Publications

Non-alcoholic fatty liver disease in patients with atrial fibrillation: a report from a global federated health network

Abstract Background Few data are available on the clinical course of patients with Atrial Fibrillation (AF) and Nonalcoholic Fatty Liver Disease (NAFLD). Purpose To evaluate the 1-year risk of all-cause death, thromboembolic events, and bleeding in AF patients with NAFLD. Methods Retrospective cohort study within the global TriNetX platform. Patients with AF were categorized into two groups: i) AF with NAFLD and ii) AF without liver diseases. The primary outcomes were the 1-year risks of a composite outcome of i) all-cause death and thrombotic events (all-cause death, acute myocardial infarction, ischemic stroke, systemic arterial thromboembolism, deep vein thrombosis, and pulmonary embolism), and hemorrhagic outcome (intracranial hemorrhage and gastrointestinal bleeding). Secondary outcomes were each component of the composite primary outcomes. Cox regression analysis before and after propensity-score-matching (PSM) was used to estimate HR and 95% confidence interval (95%CI). Sensitivity analyses were done to investigate the risk associated with cirrhosis and type of oral anticoagulant. Results We identified 22,636 AF patients with NAFLD (69±12 years, 46.7% females) and 391,014 AF patients without NAFLD (72±12 years, 42.7% females). Before PSM, AF patients with NAFLD were younger, and with a higher prevalence of cardiovascular risk factors than those without liver disease. After PSM, no difference was found between the two groups, but NAFLD patients showed a higher 1-year risk of thrombotic (HR 1.54, 95%CI 1.47-1.61) and hemorrhagic (HR 1.56, 95%CI 1.42-1.72) composite outcomes (Figure 1). The higher risk in NAFLD was consistent also for all the secondary outcomes (Figure 1). On the sensitivity analyses (Figure 2), a progressively increased risk of thrombotic and hemorrhagic events was found in non-cirrhotic and cirrhotic patients compared to patients without liver diseases, whereas non-vitamin-k antagonist (NOAC) seems to be safer and more effective than warfarin. Conclusion In AF patients, NAFLD is associated with a higher 1-year risk of all-cause death, thrombotic and hemorrhagic events. Further studies are needed to establish the best clinical approach to manage NAFLD in AF patients.Figure 1Figure 2

Imaging and biophysical modelling of thrombogenic mechanisms in atrial fibrillation and stroke

Atrial fibrillation (AF) underlies almost one third of all ischaemic strokes, with the left atrial appendage (LAA) identified as the primary thromboembolic source. Current stroke risk stratification approaches, such as the CHA₂DS₂-VASc score, rely mostly on clinical comorbidities, rather than thrombogenic mechanisms such as blood stasis, hypercoagulability and endothelial dysfunction-known as Virchow's triad. While detection of AF-related thrombi is possible using established cardiac imaging techniques, such as transoesophageal echocardiography, there is a growing need to reliably assess AF-patient thrombogenicity prior to thrombus formation. Over the past decade, cardiac imaging and image-based biophysical modelling have emerged as powerful tools for reproducing the mechanisms of thrombogenesis. Clinical imaging modalities such as cardiac computed tomography, magnetic resonance and echocardiographic techniques can measure blood flow velocities and identify LA fibrosis (an indicator of endothelial dysfunction), but imaging remains limited in its ability to assess blood coagulation dynamics. In-silico cardiac modelling tools-such as computational fluid dynamics for blood flow, reaction-diffusion-convection equations to mimic the coagulation cascade, and surrogate flow metrics associated with endothelial damage-have grown in prevalence and advanced mechanistic understanding of thrombogenesis. However, neither technique alone can fully elucidate thrombogenicity in AF. In future, combining cardiac imaging with in-silico modelling and integrating machine learning approaches for rapid results directly from imaging data will require development under a rigorous framework of verification and clinical validation, but may pave the way towards enhanced personalised stroke risk stratification in the growing population of AF patients. This Review will focus on the significant progress in these fields.

Abstract 9416: Monocyte Subsets and Exercise Capacity in Patients With Atrial Fibrillation With Preserved Left Ventricular Function

Introduction: Monocytes play important roles in inflammation, angiogenesis and tissue repair in cardiovascular disease. This study examined differences in monocyte subset numbers, subsequent markers of inflammation and cardiac fibrosis in patients with permanent atrial fibrillation and preserved left ventricular function with regards to peak exercise capacity (cardiopulmonary exercise testing and 6 minute walk test), quality of life and hospitalisation. Furthermore, the effects of spironolactone vs placebo on the quantitative measurement of these potential biomarkers were assessed in a double blind randomised study over a 2 year period. Methods: Three monocyte subsets [CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3)] were analysed by flow cytometry and ELISA to quantify makers of fibrosis in the form of Galectin 3, Type III Procollagen Peptide and Type I Procollagen Peptide. SPSS software was used to carry out statistical analysis of all 250 patients in the study cohort using stepwise multivariant linear regression analysis. Independent samples T testing between spironolactone and placebo groups were carried out. Results: Monocyte subsets CD16 Mon3 (p=0.001) and CD42 MPA3 (p=0.030) were found to be predictors of peak VO 2 . Comparison of monocyte subsets at end of study showed no differences between Mon1 (p=0.86), Mon2 (p=0.66) or Mon3 (p=0.81) subsets and their subsequent makers of inflammation and fibrosis between the treatment and placebo control group. This held true for further markers of cardiac fibrosis with regards to 6 minute walk test , quality of life assessment and hospitalisation. Conclusions: This study shows that monocyte subsets can be potential biomarkers of exercise capacity which in the form of cardiopulmonary testing is known to have morbidity and mortality implications. CD16 Mon3 were significantly related to beneficial outcomes with regards to a peak exercise capacity in respect to VO 2 max (higher CD16 Mon3 count associated with higher peak VO 2 performance). Spironolactone has no impact on primary or secondary outcome in this study.

Modelling projections for the risks related with atrial fibrillation in East Asia: a focus on ischaemic stroke and death

This modelling analysis suggests that the transition from VKA to NOACs may greatly help in reducing the burden of IS and death caused by AF in the East Asian region.

Letter by Guo et al Regarding Article, “SUPPORT-AF II: Supporting Use of Anticoagulants Through Provider Profiling of Oral Anticoagulant Therapy for Atrial Fibrillation”

Are Alpha-Adrenergic Receptor Antagonists Beneficial to Prevent Heart Failure?

Association of different oral anticoagulants use with renal function worsening in patients with atrial fibrillation: A multicentre cohort study

Patients prescribed NOACs showed a lower decline of renal function compared to those prescribed VKAs. This effect was partially lost in patients with diabetes.

Phenotype-guided risk stratification in anticoagulated atrial fibrillation patients: Cluster analysis of the Murcia AF Project III (MAFP-III)

Cluster analysis revealed distinct phenotypic profiles among patients with AF, each associated with differential risks of adverse outcomes.

Anticoagulation in elderly patients with nonvalvular atrial fibrillation: A balancing act

Atrial fibrillation: stroke prevention

Stroke prevention is central to the management of patients with atrial fibrillation (AF) which has moved towards a more holistic or integrative care approach. The published evidence suggests that management of AF patients following such a holistic approach based on the Atrial fibrillation Better Care (ABC) pathway is associated with a lower risk of stroke and adverse events. Risk assessment, re-assessment and use of direct oral anticoagulants (DOACs) are important for stroke prevention in AF. The stroke and bleeding risks of AF patients are not static and should be re-assessed regularly. Bleeding risk assessment is to address and mitigate modifiable bleeding risk factors, and to identify high bleeding risk patients for early review and follow-up. Well-controlled comorbidities and healthy lifestyles also play an important role to achieve a better clinical outcome. Digital health solutions are increasingly relevant in the diagnosis and management of patients with AF, with the potential to improve stroke prevention. In this review, we provide an update on stroke prevention in AF, including importance of holistic management, risk assessment/re-assessment, and stroke prevention for special AF populations. Evidence-based and structured management of AF patients would reduce the risk of stroke and other adverse events.

Reduced Time in Therapeutic Range and Higher Mortality in Atrial Fibrillation Patients Taking Acenocoumarol

Net Clinical Benefit of Dabigatran Over Warfarin in Patients With Atrial Fibrillation Stratified by CHA2DS2-VASc and Time in Therapeutic Range

Safety and efficacy of direct oral anticoagulants in patients with anaemia and atrial fibrillation: an observational nationwide Danish cohort study

For AF patients receiving DOACs, moderate/severe anaemia is a risk factor for serious GI bleeding, while stroke risk is the same regardless of whether anaemia was present at baseline or not.

Genome-wide association study meta-analysis highlights new role of amyloid beta deposition in spontaneous intracerebral haemorrhage

Abstract 416: Atorvastatin Versus Placebo In Icu Patients With Covid19: Ninety-day Results Of The INSPIRATION-S Trial

Backgrounds: In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a non-significant 16% reduction in 30-day composite of venous/arterial thrombosis or death in ICU patients with COVID-19. Thrombo-inflammatory response in COVID-19 may last beyond the first 30 days. Methods: This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this pre-specified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with Post-COVID-19 Functional Scale (PCFS). Results: In the primary analysis, 587 patients were included (age: 57 (Q1, Q3: 45, 68) years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio, HR: 0.80, 95% confidence interval, CI: 0.60-1.05, P=0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42-0.86, P interaction =0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (OR ordinal , 0.64, 95% CI: 0.41 to 1.01, P=0.05). Conclusions: Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset.

Assessment of blood pressure and carotid intima media thickness (CIMT) in children with primary adrenal insufficiency

P3850Refining stroke and bleeding risk prediction by adding consecutive biomarkers to CHA2DS2-VASc and HAS-BLED scores

Myopericarditis as a presentation of eosinophilic granulomatosus with polyangiitis (EGPA)

A 60-year-old woman was admitted to the hospital with worsening dyspnoea, cough and chest pain. This was on a background of weight loss, decreased appetite, mononeuritis multiplex, chronic eosinophilia and a single episode of a non-blanching rash. Investigations demonstrated a raised troponin and ischaemic changes on ECG, and she was therefore initially treated for a presumed myocardial infarction. However, her symptoms failed to improve with treatment for the acute coronary syndrome. A coronary angiogram revealed no significant flow-limiting disease, and further investigations yielded confirmation of raised eosinophils and a positive perinuclear antineutrophil cytoplasmic antibody test. An echocardiogram demonstrated a pericardial effusion, and subsequent cardiac magnetic resonance features were compatible with myopericarditis. In light of these findings, the patient was diagnosed with eosinophilic granulomatous with polyangiitis and commenced on high-dose intravenous methylprednisolone and cyclophosphamide. She made an excellent recovery and remains in remission on azathioprine and a tapering dose of corticosteroids.