Publications

Patients with a major GI bleed on OAC had a high rate of OAC discontinuation and significantly higher risk of stroke/SE, major bleeding, and mortality after hospital discharge than those without. Effective management strategies are needed for patients with risk factors for major GI bleeding.

Atrial fibrillation (AF) is associated with a significantly increased risk of stroke due to the presence of three prothrombotic mechanisms known as Virchow's triad -blood stasis, endothelial damage and hypercoagulability -which primarily occur in the left atrial appendage (LAA).Insilico evaluation of each factor can improve upon the current empirical stroke risk stratification for AF patients.Computational fluid dynamics simulations were performed on two patient-specific models of the left atrium, one in sinus rhythm (SR) and one in AF to quantify blood stasis and metrics of endothelial damage. Hypercoagulability was assessed by solving reactiondiffusion-convection equations for thrombin, fibrinogen and fibrin -three key clotting proteins, and varying initial concentrations of fibrinogen in accordance with clinical literature. An original grading system is proposed (A = low, B = moderate, C = high risk) for each component of the triad to form a patient-specific risk profile. The SR patient had a risk profile of [A, B, A] showing a low-moderate risk of thrombus formation, while the AF patient had [C, B, C], indicating a very high risk of thrombus formation and increased potential for stroke.This novel modelling approach encapsulates all fundamental mechanisms of thrombus formation and may be used to improve stroke risk assessment for AF patients.PV PV PV LA LAA LAA LAA LA LA LA

Abstract Introduction Anthracyclines (ANT are a key component in the treatment of early breast cancer but are associated with an enhanced oxidative stress which is associated with f short- and long-term adverse events. Statins are a well-known class of lipid lowering agent with anti-inflammatory properties that could potentially counteract ANT toxicity in cancer patients. Purpose To assess the potential therapeutic benefit of statins among malignant breast cancer patients treated with ANT. Methods Retrospective study utilizing a global federated health research network (TriNetX). Patients with malignant breast cancer (ICD code C50) treated with ANT were categorized in two groups: statin users (at least 1 month before the ANT treatment); and non-statin users. The primary outcome was the 5-year risk of all-cause death. Secondary outcomes were the intra-treatment (within 6 months), post-treatment (6 months-1 year) and long-term (1 year-5 years) risk of-all cause death. A further sensitivity analysis was done to assess the risk differences between hydrophilic (rosuvastatin and pravastatin) and lipophilic (atorvastatin, simvastatin, lovastatin) statins. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). Results Amongst the 36,770 patients with breast cancer identified (mean age 60±12.6 years, 98.6% female): 6,616 (17.9%) were statin users and 30,154 (81.1%) were non-statin users. Statins users were older and had more cardiovascular risk factors. After PSM, the 5-year risk of all-cause death was significantly lower in statin users (HR 0.72, 95%CI 0.63-0.83) compared to non-statins users. Analyzing the different time frames, the lowest risk of all-cause death was observed in the early period after the ATN treatment (Figure 1). The 5-year all-cause death was reduced in both the hydrophilic (HR: 0.69, 95%CI 0.58-0.83) and lipophilic statins (HR 0.72, 95%CI 0.65-0.79), when compared to non-statins users (Figure 2), with no significant differences between these two statin types (p=0.496). Conclusion Statin use was associated with a reduced risk of all-cause death in breast cancer patients treated with ATN. Further studies are needed to clarify the mechanism(s) by which statins counteract the ATN toxicity.

Abstract Background Atrial fibrillation (AF) is often asymptomatic. The prognosis of asymptomatic AF is similar or worse than symptomatic AF, but there are no such data from Middle East. Method The Gulf survey of AF events (Gulf SAFE) registry is a multi-center prospective survey of AF patients from six countries (23 centers) in the Gulf Region (n=2043). We investigated the prognostic outcomes of asymptomatic AF, in relation to clinical subtypes. Result 541 (26.5%) AF patients were asymptomatic; they tended to be older, with higher prevalence of hypertension, heart failure (HF), diabetes, stroke, renal dysfunction, and higher CHADS2, CHA2DS2-VASc, and HAS-BLED scores (all p<0.05). After multivariable adjustment, asymptomatic AF was associated with higher risks of stroke/systematic embolism (SE) (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.10–4.34), all cause-mortality (OR 2.85 [1.90–4.28]) and the composite outcome of stroke/SE, bleeding and all-cause mortality (OR 1.74 [1.26–2.41]). Asymptomatic AF was associated with fewer admissions for AF (OR 0.53 [0.32–0.83]) and HF (OR 0.58 [0.38–0.86]). The increased risk of stroke/SE in asymptomatic AF was associated with paroxysmal AF (Figure 1; P interaction=0.028). Conclusion In this large Middle East cohort, asymptomatic AF was common, less likely hospitalized but associated with unfavorable prognosis. When AF was asymptomatic, the paroxysmal subtype had a greater association with stroke/SE. Adjusted odds ratio of clinical outcomes Funding Acknowledgement Type of funding source: None

Microvesicles are members of the family of extracellular vesicles shed from the plasma membrane of activated or apoptotic cells. Microvesicles were initially characterised by their pro-coagulant activity and described as "microparticles". There is mounting evidence revealing a role for microvesicles in intercellular communication, with particular relevance to hemostasis and vascular biology. Coupled with this, the potential of microvesicles as meaningful biomarkers is under intense investigation. This Position Paper will summarise the current knowledge on the mechanisms of formation and composition of microvesicles of endothelial, platelet, red blood cell and leukocyte origin. This paper will also review and discuss the different methods used for their analysis and quantification, will underline the potential biological roles of these vesicles with respect to vascular homeostasis and thrombosis and define important themes for future research.

In AF patients, the ABC-stroke and ABC-bleeding scores demonstrated similar predictive ability for outcomes beyond stroke and bleeding, including MI, acute HF, a composite of cardiovascular events, and all-cause deaths. This is consistent with nonspecificity of biomarkers that predict "sick" patients or poor prognosis overall.

Abstract Background/Introduction Recent evidence has confirmed low bleeding risk with double antithrombotic therapy, combining oral anticoagulant (OAC) and single platelet inhibitor, in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). Among the Asian AF population, most of the patients received dual antiplatelet therapy (DAPT) without OACs, even after the introduction of non-vitamin K oral anticoagulants (NOACs). Purpose The current nationwide study assessed 3-month ischemic and bleeding risks of DAPT in comparison to triple antithrombotic therapy among the Korean AF population undergoing PCI. Methods We analyzed the claims records of 11,039 patients (mean age 70 years, 66.3% male, and mean CHA2DS2-VASc score 3.2) between 2013 to 2018. Patients were categorized into triple therapy group with vitamin K antagonists (VKAs-TT), or NOACs (NOACs-TT), and DAPT group according to the antithrombotic therapy after PCI. 3-month risks of ischemic stroke, non-fatal myocardial infarction, any in-hospital death, and major bleeding were compared between groups after baseline adjustment using inverse probability weighting. Results A total of 1,786, 1,997, and 7,256 patients were allocated to the VKAs-TT, NOACs-TT, and DAPT groups. The DAPT group had a higher prevalence of prior MI and coronary revascularization, but had lower thromboembolic and bleeding risks than the triple antithrombotic therapy groups (mean CHA2DS2-VASc score 3.8, 4.1, and 3.5; and mean HAS-BLED score 3.3, 3.4, and 3.1 for VKAs-TT, NOACs-TT, and DAPT groups, respectively). The NOACs-TT group was associated with a lower risk of ischemic stroke (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.20–0.70) and any in-hospital death (HR 0.70, 95% CI 0.49–0.98) compared with the VKAs-TT group. The DAPT group showed a lower risk of ischemic stroke (HR 0.41, 95% CI 0.27–0.63) and major bleeding (HR 0.55, 95% CI 0.37–0.84) than the VKAs-TT group, especially in patients without prior OAC treatment. The DAPT group showed a comparable ischemic risk against the NOACs-TT group, although the risk of major bleeding was lower in the DAPT group, especially among old age (HR 0.47, 95% CI 0.29–0.78) or OACs-naive patients (HR 0.50, 95% CI 0.29–0.86). Conclusion Among the Asian AF population, using short-term DAPT for 3-month after PCI was associated with a lower risk of bleeding without increasing ischemic risk compared to triple antithrombotic therapy with OAC. This may be a therapeutic option in very high bleeding risk patients who have had complex PCI necessitating focus on DAPT in the initial 3 month period. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This study was supported by grant no 3020200200 from the Seoul National University Hospital Research Fund, by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, Republic of Korea, the Ministry of Food and Drug Safety) (Project Number: 202013B14), and by the Korea National Research Foundation funded by the Ministry of Education, Science and Technology (grant 2020R1F1A106740). Figure 1Figure 2

Abstract Background Sustained atrial high-rate episodes (SAHREs) (lasting >24h) was associated with unfavorable pragnosis. Objectives To evaluate the performance of the C2HEST score in assessing individuals' risk of SAHRE. Methods The West Birminghan Atrial Fibrillation (AF) Project included 500 consecutive non-AF patients with implantable cardiac electronic device. The role of the C2HEST score for SAHRE risk stratification was evaluated. Results SAHRE was detected in 8.8% of patients (2.09%/year, 95% CI 1.47–2.71) over a mean 4.4 years of follow-up. SAHRE was associated with increased all-cause mortality (P<0.001). The risk of SAHRE increased by C2HEST score (39% higher risk per point increase). The C2HEST score had moderate predictive capability (c-index 0.706 [0.615–0.798], log-rank P=0.003) for SAHRE, which was better than other clinical scores (CHA2DS2-VASc, CHADS2, HATCH). Conclusions The C2HEST score was predictive of SAHRE, which may help to identify at-risk subjects who may need intensive device review. Central Illustration Funding Acknowledgement Type of funding source: None

Liver fibrosis is common among patients with CAD and is associated with CAD incidence, stent thrombosis, restenosis and long-term cardiovascular risk.

Contemporary management of AF was associated with a low risk of ischaemic stroke. CARS and CHA2DS2-VASc score may be useful to identify high risk patients despite treatment who may benefit from more aggressive treatment and follow-up.

Clinical trials NCT01119716.

AIMS: Risk prediction indices used in worsening heart failure (HF) vary in complexity, performance, and the type of datasets in which they were validated. We compared the performance of seven risk prediction indices in a contemporary cohort of patients hospitalized for HF. METHODS AND RESULTS: We assessed the performance of the Length of stay and number of Emergency department visits in the prior 6 months (LE), Length of stay, number of Emergency department visits in the prior 6 months, and admission N-Terminal prohormone of brain natriuretic peptide (NT-proBNP (LENT), Length of stay, Acuity, Charlson co-morbidity index, and number of Emergency department visits in the prior 6 months (LACE), Get With The Guidelines Heart Failure (GWTG), Readmission Risk Score (RRS), Enhanced Feedback for Effective Cardiac Treatment model (EFFECT), and Acute Decompensated Heart Failure National Registry (ADHERE) risk indices among consecutive patients hospitalized for HF and discharged alive from January 2017 to December 2019 in a network of hospitals in England. The primary composite outcome was 30-day all-cause mortality or readmission. We assessed model discrimination and overall accuracy using the C-statistic (higher values, better) and Brier score (lower values, better), respectively. Among 1206 patients in the cohort, 45.0% were female, mean (SD) age was 76.6 (11.7) years, and mean (SD) left ventricular ejection fraction was 43.0% (11.6). At 30 days, 236 (19.6%) patients were readmitted and 28 (2.3%) patients died, with 264 (21.9%) patients experiencing either readmission or death. The LENT index offered the combination of greatest risk discrimination and accuracy for the primary composite outcome (C-statistic: 0.97; 95% CI 0.96, 0.98; 0.29; Brier score: 0.05). The LE (C-statistic: 0.95; 95% CI 0.93, 0.96; Brier score: 0.06) and LACE (C-statistic: 0.90; 95% CI 0.88, 0.92; Brier score 0.09) indices had high discrimination and accuracy. Discrimination and accuracy were modest with the RRS (C-statistic: 0.65; 95% CI 0.61, 0.69; Brier score: 0.16) and EFFECT (C-statistic: 0.64; 95% CI 0.60, 0.67; Brier score: 0.16) score; and poor with the GWTG-HF (C-statistic: 0.62; 95% CI 0.58, 0.66; Brier score: 0.17) and ADHERE (C-statistic: 0.54; 95% CI 0.50, 0.57; Brier score: 0.17) scores. CONCLUSIONS: In a study that compared the performance of seven risk prediction indices in a contemporary cohort of patients hospitalized for HF, the simple LENT index offered the greatest combination of discrimination and accuracy for the primary composite outcome of 30-day all-cause mortality or readmission. This three-variable index -using length of hospital stay, preceding emergency department visits and admission NT-proBNP level- is a practical and reliable way to assess prognosis following hospitalization for HF.

See Article by Goto et al .

Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.