Impact of prior oral anticoagulation therapies on post-discharge outcomes after COVID-19: Results from a global federated health network analysis.

BACKGROUND: The impact of chronic oral anticoagulant (OACs) use on long-term post-discharge outcomes after coronavirus disease 2019 (COVID-19) hospitalisation remains unclear. Herein, we compared clinical outcomes up to 2-years after COVID-19 hospitalisation between patients on vitamin K antagonists (VKAs), direct-acting OACs (DOACs) and no OAC therapy. METHODS: Data from TriNetX, a global federated health research network, were used. Adult patients on VKAs, DOACs or no OAC therapy at diagnosis of COVID-19 between 20 January 2020 and 31 December 2021, who were hospitalised for COVID-19, were included. The primary outcomes were all-cause mortality, ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and the composite of intracranial haemorrhage (ICH)/gastrointestinal bleeding, at 2 years after COVID-19 hospitalisation. RESULTS: We included 110,834 patients with COVID-19. Following propensity score matching (PSM), we identified a decreased mortality risk in DOAC-treated patients compared to the no OAC cohort (RR .808, 95% CI .751-.870). A higher risk of ischaemic stroke/TIA/SE was observed in VKA users compared to DOAC users (RR 1.100, 95% CI 1.020-1.220) and in VKA users compared to patients not taking OAC (RR 1.400, 95% CI 1.140-1.720). VKA use was associated with a greater risk of ICH/gastrointestinal bleeding than DOAC users (RR 1.198, 95% CI 1.066-1.347), while DOAC users had a lower risk compared to no OAC-treated patients (RR .840, 95% CI .754-.936). CONCLUSION: COVID-19 patients taking prior DOACs were associated with lower long-term mortality risk and ICH/gastrointestinal bleeding than patients not taking OAC. Compared to patients on DOACs, VKA users were associated with higher risks of mortality, ischaemic stroke/TIA/SE and ICH/gastrointestinal bleeding.

Advances in the medical treatment and diagnosis of intracranial hemorrhage associated with oral anticoagulation.

INTRODUCTION: With the increasing prevalence of atrial fibrillation (AF), it entails expanding oral anticoagulants (OACs) use, carrying a higher risk of associated hemorrhagic events, including intracranial hemorrhage (ICH). Despite advances in OACs development with a better safety profile and reversal agent for these anticoagulants, there is still no consensus on the optimal management of patients with OACs-associated ICH. AREAS COVERED: In this review, the authors have carried out an exhaustive search on the advances in recent years. The authors provide an update on the management of ICH in anticoagulated patients, as well as an update on the latest evidence on anticoagulation resumption, recent therapeutic strategies, and investigational drugs that could play a role in the future. EXPERT OPINION: Following an ICH event in an anticoagulated patient, a comprehensive clinical evaluation is imperative. Anticoagulation should be promptly withdrawn and reversed. Once the patient is stabilized, a reintroduction of anticoagulation should be considered, typically within a timeframe of 4-8 weeks, if feasible. If re-anticoagulation is not possible, alternative options such as Left Atrial Appendage Occlusion are available.

Patients with atrial fibrillation and common exclusion criteria from clinical trials are at high risk of clinical events: the Murcia AF Project II (MAFP-II) cohort study.

BACKGROUND: Some clinical characteristics and comorbidities in atrial fibrillation (AF) patients are exclusion criteria in randomized clinical trials (RCTs) investigating oral anticoagulants (OAC). However, these conditions are present also in everyday clinical practice patients. We compared the risk of adverse clinical outcomes between patients with and without RCT exclusion criteria. METHODS: The Murcia AF Project II was an observational cohort study including AF outpatients starting vitamin K antagonists (VKAs) from July 2016 to June 2018. For the selection of the exclusion criteria, the four pivotal RCTs of direct-acting OAC (DOACs) were used as reference. During 2 years, all ischemic strokes/transient ischemic attacks, major adverse cardiovascular events (MACEs), major bleeds, and all-cause deaths were recorded. RESULTS: 1050 patients (51.5% female, median age 77 years) were included, of whom 368 (35%) met at least one exclusion criterion for RCTs. During follow-up, the incidence rate ratios for major bleeding, MACE and all-cause mortality were higher among patients with exclusion criteria (all p < 0.001). Patients fulfilling at least one exclusion criterion had increased risks of major bleeding (aHR 1.48; 95% CI 1.22-1.81; p < 0.001), MACE (aHR 1.51, 95% CI 1.10-2.09, p = 0.012), and mortality (aHR 3.22, 95% CI 2.32-4.48, p < 0.001), as well as a lower event-free survival (all log-rank p < 0.001). CONCLUSIONS: In this AF cohort taking VKAs, more than one-third had at least one RCT exclusion criteria, which translates into higher risk of major bleeding, MACE, and death. These observations should be considered when translating RCTs results to AF patients for a proper and a more patient-centered management.

Dynamic assessment of CHA2DS2-VASc and HAS-BLED scores for predicting ischemic stroke and major bleeding in atrial fibrillation patients.

INTRODUCTION AND OBJECTIVES: Stroke and bleeding risks in atrial fibrillation (AF) are often assessed at baseline to predict outcomes years later. We investigated whether dynamic changes in CHA2DS2-VASc and HAS-BLED scores over time modify risk prediction. METHODS: We included patients with AF who were stable while taking vitamin K antagonists. During a 6-year follow-up, all ischemic strokes/transient ischemic attacks (TIAs) and major bleeding events were recorded. CHA2DS2-VASc and HAS-BLED were recalculated every 2-years and tested for clinical outcomes at 2-year periods. RESULTS: We included 1361 patients (mean CHA2DS2-VASc and HAS-BLED 4.0±1.7 and 2.9±1.2). During the follow-up, 156 (11.5%) patients had an ischemic stroke/TIA and 269 (19.8%) had a major bleeding event. Compared with the baseline CHA2DS2-VASc, the CHA2DS2-VASc recalculated at 2 years had higher predictive ability for ischemic stroke/TIA during the period from 2 to 4 years. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) showed improvements in sensitivity and better reclassification. The CHA2DS2-VASc recalculated at 4 years had better predictive performance than the baseline CHA2DS2-VASc during the period from 4 to 6 years, with an improvement in IDI and an enhancement of the reclassification. The recalculated HAS-BLED at 2-years had higher predictive ability than the baseline score for major bleeding during the period from 2 to 4 years, with significant improvements in sensitivity and reclassification. A slight enhancement in sensitivity was observed with the HAS-BLED score recalculated at 4 years compared with the baseline score. CONCLUSIONS: In AF patients, stroke and bleeding risks are dynamic and change over time. The CHA2DS2-VASc and HAS-BLED scores should be regularly reassessed, particularly for accurate stroke risk prediction.

Reducing bleeding risk in patients on oral anticoagulation therapy.

INTRODUCTION: Oral anticoagulation (OAC) significantly mitigates thromboembolism risks in atrial fibrillation (AF) and venous thromboembolism (VTE) patients yet concern about major bleeding events persist. In fact, clinically relevant hemorrhages can be life-threatening. Bleeding risk is dynamic and influenced by factors such as age, new comorbidities, and drug therapies, and should not be assessed solely based on static baseline factors. AREAS COVERED: We comprehensively review the bleeding risk associated with OAC therapy. Emphasizing the importance of assessing both thromboembolic and bleeding risks, we present clinical tools for estimating stroke and systemic embolism (SSE) and bleeding risk in AF and VTE patients. We also address overlapping risk factors and the dynamic nature of bleeding risk. EXPERT OPINION: The OAC management is undergoing constant transformation, motivated by the primary objective of mitigating thromboembolism and bleeding hazards, thereby amplifying patient safety throughout the course of treatment. The future of OAC embraces personalized approaches and innovative therapies, driven by advanced pathophysiological insights and technological progress. This holds promise for improving patient outcomes and revolutionizing anticoagulation practices.

Sleep analysis of hospital and out-of-hospital emergency professionals.

INTRODUCTION: Sleep deprivation is associated with poorer cognitive functioning and a greater risk of serious diseases. Herein, we analyzed differences in the quality of sleep and excessive daytime sleepiness between hospital emergency services and out-of-hospital emergencies services, and investigated its association with sociodemographic and labor variables. METHOD: This is a cross-sectional observational study carried out between April 2019 and February 2020, including healthcare professionals from different emergency departments, who were evaluated through the following instruments: "Pittsburgh Sleep Quality Index" and "Epworth Sleepiness Scale". RESULTS: Four-hundred and four healthcare professionals were included (mean age 40.4 ± 11.1 years), predominantly women (61.4%) from hospital emergency departments (62.6%). A total of 65.3% of the workers had poor sleep quality and 27.7% had excessive sleepiness. Women had poorer sleep quality (p = 0.022) and higher sleepiness (p = 0.010) than men. Hospital emergency workers presented 2-fold increased risk of poor sleep quality (OR = 1.93, p = 0.003) and sleepiness (OR = 1.93, p = 0.009) than out-of-hospital emergency workers. The more optimistic were less likely to have poor sleep quality (OR = 0.73, p = 0.01) or sleepiness (OR = 0.70, p = 0.002). Nurses, emergency medical technicians and nursing assistants also had a higher risk of poor sleep quality compared to physicians (OR = 1.60; p = 0.043). CONCLUSIONS: Emergency healthcare professionals working in hospital emergency departments had a two-times higher risk of poor sleep quality and sleepiness than out-of-hospital emergency healthcare professionals.

Progressions in Cardiac Arrhythmia: Specific Populations and the Need for Precision Medicine.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the general population [...].

Peripheral artery disease: Update on etiology, pathophysiology, diagnosis and treatment.

Peripheral artery disease (PAD) is a condition related to atherosclerosis affecting >200 million people worldwide, and it increases cardiovascular morbidity (mainly from myocardial infarction and stroke) and mortality. Indeed, PAD patients are classified as patients at very high cardiovascular risk. The most common manifestation of PAD is intermittent claudication, which is associated with reduced mobility and leg pain. Nevertheless, asymptomatic PAD is the most frequent form of PAD worldwide; therefore, it remains underdiagnosed and undertreated. The major risk factors for PAD are smoking, diabetes mellitus, hyperlipidemia, hypertension, overweight/obesity, age, male sex, and black race. Hence, the first and most relevant approach in PAD treatment is lifestyle management, with measures such as smoking cessation, healthy diet, weight loss, and regular physical exercise. This should also be supported by an optimal pharmacological approach including lipid-lowering drugs, antihypertensive drugs, antidiabetic agents, and antithrombotics.

Adverse Clinical Outcomes and Associated Predictors in Rivaroxaban-Treated Atrial Fibrillation Patients With Renal Impairment.

Renal impairment confers worse prognosis in patients with atrial fibrillation (AF) but there is scarce evidence about the influence of direct-acting oral anticoagulants in routine clinical practice. Herein, we compared clinical outcomes between patients with AF with and without renal impairment on rivaroxaban and investigated predictors for clinical outcomes in patients with AF with renal impairment. This was a multicenter study including patients with AF on rivaroxaban for at least 6 months. During 2.5 years follow-up, ischemic strokes (IS)/transient ischemic attacks (TIA)/systemic embolisms (SE)/myocardial infarctions (MI), major bleeding, and major adverse cardiovascular events (MACE) were recorded. Creatinine clearance (CrCl) was estimated using the Cockroft-Gault equation, renal impairment was defined as a CrCl <60 ml/min, and 1,433 patients (34.8% with CrCl <60 ml/min) were included. Patients with CrCl <60 ml/min showed higher event rates for major bleeding (1.87%/year vs 0.62%/year; p = 0.003) and MACE (1.97%/year vs 0.62%/year; p = 0.002) but similar event rates for IS/TIA/SE/MI (0.66%/year vs 0.67%/year; p = 0.955). In patients with renal impairment, CHA2DS2-VASc was associated with higher risk of IS/TIA/SE/MI; HAS-BLED and any dependency level were associated with higher risk of major bleeding; and male gender and heart failure were associated with higher risk of MACE. Antiplatelets were independently associated with increased risk of IS/TIA/SE/MI and MACE. In conclusion, in patients with AF on rivaroxaban, the incidence of IS/TIA/SE/MI did not increase in those with renal impairment, suggesting that rivaroxaban may be an effective option in this subgroup. In patients with AF, male gender, heart failure, dependency, antiplatelets, CHA2DS2-VASc, and HAS-BLED were associated with increased risk of adverse outcomes.

Epilepsy-Heart Syndrome: Incidence and Clinical Outcomes of Cardiac Complications in patients with Epilepsy.

The risks of cardiovascular events (CVEs) in people with epilepsy (PWE) are not well understood. To establish the short- and long-term burden of CVEs in PWE. Electronic health records from a global federated health research network (TriNetX) were used to establish a cohort of PWE. Primary outcomes were: (1) the proportion of people experiencing a composite outcome of cardiac arrest, acute heart failure (HF), acute coronary syndrome (ACS), atrial fibrillation (AF), severe ventricular arrhythmia or all-cause death within 30 days of a seizure; and (2) the 5-year risk for a composite outcome of ischemic heart diseases, stroke, hospitalization, or all-cause death in the PWE experiencing early CVEs. Cox-regression analyses with propensity score matching was used to produce hazard ratios (HRs) and 95% confidence intervals (CI). In 271,172 PWE (mean age 50 ± 20 years; 52% females), the 30-day risk of CVEs following seizure was: 8.7% for the composite outcome, 0.9% for cardiac arrest, 0.8% for HF, 1.2% for ACS, 4.1% for AF, 0.7% for severe ventricular arrhythmias, and 1.6% for all-cause death. For the 15,120 PWE experiencing CVEs within 30 days of seizure, the 5-year adjusted risks for all composite outcomes measured were significantly increased (overall HR: 2.44, 95% CI 2.37-2.51), ischemic heart diseases HR 3.23 (95% CI 3.10-3.36), stroke HR 1.56 (95% CI 1.48-1.64), hospitalization HR 2.03 (95% CI 1.97-2.10), and all-cause death HR 2.75 (95% CI 2.61-2.89). The large proportions of PWE with active disease that experience CVEs and the poor long-term outcome associated suggest the existence of an "epilepsy-heart syndrome."

High medium-term incidence of major cardiovascular events in discharged patients with unstable angina.

The introduction of high-sensitivity troponin (hsTn) assays has reduced the diagnosis of unstable angina (UA) in favor of non-ST elevation myocardial infarction (NSTEMI) in the context of non-ST elevation acute coronary syndrome (NSTEACS). It is unclear whether the detection of these hsTn levels affects the prognosis and therefore whether a different therapeutic approach is warranted. This study aims to determine whether using hsTn results in medium-term prognostic differences in patients with UA and NSTEMI. Methods: This multicenter, prospective registry study included consecutive patients who underwent hsTn assays and were discharged with a diagnosis of NSTEACS. Patients were followed for two years. Outcomes were the occurrence of major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke), major bleeding, and all-cause mortality. Results: Patients with UA and NSTEMI did not show differences in terms of the invasive interventions received, the coronary artery disease diagnosed, the type of revascularization performed, or the proportion presenting MACE (UA 18.1% vs. NSTEMI 18.9%; p = 0.79). However, patients with NSTEMI had higher cardiovascular mortality at two years (UA 4% vs. NSTEMI 9.2%; p = 0.012), as well as, all-cause mortality (UA vs. 7.9% vs. NSTEMI 16.4%; p = 0.002). Conclusions: Medium-term incidence of MACE was similar in patients with UA and NSTEMI, but cardiovascular and all-cause mortality in NSTEMI patients was over twice that of patients with UA.

Impact of the COVID-19 pandemic on stress and sleep in emergency room professionals.

AIMS AND OBJECTIVES: To analyze stress levels, sleep quality, sleepiness and chronotypes on emergency room (ER) professionals before and during the COVID-19. BACKGROUND: ER healthcare professionals are exposed to high stress levels, and they often present with poor sleep quality. DESIGN: Observational study conducted into two different phases (before the COVID-19 and during the first wave of the COVID-19). METHOD: Physicians, nurses and nursing assistants working in the ER were included. Stress, sleep quality, daytime sleepiness and chronotypes were assessed by the Stress Factors and Manifestations Scale (SFMS), the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Horne and Österberg Morningness-Eveningness questionnaire, respectively. The first phase of the study was performed between December 2019 and February 2020, and the second between April and June 2020. The STROBE checklist was used to report the present study. RESULTS: In total, 189 ER professionals in the pre-COVID-19 phase and 171 (of the initial 189) during COVID-19 were included. The proportion of workers with a morning circadian rhythm increased during the COVID-19, and stress levels were significantly higher during COVID-19 compared to the previous phase (38.34 ± 10.74 vs. 49.97 ± 15.81). ER professionals with poor sleep quality presented higher stress in the pre-COVID-19 phase (40.60 ± 10.71 vs. 32.22 ± 8.19) and during COVID-19 (55.27 ± 15.75 vs. 39.66 ± 9.75). Similarly, workers with excessive sleepiness had higher stress in the pre-COVID-19 phase (42.06 ± 10.95 vs. 36.64 ± 10.24) and during COVID-19 (54.67 ± 18.10 vs. 48.44 ± 14.75). Positive associations were also found between the SFMS and the PSQI, as well as with the ESS in both phases of the study. CONCLUSIONS: Emergency room professionals had increased stress levels during the COVID-19 pandemic. Stress was particularly higher in those with poor sleep quality or with excessive daytime sleepiness. RELEVANCE TO CLINICAL PRACTICE: These results should aim to impulse the implementation of measures to improve the working conditions of ER professionals.

Clinical implications of different types of dementia in patients with atrial fibrillation: Insights from a global federated health network analysis.

BACKGROUND: Atrial fibrillation (AF) associates with higher Alzheimer's disease (AD) and vascular dementia risks but the clinical implications have been scarcely investigated. We examined the association between AD or vascular dementia and adverse outcomes in AF patients. METHODS: Cohort study between January 2000 and 2017. AF patients were divided into two groups according to vascular dementia or AD, and balanced using propensity score matching (PSM). During 4-years of follow-up, incident intracranial hemorrhages (ICH), the composite of ischemic stroke/transient ischemic attack (TIA), hospitalizations, and all-cause deaths, were recorded. RESULTS: Two thousand three hundred seventy-seven AF patients with dementia (1225 with vascular dementia, and 1152 with AD) were identified. Following a PSM, 615 patients were included in each cohort (i.e., 1:1) and all variables were well-matched. After PSM, 22 (3.6%) patients with vascular dementia and 55 (8.1%) patients with AD had incident ICH during follow-up (hazard ratio [HR]: 2.22, 95% confidence interval [CI]: 1.33-3.70, log-rank p = 0.002). Overall, 237 (38.5%) patients with vascular dementia and 193 (31.4%) patients with AD, developed an ischemic stroke/TIA. The risk of ischemic stroke/TIA was 1.32-fold higher in vascular dementia (HR: 1.32, 95% CI: 1.09-1.59, log-rank p = 0.003). The risk of rehospitalization (HR: 1.14, 95% CI: 1.01-1.31), and mortality (HR: 1.25, 95% CI: 1.01-1.58) were also higher among AF patients with vascular dementia compared to AD. CONCLUSIONS: The two forms of dementia in AF patients are associated with different prognosis, with AD being associated with a higher risk of ICH, and vascular dementia with a higher risk of stroke/TIA, hospitalization, and mortality.

Cerebrovascular, Cognitive and Cardiac Benefits of SGLT2 Inhibitors Therapy in Patients with Atrial Fibrillation and Type 2 Diabetes Mellitus: Results from a Global Federated Health Network Analysis.

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.

Impact of renal function on Ticagrelor-induced antiplatelet effects in coronary artery disease patients.

Background: Chronic renal failure (CKD) is associated with the presence of increased platelet reactivity and lower clinical benefit of clopidogrel. Ticagrelor has a more favorable pharmacodynamic and pharmacokinetic profile compared to clopidogrel, which has translated into better clinical outcomes in patients with acute coronary syndrome (ACS). We conducted a prospective mechanistic cohort study in order to investigate the impact of renal failure on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with acute ACS. Methods: Patients were divided into two groups based on their estimated renal clearances (eGFR ≥ 60 mL/min and eGFR < 60 mL/min). Platelet function was determined using the VerifyNow system at baseline, after the ticagrelor loading dose and at discharge. In addition, levels of ticagrelor and its active metabolite (AR-C124910XX) were determined in the first hour after loading dose. Results: 48 patients were recruited (eGFR ≥ 60 mL/min: 35 and eGFR < 60 mL/min: 13). There were no significant differences between the groups in terms of platelet inhibition after the loading or after 7 days of treatment (p = 0.219). However, the levels of ticagrelor and its active metabolite were lower in subjects with normal renal function than in CKD, especially at 4 (p = 0.02 and 0.04 respectively) and 6 h of loading (p = 0.042 and 0.08 respectively). Conclusion: No differences in platelet inhibition were observed after treatment with ticagrelor in patients with different renal function, although patients with renal impairment showed higher levels of ticagrelor and AR-C124910XX after 4 h of the loading dose.

Impact of particulate matter on the incidence of atrial fibrillation and the risk of adverse clinical outcomes: A review.

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.

Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea.

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 < .05). Also, lower Cx40 levels in POAF and/or OSA patients (50.0% vs. 81.8%, p = .033) were found. The presence of interstitial fibrosis (according to myocardial collagen by Masson's trichrome) was raised in OSA patients (86.7% vs. 53.7%, p = .024). Several biomarkers and miRNAs involved in inflammation and fibrosis were dysregulated in OSA patients, which together with a higher degree of interstitial fibrosis, altered miRNA, and Cxs expression predisposes to the development of a substrate that increases the AF risk.

Simplified Geleijnse score for identifying chest pain features associated with coronary ischemia.

BACKGROUND: The Geleijnse score, which was proposed to assess for coronary ischemia, has practical limitations. OBJECTIVES: Our aim was to design and evaluate a simplified version of the Geleijnse score. METHODS: We enrolled patients with suspected coronary heart disease but negative troponin T or absence of enzymatic curve, and a non-diagnostic 12-lead ECG. The initial study was performed in a retrospective derivation cohort and the results were subsequently validated in a prospective cohort. RESULTS: From 109 patients included in the derivation cohort, 33 (30.3%) received a diagnosis of coronary heart disease. Chest pain with both arms radiation (OR 3.54), severe intensity (OR 2.41), improvement by nitroglycerin (OR 1.61), associated dyspnea (OR 1.97) and prior exertional angina history (OR 2.91) were independently associated with an ischemic origin on multivariate logistic regression analysis. ROC curves comparison demonstrated both the original and simplified scores presented modest predictive ability with significant difference when analyzed using dichotomous cut-offs (0.647 [simplified] vs. 0.544 [original], p = 0.042) but not as a continuous variable (0.670 [simplified] vs. 0.621 [original], p = 0.396). In 305 patients from the validation cohort, the simplified score presented extensively increased predictive accuracy than the Geleijnse, in the continuous (c-indexes = 0.735 vs. 0.685, p = 0.040) and the dichotomic (c-indexes = 0.682 vs. 0.514, p<0.001) forms. CONCLUSIONS: A simplified version of the Geleijnse score, including some routine clinical manifestations associated with coronary heart disease, presented significantly better predictive ability compared to the original score.

Thoracic aortic aneurysm and atrial fibrillation: clinical associations with the risk of stroke from a global federated health network analysis.

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 < 0.001) 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.