort study suggest that all types of smoking were associated with a significantly higher risk of dementia in patients with new-onset AF. Smoking cessation after AF diagnosis was associated with a lower risk of dementia than among current smokers. These findings may support promoting smoking cessation to reduce dementia risk in patients with new-onset AF.

Oral anticoagulants (OACs) are medications commonly used in patients with atrial fibrillation and other cardiovascular conditions. Both warfarin and direct oral anticoagulants are susceptible to drug-drug interactions (DDIs). DDIs are an important cause of adverse drug reactions and exact a large toll on the health care system. DDI for warfarin mainly involve moderate to strong inhibitors/inducers of cytochrome P450 (CYP) 2C9, which is responsible for the elimination of the more potent S-isomer of warfarin. However, inhibitor/inducers of CYP3A4 and CYP1A2 may also cause DDI with warfarin. Recognition of these precipitating agents along with increased frequency of monitoring when these agents are initiated or discontinued will minimize the impact of warfarin DDI. Direct oral anticoagulants are mainly affected by medications strongly affecting the permeability glycoprotein (P-gp), and to a lesser extent, strong CYP3A4 inhibitors/inducers. Dabigatran and edoxaban are affected by P-gp modulation. Strong inducers of CYP3A4 or P-gp should be avoided in all patients taking direct oral anticoagulant unless previously proven to be otherwise safe. Simultaneous strong CYP3A4 and P-gp inhibitors should be avoided in patients taking apixaban and rivaroxaban. Concomitant antiplatelet/anticoagulant use confers additive risk for bleeding, but their combination is unavoidable in many cases. Minimizing duration of concomitant anticoagulant/antiplatelet therapy as indicated by evidence-based clinical guidelines is the best way to reduce the risk of bleeding.

BackgroundAn integrated and holistic approach is increasingly advocated in patients with atrial fibrillation (AF), based on the “Atrial fibrillation Better Care (ABC) pathway: A, Avoid stroke with anticoagulation; B, better symptom management; C, cardiovascular and comorbidity risk management.” The aim of this study was to examine the prevalence of adherence to each component of the ABC pathway and to analyze its impact on long-term prognosis in the “real-world” cohort of AF patients from the FANTASIIA registry.MethodsThis prospective study included consecutive AF outpatients anticoagulated with direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA) from June 2013 to October 2014. From the ABC pathway, adherence to the “A criterion” was defined by a time in the therapeutic range (TTR) ≥ 70% or correct dose with DOAC; “B criterion” adherence was defined by a European Heart Rhythm Association (EHRA) Symptom Scale I-II; and “C criterion” adherence was defined as optimized risk factors and comorbidity management. Baseline features and embolic events, severe bleeding, and all-cause and cardiovascular mortality rates up to 3 years of follow-up were analyzed, and a Cox multivariate analysis was performed to investigate the role of each component of the ABC pathway in predicting major events.ResultsA total of 1,955 AF patients (age: 74.4 ± 9.4 years; 43.2% female patients) were included in this study: adherence to A criterion was observed in 920 (47.1%) patients; adherence to B criterion was observed in 1,791 (91.6%) patients; and adherence to C criterion was observed in 682 (34.8%) patients. Only 394 (20.2%) of the whole population had good control of AF according to the ABC pathway. After a median follow-up of 1,078 days (IQR: 766–1,113), adherence to A criterion was independently associated with reduced cardiovascular mortality [HR: 0.67, 95%CI (0.45–0.99); p = 0.048] compared with non-adherence. Adherence to the B criterion was independently associated with reduced stroke [HR: 0.28, 95%CI (0.14–0.59); p < 0.001], all-cause mortality [HR: 0.49, 95%CI (0.35–0.69); p < 0.001], cardiovascular mortality [HR: 0.39, 95%CI (0.25–0.62); p < 0.001], and major adverse cardiovascular events (MACE) [HR: 0.41, 95%CI (0.28–0.62); p < 0.001] compared with non-adherence. AF patients with C criterion adherence had a significantly lower risk of myocardial infarction [HR: 0.31, 95%CI (0.15–0.66); p < 0.001]. Fully adherent ABC patients had a significant reduction in MACE [HR: 0.64, 95%CI (0.42–0.99); p = 0.042].ConclusionIn real-world anticoagulated AF patients from FANTASIIA registry, we observed a lack of adherence to integrated care management of AF following the ABC pathway. AF managed according to the ABC pathway was associated with a significant reduction in adverse outcomes during long follow-up, suggesting the benefit of a holistic and integrated approach to AF management.

BACKGROUND: The management of patients with atrial fibrillation (AF) and malignancy is challenging given the paucity of evidence supporting their appropriate clinical management. PURPOSE: To evaluate the outcomes of patients with active or prior malignancy in a contemporary cohort of European AF patients. METHODS: Patients enrolled in the EURObservational Research Programme in AF General Long-Term Registry were categorized into 3 categories: No Malignancy (NoMal), Prior Malignancy (PriorMal) and Active Malignancy (ActiveMal). The primary outcomes were all-cause death and the composite outcome MACE. RESULTS: A total of 10 383 patients were analysed. Of these, 9597 (92.4%) were NoMal patients, 577 (5.6%) PriorMal and 209 (2%) ActiveMal. Lack of any antithrombotic treatment was more prevalent in ActiveMal patients (12.4%) as compared to other groups (5.0% vs 6.3% for PriorMal and NoMal, p

Additional file 1. PRISMA-P Checklist. Checklist for use with systematic review protocol submissions.

Additional file 1: Fig. S1. Flow diagram showing the selection of participants in this study. Table S1. Comparisons of baseline characteristics between included and excluded participants in UK biobank. Table S2. Results from sensitivity analyses for the relationship between different HbA1c groups and risk of CVD. Fig. S2. Hazard ratios for risk of CHD, stroke, and CVD death in relation to different HbAlc levels (shadows indicating 95% confidence intervals for hazard ratios). Fig. S3. Hazard ratios for risk of CVD events in relation to different HbAlc levels stratified by sex (shadows indicating 95% confidence intervals for hazard ratios). Fig. S4. Hazard ratios for risk of CVD events in relation to different HbAlc levels stratified by age group (shadows indicating 95% confidence intervals for hazard ratios). Fig. S5. Hazard ratios for risk of CVD events in relation to different HbAlc levels stratified by diabetes (shadows indicating 95% confidence intervals for hazard ratios). Fig. S6. Hazard ratios for risk of CVD events in relation to different HbAlc levels stratified by MH status (shadows indicating 95% confidence intervals for hazard ratios). Fig. S7. Sensitivity analysis results of hazard ratios for risk of CVD events, CHD, stroke, and CVD death in relation to different HbAlc levels (shadows indicating 95% confidence intervals for hazard ratios). Fig. S8. Sensitivity analysis results of hazard ratios for risk of CVD events, CHD, stroke, and CVD death in relation to different HbAlc levels (models further adjusted for urate-lowering drugs and serum urate, shadows indicating 95% confidence intervals for hazard ratios)

Additional file 1: Table S1. Items Included into the Frailty Index. Table S2. Baseline Characteristics of the Cohort. Table S3. Cox Regression for the risk of major outcomes according to clinical complexity and subgroups. Table S4. Baseline characteristics according to cluster allocation. Figure S1. Kaplan Meier Curves for the risk of MACE according to cluster analysis. Figure S2. Kaplan Meier Curves for the risk of composite outcome according to cluster analysis. Figure S3. Delay of Event analysis for MACE, ABC adherent vs. non-adherent in cluster 1 subgroup. Figure S4. Delay of Event analysis for Composite Outcome, ABC adherent vs. non-adherent in cluster 1 subgroup.

Additional file 1: Supplemental Table 1. The preferred reporting items for systematic review and meta-analysis (PRISMA) 2020 statement. Supplemental Table 2. The search strategies of this meta-analysis until August 06, 2022. Supplemental Table 3. The excluded studies during the full-text screenings. Supplemental Table 4. The detailed characteristics of the included studies. Supplemental Table 6. Effect estimates and adjusted confounders of the included studies. Supplementary Table 7. Risk of bias assessment of the EAST-AFNET 4 trial. Supplementary Table 8. Quality assessment for post-hoc analyses of RCTs and observational cohorts using the NOS tool. Supplementary Table 9. The sensitivity analysis for the primary outcome after excluding one study at a time. Supplemental Figure 1. Assessment of the association of early rhythm control with primary composite outcome assessed by the IVhet model and QE model. Supplemental Figure 2. Assessment of the association of early rhythm control with adverse outcomes after excluding the study of Yang et al. Supplemental Figure 3. Assessment of associations of early rhythm control with the secondary outcomes assessed by the IVhet model. Supplemental Figure 4. Assessment of associations of early rhythm control with the secondary outcomes assessed by the QE model. Supplemental Figure 5. Assessment of associations of early rhythm control with adverse outcomes in the real-world settings after excluding the study of the RCT data. Supplemental Figure 6. Association of early rhythm control with adverse outcomes: subgroup analyses based on RCT versus real-world data. Supplemental Figure 7. The publication bias assessed by using the funnel plot.

Supplemental material, sj-docx-1-wso-10.1177_17474930211062478 for MRI and CT imaging biomarkers of cerebral amyloid angiopathy in lobar intracerebral hemorrhage by Ghil Schwarz, Gargi Banerjee, Isabel C Hostettler, Gareth Ambler, David J Seiffge, Hatice Ozkan, Simone Browning, Robert Simister, Duncan Wilson, Hannah Cohen, Tarek Yousry, Rustam Al-Shahi Salman, Gregory Y H Lip, Martin M Brown, Keith W Muir, Henry Houlden, Rolf J��ger and David J Werring in International Journal of Stroke

Additional file 1. Topic guide for patient focus groups about AF and anticoagulation.

Supplemental material, sj-docx-1-wso-10.1177_17474930221109149 for Efficacy and safety of vitamin-K antagonists and direct oral anticoagulants for stroke prevention in patients with heart failure and sinus rhythm: An updated systematic review and meta-analysis of randomized clinical trials by Weijia Li, Jiyoung Seo, Damianos G Kokkinidis, Leonidas Palaiodimos, Sanjana Nagraj, Eleni Korompoki, Haralambos Milionis, Wolfram Doehner, Gregory Y. H. Lip and George Ntaios in International Journal of Stroke

Additional file 1: Table S1 International Classification of Diseases (10th edition) Clinical Modification (ICD 10-CM) codes used to define comorbidities and clinical outcomes in this study.

Additional file 2. Search strategy syntax for MEDLINE through Ovid. Detailed search strategy syntax used for MEDLINE through Ovid.

Aim To investigate the association of anthropometric parameters [height, weight, body mass index (BMI), body surface area (BSA), and lean body mass (LBM)] with outcomes in atrial fibrillation (AF). Methods and results Ten-thousand two-hundred twenty patients were enrolled [40.3% females, median age 70 (62–77) years, followed for 728 (interquartile range 653–745) days]. Sex-specific tertiles were considered for the five anthropometric variables. At the end of follow-up, survival free from all-cause death was worse in the lowest tertiles for all the anthropometric variables analyzed. On multivariable Cox regression analysis, an independent association with all-cause death was found for the lowest vs. middle tertile when body weight (hazard ratio [HR] 1.66, 95%CI 1.23–2.23), BMI (HR 1.65, 95%CI 1.23–2.21), and BSA (HR 1.49, 95%CI 1.11–2.01) were analysed in female sex, as well as for body weight in male patients (HR 1.61, 95%CI 1.25–2.07). Conversely, the risk of MACE was lower for the highest tertile (vs. middle tertile) of BSA and LBM in males and for the highest tertile of weight and BSA in female patients. A higher occurrence of haemorrhagic events was found for female patients in the lowest tertile of height [odds ratio (OR) 1.90, 95%CI 1.23–2.94] and LBM (OR 2.13, 95%CI 1.40–3.26). Conclusions In AF patients height, weight, BMI, BSA, and LBM were associated with clinical outcomes, with all-cause death being higher for patients presenting lower values of these variables, i.e. in the lowest tertiles of distribution. The anthropometric variables independently associated with other outcomes were also different between male and female subjects.

Background: Several anthropometric measurements are used to assess cardiovascular risk and progress during clinical treatment. Most commonly used anthropometric measurements include total body weight and body mass index (BMI), with several other simple anthropometric measures typically underused in clinical practice. Herein, we review the evidence on the relationship between different anthropometric measurements and cardiovascular risk in patients with and without cardiovascular disease (CVD). Methods: Data for this review were identified by searches in PubMed, the Web of Science, Google Scholar, and references from relevant articles by using appropriate and related terms. The last search was performed on June 22, 2022. Articles published in English and Spanish were reviewed and included, if appropriate. We included studies detailing the relationship between skinfolds thickness, waist-to-hip ratio (WHR) and Conicity index with cardiovascular risk in adults with/without CVD. Results: In patients from the general population, elevated subscapular and triceps skinfolds showed a positive relationship with the development of hypertension, diabetes mellitus, hypercholesterolemia, cardiovascular mortality, and all-cause mortality. A higher subscapular skinfold was also associated with increased risk of coronary artery disease and stroke. A higher WHR, as well as other less common anthropometric measurements such as the Conicity index, was associated with an increased risk of myocardial infarction, incident CVD, major adverse cardiovascular events, and mortality in both patients with and without previous CVD. Conclusions: Non-traditional anthropometric measurements including skinfolds and WHR seem to improve the prediction of cardiovascular risk in the general population, and recurrent events in patients with previous CVD. Use of additional anthropometric techniques according to an objective and standardized method, may aid cardiovascular risk stratification in patients from the general population and the evaluation of therapeutic interventions for patients with CVD.

Aims The safety of digoxin therapy in atrial fibrillation (AF) remains ill-defined. We aimed to evaluate the effects of digoxin over beta-blocker therapy in AF. Methods and results Patients with AF who were treated with either digoxin or a beta blocker from the ESC–EHRA EORP AF (European Society of Cardiology–European Heart Rhythm Association EURObservational Research Programme Atrial Fibrillation) General Long-Term Registry were included. Outcomes of interest were all-cause mortality, cardiovascular (CV) mortality, non-CV mortality, quality of life, and number of patients with unplanned hospitalizations. Of 6377 patients, 549 (8.6%) were treated with digoxin. Over 24 months, there were 550 (8.6%) all-cause mortality events and 1304 (23.6%) patients with unplanned emergency hospitalizations. Compared to beta blocker, digoxin therapy was associated with increased all-cause mortality [hazard ratio (HR) 1.90 (95% confidence interval, CI, 1.48–2.44)], CV mortality [HR 2.18 (95% CI 1.47–3.21)], and non-CV mortality [HR 1.68 (95% CI 1.02–2.75)] with reduced quality of life [health utility score 0.555 (±0.406) vs. 0.705 (±0.346), P Conclusion Poor outcomes related to the use of digoxin over beta-blocker therapy in terms of excess mortality and reduced quality of life are associated with the presence of other risk factors rather than digoxin per se. The choice of digoxin or beta-blocker therapy had no influence on the incidence of unplanned hospitalizations.

Additional file 9: Supplementary Table 7. Results of publication bias assessment using funnel plot asymmetry, trim and fill method, and Egger’s test

Supplemental material, sj-docx-1-tag-10.1177_1756284821997352 for Burden of major gastrointestinal bleeding among oral anticoagulant-treated non-valvular atrial fibrillation patients by Steven Deitelzweig, Allison Keshishian, Amiee Kang, Amol D. Dhamane, Xuemei Luo, Neeraja Balachander, Lisa Rosenblatt, Jack Mardekian, Jenny Jiang, Huseyin Yuce and Gregory Y. H. Lip in Therapeutic Advances in Gastroenterology

Additional file 1: Figure S1. Funnel plots and results of Egger’s test for asymmetry. Figure S2. Proposed mechanisms through which SGLT2 inhibitors reduce risk of arrhythmias. Table S1. PRISMA checklist. Table S2. Search strategy. Table S3. Risk of bias assessment. Table S4. Results of sensitivity analyses. Table S5. GRADE assessment.

Additional file 1: Table S1. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes used in the study. Table S2. Subgroup analysis by age group. Table S3. Sensitivity analysis excluding patients with chronic kidney diseases. Table S4. Sensitivity analysis by excluding patients diagnosed with diabetes during the first 30 days of the follow-up period. Fig. S1. Cumulative incidence of diabetes in patients receiving anticoagulants (warfarin, apixaban, dabigatran, and rivaroxaban) after atrial fibrillation. Fig. S2. Cumulative incidence of diabetes in patients receiving anticoagulants (warfarin, apixaban/rivaroxaban, and dabigatran) after atrial fibrillation.

Additional file 1. Additional figures and tables.

Additional file 3: Supplementary Table 1. MOOSE Checklist for Meta-analyses of Observational Studies.

Additional file 8: Supplementary Table 6. GRADE assessment of quality of evidence.

Additional file 1. Additional figure and tables.

Additional file 1 : Table S1. Use of Antithrombotic drugs according to Patient Clusters in patients with High Thromboembolic Risk. STROBE Checklist. Appendix. EURObservational Research Programme Atrial Fibrillation (EORP-AF) Long-Term General Registry Committees and Investigators.

Additional file 1: Table S1. Baseline echocardiographic characteristics of HFpEF patients stratified according to the C2HEST score risk strata. Table S2. The C2HEST score and the risk of incident AF in the competing risk regression model. Table S3. Baseline characteristics of patients with and without incident AF during follow-up. Table S4. Components of C2HEST score and the risk of outcomes in univariate Cox proportional hazard model (all-cause death) and competing risk regression model (other outcomes). Table S5. Sensitivity analyses of C2HEST score risk strata and the risk of AF and other outcomes. Table S6. Subgroup analysis (C2HEST score was included as continuous variable). Fig. S1. Receiver operating characteristic (ROC) curves for the C2HEST score (with “HF” as a scoring item instead of “systolic HF”) in predicting a) atrial fibrillation, b) all-cause death, c) cardiovascular death, d) stroke, e) any hospitalization and f) heart failure hospitalization during follow-up. Fig. S2. Receiver operating characteristic (ROC) curves for the C2HEST score (with “hyperthyroidism” replaced by “thyroid disease”) in predicting a) atrial fibrillation, b) all-cause death, c) cardiovascular death, d) stroke, e) any hospitalization and f) heart failure hospitalization during follow-up.

OBJECTIVE To determine whether CT-based cerebral small vessel disease (SVD) biomarkers are associated with 6-month functional outcome after intracerebral hemorrhage (ICH) and whether these biomarkers improve the performance of the preexisting ICH prediction score. METHODS We included 864 patients with acute ICH from a multicenter, hospital-based prospective cohort study. We evaluated CT-based SVD biomarkers (white matter hypodensities [WMH], lacunes, brain atrophy, and a composite SVD burden score) and their associations with poor 6-month functional outcome (modified Rankin Scale score >2). The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow test were used to assess discrimination and calibration of the ICH score with and without SVD biomarkers. RESULTS In multivariable models (adjusted for ICH score components), WMH presence (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.12-2.06), cortical atrophy presence (OR 1.80, 95% CI 1.19-2.73), deep atrophy presence (OR 1.66, 95% CI 1.17-2.34), and severe atrophy (either deep or cortical) (OR 1.94, 95% CI 1.36-2.74) were independently associated with poor functional outcome. For the revised ICH score, the AUROC was 0.71 (95% CI 0.68-0.74). Adding SVD markers did not significantly improve ICH score discrimination; for the best model (adding severe atrophy), the AUROC was 0.73 (95% CI 0.69-0.76). These results were confirmed when lobar and nonlobar ICH were considered separately. CONCLUSIONS The ICH score has acceptable discrimination for predicting 6-month functional outcome after ICH. CT biomarkers of SVD are associated with functional outcome, but adding them does not significantly improve ICH score discrimination. TRIAL REGISTRATION INFORMATION ClinicalTrials.gov Identifier: NCT02513316.

Additional file 1: Table S1. ICD-10-CM codes and LOINCs for the identification of COVID-19. Table S2. Clinical outcomes and ICD-10-CM codes.

Additional file 7: Supplementary Table 5. Risk of bias of included studies using Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) Tool.

Additional file 4: Supplementary Table 2. Literature search strategy for each relevant database.

Additional file 2: Table S1. Comparison of AF- patients’ comorbidities between DM- and DM+ groups. Table S2. Odds ratio of atrial fibrillation prevalence in Polish population with concomitant diabetes mellitus in correlation to age and gender.

Additional file 1: Figure S1. NOMED-AF – study profile.

Additional file 5: Supplementary Table 3. List of excluded studies and reasons for exclusion.

Additional file 1.

The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver. Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

Additional file 1: Table S1. International Classification of Disease (9thand 10thedition) Clinical Modification (ICD 9-CMand ICD 10-CM) codes used to define the co-morbidities and clinical outcome in the study cohort. Table S2. International Classification of Disease (9thand 10thedition) Clinical Modification (ICD 9-CM and ICD 10-CM) codes used to define the major adverse limb outcome in the study cohort.