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Background and Importance: The MIMO clinical trial showed that patients with acute cardiogenic pulmonary edema (ACPE) treated with midazolam had fewer serious adverse events than those treated with morphine. Atrial fibrillation (AF) is a common comorbidity in heart failure and affects patient's outcome., Objective: The primary endpoint of this substudy is to know if AF modified the reduced risk of serious adverse events in the midazolam arm compared to morphine. The first secondary endpoint is to know if AF modified the reduced risk of serious adverse events or death at 30 days in the midazolam arm. The second secondary objective of this substudy is to analyze whether AF modified the reduced risk of midazolam against morphine on the total number of serious adverse events per patient., Design: We conducted a secondary analysis of the MIMO trial. Patients more than 18 years old clinically diagnosed with ACPE and with dyspnea and anxiety were randomized (1:1) at emergency department arrival to receive either intravenous midazolam or morphine., Outcome Measures and Analysis: In this post hoc analysis, we calculated the relative risk (RR) of serious adverse events in patients with and without AF. Calculating the Cochran-Mantel-Haenszel interaction test, we evaluated if AF modified the reduced risk of serious adverse events in the midazolam arm compared to morphine., Main Results: One hundred eleven patients (median = 78.9 years; IQR, 72.3-83.7; women, 52.2%) were randomized in the MIMO trial, 55 to receive midazolam and 56 to morphine. All randomized patients received the assigned drug and there were no losses to follow-up. Forty-four patients (39.6%) had AF. In the AF group, the RR for the incidence of serious adverse events in the midazolam versus morphine arm was 0.42 (95% CI, 0.14-1.3). In the group without AF, the RR was 0.46 (95% CI, 0.21-1). The presence of AF did not modify the reduced risk of serious adverse events in the midazolam arm compared with morphine ( P for interaction = 0.88)., Conclusion: This post hoc analysis of the MIMO trial suggests that the reduced risk of serious adverse events in the midazolam group compared to morphine is similar in patients with and without AF., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Atrial fibrillation (AF), the most common arrhythmia in the adult population worldwide, represents a significant burden in terms of cardiovascular mortality and morbidity and has repercussions on health economics. Oral anticoagulation (OAC) is key to stroke prevention in AF and, in recent years, results from landmark clinical trials of non-vitamin K oral anticoagulants (NOAC) have triggered a paradigm shift in thrombocardiology. Despite these advances, there is still a significant residual vascular risk associated with silent AF, bleeding, premature sudden death and heart failure. The authors review AF epidemiologic data, the importance of new tools for early AF detection, the current role of catheter ablation for rhythm control in AF, the state-of-the-art in periprocedural OAC, the optimal management of major bleeding, the causes of residual premature death and future strategies for improvements in AF prognosis., (Copyright © 2020 Sociedade Portuguesa de Cardiologia. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To evaluate whether circulating cardiac troponin I (cTnI) levels are associated with worst outcomes in patients with atrial fibrillation (AF)., Methods: Consecutive patients visiting the emergency room (ER) with a new episode of a previously diagnosed AF or a new diagnosis of AF during ER admission between January 1st, 2010 and December 31st, 2015, were enrolled in the study (n = 2617). After applying exclusion criteria and eliminating repeated episodes, 2013 patients were finally included. Of these, 1080 patients with at least one cTnI measurement in the ER were selected and classified into 4 groups according to cTnI quartiles: Q1 (n = 147) cTnI <10 ng/L (Group 1); Q2 (n = 254): 10-19 ng/L (Group 2); Q3 (n = 409): 20-40 ng/L (Group 3); and Q4 (n = 270): cTnI >40 ng/L (Group 4). The median follow-up period was 47.8 ± 32.8 months. The primary endpoint was all-cause death during the follow-up., Results: A higher mortality was found in group 4 compared with the other groups (58.9% vs. 28.5%, respectively, p < 0.001), along with, hospitalizations (40.4% vs. 30.7%, p = 0.004), and readmissions due to decompensated heart failure (26.7% vs. 2.5%, p = 0.002). The probability of survival without AF recurrences was lower in the Q4 (p = 0.045). Moreover, cTnI levels >40 ng/L (Q4) were an independent risk factor of death (HR, 2.03; 95% CI, 1.64-2.51; p < 0.001)., Conclusion: The assessment of cTnI at ER admission could be a useful strategy for risk stratification of patients diagnosed with AF by identifying a subgroup with medium-term to long-term increased risk of adverse events and mortality., Competing Interests: Declaration of Competing Interest The authors have no association with commercial entities that could be viewed as having an interest in the general area of the submitted manuscript., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age appropriateness of oral anticoagulants (OAC) according to the FORTA (Fit fOR The Aged) classification (OAC-FORTA). Three years after its first version (OAC-FORTA 2016), an update was initiated to create OAC-FORTA 2019., Methods: A structured review of randomized controlled clinical trials and summaries of individual product characteristics was performed to detect newly emerged evidence on oral anticoagulants in older patients with AFib. This review was used by an interdisciplinary panel of European experts (N = 10) in a Delphi process to label OACs according to FORTA., Results: A total of 202 records were identified and 11 studies finally included. We found four new trials providing relevant data on efficacy and safety of warfarin, apixaban, dabigatran or rivaroxaban in older patients with AFib. In the majority of studies comparing the non-vitamin-K oral anticoagulants (NOACs) with warfarin, NOACs were superior to warfarin regarding at least one relevant clinical endpoint. The mean consensus coefficient significantly increased from 0.867 (OAC-FORTA 2016) to 0.931 (p < 0.05) and the proposed FORTA classes were confirmed in all cases during the first round (consensus coefficient > 0.8). Warfarin, dabigatran, edoxaban and rivaroxaban were assigned to the FORTA B label, acenocoumarol, fluindione and phenprocoumon were labeled FORTA C and only apixaban was rated as FORTA A., Conclusion: OAC-FORTA 2019 confirms that AFib can be successfully treated with positively labeled antithrombotics at advanced age.

Objective: To assess the predictors of de novo atrial fibrillation in patients in a non-cardiac intensive care unit., Methods: A total of 418 hospitalized patients were analyzed between January and September 2016 in a non-cardiac intensive care unit. Clinical characteristics, interventions, and biochemical markers were recorded during hospitalization. In-hospital mortality and length of hospital stay in the intensive care unit were also evaluated., Results: A total of 310 patients were included. The mean age of the patients was 61.0 ± 18.3 years, 49.4% were male, and 23.5% presented de novo atrial fibrillation. The multivariate model identified previous stroke (OR = 10.09; p = 0.016) and elevated levels of pro-B type natriuretic peptide (proBNP, OR = 1.28 for each 1,000pg/mL increment; p = 0.004) as independent predictors of de novo atrial fibrillation. Analysis of the proBNP receiver operating characteristic curve for prediction of de novo atrial fibrillation revealed an area under the curve of 0.816 (p < 0.001), with a sensitivity of 65.2% and a specificity of 82% for proBNP > 5,666pg/mL. There were no differences in mortality (p = 0.370), but the lengths of hospital stay (p = 0.002) and stay in the intensive care unit (p = 0.031) were higher in patients with de novo atrial fibrillation., Conclusions: A history of previous stroke and elevated proBNP during hospitalization were independent predictors of de novo atrial fibrillation in the polyvalent intensive care unit. The proBNP is a useful and easy- and quick-access tool in the stratification of atrial fibrillation risk.

Patients with atrial fibrillation (AF) often undergo troponin (Tn) testing in the emergency department (ED), but the clinical significance of mildly elevated values remains unclear. We evaluated short-term 30-day post-discharge outcomes in AF patients according to troponin levels. Out of 2181 AF patients evaluated in the ED (June 2014 to June 2015), we included consecutive admitted patients. Patients were grouped into those with normal Tn values (≤ 0.05 ng/mL), mild elevations (> 0.05-0.5 ng/mL, 10× URL) and marked elevations (> 0.5 ng/mL). Outcomes included acute coronary syndrome (ACS), revascularization, all-cause mortality and combined end point; the secondary outcome was ischemic stroke. A total of 348 patients (90.9%) had Tn testing, which was associated with longer in-hospital stay (median 2.04 vs. 0.74 days in unmeasured Tn, p = 0.014); 37.1% did not have clinical suspicion of ACS. Mild Tn elevation occurred in 19.0% and 6.3% had markedly elevated values. Compared to normal values, mild elevations had higher absolute incidence, without statistical significance, of ACS (1.5 vs. 0.0%, p = 0.202), revascularization (1.5 vs. 0.0%, p = 0.202), all-cause mortality (12.1 vs. 6.9%, p = 0.200), combined end point (13.3 vs. 6.9%, p = 0.084) or ischemic stroke (4.5 vs. 2.3%, p = 0.394). Tn testing is routine in admitted AF patients, even without suspicion of ACS, and is associated with prolonged stay. Mild Tn elevation is associated with a nonsignificant trend toward higher adverse events. Larger-scale studies are needed to evaluate the cost-effectiveness of Tn testing for prognosis in admitted AF patients, as this prolongs stay and has unclear impact on patient management.

Background: Age appropriateness of anticoagulants for stroke prevention in atrial fibrillation is uncertain., Objective: To review oral anticoagulants for the treatment of atrial fibrillation in older (age >65 years) people and to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability using the Fit-fOR-The-Aged (FORTA) classification., Methods: We performed a structured comprehensive review of controlled clinical trials and summaries of individual product characteristics to assess study and total patient numbers, quality of major outcome data and data of geriatric relevance. The resulting evidence was discussed in a round table with an interdisciplinary panel of ten European experts. Decisions on age appropriateness were made using a Delphi process., Results: For the eight drugs included, 380 citations were identified. The primary outcome results were reported in 32 clinical trials with explicit and relevant data on older people. Though over 24,000 patients aged >75/80 years were studied for warfarin, data on geriatric syndromes were rare (two studies reporting on frailty/falls/mental status) and missing for all other compounds. Apixaban was rated FORTA-A (highly beneficial). Other non-vitamin K antagonist oral anticoagulants (including low/high-intensity dabigatran and high-intensity edoxaban) and warfarin were assigned to FORTA-B (beneficial). Phenprocoumon, acenocoumarol and fluindione were rated FORTA-C (questionable), mainly reflecting the absence of data., Conclusions: All non-vitamin K antagonist oral anticoagulants and warfarin were classified as beneficial or very beneficial in older persons (FORTA-A or -B), underlining the overall positive assessment of the risk/benefit ratio for these drugs. For other vitamin-K antagonists regionally used in Europe, the lack of evidence should challenge current practice.

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A correction to this paper has been published: https://doi.org/10.1007/s40266-021-00873-3 [ABSTRACT FROM AUTHOR]