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Background/Objectives: New-onset atrial fibrillation (AF) after cardiac surgery is associated with patient-important outcomes. Uncertainty persists regarding its prevention, detection, and management. This review seeks to identify, compile, and describe ongoing registered research studies involving patients with or at risk for post-operative AF (POAF) after cardiac surgery. Methods: We searched clinical trial registries in January 2023 for studies focusing on POAF prediction, prevention, detection, or management. We extracted data from each record and performed descriptive analyses. Results: In total, 121 studies met the eligibility criteria, including 82 randomized trials. Prevention studies are the most common ( n = 77, 63.6%), followed by prediction ( n = 21, 17.4%), management ( n = 16, 13.2%), and detection studies ( n = 7, 5.8%). POAF after cardiac surgery is an area of active research. Conclusions: There are many ongoing randomized prevention studies. However, two major clinical gaps persist; future randomized trials should compare rate and rhythm control in patients who develop POAF, and long-term follow-up studies should investigate strategies to monitor for AF recurrence in patients with POAF.

Background: Given that peripheral arterial disease (PAD) disproportionately affects people of lower socioeconomic status, out-of-pocket expenses for preventive medications are a major barrier to their use. We carried out a cost comparison of drug therapies for PAD to identify prescribing strategies that minimize out-of-pocket expenses for these medications., Methods: Between March and June 2019, we contacted outpatient pharmacies in Hamilton, Ontario, Canada, to assess pricing of pharmacologic therapies at dosages included in the 2016 American College of Cardiology/American Heart Association guideline for management of lower extremity PAD. We also gathered pricing information for supplementary charges, including delivery, pill splitting and blister packaging. We calculated prescription prices with and without dispensing fees for 30-day brand-name and generic prescriptions, and 90-day generic prescriptions., Results: Twenty-four pharmacies, including hospital-based, independent and chain, were included in our sample. In the most extreme scenario, total 90-day medication costs could differ by up to $1377.26. Costs were affected by choice of agent within a drug class, generic versus brand-name drug, quantity dispensed, dispensing fee and delivery cost, if any., Conclusion: By opting for prescriptions for 90 days or as long as possible, selecting the lowest-cost generic drugs available in each drug class, and identifying dispensing locations with lower fees, prescribers can minimize out-of-pocket patient medication expenses. This may help improve adherence to guideline-recommended therapies for the secondary prevention of vascular events in patients with PAD., Competing Interests: Competing interests: William McIntyre reports consulting fees from Tri-Med, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Servier Laboratories and Bayer. Noel Chan reports funding from the Canadian Institutes of Health Research and the Heart and Stroke Foundation, outside the submitted work, and honoraria for talks from Diagnostica Stago and Boehringer. Vinai Bhagirath reports an unrestricted educational grant from Pfizer, outside the submitted work, and honoraria from Bayer. Richard Whitlock reports grants from AtriCure and Bayer, outside the submitted work, consulting fees from PhaseBio Pharmaceuticals, Artivion and AtriCure, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AtriCure and LeMaitre Vascular, and support for attending meetings and/or travel from AtriCure and Boehringer Ingelheim. He has participated on a data safety monitoring board and advisory board for Artivion and PhaseBio. Sonia Anand reports consulting fees from Janssen Pharmaceuticals and Bayer, outside the submitted work. Emilie Belley-Côté reports grants or contracts from Bayer, BMS-Pfizer and Roche Diagnostics, outside the submitted work. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Background: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery., Methods: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis., Results: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr)., Conclusions: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Background: Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common because of perceived benefits., Methods: We searched CENTRAL, MEDLINE, CINAHL, PsycInfo, and Web of Science from inception to June 2021. Pairs of reviewers identified randomised controlled trials and prospective observational studies comparing perioperative use of benzodiazepines with other agents or placebo in patients undergoing surgery. Two reviewers independently abstracted data, which we combined using a random-effects model. Our primary outcomes were delirium, intraoperative awareness, and mortality., Results: We included 34 randomised controlled trials (n=4354) and nine observational studies (n=3309). Observational studies were considered separately. Perioperative benzodiazepines did not increase the risk of delirium (n=1352; risk ratio [RR] 1.43; 95% confidence interval [CI]: 0.9-2.27; I 2 =72%; P=0.13; very low-quality evidence). Use of benzodiazepines instead of dexmedetomidine did, however, increase the risk of delirium (five studies; n=429; RR 1.83; 95% CI: 1.24-2.72; I 2 =13%; P=0.002). Perioperative benzodiazepine use decreased the risk of intraoperative awareness (n=2245; RR 0.26; 95% CI: 0.12-0.58; I 2 =35%; P=0.001; very low-quality evidence). When considering non-events, perioperative benzodiazepine use increased the probability of not having intraoperative awareness (RR 1.07; 95% CI: 1.01-1.13; I 2 =98%; P=0.03; very low-quality evidence). Mortality was reported by one randomised controlled trial (n=800; RR 0.90; 95% CI: 0.20-3.1; P=0.80; very low quality)., Conclusions: In this systematic review and meta-analysis, perioperative benzodiazepine use did not increase postoperative delirium and decreased intraoperative awareness. Previously observed relationships of benzodiazepine use with delirium could be explained by comparisons with dexmedetomidine., Systematic Review Protocol: PROSPERO CRD42019128144., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: We conducted a systematic review and meta-analysis of randomized controlled trials comparing direct oral anticoagulants (DOACs) to vitamin K antagonists (VKAs) in the first 90 days after bioprosthetic valve implantation., Methods: We systematically searched Embase, Medline and CENTRAL. We screened titles, abstracts and full texts, extracted data and assessed the risk of bias in duplicate. We pooled data using the Mantel-Haenzel method and random effects modelling. We conducted subgroup analyses based on the type of valve (transcatheter versus surgical) and timing of initiation of anticoagulation (<7 vs >7 days after valve implantation). We assessed the certainty of evidence using the Grading of Recommendations, Assessments, Development and Evaluation approach., Results: We included 4 studies of 2284 patients with a median follow-up of 12 months. Two studies examined transcatheter valves (1877/2284 = 83%) and 2 examined surgical valves (407/2284 = 17%). We found no statistically significant differences between DOACs and VKAs with regard to thrombosis, bleeding, death or subclinical valve thrombosis. However, there was a subgroup trend towards more bleeding with DOACs when initiated within 7 days of valve implantation., Conclusions: In the existing randomized literature on DOACs versus VKAs in the first 90 days after bioprosthetic valve implantation, there appears to be no difference with regard to thrombosis, bleeding or death. Interpretation of the data is limited by small numbers of events and wide confidence intervals. Future studies should focus on surgical valves and should include long-term follow-up to assess any potential impact of randomized therapy on valve durability., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims: Electrical cardioversion is commonly used to restore sinus rhythm in patients with atrial fibrillation (AF), but procedural technique and clinical success vary. We sought to identify techniques associated with electrical cardioversion success for AF patients., Methods and Results: We searched MEDLINE, EMBASE, CENTRAL, and the grey literature from inception to October 2022. We abstracted data on initial and cumulative cardioversion success. We pooled data using random-effects models. From 15 207 citations, we identified 45 randomized trials and 16 observational studies. In randomized trials, biphasic when compared with monophasic waveforms resulted in higher rates of initial [16 trials, risk ratio (RR) 1.71, 95% CI 1.29-2.28] and cumulative success (18 trials, RR 1.10, 95% CI 1.04-1.16). Fixed, high-energy (≥200 J) shocks when compared with escalating energy resulted in a higher rate of initial success (four trials, RR 1.62, 95% CI 1.33-1.98). Manual pressure when compared with no pressure resulted in higher rates of initial (two trials, RR 2.19, 95% CI 1.21-3.95) and cumulative success (two trials, RR 1.19, 95% CI 1.06-1.34). Cardioversion success did not differ significantly for other interventions, including: antero-apical/lateral vs. antero-posterior positioned pads (initial: 11 trials, RR 1.16, 95% CI 0.97-1.39; cumulative: 14 trials, RR 1.01, 95% CI 0.96-1.06); rectilinear/pulsed biphasic vs. biphasic truncated exponential waveform (initial: four trials, RR 1.11, 95% CI 0.91-1.34; cumulative: four trials, RR 0.98, 95% CI 0.89-1.08) and cathodal vs. anodal configuration (cumulative: two trials, RR 0.99, 95% CI 0.92-1.07)., Conclusions: Biphasic waveforms, high-energy shocks, and manual pressure increase the success of electrical cardioversion for AF. Other interventions, especially pad positioning, require further study., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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., Competing Interests: Conflicts of interest: The authors have no conflict of interest relevant to the submitted work. R.P.W. reports grants and speaker fees from Boeringer-Ingelheim; speaker fees from Atricure, Phasebio and Cryolife; grants from Bayer and BMS-Pfizer, outside the submitted work. E.P.B.-C. reports grants from BMS-Pfizer, Bayer, and Roche Diagnostics, outside the submitted work. J.S.H. reports Research grants and speaking fees from Medtronic, Boston scientific, Abott, BMS/Pfizer, Servier, Bayer, Novartis, Myokardia, ARCA Biopharm, and Cipher Pharm outside the submitted work. W.F.M. reports speaking fees from Servier and Bayer and Boehringer Ingelheim, outside the submitted work. E.D. reports grants from Boeringer-Ingelheim and Roche Diagnostics. The other authors have no conflict of interest to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Many patients with end-stage kidney disease (ESKD) have valvular heart disease requiring surgery. The optimal prosthetic valve is not established in this population. We performed a systematic review and meta-analysis to assess outcomes of patients with dialysis-dependent ESKD who received mechanical or bioprosthetic valves., Methods: We searched Cochrane Central, Medline and Embase from inception to January 2020. We performed screening, full-text assessment, risk of bias and data collection, independently and in duplicate. Data were pooled using a random-effects model., Results: We identified 28 observational studies ( n = 9857 patients, including 6680 with mechanical valves and 3717 with bioprosthetic valves) with a median follow-up of 3.45 years. Twenty-two studies were at high risk of bias and 1 was at critical risk of bias from confounding. Certainty in evidence was very low for all outcomes except bleeding. Mechanical valves were associated with reduced mortality at 30 days (relative risk [RR] 0.79, 95% confidence interval [CI] 0.65-0.97, I 2 = 0, absolute effect 27 fewer deaths per 1000) and at 6 or more years (mean 9.7 yr, RR 0.83, 95% CI 0.72-0.96, I 2 = 79%, absolute effect 145 fewer deaths per 1000), but increased bleeding (incidence rate ratio [IRR] 2.46, 95% CI 1.41-4.27, I 2 = 59%, absolute effect 91 more events per 1000) and stroke (IRR 1.63, 95% CI 1.21-2.20, I 2 = 0%, absolute effect 25 more events per 1000)., Conclusion: Mechanical valves were associated with reduced mortality, but increased rate of bleeding and stroke. Given very low certainty for evidence of mortality and stroke outcomes, patients and clinicians may choose prosthetic valves based on factors such as bleeding risk and valve longevity., Study Registration: PROSPERO no. CRD42017081863., Competing Interests: Competing interests: Emilie Belley-Côté reports grants Roche, Bayer and Bristol-Myers Squibb-Pfizer, and is chair of the data safety monitoring board of the BEEF-BURGER trial. Matthias Bossard reports consulting fees from Abbott Vascular, Amgen, AstraZeneca, Daichii and Vifor. He also reports speaker fees from Abbott Vascular, Amgen, AstraZeneca, Mundipharma, Bayer, Daichii and Vifor. Richard Whitlock reports grants from Boehringer Ingelheim, Bayer and Abbott; consulting fees from Phasebio, Atricure, Cryolife; and participation on a data safety monitoring board with Phasebio. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

From 2005 to 2015, the publication of noninferiority trials increased by six-fold. Noninferiority trials assess whether a new treatment's efficacy is comparable with that of the standard of care and have several appeals. Noninferiority trials can evaluate for both noninferiority and superiority of a new treatment. In addition, multiple treatment modalities exist, and new treatments may be advantageous for reasons beyond efficacy. Common elements of trial design such as the research question, outcomes, statistical analysis, and interpretation of results differ meaningfully between noninferiority trials and superiority trials. The noninferiority margin, constancy assumption, and assay sensitivity are unique aspects of noninferiority trials. As with all randomized controlled trials, patient engagement in and reporting of noninferiority trials are also important. In this review, we discuss the methodological considerations and limitations of noninferiority trials., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Randomized controlled trials (RCTs) are the most robust study design for evaluating the safety and efficacy of a therapeutic intervention. However, their internal validity are at risk when evaluating surgical interventions. This review summarizes existing expertise- based trials in surgery and related methodological concepts to guide surgeons performing this work. We provide caseloads required to reach the learning curve for various surgical interventions and report criteria for expertise from published and unpublished expertise-based trials. In addition, we review design and implementation concepts of expertise-based trials, including recruitment of surgeons, crossover, ethics, generalizability, sample size and definitions for learning curve. Several RCTs have used an expertise-based design. We found that the majority of definitions used for expertise were vague, heterogeneous, and inconsistent across trials evaluating the same surgical intervention. Statistical methods exist to adjust for the learning curve; however, there is limited guidance. We developed the following criteria for surgical expertise for future trials: 1) decide on the proxy to be used for the learning curve, and 2) assess eligible surgeons by comparing their performance to the previously defined expertise criteria., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

Background: Perioperative atrial fibrillation (POAF) after cardiac surgery has been associated with an increased risk of stroke in some studies. However, the exact magnitude of this association during short-term and long-term follow-up remains unclear., Methods: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for the time period from database inception to October 2020. We included observational studies with ≥ 100 patients that reported data on short-term or long-term stroke risk in patients with and without POAF after cardiac surgery. Data were pooled using random-effects models. We reported summary risk ratios (RRs) for studies reporting multivariable adjusted results and calculated absolute risk differences (ARDs) with 95% confidence intervals (CIs)., Results: A total of 55 studies with 540,209 patients were included. POAF was associated with both an increased relative risk (RR 1.69; 95% CI, 1.41-2.03; I 2  = 82%; 9 studies) and absolute risk of short-term stroke (4.5% vs 2.5%; ARD 2.0%; 95% CI, 1.28-2.89). POAF was associated with an increased relative risk (RR 1.20; 95% CI, 1.12-1.29; I 2  = 16%; 10 studies) and absolute risk of long-term stroke (1.06 vs 0.88 per 100 patient-years; ARD 0.18 per 100 patient-years; 95% CI, 0.07-0.26). Sensitivity analyses of high-quality studies and studies reporting either ischemic or embolic strokes yielded similar findings., Conclusions: POAF after cardiac surgery was associated with an increased risk of both short-term and long-term stroke. However, the long-term stroke ARD was small, and whether these patients will benefit from long-term oral anticoagulation therapy is unclear., (© 2021 The Authors.)

Aims: Single oral dose anti-arrhythmic drugs (AADs) are used to cardiovert recent-onset atrial fibrillation (AF); however, the optimal agent is uncertain., Methods: We performed a systematic review and network meta-analysis of randomized trials testing single oral dose AADs vs. any comparator to cardiovert AF <7 days duration. We searched MEDLINE, Embase, and CENTRAL to April 2020. The primary outcome was successful cardioversion at timepoint nearest 8 h after administration., Results: From 12 712 citations, 22 trials (2320 patients) were included. Thirteen trials included patients with some degree of heart failure; 19 included patients with some degree of ischaemic heart disease vs. placebo or rate-control (32% success) at 8 h, flecainide [73%, network odds ratio (OR) 7.6, 95% credible interval (CrI) 4.4-14.0], propafenone (70%, OR 4.6, CrI 2.9-7.3), and pilsicainide (59%, OR 10.0, CrI 1.8-69.0), but not amiodarone (28%, OR 1.0, CrI 0.4-2.8) were superior. Flecainide (OR 7.5, CrI 2.6-24.0) and propafenone (OR 4.5, CrI 1.6-13.0) were superior to amiodarone; propafenone vs. flecainide did not statistically differ (OR 0.6, CrI 0.3-1.1). At longest follow-up, amiodarone was superior to placebo (OR 11.0, CrI 3.2-41.0), flecainide vs. amiodarone (OR 0.79, CrI 0.19-3.1), and propafenone vs. amiodarone (OR 0.36, CrI 0.092-1.4) were not statistically different, and flecainide was superior to propafenone (OR 2.2, CrI 1.1-4.8). Atrial and ventricular tachyarrhythmias, bradyarrhythmias, and hypotension were rare with PO AADs., Conclusion: Single oral dose Class 1C AADs are effective and safe for cardioversion of recent-onset AF. Flecainide may be superior to propafenone. Amiodarone is a slower acting alternative., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

In 1960, Dr Nina Starr Braunwald became the first woman to perform open heart surgery. Sixty years later, despite the fact that women outnumbered men in American medical school in 2017, men still dominate the field of cardiac surgery. Women surgeons remain underrepresented in cardiac surgery; 11% of practicing cardiac surgeons in Canada were women in 2015, and 6% of practicing adult cardiac surgeons in the US were women in 2019. Although women remain a minority in other surgical specialties also, cardiothoracic surgery remains one of the most unevenly-gender distributed specialties. Why are there so few women cardiac surgeons, and why does it matter? Evidence is emerging regarding the benefits of diversity for a variety of industries, including healthcare. In order to attract and retain the best talent, we must make the cardiac surgery environment more diverse, equitable, and inclusive. Some causes of perpetuation of the gender gap have been documented in the literature-these include uneven compensation and career advancement opportunities, outdated views on family dynamics, and disproportionate scrutiny of women surgeons, causing additional workplace frictions for women. Diversity is an organizational strength, and gender-diverse institutions are more likely to outperform their non-gender-diverse counterparts. Modifiable issues perpetuate the gender gap, and mentorship is key in helping attract, develop, and retain the best and brightest within cardiac surgery. Facilitating mentorship opportunities is key to reducing barriers and bridging the gap., (© 2021 The Authors.)

Background: Appropriate training of health professionals has been recommended to increase organ donation rates. Some studies have shown insufficient knowledge among medical students. This survey aims to describe their knowledge and attitude toward organ donation (OD)., Method: We designed, pre-tested and conducted an online survey of all undergraduate medical students from Montreal, Laval and Sherbrooke universities in 2016-2017. Multivariate linear regression identified factors associated with a better knowledge score., Results: Twenty-two percent (750/3344) of students completed the survey. Ninety-one percent of students adequately knew that neurological death is irreversible; 76% acknowledged that someone could be neurologically deceased while his heart is still beating; 69% were not aware of circulatory determination of death. For only one knowledge item, senior students had a better answer than junior students. Total knowledge score was associated with exposure to OD during medical studies and comfort in answering patients' questions about OD (p < 0,001). Regarding attitude, 96% of respondents wished to become organ donors after death and 92% supported OD training during their medical training., Conclusion: Despite a favourable attitude, medical students have limited knowledge of OD. Findings suggest the need for a formal curriculum about OD, as students expressed.

Background: The prevalence of left atrial (LA) thrombus in patients with atrial fibrillation (AF) or atrial flutter (AFL) on guideline-directed anticoagulation is not well known, yet this may inform transesophageal echocardiogram (TEE) use before cardioversion or catheter ablation., Objectives: The purpose of this study was to quantify LA thrombus prevalence among patients with AF/AFL on guideline-directed anticoagulation and to identify high-risk subgroups., Methods: EMBASE, MEDLINE, and CENTRAL were systematically searched from inception to July 2020 for studies reporting on LA thrombus prevalence among patients with AF/AFL undergoing TEE following at least 3 weeks of continuous therapeutic oral anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Meta-analysis was performed using random effects models., Results: Thirty-five studies describing 14,653 patients were identified. The mean-weighted LA thrombus prevalence was 2.73% (95% confidence interval [CI]: 1.95% to 3.80%). LA thrombus prevalence was similar for VKA- and DOAC-treated patients (2.80%; 95% CI: 1.86% to 4.21% vs. 3.12%; 95% CI: 1.92% to 5.03%; p = 0.674). Patients with nonparoxysmal AF/AFL had a 4-fold higher LA thrombus prevalence compared with paroxysmal patients (4.81%; 95% CI: 3.35% to 6.86% vs. 1.03%; 95% CI: 0.52% to 2.03%; p < 0.001). LA thrombus prevalence was higher among patients undergoing cardioversion versus ablation (5.55%; 95% CI: 3.15% to 9.58% vs. 1.65%; 95% CI: 1.07% to 2.53%; p < 0.001). Patients with CHA 2 DS 2 -VASc scores ≥3 had a higher LA thrombus prevalence compared with patients with scores ≤2 (6.31%; 95% CI: 3.72% to 10.49% vs. 1.06%; 95% CI: 0.45% to 2.49%; p < 0.001)., Conclusions: LA thrombus prevalence is high in subgroups of anticoagulated patients with AF/AFL, who may benefit from routine pre-procedural TEE use before cardioversion or catheter ablation., Competing Interests: Funding Support and Author Disclosures Dr. Wong holds a McMaster University Department of Medicine Early-Career Research Award. Dr. Healey holds the Stuart Connolly Chair in Cardiology Research at the Population Health Research Institute, and the Salim Yusuf Chair at Hamilton Health Sciences. All the authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

To estimate the incidence of new-onset atrial fibrillation in critically ill patients., Design: Prospective cohort., Setting: Medical-surgical ICU., Subjects: Consecutive patients without a history of atrial fibrillation but with atrial fibrillation risk factors., Interventions: Electrocardiogram patch monitor until discharge from hospital or up to 14 days., Measurements and Main Results: A total of 249 participants (median age of 71 yr [interquartile range] 64-78 yr; 35% female) completed the study protocol of which 158 (64%) were admitted to ICU for medical illness, 78 (31%) following noncardiac surgery, and 13 (5%) with trauma. Median Acute Physiology and Chronic Health Evaluation II score was 16 (interquartile range, 12-22). Median duration of patch electrocardiogram monitoring, ICU, and hospital lengths of stay were 6 (interquartile range, 3-12), 4 (interquartile range, 2-8), and 11 days (interquartile range, 5-23 d), respectively.Atrial fibrillation ≥ 30 seconds was detected by the patch in 44 participants (17.7%), and three participants (1.2%) had atrial fibrillation detected clinically after patch removal, resulting in an overall atrial fibrillation incidence of 18.9% (95% CI, 14.2-24.3%).Total duration of atrial fibrillation ranged from 53 seconds to the entire monitoring time. The proportion of participants with ≥1 episode(s) of ≥6 minute, ≥1 hour, ≥12 hour and ≥24 hour duration was 14.8%, 13.2%, 7.0%, and 5.3%, respectively. The clinical team recognized only 70% of atrial fibrillation cases that were detected by the electrocardiogram patch., Conclusions: Among patients admitted to an ICU, the incidence of new-onset atrial fibrillation is approximately one in five, although approximately one-third of cases are not recognized by the clinical team., Competing Interests: Dr. McIntyre is supported by personnel awards from Canadian Stroke Prevention Intervention Network and the Canadian Institutes for Health Research (CIHR). Dr. Spence is supported by a personnel award from CIHR. Dr. Belley-Côté is supported by a personnel award from the McMaster University Department of Medicine. Dr. Whitlock is supported by a mid-career award from the Heart and Stroke Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Interventions to optimize spinal cord perfusion via support of mean arterial pressure (MAP) or spinal cord perfusion pressure (SCPP) are thought to play a critical role in the management of patients with acute traumatic spinal cord injuries, but there is ongoing controversy about efficacy and safety. We aimed to determine the effects of optimizing spinal cord perfusion on neurological recovery and risks for adverse events. We searched multiple databases for published and unpublished reports. Two reviewers independently screened articles, extracted data, and evaluated risk of bias. We synthesized data and evaluated confidence in anticipated treatment effects according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. We identified 20 eligible observational studies and 1 eligible randomized controlled trial. According to low or very low quality evidence, the effect of MAP support on neurological recovery after acute traumatic spinal cord injury is uncertain, and the use of vasopressors to support MAP may be associated with increased rates of predominantly cardiac adverse events. Increased SCPP appears likely to be associated with improved neurological recovery, but SCPP monitoring via intradural catheters at the anatomical site of injury may involve increased risks of cerebrospinal fluid leakage requiring revision surgery or pseudomeningocele. No study directly compared the effects of specific MAP goal ranges, SCPP ranges, SCPP monitoring techniques, or durations of treatment. Very low quality evidence suggests that norepinephrine may have less risk of adverse events than dopamine. The current literature is insufficient to make strong recommendations about interventions to support spinal cord perfusion via MAP or SCPP goals in patients with acute traumatic spinal cord injuries. Data are compatible with a variety of treatment decisions, and individualized approaches may be optimal. Further investigation to clarify the risks, benefits, and alternatives to MAP or SCPP support in this population is warranted.

Managing severe valvular heart disease with mechanical valve replacement necessitates lifelong anticoagulation with a vitamin K antagonist. Optimal anticoagulation intensity for patients with mechanical valves remains uncertain; current recommendations are inconsistent across guideline bodies and largely based on expert opinion. In this review, we outline the history of anticoagulation therapy in patients with mechanical heart valves and critically evaluate current antithrombotic guidelines for these patients. We conclude that randomized trials evaluating optimal anticoagulation intensity in patients with mechanical valves are needed, and that future guidelines must better justify antithrombotic treatment recommendations.

Introduction: Saphenous vein graft (SVG) is the most common conduit used for coronary artery bypass grafting (CABG) surgery. Unfortunately, SVG are associated with poor long-term patency rates; a significant predictor of re-operation rates and survival. As such, medical therapy to prevent SVG narrowing or occlusion is of paramount importance. Aspirin (ASA) monotherapy is the standard of care after CABG, to improve long-term major adverse cardiovascular events (MACE) and graft patency. Benefits of dual antiplatelet therapy (DAPT) have not been well established in all CABG patients. We present a protocol for a network meta-analysis (NMA) comparing the effects of various antiplatelet therapy regimens on SVG patency, mortality, and bleeding among adult patients following CABG., Methods: We will search CENTRAL, MEDLINE, EMBASE, CINAHL ACPJC, and grey literature sources (AHA, ACC, ESC, and CCC conference proceedings, ISRCTN Register, and WHO ICTRP) for randomized controlled trials (RCTs) which fit our criteria. RCTs that evaluate different antiplatelet regimens at least 3-months after CABG and have any of SVG patency, mortality, MACE, and major bleeding as outcomes will be selected. We will perform title and abstract screening, full-text screening, and data extraction independently and in duplicate. Two independent reviewers will also assess risk of bias (ROB) for each study, as well as evaluate quality of evidence using the GRADE framework. We will use R to perform the NMA and use low-dose ASA as reference within our network. We will report results as odds ratios with confidence intervals for direct comparisons, and credible intervals for indirect or mixed comparisons. We will use the surface under the cumulative ranking curve (SUCRA) to estimate the ranking of interventions., Discussion: Given the limited direct comparison of various antiplatelet regimens, a network approach is ideal to clarify the optimum antiplatelet therapy after CABG. We hope that our NMA will be the largest quantitative synthesis evaluating antiplatelet regimens among patients requiring CABG. It should inform clinicians and guideline developers in selecting the most effective and safest antiplatelet regimen.Systematic Review registration: International Prospective Register for Systematic Reviews (PROSPERO)-CRD42019127695.

Background: Among adults undergoing contemporary noncardiac surgery, little is known about the frequency and timing of death and the associations between perioperative complications and mortality. We aimed to establish the frequency and timing of death and its association with perioperative complications., Methods: We conducted a prospective cohort study of patients aged 45 years and older who underwent inpatient noncardiac surgery at 28 centres in 14 countries. We monitored patients for complications until 30 days after surgery and determined the relation between these complications and 30-day mortality using a Cox proportional hazards model., Results: We included 40 004 patients. Of those, 715 patients (1.8%) died within 30 days of surgery. Five deaths (0.7%) occurred in the operating room, 500 deaths (69.9%) occurred after surgery during the index admission to hospital and 210 deaths (29.4%) occurred after discharge from the hospital. Eight complications were independently associated with 30-day mortality. The 3 complications with the largest attributable fractions (AF; i.e., potential proportion of deaths attributable to these complications) were major bleeding (6238 patients, 15.6%; adjusted hazard ratio [HR] 2.6, 95% confidence interval [CI] 2.2-3.1; AF 17.0%); myocardial injury after noncardiac surgery [MINS] (5191 patients, 13.0%; adjusted HR 2.2, 95% CI 1.9-2.6; AF 15.9%); and sepsis (1783 patients, 4.5%; adjusted HR 5.6, 95% CI 4.6-6.8; AF 12.0%)., Interpretation: Among adults undergoing noncardiac surgery, 99.3% of deaths occurred after the procedure and 44.9% of deaths were associated with 3 complications: major bleeding, MINS and sepsis. Given these findings, focusing on the prevention, early identification and management of these 3 complications holds promise for reducing perioperative mortality. Study registration: ClinicalTrials.gov, no. NCT00512109., Competing Interests: Competing interests: Clara Chow received support from the National Health and Medical Research Council of Australia and The Heart Foundation (Australia) for a career development fellowship. Robert Sapsford received nonfinancial support in the form of a research nurse funded by the National Institutes of Health Research, and lecture fees from Eli Lilly, MSD and Novo Nordisk. Denis Xavier received grants from Cadila Pharmaceuticals, Boehringer Ingelheim, Astra Zeneca India, Sanofi Aventis, Pfizer, Bristol–Myers Squibb, Medical Research Council (United Kingdom) and Wellcome Trust outside the submitted work. Emmanuelle Duceppe received a grant as a coapplicant on an investigator-initiated study and lecture fees from Roche Diagnostics. Philip J. Devereaux is a member of a research group with a policy of not accepting honorariums or other payments from industry for their own personal financial gain. They do accept honorariums or payments from industry to support research endeavours and costs to participate in meetings. Based on study questions Dr. Devereaux has originated and grants he has written, he has received grants from Abbott Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers-Squibb, Coviden, Octapharma, Philips Healthcare, Roche Diagnostics, Siemens and Stryker. Dr Devereaux has participated in advisory board meetings for GlaxoSmithKline and Boehringer Ingelheim. He also attended an expert panel meeting with AstraZeneca and Boehringer Ingelheim. Roche Diagnostics provided Troponin T assays and financial support for the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) Study. No other competing interests were declared., (© 2019 Joule Inc. or its licensors.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

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., (© 2018 Wiley Periodicals, Inc.)

Background: The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration., Discussion: Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75-80 mmHg) versus lower (60-65 mmHg) mean arterial pressure (MAP) targets for vasopressor therapy in shock. In this trial, potential protocol deviations were defined as MAP values outside the targeted range for >4 consecutive hours during vasopressor therapy without synchronous and consistent adjustments of vasopressor doses. An adjudication committee reviewed each potential deviation to determine if it was clinically-justified or not. There are four reasons for this contextual measurement and reporting of protocol adherence. First, between-arm separation is a robust measure of adherence to complex protocols. Second, adherence assessed by protocol deviations varies in function of the definition of deviations and the frequency of measurements. Third, distinguishing clinically-justified vs. not clinically-justified protocol deviations acknowledges clinically sensible bedside decision-making and offers a clear terminology before the trial begins. Finally, multiple metrics exist to report protocol deviations, which provides different information but complementary information on protocol adherence., Conclusions: In trials of interventions requiring continuous titration, metrics used for defining protocol deviations have a considerable impact on the interpretation of protocol adherence. Definitions for protocol deviations should be prespecified and correlated with between-arm separation, if it can be measured.

Background: The effect on cardiovascular outcomes of withholding angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in chronic users before noncardiac surgery is unknown., Methods: In this international prospective cohort study, the authors analyzed data from 14,687 patients (including 4,802 angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users) at least 45 yr old who had in-patient noncardiac surgery from 2007 to 2011. Using multivariable regression models, the authors studied the relationship between withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and a primary composite outcome of all-cause death, stroke, or myocardial injury after noncardiac surgery at 30 days, with intraoperative and postoperative clinically important hypotension as secondary outcomes., Results: Compared to patients who continued their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, the 1,245 (26%) angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users who withheld their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the 24 h before surgery were less likely to suffer the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1,245 [12.0%] vs. 459/3,557 [12.9%]; adjusted relative risk, 0.82; 95% CI, 0.70 to 0.96; P = 0.01) and intraoperative hypotension (adjusted relative risk, 0.80; 95% CI, 0.72 to 0.93; P < 0.001). The risk of postoperative hypotension was similar between the two groups (adjusted relative risk, 0.92; 95% CI, 0.77 to 1.10; P = 0.36). Results were consistent across the range of preoperative blood pressures. The practice of withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was only modestly correlated with patient characteristics and the type and timing of surgery., Conclusions: Withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers before major noncardiac surgery was associated with a lower risk of death and postoperative vascular events. A large randomized trial is needed to confirm this finding. In the interim, clinicians should consider recommending that patients withhold angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers 24 h before surgery.

Objective: Acute kidney injury is common after cardiac surgery and associated with postoperative mortality. Perioperative cardiac biomarkers may predict acute kidney injury and mortality. We evaluated whether cardiac biomarkers were associated with severe acute kidney injury, defined as a doubling in serum creatinine or requiring renal replacement therapy during hospital stay after surgery, and mortality., Methods: In a prospective multicenter cohort of adults undergoing cardiac surgery, we measured the following biomarkers in preoperative and postoperative banked plasma: high-sensitivity troponin T, cardiac troponin I, creatine kinase-MB, and N-terminal prohormone of brain natriuretic peptide., Results: In the patients who were discharged alive, severe acute kidney injury occurred in 37 of 960 (3.9%), and 43 of 960 (4.5%) died within 1 year of follow-up. N-terminal prohormone of brain natriuretic peptide was the only preoperative biomarker that was independently associated with severe acute kidney injury (with log transformation, adjusted odds ratio, 1.4; 95% confidence interval, 1.0-1.9). Biomarkers measured within 6 hours of surgery (day 1) were all associated with severe acute kidney injury. Preoperative N-terminal prohormone of brain natriuretic peptide was also independently associated with 1-year mortality (with log transformation, adjusted odds ratio, 1.7; 95% confidence interval, 1.2-2.2). Patients in the highest tertile for N-terminal prohormone of brain natriuretic peptide preoperatively (>1006.4 ng/L) had marked increases in their risk for 1-year mortality (adjusted odds ratio, 27.2; 95% confidence interval, 3.5-213.5). Day 1 N-terminal prohormone of brain natriuretic peptide was associated with mortality independently of change in serum creatinine from preoperative baseline., Conclusions: Of the studied biomarkers, N-terminal prohormone of brain natriuretic peptide was the only preoperative biomarker independently associated with severe acute kidney injury and mortality. Early increases in postoperative cardiac biomarkers were associated with severe acute kidney injury after cardiac surgery. Future research should focus on whether interventions that lower N-terminal prohormone of brain natriuretic peptide can affect postoperative outcomes., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Previous meta-analyses of methylprednisolone (MPS) for patients with acute traumatic spinal cord injuries (TSCIs) have not addressed confidence in the quality of evidence used for pooled effect estimates, and new primary studies have been recently published. We aimed to determine whether MPS improves motor recovery and is associated with increased risks for adverse events. We searched MEDLINE, EMBASE, and The Cochrane Library, and two reviewers independently screened articles, extracted data, and evaluated risk of bias. We pooled outcomes from randomized, controlled trials (RCTs) and controlled observational studies separately and used the Grades of Recommendation, Assessment, Development, and Evaluation approach to evaluate confidence. We included four RCTs and 17 observational studies. MPS was not associated with an increase in long-term motor score recovery (two RCTs: 335 participants; mean difference [MD], -1.11; 95% confidence interval [CI], -4.75 to 2.53; p = 0.55, low confidence; two observational studies: 528 participants; MD, 1.37; 95% CI, -3.08 to 5.83; p = 0.55, very low confidence) or improvement by at least one motor grade (three observational studies: 383 participants; risk ratio [RR], 0.84; 95% CI, 0.53-1.33; p = 0.46, very low confidence). Evidence from two RCTs demonstrated superior short-term motor score improvement if MPS was administered within 8 h of injury (two RCTs: 250 participants; MD, 4.46; 95% CI, 0.97-7.94; p = 0.01, low confidence), but risk of bias and imprecision limit confidence in these findings. Observational studies demonstrated a significantly increased risk for gastrointestinal bleeding (nine studies: 2857 participants; RR, 2.18; 95% CI, 1.13-4.19; p = 0.02, very low confidence), but RCTs did not. Pooled evidence does not demonstrate a significant long-term benefit for MPS in patients with acute TSCIs and suggests it may be associated with increased gastrointestinal bleeding. These findings support current guidelines against routine use, but strong recommendations are not warranted because confidence in the effect estimates is limited.

Acute and recurring pericarditis are frequently encountered clinical entities. Given that severe complications such as tamponade and constrictive pericarditis occur rarely, the majority of patients suffering from acute pericarditis will have a benign clinical course. However, pericarditis recurrence, with its painful symptoms, is frequent. In effect, recent studies have demonstrated a beneficial role of colchicine in preventing recurrence, while also suggesting an increase in recurrences with the use of corticosteroids, the traditional first-line agent.