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Background An association with aortic aneurysm has been reported among patients with atrial fibrillation (AF). The aims of this study were to investigate the prevalence of thoracic aorta aneurysm (TAA) among patients with AF and to assess whether the co-presence of TAA is associated with a higher risk of adverse clinical outcomes. Methods and results Using TriNetX, a global federated health research network of anonymised electronic medical records, all adult patients with AF, were categorised into two groups based on the presence of AF and TAA or AF alone. Between 1 January 2017 and 1 January 2019, 874,212 people aged ≥ 18 years with AF were identified. Of these 17,806 (2.04%) had a TAA. After propensity score matching (PSM), 17,805 patients were included in each of the two cohorts. During the 3 years of follow-up, 3079 (17.3%) AF patients with TAA and 2772 (15.6%) patients with AF alone, developed an ischemic stroke or transient ischemic attack (TIA). The risk of ischemic stroke/TIA was significantly higher in patients with AF and TAA (HR 1.09, 95% CI 1.04–1.15; log-rank p value The risk of major bleeding was higher in patients with AF and TAA (OR 1.07, 95% CI 1.01–1.14), but not significant in time-dependent analysis (HR 1.04, 95% CI 0.98–1.10; log-rank p value = 0.187), Conclusion This retrospective analysis reports a clinical concomitance of the two medical conditions, and shows in a PSM analysis an increased risk of ischemic events in patients affected by TAA and AF compared to AF alone.

Background: Atrial fibrillation (AF) is common and increases the risk of stroke and mortality. Previous studies have suggested that air pollution is an important risk factor for new-onset AF. Herein, we review the evidence regarding: 1) the association between exposure to particulate matter (PM) and new-onset AF, and 2) the risk of worse clinical outcomes in patients with pre-existent AF and their relation to PM exposure.Methods: A selection of studies between 2000 and 2023 linking PM exposure and AF was performed through searches in PubMed, Scopus, Web of Science, and Google Scholar.Results: 17 studies from different geographical areas demonstrated that exposure to PM was associated with an increased risk of new-onset AF, although the results were heterogeneous regarding the temporal pattern (short- or long-term) ultimately related to AF. Most of the studies concluded that the risk of new-onset AF increased between 2 %-18 % per 10 μg/m3 increment in PM2.5 or PM10 concentrations, whereas the incidence (percentage of change of incidence) increased between 0.29 %-2.95 % per 10 μg/m3 increment in PM2.5 or PM10. Evidence about the association between PM and adverse events in patients with pre-existent AF was scarce but 4 studies showed a higher risk of mortality and stroke (between 8 %-64 % in terms of hazard ratio) in patients with pre-existent AF when PM exposure was higher.Conclusions: Exposure to PM (both PM2.5 and PM10) is a risk factor for AF, and a risk factor for mortality and stroke in patients who already suffer from AF. Since the relationship between PM and AF is independent of the region of the world, PM should be considered as a global risk factor for both AF and worse clinical outcomes in AF patients. Specific measures to prevent air pollution exposure need to be adopted. Background: Atrial fibrillation (AF) is common and increases the risk of stroke and mortality. Previous studies have suggested that air pollution is an important risk factor for new-onset AF. Herein, we review the evidence regarding: 1) the association between exposure to particulate matter (PM) and new-onset AF, and 2) the risk of worse clinical outcomes in patients with pre-existent AF and their relation to PM exposure.Methods: A selection of studies between 2000 and 2023 linking PM exposure and AF was performed through searches in PubMed, Scopus, Web of Science, and Google Scholar.Results: 17 studies from different geographical areas demonstrated that exposure to PM was associated with an increased risk of new-onset AF, although the results were heterogeneous regarding the temporal pattern (short- or long-term) ultimately related to AF. Most of the studies concluded that the risk of new-onset AF increased between 2 %-18 % per 10 μg/m3 increment in PM2.5 or PM10 concentrations, whereas the incidence (percentage of change of incidence) increased between 0.29 %-2.95 % per 10 μg/m3 increment in PM2.5 or PM10. Evidence about the association between PM and adverse events in patients with pre-existent AF was scarce but 4 studies showed a higher risk of mortality and stroke (between 8 %-64 % in terms of hazard ratio) in patients with pre-existent AF when PM exposure was higher.Conclusions: Exposure to PM (both PM2.5 and PM10) is a risk factor for AF, and a risk factor for mortality and stroke in patients who already suffer from AF. Since the relationship between PM and AF is independent of the region of the world, PM should be considered as a global risk factor for both AF and worse clinical outcomes in AF patients. Specific measures to prevent air pollution exposure need to be adopted.

Sternal surgical wound infection (SSWI) in cardiac surgery is associated with increased morbidity. We investigated the incidence of SSWI, the main germs implicated and predictors of SSWI. Prospective study including patients undergoing full median sternotomy between January 2017 and December 2019. Patients were followed-up for 3 months after hospital discharge. All sternal wound infections up to 90 days after discharge were considered SSWI. 1004 patients were included. During follow-up, 68 (6.8%) patients presented SSWI. Patients with SSWI had a higher incidence of postoperative renal failure (29.4% vs 17.1%, P = .007), a higher incidence of early postoperative reoperation for non-infectious causes (42.6% vs 9.1%, P .001), longer ICU stay (3 [2-9] days vs 2 [2-4] days, P = .006), and longer hospital stay (24.5 [14.8-38.3] days vs 10 [7-18] days, P .001). Gram-positive germs were presented in 49% of the cultures, and gram-negative bacteria in 35%. Early reoperation for non-infectious causes (OR 4.90, 95% CI 1.03-23.7), and a longer ICU stay (OR 1.37 95% CI 1.10-1.72) were independent predictors of SSWI. SSWI is rare but leads to more postoperative complications. The need for early reoperation because of non-infectious cause and a longer ICU stay were independently associated with SSWI.

AIM: To investigate the impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the risk of incident heart failure and adverse cardiovascular outcomes.METHODS: All patients with diabetes who were registered between January 2018 and December 2019 were identified from a federated electronic medical record database (TriNetX) and followed up for 2 years. A 1:1 propensity-score matching (PSM) analysis was performed to balance the SGLT2 inhibitor and non-SGLT2 inhibitor cohorts. The primary outcome was incident heart failure. Secondary outcomes included all-cause mortality, cardiac arrest, ventricular tachycardia/ventricular fibrillation (VT/VF), incident atrial fibrillation (AF), ischaemic stroke/transient ischaemic attack (TIA), composite of arterial and venous thrombotic events, and composite of incident VT/VF and cardiac arrest.RESULTS: A total of 131 189 and 2 692 985 patients were treated with and without SGLT2 inhibitors, respectively. After PSM, 131 188 patients remained in each group. The risk of incident heart failure was significantly lower in the SGLT2 inhibitor cohort compared to the non-SGLT2 inhibitor cohort (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.68-0.73). SGLT2 inhibitor use was also associated with a significantly lower risk of all-cause mortality (HR 0.61, 95% CI 0.58-0.64), cardiac arrest (HR 0.70, 95% CI 0.63-0.78), incident AF (HR 0.81, 95% CI 0.76-0.84), ischaemic stroke/TIA (HR 0.90, 95% CI 0.88-0.93), composite of arterial and venous thrombotic events (HR 0.90, 95% CI 0.88-0.92), and composite of incident VT/VF and cardiac arrest (HR 0.76, 95% CI 0.71-0.81). There were no significant differences for VT/VF (HR 0.94, 95% CI 0.88-1.00).CONCLUSION: Use of SGLT2 inhibitors was associated with a significant reduction in the risk of incident heart failure and adverse cardiovascular outcomes but not ventricular arrhythmias.

Obstructive sleep apnea (OSA) promotes atrial remodeling and fibrosis, providing a substrate for atrial fibrillation (AF). Herein, we investigate the pathophysiological mechanisms of AF in association with OSA in a cohort of cardiac surgery patients. A prospective study including patients undergoing cardiac surgery. Biomarkers reflective of AF pathophysiology (interleukin [IL-6], C-reactive protein [CRP], von Willebrand factor [vWF], N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity Troponin T [hs-TnT], and Galectin-3 [Gal-3]) was assessed by functional or immunological assays. miRNAs involved in AF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Using atrial tissue samples, fibrosis was assessed by Masson's trichrome. Connexin 40 and 43 (Cx40; Cx43) were evaluated by immunolabeling. Fifty-six patients (15 with OSA and 41 non-OSA) were included in this hypothesis-generating pilot study. OSA group had a higher incidence of postoperative AF (POAF) (46.7% vs. 19.5%; p = .042), presented an increased risk of POAF (OR 3.61, 95% CI 1.01-12.92), and had significantly higher baseline levels of NT-proBNP (p = .044), vWF (p = .049), Gal-3 (p = .009), IL-6 (p = .002), and CRP (p = .003). This group presented lower levels of miR-21 and miR-208 (both p

Background The effects of left atrial appendage (LAA) occlusion compared to non-vitamin K antagonist oral anticoagulant (NOAC) therapy in patients with atrial fibrillation (AF) remain unknown. Aims We aimed to evaluate the outcomes in patients with AF who received LAA occlusion vs. NOAC therapy. Methods We utilised data from TriNetX which is a global federated health research network currently containing data for 88.5 million patients. ICD-10 codes were employed to identify AF patients treated with either LAA occlusion or NOAC between 1st December 2010 and 17th January 2019. Clinical outcomes of interest were analysed up to 2 years. Results 108,697 patients were included. Patients who underwent LAA occlusion were younger, more likely to be white Caucasian and male, had a greater incidence of comorbidities, and were less likely to be prescribed other cardiovascular medications. Using propensity score matching, the risk of all-cause mortality was significantly lower among patients who received LAA occlusion compared to NOAC therapy [1.51% vs. 5.60%, RR 0.27 (95% CI 0.14–0.54)], but there were no statistical differences in the composite thrombotic or thromboembolic events [8.17% vs. 7.72%, RR 1.06 (95% CI 0.73–1.53)], ischaemic stroke or TIA [4.69% vs. 5.45%, RR 0.86 (95% CI 0.54–1.38)], venous thromboembolism [1.66% vs. 1.51%, RR 1.10 (95% CI 0.47–2.57)] and intracranial haemorrhage [1.51% vs. 1.51%, RR 1.00 (95% CI 0.42–2.39)]. Conclusion Overall, LAA occlusion might be a suitable alternative to NOAC therapy for stroke prevention in patients with AF. Graphical abstract

Background The Atrial fibrillation Better Care (ABC) pathway was proposed for a more holistic or integrated care approach to atrial fibrillation (AF) management. We investigated whether adherence with the ABC pathway reduced the risk of adverse clinical outcomes in real-world AF patients starting vitamin K antagonist (VKAs) therapy. Methods Prospective cohort study including AF outpatients starting VKA therapy from July 2016 to June 2018. Patients were considered as adherent if all ABC pathway criteria (A: Avoid stroke; B: Better symptom control; and C: Cardiovascular risk factors/comorbidities management) were fulfilled. The primary endpoints were all-cause mortality, net clinical outcomes (NCOs), major adverse cardiovascular events (MACE), and composite thrombotic/thromboembolic events at 2 years. Results We enrolled 1045 patients (51.6% female; median age 77 [70–83] years). Of these, 63.0% (658) were adherent to the ABC pathway and 37% (387) were considered non-adherent. Compared to non-adherent patients, those who were ABC adherent had lower event rates for all-cause mortality (13.76 vs. 6.56; p. 11.94; pp=0.006) during the follow-up. Adjusted Cox regression analyses demonstrated that the ABC pathway adherent care reduced the risks of all-cause mortality (aHR 0.57, 95% CI 0.42–0.78), NCOs (aHR 0.72, 95% CI 0.56–0.92), and cardiovascular mortality (aHR 0.54, 95% CI 0.32–0.90). Event-free survivals for all-cause mortality, NCOs (both log-rank p-values p-value = 0.004) were also higher in ABC pathway adherent patients. Conclusions In this real-world prospective cohort of AF patients starting VKA therapy, adherence to the ABC pathway management at baseline significantly reduced the risk of NCOs, all-cause mortality, and cardiovascular death at 2 years.

Aims: The net benefit of oral anticoagulants (OACs) in atrial fibrillation (AF) is poorly understood. We aimed to determine the NNT for net effect (NNT net) using calculator of absolute stroke risk (CARS) in anticoagulated patients with AF in real-world and clinical trial cohorts. Methods: Post-hoc analysis of patient-level data from the real-world Murcia AF Project and AMADEUS clinical trial. Baseline risk of stroke was determined using CARS. The risk of stroke and major bleeding events with OAC were determined using the number of respective events at 1-year. NNT net was calculated as a reciprocal of the net effect of absolute risk reduction with OAC (NNT net = 1/(absolute risk reduction of stroke[ARR stroke] − absolute risk increase of major bleeding[ARI bleeding])). Results: In total, 3511 patients were included (1306 [37.2%] real-world patients and 2205 [62.8%] clinical trial participants). The absolute 1-year stroke risk was similar across both cohorts. In the real-world cohort, OAC was associated with a 4.0% ARR stroke, 25 NNT benefit, 1.0% ARI bleeding, 100 NNT harm and 34 NNT net. In the clinical trial cohort, OAC was associated with a 3.8% ARR stroke, 27 NNT benefit, 1.6% ARI bleeding, 63 NNT harm and 46 NNT net. In both cohorts, the NNT net was significantly lower in patients with an excess stroke risk of ≥2% by CARS. Conclusion: Overall, the NNT net approach in AF incorporates information regarding baseline risk of stroke and major bleeding, and relative effects of OAC with the potential to include multiple additional outcomes and weighting of events based on their perceived effects by individual patients.

Aims Vitamin K antagonists (VKAs) are effective drugs reducing the risk for stroke in atrial fibrillation (AF), but the benefits derived from such therapy depend on the international normalized ratio (INR) maintenance in a narrow therapeutic range. Here, we aimed to determine independent variables driving poor anticoagulation control [defined as a time in therapeutic range (TTR) Methods and results The SULTAN registry is a multicentre, prospective study, involving patients with non-valvular AF from 72 cardiology units expert in AF in Spain. At inclusion, all patients naïve for oral anticoagulation were started with VKAs for the first time. For the analysis, the first month of anticoagulation and those patients with Conclusion This study demonstrated that the quality of anticoagulation in AF patients newly starting VKAs is sub-optimal. Previous coronary artery disease and concomitant use of amiodarone were identified as independent variables affecting the poor quality of VKA therapy during the first year.

Background Sleep disorders are composed of a group of diseases of increasing prevalence and with social-health implications to be considered a public health problem. Sleep habits and specific sleep behaviors have an influence on the academic success of students. However, the characteristics of sleep and sleep habits of university students as predictors of poor academic performance have been scarcely analyzed. In the present study, we aimed to investigate sleep habits and their influence on academic performance in a cohort of Nursing Degree students. Methods This was a cross-sectional and observational study. An anonymous and self-administered questionnaire was used, including different scales such as the ‘Morningness and Eveningness scale’, an author-generated sleep habit questionnaire, and certain variables aimed at studying the socio-familial and academic aspects of the Nursing students. The association of sleep habits and other variables with poor academic performance was investigated by logistic regression. The internal consistency and homogeneity of the ‘sleep habits questionnaire’ was assessed with the Cronbach’s alpha test. Results Overall, 401 students (mean age of 22.1 ± 4.9 years, 74.8 % females) from the Nursing Degree were included. The homogeneity of the ‘sleep habits questionnaire’ was appropriate (Cronbach’s alpha = 0.710). Nursing students were characterized by an evening chronotype (20.2 %) and a short sleep pattern. 30.4 % of the Nursing students had bad sleep habits. Regarding the academic performance, 47.9 % of the students showed a poor one. On multivariate logistic regression analysis, a short sleep pattern (adjusted OR = 1.53, 95 % CI 1.01–2.34), bad sleep habits (aOR = 1.76, 95 % CI 1.11–2.79), and age Conclusions Almost 1/3 of the Nursing students were identified as having bad sleep habits, and these students were characterized by an evening chronotype and a short sleep pattern. A short sleep pattern, bad sleep habits, and age

Objective The ‘Atrial fibrillation Better Care’ (ABC) pathway has been recently proposed as a holistic approach for the comprehensive management of patients with atrial fibrillation (AF). We performed a systematic review of current evidence for the use of the ABC pathway on clinical outcomes. Methods and Results We performed a systematic review and meta-analysis according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and EMBASE were searched for studies reporting the prevalence of ABC-pathway-adherent management in AF patients, and its impact on clinical outcomes (all-cause death, cardiovascular death, stroke, and major bleeding). Meta-analysis of odds ratio (OR) was performed with random-effects models; subgroup analysis and meta-regression were performed to account for heterogeneity. Among the eight studies included, we found a pooled prevalence of ABC-adherent management of 21% (95% confidence interval, CI: 13–34%), with a high grade of heterogeneity, explained by the increasing adherence to each ABC criterion. Patients treated according to the ABC pathway showed a lower risk of all-cause death (OR: 0.42; 95% CI: 0.31–0.56), cardiovascular death (OR: 0.37; 95% CI: 0.23–0.58), stroke (OR: 0.55; 95% CI: 0.37–0.82) and major bleeding (OR: 0.69; 95% CI: 0.51–0.94), with moderate heterogeneity. Prevalence of comorbidities was moderators of heterogeneity for all-cause and cardiovascular death, while longer follow-up was associated with increased effectiveness for all outcomes. Conclusion Adherence to the ABC pathway was suboptimal, being adopted in one in every five patients. Adherence to the ABC pathway was associated with a reduction in the risk of major adverse outcomes.

INTRODUCTION: For a long time, vitamin K antagonists (VKA) were the only oral anticoagulation therapy available to reduce adverse events in atrial fibrillation (AF) patients. Direct-acting oral anticoagulants (DOAC) are at least as effective and safe as VKA with few drug interactions, rapid onset, and short half-life. Four DOACs, dabigatran, apixaban, rivaroxaban, and edoxaban, have demonstrated efficacy and safety for treatment in AF patients.AREAS COVERED: The purpose of this review article is to analyze the current evidence in clinical trials and in real-world populations and performed a new analysis with the estimated effect of those DOACs over the VKA population from the FANTASIIA registry.EXPERT OPINION: In the absence of randomized, controlled head-to-head comparisons between DOACs, high-quality observational data can provide useful information on the comparative effectiveness of DOACs. Current clinical guidelines recommend the management of oral anticoagulation in AF patients with DOACs over VKA for stroke prevention; however, many guidelines generally do not suggest a specific DOAC choice in clinical practice. The revised evidence in this manuscript and our real experience reflects that apixaban and dabigatran show the best efficacy and safety profile.

The 2020 ESC atrial fibrillation (AF) guidelines suggest the novel 4S-AF scheme for the characterization of AF. Imaging techniques could be helpful for this objective in everyday clinical practice, and information derived from these techniques reflects basic aspects of the pathophysiology of AF, which may facilitate treatment decision-making, and optimal management of AF patients. The aim of this review is to provide an overview of the mechanisms associated with atrial fibrosis and to describe imaging techniques that may help the management of AF patients in clinical practice. Transthoracic echocardiography is the most common procedure given its versatility, safety, and simplicity. Transesophageal echocardiography provides higher resolution exploration, and speckle tracking echocardiography can provide incremental functional and prognostic information over conventional echocardiographic parameters. In addition, LA deformation imaging, including LA strain and strain rate, are related to the extent of fibrosis. On the other hand, multidetector-row computed tomography and cardiac magnetic resonance provide higher resolution data and more accurate assessment of the dimensions, structure, and spatial relationships of the LA. Imaging is central when deciding on catheter ablation or cardioversion, and helps in selecting those patients who will really benefit from these procedures. Moreover, imaging enhances the understanding of the underlying mechanisms of atrial remodeling and might assists in refining the risk of stroke, which help to select the best medical therapies/interventions. In summary, evaluation of LA enlargement, LA remodeling and fibrosis with imaging techniques adds clinical and prognostic information and should be assessed as a part of routine comprehensive AF evaluation.

Background The risk of stroke according to clinical classification of atrial fibrillation (AF) remains poorly defined. Here, we assessed the impact of AF type on stroke risk in vitamin K antagonist-treated patients with AF in ‘real-world’ and ‘clinical trial’ cohorts. Methods Post-hoc analysis of patient-level data from the Murcia AF Project and AMADEUS trial. Clinical classification of AF was based on contemporary recommendations from international guidelines. Study endpoint was the incidence rate of ischaemic stroke. Stroke risk was determined using CHA2DS2-VASc score and CARS. A modified CHA2DS2-VAS‘c’ score that applied one additional point for a ‘c’ criterion of continuous AF (i.e. non-paroxysmal AF) was calculated. Results We included 5,917 patients: 1,361 (23.0%) real-world and 4,556 (77.0%) clinical trial. Baseline demographics were balanced in the real-world cohort but clinical trial participants with non-pAF (vs. pAF) were older, male-predominant and had more comorbidities. Crude stroke rates were comparable between the groups in real-world patients (IRR 0.72 [95% CI,0.37-1.28], p = 0.259) though clinical trial participants with non-pAF had a significantly higher crude rate of stroke events (IRR 4.66 [95%,CI,2.41-9.48], p p = 0.239) and clinical trial (adjusted HR 1.16 [95% CI,0.62-2.20], p = 0.646) cohorts, after accounting for other risk factors. There was no significant improvement in the CHA2DS2-VAS‘c’ compared to CHA2DS2-VASc score in either cohorts (p > 0.05). Conclusions Overall, our results support the need for anticoagulation based on thromboembolic risk profile rather than AF type.

Atherosclerosis is a chronic, progressive, inflammatory disease in the vasculature and is common in both coronary and peripheral arteries. Human beings harbor a complex and dynamic population of microorganisms defined as the microbiota. Importantly, alterations in the bacterial composition (dysbiosis) and the metabolic compounds produced by these bacteria have been associated with the pathogenesis of many inflammatory diseases and infections. There is also a close relationship between intestinal microbiota and cardiovascular diseases. The aim of this review was to analyze how changes in the gut microbiota and their metabolites might affect coronary artery diseases. The most representative groups of bacteria that make up the intestinal microbiota are altered in coronary artery disease patients, resulting in a decrease in Bacteroidetes and an increase in Firmicutes. In relation to metabolites, trimethylamine-N-oxide plays an important role in atherosclerosis and may act as a cardiovascular risk predictor. In addition, the use of probiotics, prebiotics, diet modulation, and fecal transplantation, which may represent alternative treatments for these diseases, is thoroughly discussed. Finally, the role of lipid-lowering treatments is also analyzed as they may affect and alter the gut microbiota and, conversely, gut microbiota diversity could be associated with resistance or sensitivity to these treatments.

Background: The use of rapid deployment and sutureless aortic prostheses is increasing. Previous reports have shown promising results on haemodynamic performance and mortality rates. However, the impact of these bioprostheses on left ventricular mass (LVM) regression remains unknown. We decided to study the changes in remodelling and LVM regression in isolated severe aortic stenosis treated with conventional or Perceval® or Intuity® valves. Method and Results: From January 2011 to January 2016, 324 bioprostheses were implanted in our centre. The collected characteristics were divided into 3 groups: conventional valves, Perceval®, and Intuity®, and they were analysed after 12 months. There were 183 conventional valves (56%), 72 Perceval® (22%), and 69 Intuity® (21.2%). The statistical analysis showed significant differences in transprosthetic postoperative peak gradient (23 [18–29] mm Hg vs. 21 [16–29] mm Hg and 18 [14–24] mm Hg, p < 0.001), ventricular mass electrical criteria regression (Sokolow and Cornell products), and 1-year survival (90 vs. 93% and 97%, log rank p value = 0.04) in conventional, Perceval®, and Intuity® groups. Conclusions: We observed differences in haemodynamic, electrocardiographic, and echocardiographic parameters related to the different types of prosthesis. Patients with the Intuity® prosthesis had the highest reduction in peak aortic gradient and the higher ventricular mass regression. Besides, patients with the Intuity® prosthesis had less risk of mortality during follow-up than the other two groups. Further studies are needed to confirm these findings.

Alzheimer's disease (AD) is the most common form of dementia. It affects approximately 6% of people over the age of 65 years. It is a clinicopathological, degenerative, chronical and progressive disease that exhibits a deterioration of memory, orientation, speech and other functions. Factors contributing to the pathogenesis of the disease are the presence of extracellular amyloid deposits, called neuritic senile plaques, and fibrillary protein deposits inside neurons, known as neurofibrillary bundles, that appear mainly in the frontal and temporal lobes. AD has a long preclinical latency and is difficult to diagnose and prevent at early stages. Despite the advent of novel high-throughput technologies, it is a great challenge to identify precise biomarkers to understand the progression of the disease and the development of new treatments. In this sense, important knowledge is emerging regarding novel molecular and biological candidates with diagnostic potential, including microRNAs that have a key role in gene repression. On the other hand, proteomic approaches offer a platform for the comprehensive analysis of the whole proteome in a certain physiological time. Proteomic technology investigates protein expression directly and reveals post-translational modifications known to be determinant for many human diseases. Clinically, there is growing evidence for the role of proteomic and metabolomic technologies in AD biomarker discovery. This review discusses the role of several miRNAs identified using genomic technologies, and the importance of novel proteomic and metabolomic approaches to identify new proteins and metabolites that may be useful as biomarkers for monitoring the progression and treatment of AD.

Introduction: Atrial fibrillation is the most common sustained cardiac rhythm disorder, which currently affects 1–2% of the global population. Furthermore, the incidence and prevalence of atrial fibrillation is rising. Biomarkers have the potential to improve clinical management of patients and therefore reduce the burden on health systems in the future. Areas covered: A variety of pathways and mechanisms have been associated with atrial fibrillation. This paper provides an overview of a range of blood-based, imaging and genetic biomarkers that are associated with mechanisms and outcomes in atrial fibrillation and their potential use in a clinical setting. Expert commentary: Atrial fibrillation is becoming increasingly prevalent. Current biomarkers associated with atrial fibrillation such as those involved in myocardial stress, inflammation, hemostasis and fibrosis do not currently provide much additional practical value beyond recommended scores based only on clinical risk factors.

Introduction: Oral anticoagulants (OAC) reduce stroke/systemic embolism and mortality risks in atrial fibrillation (AF). However, there is an inherent bleeding risk with OAC, where intracranial hemorrhage (ICH) is the most feared, disabling, and lethal complication of this therapy. Therefore, the optimal management of OAC-associated ICH is not well defined despite multiple suggested strategies. Areas covered: In this review, the authors describe the severity and risk factors for OAC-associated ICH and the associated implications for using DOACs in AF patients. We also provide an overview of the management of OAC-associated ICH and treatment reversal strategies, including specific and nonspecific reversal agents as well as a comprehensive summary of the evidence about the resumption of DOAC and the optimal timing. Expert opinion: In the setting of an ICH, supportive care/measures are needed, and reversal of anticoagulation with specific agents (including administration of vitamin K, prothrombin complex concentrates, idarucizumab and andexanet alfa) should be considered. Most patients will likely benefit from restarting anticoagulation after an ICH and permanently withdrawn of OAC is associated with worse clinical outcomes. Although the timing of OAC resumption is still under debate, reintroduction after 4–8 weeks of the bleeding event may be possible, after a multidisciplinary approach to decision-making.

Background. Most evidence regarding anticoagulation and COVID-19 refers to the hospitalization setting, but the role of oral anticoagulation (OAC) before hospital admission has not been well explored. We compared clinical outcomes and short-term prognosis between patients with and without prior OAC therapy who were hospitalized for COVID-19. Methods. Analysis of the whole cohort of the HOPE COVID-19 Registry which included patients discharged (deceased or alive) after hospital admission for COVID-19 in 9 countries. All-cause mortality was the primary endpoint. Study outcomes were compared after adjusting variables using propensity score matching (PSM) analyses. Results. 7698 patients were suitable for the present analysis (675 (8.8%) on OAC at admission: 427 (5.6%) on VKAs and 248 (3.2%) on DOACs). After PSM, 1276 patients were analyzed (638 with OAC; 638 without OAC), without significant differences regarding the risk of thromboembolic events (OR 1.11, 95% CI 0.59–2.08). The risk of clinically relevant bleeding (OR 3.04, 95% CI 1.92–4.83), as well as the risk of mortality (HR 1.22, 95% CI 1.01–1.47; log-rank p value = 0.041), was significantly increased in previous OAC users. Amongst patients on prior OAC only, there were no differences in the risk of clinically relevant bleeding, thromboembolic events, or mortality when comparing previous VKA or DOAC users, after PSM. Conclusion. Hospitalized COVID-19 patients on prior OAC therapy had a higher risk of mortality and worse clinical outcomes compared to patients without prior OAC therapy, even after adjusting for comorbidities using a PSM. There were no differences in clinical outcomes in patients previously taking VKAs or DOACs. This trial is registered with NCT04334291/EUPAS34399.

In atrial fibrillation (AF) patients on vitamin K antagonists, a progressive deterioration of renal function is common but there is limited evidence with long-term use of rivaroxaban. Herein, we investigated the change in renal function in AF patients after 2 years of rivaroxaban treatment.The EMIR registry is an observational and multicentre study including AF patients treated with rivaroxaban for at least 6 months prior to inclusion. Changes in analytical parameters were recorded during 2 years of follow-up. Renal function was estimated using the Cockroft-Gault equation.1433 patients (638, 44.5% women, mean age of 74.2 ± 9.7 years) were included. Creatinine clearance (CrCl) was available at baseline and at 2 years in 1085 patients. At inclusion, 33.2% of patients had impaired renal function (CrCl 60 ml/min). At 2 years, we were not able to find changes in the proportion of patients with impaired renal function, which increased to 34.6% (p = 0.290). However, the baseline mean CrCl was 76.0 ± 30.5 ml/min and slightly improved at 2 years (77.0 ± 31.8 ml/min; p = 0.014). Overall, the proportion of patients with CrCl60 ml/min at baseline that had CrCl ≥60 ml/min at 2 years was significantly higher compared to that of patients with CrCl ≥60 ml/min at baseline and CrCl60 ml/min after (22.2% vs. 13.1%; p 0.001) CONCLUSIONS: In AF patients on long-term rivaroxaban therapy, a decrease in renal function was not observed. We even observed a slight improvement in the patients with renal impairment. These results reinforce the idea that rivaroxaban may be a safe option even in patients with renal impairment.

Background: Healthcare workers are continuously exposed to a high level of stress, especially emergency department professionals. In the present research, we aimed to determine the internal consistency and validity of the Stress Factors and Manifestations Scale for in-hospital and out-of-hospital emergency workers. Methods: A quantitative, prospective, cross-sectional, and observational study including 269 emergency service professionals. Results: The scale was composed of 21 items, with a Cronbach’s α value of 0.908. The hospital workers (38.4 ± 10.8 vs. 35.1 ± 9.9, p = 0.014) and women (39.3 ± 11.4 vs. 34.2 ± 8.6, p < 0.001) had higher levels of stress. The sensitivity, specificity, and predictive values of the scale were adequate. Conclusion: In the present study, including in-hospital and out-of-hospital emergency workers, the Stress Factors and Manifestations Scale presented appropriate usefulness, internal consistency, and validity, with optimal predictive ability. Higher levels of anxiety, female gender, being less optimistic, and working in hospital emergency departments were related to increased stress levels. Further studies are warranted to validate our results and potentially extend the Stress Factors and Manifestations Scale to other contexts.

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are effective anti-diabetic drugs improving cardiovascular outcomes in type 2 diabetes mellitus (T2DM) patients. This study investigated cardiovascular, cerebrovascular and cognitive outcomes of SGLT2i therapy in patients with atrial fibrillation (AF) and T2DM. Methods: Observational study using TriNetX, a global health research network of anonymised electronic medical records from real-world patients between January 2018 and December 2019. The network includes healthcare organisations globally but predominately in the United States. AF patients (ICD-10-CM code: I48) with T2DM were divided according to SGLT2i use or not, and balanced using propensity score matching (PSM). Patients were followed-up for 3-years. The primary endpoints were ischaemic stroke/transient ischemic attack (TIA), intracranial haemorrhage (ICH), and incident dementia. Secondary endpoints were incident heart failure and mortality. Results: We identified 89,356 AF patients with T2DM of which 5061 (5.7%) were taking a SGLT2i. After PSM, 5049 patients (mean age 66.7 ± 10.6 years; 28.9% female) were included in each group. At 3-years follow-up, the risk of ischaemic stroke/TIA was higher in patients not receiving SGLT2i (HR 1.12, 95% CI 1.01–1.24) and for ICH (HR 1.57, 95% CI 1.25–1.99) and incident dementia (HR 1.66, 95% CI 1.30–2.12). Incident heart failure (HR 1.50, 95% CI 1.34–1.68) and mortality (HR 1.77, 95% CI 1.58–1.99) risks were increased in AF patients not receiving SGLT2i. Conclusions: In our large ‘real world’ analysis of patients with concomitant AF and T2DM, SGLT2i reduced the risk of cerebrovascular events, incident dementia, heart failure and death.

Objective Several scores were available for predicting atrial fibrillation (AF) recurrence following radiofrequency ablation. Exploring their differences in patients with concurrent AF and pulmonary diseases (PDs) would be helpful for making AF treatment decisions. Methods and Results From January 2008 to April 2015, 304 patients with concurrent AF and PDs treated with catheter ablation were divided into 2 groups according to whether they experienced AF recurrence in our centers. During a mean of 13.42-month of follow-up, factors correlating with late AF recurrence included heart failure (HF) history, (HR[hazard ratio]: 2.79, 95% CI [confidence interval]: 1.49-5.22, p=0.001), current smoking (1.73, 1.13-2.68, p=0.01) and early AF recurrence (3.85, 95% CI: 2.62-5.66, p

We investigated the impact of diabetes mellitus (DM) in acute coronary syndrome (ACS) patients, and the 2-year prognosis based on antiplatelet therapy.This is a prospective and multicenter registry including hospitalized ACS patients. Clinical management and antiplatelet therapy at discharge were recorded. Bleeding events, all-cause mortality and major adverse cardiovascular events (MACEs) were recorded during 2-years and compared according to DM and the P2YFrom 1717 ACS patients, 653 (38%) had DM. Diabetic patients were older, more commonly females, with higher prevalence of comorbidities and more conservative management. After excluding antiplatelet monotherapy or oral anticoagulation, clopidogrel was prescribed in 59.6% of DM patients. Cox regression analysis showed that DM was an independent risk factor for MACE (aHR 1.39, 95% CI 1.05-1.83). The use of clopidogrel instead of ticagrelor/prasugrel was also independently associated with MACE (aHR 1.71, 95% CI 1.11-2.63), and all-cause mortality (aHR 2.47, 95% CI 1.23-4.96) in diabetic patients (log-rank p-values 0.001).In ACS patients, DM was associated with higher risk of MACE. In such patients, the use of ticagrelor/prasugrel reduced MACE and mortality compared to clopidogrel. Novel P2Y

BACKGROUND: Atrial fibrillation (AF) increases the risk of thromboembolism. We investigate the efficacy and safety of oral anticoagulation (OAC) therapy and explored the number needed to treat for net effect (NNTnet) of OAC in the Spanish cohort of the EURObservational Research Programme-AF (EORP-AF) Long-term General Registry. METHODS: The EORP-AF General Registry is a prospective, multicentre registry conducted in ESC countries, including consecutive AF patients. For the present analysis, we used the Spanish cohort, and the primary outcome was any thromboembolism (TE)/acute coronary syndrome (ACS)/cardiovascular death during the first year of follow-up. RESULTS: 729 AF patients were included (57.1% male, median age 75 [IQR 67-81] years, median CHA(2) DS(2) -VASc and HAS-BLED of 3 [IQR 2-5] and 2 [IQR 1-2], respectively). 548 (75.2%) patients received OAC alone (318 [43.6%] on VKAs and 230 [31.6%] on DOACs). After 1 year, the use of OAC alone showed lower rates of any TE/ACS/cardiovascular death (3.0%/year; p

BACKGROUND: Multimorbidity is common in atrial fibrillation (AF) patients. Charlson comorbidity index (CCI) is used to evaluate multimorbidity in the general population. Limited long-term data are available on the relationship between CCI and AF. We examined the association between CCI, anticoagulation control and outcomes in AF patients.METHODS: We studied 1956 from the FANTASIIA registry, an observational Spanish nationwide study on anticoagulated AF patients. Time in therapeutic range (TTR) was used to evaluate anticoagulation control. Stroke/TIA, major bleeding, cardiovascular (CV) death and all-cause death were study outcomes.RESULTS: Mean ± SD CCI was 1.1 ± 1.2. Based on CCI quartiles, patients were categorised in four groups: 676 (34.6%) in Q1 (CCI 0); 683 (34.9%) in Q2 (CCI 1); 345 (17.6%) in Q3 (CCI 2); and 252 (12.9%) in Q4 (CCI ≥3). In vitamin K antagonist treated patients, the highest CCI quartile was inversely associated with TTR >70% (odds ratio:0.67, 95% confidence interval (CI):0.45-0.99). During observation, a progressively higher rate of major bleeding, CV death and all-cause death was found across the quartiles (all p < 0.001). The final Cox multivariable regression analysis showed an association with increasing risk for major bleeding occurrence in Q3 and Q4 (hazard ratio (HR):1.69, 95%CI:1.00-2.87 and HR:1.92, 95%CI:1.08-3.41). An increasing risk for all-cause death and CV death was found across CCI quartiles.CONCLUSIONS: In a nationwide contemporary cohort of AF anticoagulated patients, multimorbidity was inversely associated with good anticoagulation control. A progressively higher risk for major bleeding, CV death and all-cause death was found across CCI quartiles.

Background Atrial fibrillation (AF) increases the risk of stroke and mortality, and concomitant renal impairment confers a worse prognosis. However, those factors that may limit the use of direct-acting oral anticoagulants in AF patients with renal impairment have not been further investigated, as they confer a higher risk of adverse events in this patient population. Purpose To investigate predictors of adverse clinical outcomes in AF patients with renal impairment who were treated with rivaroxaban. Methods The EMIR study is an observational, multicenter study including patients with AF treated with rivaroxaban for at least the previous 6 months. During 2.5 years of follow-up, the occurrence of thromboembolic events (the composite of isquemic stroke, transient ischemic attack, systemic embolism and myocardial infarction [MI]), major bleeding (ISTH definition) and major adverse cardiovascular events (MACE: fatal/non-fatal MI, myocardial revascularization and cardiovascular death) were recorded. For the present analysis, creatinine clearance (CrCl) was estimated by using the Cockroft-Gault equation and renal impairment was defined as a CrCl Results 1433 patients were included (44.5% female; mean age 74.2±9.7 years), of which 498 (35.1%) had CrCl Conclusions Rivaroxaban showed excellent results in moderate renal impairment. However, the annual rate of major bleeding and MACE was higher in AF patients with impaired renal function. In patients with AF and renal impairment, male sex, the presence of heart failure, dependency, the concomitant use of antiplatelets, and greater comorbidity according to the CHA2DS2-VASc and HAS-BLED, were associated with higher risk of adverse clinical outcomes. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer

Background The most widely accepted clinical classification of atrial fibrillation (AF) is according to temporal rhythm-based patterns, reflecting the notion that most patients initially suffer from transient episodes that prolong over time due to atrial substrate remodelling as the disease progresses. Therefore, it may be speculated that patients with extended episodes of “continuous” AF (persistent, long-standing persistent and permanent AF) may be at higher risk of stroke complications compared to paroxysmal AF (pAF). However, the risk of stroke according to clinical classification of AF remains poorly defined. In this study, we assessed the impact of AF type on stroke risk in patients with AF from “real-world” and “clinical trial” cohorts. Methods Post-hoc analysis of patient-level data from the Murcia AF Project and AMADEUS trial. All patients were anticoagulated. Patients were grouped into those with pAF and non-pAF. pAF was defined as AF that terminates spontaneously or with intervention within seven days of onset. Non-pAF was defined as AF that lasted longer than seven days, including persistent, long-standing persistent and permanent AF subtypes. Study endpoint was the incidence rate of ischaemic stroke. A modified CHA2DS2-VAS“c” score that applied one additional point for a “c” criterion of continuous AF (i.e. non-pAF) was calculated. Results 5,917 patients were included; 1,361 (23.0%) real-world and 4,556 (77.0%) clinical trial. Real-world patients had a median age of 76 (interquartile range [IQR] 71–81) years with 51.3% females compared to a median age of 71 (IQR 64–77) years with 33.5% females among clinical trial participants. Baseline demographics were comparable in both groups in the real-world cohort but clinical trial participants with non-pAF were older, predominantly male and had more comorbidities compared to those with pAF. Crude stroke rates were comparable between the groups in real-world patients (incidence rate ratio [IRR] 0.72 [95% CI, 0.37–1.28], p=0.259) though clinical trial participants with non-pAF (vs. pAF) had a significantly higher crude rate of stroke events (IRR 4.66 [95% CI, 2.41–9.48], p0.05). Conclusion Overall, there was no association between the temporal rhythm-based patterns of AF and stroke risk among anticoagulated patients, suggesting that this should not be a consideration when assessing the need for anticoagulation in AF. Funding Acknowledgement Type of funding sources: None.

Aims The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischaemic Cardiovascular Disease Long Term (CICD LT) registry aims to study the clinical profile, treatment modalities, and outcomes of patients diagnosed with CICD in a contemporary environment in order to assess whether these patients at high cardiovascular (CV) risk are treated according to ESC guidelines on prevention or on stable coronary disease and to determine mid- and long-term outcomes and their determinants in this population. Methods and results Nine thousand one hundred and seventy-four patients over 18 years with documented CICD defined by a history acute coronary syndrome with/without ST elevation, previous coronary revascularization, or stable coronary artery disease were enrolled between 1 May 2015 and 31 July 2018. Individual patient data on clinical profile, biology, and treatment modalities were collected across 154 centres from 20 ESC countries. Two years of follow-up is scheduled in order to determine the following clinical outcomes: all-cause and CV death, all-cause and CV hospitalizations, changes in medications, and quality of life using the EuroQol5D-5L score. Conclusion The CICD LT is an international registry of care and outcomes of patients hospitalized with CICD which will provide insights into the contemporary profile and management of patients with this common disease.