Atrial Fibrillation Recurrence in Patients With Transient New-Onset Atrial Fibrillation Detected During Hospitalization for Noncardiac Surgery or Medical Illness : A Matched Cohort Study.

BACKGROUND: Atrial fibrillation (AF) is often detected for the first time in patients who are hospitalized for another reason. Long-term risks for AF recurrence in these patients are unclear. OBJECTIVE: To estimate risk for AF recurrence in patients with new-onset AF during a hospitalization for noncardiac surgery or medical illness compared with a matched population without AF. DESIGN: Matched cohort study. (ClinicalTrials.gov: NCT03221777). SETTING: Three academic hospitals in Hamilton, Ontario, Canada. PARTICIPANTS: The study enrolled patients hospitalized for noncardiac surgery or medical illness who had transient new-onset AF. For each participant, an age- and sex-matched control participant with no history of AF from the same hospital ward was recruited. All participants left the hospital in sinus rhythm. MEASUREMENTS: 14-day electrocardiographic (ECG) monitor at 1 and 6 months and telephone assessment at 1, 6, and 12 months. The primary outcome was AF lasting at least 30 seconds on the monitor or captured by ECG 12-lead during routine care at 12 months. RESULTS: Among 139 participants with transient new-onset AF (70 patients with medical illness and 69 surgical patients) and 139 matched control participants, the mean age was 71 years (SD, 10), the mean CHA2DS2-VASc score was 3.0 (SD, 1.5), and 59% were male. The median duration of AF during the index hospitalization was 15.8 hours (IQR, 6.4 to 49.6 hours). After 1 year, recurrent AF was detected in 33.1% (95% CI, 25.3% to 40.9%) of participants in the transient new-onset AF group and 5.0% (CI, 1.4% to 8.7%) of matched control participants; after adjustment for the number of ECG monitors worn and for baseline clinical differences, the adjusted relative risk was 6.6 (CI, 3.2 to 13.7). After exclusion of participants who had electrical or pharmacologic cardioversion during the index hospitalization (n = 40) and their matched control participants and limiting to AF events detected by the patch ECG monitor, recurrent AF was detected in 32.3% (CI, 23.1% to 41.5%) of participants with transient new-onset AF and 3.0% (CI, 0% to 6.4%) of matched control participants. LIMITATIONS: Generalizability is limited, and the study was underpowered to evaluate subgroups and clinical predictors. CONCLUSION: Among patients who have transient new-onset AF during a hospitalization for noncardiac surgery or medical illness, approximately 1 in 3 will have recurrent AF within 1 year. PRIMARY FUNDING SOURCE: Peer-reviewed grants.

Pre-treatment with antiarrhythmic drugs for elective electrical cardioversion of atrial fibrillation: a systematic review and network meta-analysis.

AIMS: Our objective was to compare the efficacy of pre-treatment with different classes of anti-arrhythmic drugs (AADs) in patients with atrial fibrillation (AF) undergoing electrical cardioversion. METHODS AND RESULTS: We performed a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing different AADs in patients with AF undergoing electrical cardioversion. We grouped AADs into five network nodes: no treatment or rate control, Class Ia, Class Ic, Class III, and amiodarone. Outcomes were (i) acute restoration and (ii) maintenance of sinus rhythm. We searched MEDLINE and EMBASE from inception until June 2020. We used Python 3.8.3 and R 3.6.2 for data analysis. We evaluated the overall certainty of evidence with the GRADE framework. We included 28 RCTs. Compared with no treatment or rate control, Class III AADs [odds ratio (OR): 2.41; 95% credible interval (CrI): 1.37 to 4.62, high certainty] and amiodarone (OR: 2.58; 95% CrI: 1.54 to 4.37, high certainty) improved restoration of sinus rhythm. Amiodarone improved long-term maintenance of sinus rhythm when compared with no treatment or rate control (OR: 5.37; 95% CrI: 4.00-7.39, high certainty), Class Ic (OR: 1.89; 95% CrI: 1.05-3.45, moderate certainty) and Class III AADs (OR: 2.19; 95% CrI: 1.39-3.26, high certainty). CONCLUSION: Before electrical cardioversion of AF, treatment with Class III AADs or amiodarone improves the acute restoration of sinus rhythm. Amiodarone is most likely to improve the maintenance of sinus rhythm after electrical cardioversion, but Class Ic and Class III AADs are also effective.

Oral anticoagulation for patients with atrial fibrillation in the ED: RE-LY AF registry analysis.

Oral anticoagulation (OAC) reduces stroke risk in patients with atrial fibrillation (AF). We sought to determine predictors of OAC initiation in AF patients presenting to the emergency department (ED). Secondary analysis of the RE-LY AF registry which enrolled individuals from 47 countries between 2007 and 2011 who presented to an ED with AF and followed them for 1 year. A total of 4149 patients with AF as their primary diagnosis who were not already taking OAC and had a CHA2DS2-VASc ≥ 1 for men or ≥ 2 for women were included in this analysis. Of these individuals, 26.8% were started on OAC (99.2% vitamin K antagonists) in the ED and 29.8% were using OAC one year later. Factors associated with initiating OAC in the ED included: specialist consultation (relative risk [RR] 1.84, 95%CI 1.44-2.36), rheumatic heart disease (RR 1.60, 95%CI 1.29-1.99), persistence of AF at ED discharge (RR 1.33, 95%CI 1.18-1.50), diabetes mellitus (RR 1.32, 95%CI 1.19-1.47), and hospital admission (RR 1.30, 95%CI 1.14-1.47). Heart failure (RR 0.83, 95%CI 0.74-0.94), antiplatelet agents (RR 0.77, 95%CI 0.69-0.84), and dementia (RR 0.61, 95%CI 0.40-0.94) were inversely associated with OAC initiation. Patients taking OAC when they left the ED were more likely using OAC at 1-year (RR 2.81, 95%CI 2.55-3.09) and had lower rates of death (RR 0.55, 95%CI 0.38-0.79) and stroke (RR 0.59, 95%CI 0.37-0.96). In patients with AF presenting to the ED, prompt initiation of OAC and specialist involvement are associated with a greater use of OAC 1 year later and may result in improved clinical outcomes.

Incidence and recurrence of new-onset atrial fibrillation detected during hospitalization for non-cardiac surgery: a systematic review and meta-analysis.

PURPOSE: This systematic review aimed to summarize reports of the incidence and long-term recurrence of new-onset atrial fibrillation (AF) associated with non-cardiac surgery. SOURCES: We searched CENTRAL, MEDLINE and EMBASE from inception to November 2019. We included studies that reported on the incidence of new-onset perioperative AF during hospitalization for non-cardiac surgery and/or AF recurrence in such patients following discharge. Reviewers screened articles and abstracted data independently and in duplicate. We assessed study quality by appraising methodology for collecting AF history, incident AF during hospitalization, and AF recurrence after discharge. PRINCIPAL FINDINGS: From 39,233 citations screened, 346 studies that enrolled a total of 5,829,758 patients met eligibility criteria. Only 27 studies used prospective, continuous inpatient electrocardiographic (ECG) monitoring to detect incident AF. Overall, the incidence of postoperative AF during hospitalization ranged from 0.004 to 50.3%, with a median [interquartile range] of 8.7 [3.8-15.0]%. Atrial fibrillation incidence varied with type of surgery. Prospective studies using continuous ECG monitoring reported significantly higher incidences of AF than those that did not (13.9% vs 1.9%, respectively; P < 0.001). A total of 13 studies (25,726 patients) with follow-up up to 5.4 years reported on AF recurrence following hospital discharge; only one study used a prospective systematic monitoring protocol. Recurrence rates ranged from 0 to 37.3%. CONCLUSIONS: Rates of AF incidence first detected following non-cardiac surgery and long-term AF recurrence vary markedly. Differences in the intensity of ECG monitoring and type of surgery may account for this variation. TRIAL REGISTRATION: PROSPERO (CRD42017068055); registered 1 September 2017.

RéSUMé: OBJECTIF: Cette revue systématique visait à résumer les comptes rendus sur l'incidence et la récurrence à long terme de la fibrillation auriculaire (FA) de novo associée à une chirurgie non cardiaque. SOURCES: Nous avons effectué des recherches dans les bases de données CENTRAL, MEDLINE et EMBASE de leur création à novembre 2019. Nous avons inclus les études ayant examiné l'incidence de nouvelle FA périopératoire pendant l'hospitalisation pour une chirurgie non cardiaque et/ou la récurrence de la FA chez de tels patients après leur congé. Les chercheurs ont passé en revue les articles et les données extraites de manière indépendante et en double. Nous avons estimé la qualité des études en évaluant la méthodologie de collecte des antécédents de FA, de l'incident de FA pendant l'hospitalisation et de la récurrence de FA après le congé. CONSTATATIONS PRINCIPALES: Sur les 39 233 citations examinées, 346 études portant sur un total de 5 829 758 patients ont répondu à nos critères d'admissibilité. Seulement 27 études ont utilisé un monitorage électrocardiographique (ECG) continu prospectif et des patients hospitalisés pour détecter les incidents de FA. Dans l'ensemble, l'incidence de FA postopératoire pendant l'hospitalisation allait de 0,004 à 50,3 %, avec une médiane [écart interquartile] de 8,7 [3,8-15,0] %. L'incidence de fibrillation auriculaire variait en fonction du type de chirurgie. Des études prospectives utilisant un monitorage continu par ECG ont fait état d'incidences significativement plus élevées de FA que celles sans monitorage continu (13,9 % vs 1,9 %, respectivement; P < 0,001). Au total, 13 études (25 726 patients) avec un suivi allant jusqu'à 5,4 ans ont rapporté leurs données sur la récurrence de FA après le congé de l'hôpital; seule une étude a utilisé un protocole de monitorage prospectif systématique. Les taux de récurrence allaient de 0 à 37,3 %. CONCLUSION: Les taux d'incidence de nouvelle FA détectés après une chirurgie non cardiaque et la récurrence à long terme de FA varient considérablement. Les différences du degré de monitorage par ECG et le type de chirurgie pourraient expliquer cette variation. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42017068055); enregistrée le 1er septembre 2017.

Continued versus interrupted direct oral anticoagulation for cardiac electronic device implantation: A systematic review.

BACKGROUND: Many patients undergoing cardiac device implantation are taking direct oral anticoagulation (DOAC). Continuing DOAC during device implantation may increase periprocedural bleeding risk; however, interrupting DOACs may increase thromboembolic risk. OBJECTIVE: To compare the incidence of clinically significant pocket hematoma and thromboembolism in patients who have their DOAC continued or interrupted for cardiac device implantation. METHODS: We searched MEDLINE, EMBASE, and randomized controlled trial (CENTRAL) until December 2019 and included randomized controlled trials (RCTs) and observational studies that compared outcomes after continuing or interrupting DOAC during cardiac device implantation. Independently and in duplicate, reviewers screened titles, abstracts, and full text of potentially eligible studies. They then evaluated risk of bias and abstracted data. RCT data were pooled using a fixed-effect model. Quality of evidence was assessed using grading of recommendations assessment, development and evaluation (GRADE). RESULTS: Two RCTs, representing 763 patients, and three observational studies met eligibility criteria. In RCTs, continuing DOAC for device implantation compared to interrupting DOAC resulted in no significant difference in clinically significant pocket hematoma (2.1% vs 1.8%; RR 1.15; 95% CI 0.44-3.05) or thromboembolism (0.03% vs 0.03%; RR 1.02; 95% CI 0.06-16.21). Quality of evidence for both outcomes was moderate due to imprecision. Observational studies showed similar results. CONCLUSIONS: Continuing DOACs for device implantation results in little to no difference in the incidence of clinically significant pocket hematoma or thromboembolism. Given the ease of stopping and restarting DOACs, interrupting DOACs may be the preferred strategy for most patients. However, whenever continuous therapeutic anticoagulation is desired, DOAC continuation should be preferred over bridging with parenteral anticoagulation.

Risk of venous and arterial thrombosis in non-surgical patients receiving systemic tranexamic acid: A systematic review and meta-analysis.

BACKGROUND: Antifibrinolytic agents such as tranexamic acid (TXA) are commonly used as adjunctive therapies to prevent and treat excessive bleeding. In non-surgical settings, TXA is known to reduce bleeding related mortality. However, impact of TXA use on thrombosis is uncertain. METHODS: We systematically searched the MEDLINE, EMBASE, and CENTRAL databases from January 1985 to August 2018. Studies with the following characteristics were included: (i) RCT design; (ii) compared systemic (oral or intravenous) TXA for prevention or treatment of bleeding for non-surgical indications and placebo or no TXA, and (iii) reported thrombotic events or mortality. A Mantel-Haenzel, random-effects model was used to calculate risk ratios, and risk of bias was assessed using the Cochrane risk of bias tool. RESULTS: Our search identified 22 studies representing 49,538 patients. Those receiving TXA had a significantly lower risk of death from any cause (RR = 0.92; 95% CI = 0.87-0.98; I2 = 0%). There was no significant increase in the risk of stroke (RR = 1.10; 95% CI = 0.68-1.78; I2 = 31%), myocardial infarction (RR = 0.88; 95% CI = 0.43-1.84; I2 = 46%), pulmonary embolism (RR = 0.97; 95% CI = 0.75-1.26; I2 = 0%), or deep vein thrombosis (RR = 0.99; 95% CI = 0.70-1.41; I2 = 0%) from use of TXA. The results were similar when restricted to studies at low risk of bias. CONCLUSIONS: In our systematic review and meta-analysis, the use of tranexamic acid reduced all-cause mortality without increased risk of venous or arterial thrombotic complications.

Pre- and post-treatment with amiodarone for elective electrical cardioversion of atrial fibrillation: a systematic review and meta-analysis.

AIMS: Clinicians frequently pre-treat patients with amiodarone to increase the efficacy of electrical cardioversion for atrial fibrillation (AF). Our objective was to determine the precise effects of amiodarone pre- and post-treatment on conversion efficacy and sinus rhythm maintenance. METHODS AND RESULTS: We conducted a systematic review and meta-analysis of trials comparing pre- and post-treatment for electrical cardioversion with amiodarone vs. no therapy on (i) acute restoration and (ii) maintenance of sinus rhythm after 1 year. We searched MEDLINE and EMBASE from inception to July 2018 for randomized controlled trials. We evaluated the risk of bias for individual studies with the Cochrane tool and overall quality of evidence with the GRADE framework. We identified eight eligible studies (n = 1012). Five studies were deemed to have unclear or high risk of selection bias. We found the evidence to be of high quality based on GRADE. Treatment with amiodarone (200-800 mg daily for 1-6 weeks pre-cardioversion; 0-200 mg daily post-cardioversion) was associated with higher rates of acute restoration [relative risk (RR) 1.22, 95% confidence interval (CI) 1.07-1.39, P = 0.004, n = 1012, I2 = 65%] and maintenance of sinus rhythm over 13 months (RR 4.39, 95% CI 2.99-6.45, P < 0.001, n = 695, I2 = 0%). The effects of amiodarone for acute restoration were maintained when considering only studies at low risk of bias (RR 1.22, 95% CI 1.10-1.36, P < 0.001, n = 572, I2 = 0%). Adverse effects were typically non-serious, occurring in 3.4% (6/174) of subjects receiving amiodarone. CONCLUSION: High-quality evidence demonstrated that treatment with amiodarone improved the restoration and maintenance of sinus rhythm after electrical cardioversion of AF. Short-term amiodarone was well-tolerated.

Design and rationale of the atrial fibrillation occurring transiently with stress (AFOTS) follow-up cohort study.

Atrial fibrillation occurring transiently with stress (AFOTS) describes the first detection of AF in a patient who is hospitalized for a non-cardiac medical illness or following non-cardiac surgery. Uncertainty exists whether episodes of AFOTS are due to reversible precipitants and will not recur after recovery, or if they are paroxysmal atrial fibrillation (AF) that is detected during inpatient cardiac monitoring. Previous studies have used retrospective, non-systematic and ultimately low-sensitivity protocols to investigate the recurrence of AF in patients with AFOTS. The prospective, multi-center, investigator-initiated AFOTS Follow-Up Cohort Study will enroll 138 case patients with AFOTS in the setting of non-cardiac surgery or medical illness, matched 1:1 with control patients for age, sex, stressor, and hospital unit. Participants will wear a 14-day ECG heart monitor at 1 and 6 months after hospital discharge. Over 12 months of follow-up, we will collect data regarding participant's medications, and clinical events. The primary endpoint is detection of 30 or more seconds of AF after hospital discharge. To date, 50% of the target sample has been enrolled. The study is expected to complete enrolment in mid-2019 and conclude 1 year later. The AFOTS follow-up study will employ a systematic protocol to detect AF and will provide a precise and valid estimate of AF recurrence following AFOTS. This study will establish whether patients with AFOTS have an increased propensity to AF after hospitalization as compared to matched controls and may inform the management of this population.

Calpain2 mediates Rab5-driven focal adhesion disassembly and cell migration.

The early endosome protein Rab5 was recently shown to promote cell migration by enhancing focal adhesion disassembly through mechanisms that remain elusive. Focal adhesion disassembly is associated to proteolysis of talin, in a process that requires calpain2. Since calpain2 has been found at vesicles and endosomal compartments, we hypothesized that Rab5 stimulates calpain2 activity, leading to enhanced focal adhesion disassembly in migrating cells. We observed that calpain2 co-localizes with EEA1-positive early endosomes and co-immunoprecipitates with EEA1 and Rab5 in A549 lung carcinoma cells undergoing spreading, whereas Rab5 knock-down decreased the accumulation of calpain2 at early endosomal-enriched fractions. In addition, Rab5 silencing decreased calpain2 activity, as shown by cleavage of the fluorogenic substrate tBOC-LM-CMAC and the endogenous substrate talin. Accordingly, Rab5 promoted focal adhesion disassembly in a calpain2-dependent manner, as expression of GFP-Rab5 accelerated focal adhesion disassembly in nocodazole-synchronized cells, whereas pharmacological inhibition of calpain2 with N-acetyl-Leu-Leu-Met prevented both focal adhesion disassembly and cell migration induced by Rab5. In summary, these data uncover Rab5 as a novel regulator of calpain2 activity and focal adhesion proteolysis leading to cell migration.