Efficacy and Safety of Botulinum Toxin Type A for the Prevention of Postoperative Atrial Fibrillation.

BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with increased morbidity and mortality. Epicardial injection of botulinum toxin may suppress POAF. OBJECTIVES: This study sought to assess the safety and efficacy of AGN-151607 for the prevention of POAF after cardiac surgery. METHODS: This phase 2, randomized, placebo-controlled trial assessed the safety and efficacy of AGN-151607, 125 U and 250 U vs placebo (1:1:1), for the prevention of POAF after cardiac surgery. Randomization was stratified by age (<65, ≥65 years) and type of surgery (nonvalvular/valve surgery). The primary endpoint was the occurrence of continuous AF ≥30 seconds. RESULTS: Among 312 modified intention-to-treat participants (placebo, n = 102; 125 U, n = 104; and 250 U, n = 106), the mean age was 66.9 ± 6.8 years; 17% were female; and 64% had coronary artery bypass graft (CABG) only, 12% had CABG + valve, and 24% had valve surgery. The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125-U group (relative risk [RR] vs placebo: 0.80; 95% CI: 0.58-1.10; P = 0.16), and 47.2% of the 250-U group (RR vs placebo: 1.04; 95% CI: 0.79-1.37; P = 0.78). The primary endpoint was reduced in the 125-U group in those ≥65 years of age (RR: 0.64; 95% CI: 0.43-0.94; P = 0.02) with a greater reduction in CABG-only participants ≥65 years of age (RR: 0.49; 95% CI: 0.27-0.87; P = 0.01). Rehospitalization and rates of adverse events were similar across the 3 groups. CONCLUSIONS: There were no significant differences in the rate of POAF with either dose compared with placebo; however, there was a lower rate of POAF in participants ≥65 years undergoing CABG only and receiving 125 U of AGN-151607. These hypothesis-generating findings require investigation in a larger, adequately powered randomized clinical trial. (Botulinum Toxin Type A [AGN-151607] for the Prevention of Post-operative Atrial Fibrillation in Adult Participants Undergoing Open-chest Cardiac Surgery [NOVA]; NCT03779841); A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Evaluate the Efficacy and Safety of Botulinum Toxin Type A [AGN 151607] Injections into the Epicardial Fat Pads to Prevent Post-Operative Atrial Fibrillation in Patients Undergoing Open-Chest Cardiac Surgery; 2017-004399-68).

Does cardiovascular preparticipation screening cause psychological distress in athletes? A systematic review.

OBJECTIVE: To evaluate the psychological implications of cardiovascular preparticipation screening (PPS) in athletes. DESIGN: Systematic review. DATA SOURCES: MEDLINE, EMBASE, PubMed, CINAHL, SPORTDiscus, APA PsycInfo, Cochrane Library and grey literature sources. STUDY ELIGIBILITY CRITERIA: Observational and experimental studies assessing a population of athletes who participated in a cardiovascular PPS protocol, where psychological outcomes before, during and/or after PPS were reported. METHODS: Results of included studies were synthesised by consolidating similar study-reported measures for key psychological outcomes before, during and/or after screening. Summary measures (medians, ranges) were computed across studies for each psychological outcome. RESULTS: A total of eight studies were included in this review (median sample size: 479). Study cohorts consisted of high school, collegiate, professional and recreational athletes (medians: 59% male, 20.5 years). Most athletes reported positive reactions to screening and would recommend it to others (range 88%-100%, five studies). Increased psychological distress was mainly reported among athletes detected with pathological cardiac conditions and true-positive screening results. In comparison, athletes with false-positive screening results still reported an increased feeling of safety while participating in sport and were satisfied with PPS. A universal conclusion across all studies was that most athletes did not experience psychological distress before, during or after PPS, regardless of the screening modality used or accuracy of results. CONCLUSION: Psychological distress associated with PPS in athletes is rare and limited to athletes with true-positive findings. To mitigate downstream consequences in athletes who experience psychological distress, appropriate interventions and resources should be accessible prior to the screening procedure. PROSPERO REGISTRATION NUMBER: CRD42021272887.

Design and Rationale of a Phase 2 Study of NeurOtoxin (Botulinum Toxin Type A) for the PreVention of Post-Operative Atrial Fibrillation - The NOVA Study.

BACKGROUND: Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in two clinical studies of cardiac surgery patients, without new safety observations. METHODS: The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety. CONCLUSIONS: The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.

A Gas-Powered, Patient-Responsive Automatic Resuscitator for Use in Acute Respiratory Failure: A Bench and Experimental Study.

BACKGROUND: During the COVID-19 pandemic, a need for innovative, inexpensive, and simple ventilator devices for mass use has emerged. The Oxylator (CPR Medical Devices, Markham, Ontario, Canada) is an FDA-approved, fist-size, portable ventilation device developed for out-of-hospital emergency ventilation. It has not been tested in conditions of severe lung injury or with added PEEP. We aimed to assess the performance and reliability of the device in simulated and experimental conditions of severe lung injury, and to derive monitoring methods to allow the delivery of safe, individualized ventilation during situations of surge. METHODS: We bench-tested the functioning of the device with an added PEEP valve extensively, mimicking adult patients with various respiratory mechanics during controlled ventilation, spontaneous breathing, and prolonged unstable conditions where mechanics or breathing effort was changed at every breath. The device was further tested on a porcine model (4 animals) after inducing lung injury, and these results were compared with conventional ventilation modes. RESULTS: The device was stable and predictable, delivering a constant flow (30 L/min) and cycling automatically at the inspiratory pressure set (minimum of 20 cm H2O) above auto-PEEP. Changes in respiratory mechanics manifested as changes in respiratory timing, allowing prediction of tidal volumes from breathing frequency. Simulating lung injury resulted in relatively low tidal volumes (330 mL with compliance of 20 mL/cm H2O). In the porcine model, arterial oxygenation, CO2, and pH were comparable to conventional modes of ventilation. CONCLUSIONS: The Oxylator is a simple device that delivered stable ventilation with tidal volumes within a clinically acceptable range in bench and porcine lung models with low compliance. External monitoring of respiratory timing is advisable, allowing tidal volume estimation and recognition of changes in respiratory mechanics. The device can be an efficient, low-cost, and practical rescue solution for providing short-term ventilatory support as a temporary bridge, but it requires a caregiver at the bedside.

Major Adverse Cardiovascular Events Associated With Postoperative Atrial Fibrillation After Noncardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent occurrence after noncardiac surgery. It remains unclear whether POAF is associated with an increased risk of major adverse events. We aimed to elucidate the risk of stroke, myocardial infarction, and death associated with POAF following noncardiac surgery by a meta-analysis of randomized controlled studies and observational studies. METHODS: We searched electronic databases from inception up to August 1, 2019 for all studies that reported stroke or myocardial infarction in adult patients who developed POAF following noncardiac surgery. We used random-effects models to summarize the studies. RESULTS: The final analyses included 28 studies enrolling 2 612 816 patients. At 1-month (10 studies), POAF was associated with an ≈3-fold increase in the risk of stroke (weighted mean 2.1% versus 0.7%; odds ratio [OR], 2.82 [95% CI, 2.15-3.70]; P<0.001). POAF was associated with ≈4-fold increase in the long-term risk of stroke with (weighted mean, 2.0% versus 0.6%; OR, 4.12 [95% CI, 3.32-5.11]; P≤0.001) in 8 studies with ≥12-month follow-up. There was a significant overall increase in the risk of stroke and myocardial infarction associated with POAF (weighted mean, 2.5% versus 0.9%; OR, 3.44 [95% CI, 2.38-4.98]; P<0.001) and (weighted mean, 12.6% versus 2.7%; OR, 4.02 [95% CI, 3.08-5.24]; P<0.001), respectively. Furthermore, POAF was associated with a 3-fold increase in all-cause mortality at 30 days (weighted mean, 15.0% versus 5.4%; OR, 3.36 [95% CI, 2.13-5.31]; P<0.001). CONCLUSIONS: POAF was associated with markedly higher risk of stroke, myocardial infarction, and all-cause mortality following noncardiac surgery. Future studies are needed to evaluate the impact of optimal cardiovascular pharmacotherapies to prevent POAF and to decrease the risk of major adverse events in these high-risk patients.

Long-term outcomes of chronic coronary syndrome worldwide: insights from the international CLARIFY registry.

AIMS: Over the last decades, the profile of chronic coronary syndrome has changed substantially. We aimed to determine characteristics and management of patients with chronic coronary syndrome in the contemporary era, as well as outcomes and their determinants. METHODS AND RESULTS: Data from 32 703 patients (45 countries) with chronic coronary syndrome enrolled in the prospective observational CLARIFY registry (November 2009 to June 2010) with a 5-year follow-up, were analysed. The primary outcome [cardiovascular death or non-fatal myocardial infarction (MI)] 5-year rate was 8.0% [95% confidence interval (CI) 7.7-8.3] overall [male 8.1% (7.8-8.5); female 7.6% (7.0-8.3)]. A cox proportional hazards model showed that the main independent predictors of the primary outcome were prior hospitalization for heart failure, current smoking, atrial fibrillation, living in Central/South America, prior MI, prior stroke, diabetes, current angina, and peripheral artery disease. There was an interaction between angina and prior MI (P = 0.0016); among patients with prior MI, angina was associated with a higher primary event rate [11.8% (95% CI 10.9-12.9) vs. 8.2% (95% CI 7.8-8.7) in patients with no angina, P < 0.001], whereas among patients without prior MI, event rates were similar for patients with [6.3% (95% CI 5.4-7.3)] or without angina [6.4% (95% CI 5.9-7.0)], P > 0.99. Prescription rates of evidence-based secondary prevention therapies were high. CONCLUSION: This description of the spectrum of chronic coronary syndrome patients shows that, despite high rates of prescription of evidence-based therapies, patients with both angina and prior MI are an easily identifiable high-risk group who may deserve intensive treatment. CLINICAL REGISTRY: ISRCTN43070564.

Canadian Cardiovascular Society Cardiovascular Screening of Competitive Athletes: The Utility of the Screening Electrocardiogram to Predict Sudden Cardiac Death.

Prevention of sudden cardiac arrest/death (SCA/D) among athletes is a universal goal, although the optimal strategy for its achievement is controversial, with the inclusion of the 12-lead electrocardiogram (ECG) at the center of the debate. The ECG exhibits superior sensitivity over history and physical examination to detect conditions associated with SCA/D. However, the identification of disease does not necessarily lead to a significant reduction in SCA/D. The "Canadian Cardiovascular Society/Canadian Heart Rhythm Society Joint Position Statement on the Cardiovascular Screening of Competitive Athletes" recommended against the routine performance of an ECG for the initial cardiovascular screening of competitive athletes. The incidence of SCA/D among athletes (<35 years of age), the risk of SCA/D during sport participation among individuals with abnormalities found on screening ECG, the efficacy of the ECG to identify conditions associated with SCA/D, and the positive predictive value of an abnormal ECG to predict SCA/D are critically examined. This review presents the evidence informing the panel's recommendation.

Canadian Cardiovascular Society/Canadian Heart Rhythm Society Joint Position Statement on the Cardiovascular Screening of Competitive Athletes.

Sudden cardiac death (SCD), especially in a young seemingly healthy individual, is a tragic and highly publicized event, which is often followed by a strong emotional reaction from the public and medical community." Although rare, SCD in the young is devastating to families and communities, underpinning our society's desire to avoid any circumstances predisposing to the loss of human life during exertion. The Canadian Cardiovascular Society Position Statement on the cardiovascular screening of athletes provides evidence-based recommendations for Canadian sporting organizations and institutions with a focus on the role of routine electrocardiogram (ECG) screening in preventing SCD. We recommend that the cardiac screening and care of athletes within the Canadian health care model comprise a sequential (tiered) approach to the identification of cardiac risk, emphasizing the limitations of screening, the importance of shared decision-making when cardiac conditions are diagnosed, and the creation of policies and procedures for the management of emergencies in sport settings. Thus, we recommend against the routine (first-line or blanket mass performance of ECG) performance of a 12-lead ECG for the initial cardiovascular screening of competitive athletes. Organization/athlete-centred cardiovascular screening and care of athletes program is recommended. Such screening should occur in the context of a consistent, systematic approach to cardiovascular screening and care that provides: assessment, appropriate investigations, interpretation, management, counselling, and follow-up. The recommendations presented comprise a tiered framework that allows institutions some choice as to program creation.

Sleep Apnea Increases the Risk of New Hospitalized Atrial Fibrillation: A Historical Cohort Study.

OBJECTIVES: This study examined the relationship between newly diagnosed OSA and incident hospitalized atrial fibrillation (AF) over the subsequent 10 years in a large arrhythmia-free cohort. METHODS: Adults referred between 1994 and 2010 to a large academic hospital with suspected OSA who were arrhythmia-free at the time of the first diagnostic sleep study were included. Clinical data were linked to provincial health administrative data to define outcome. Cox regressions were used to investigate the relationship between severity of OSA as measured by the apnea-hypopnea index (AHI) and degree of nocturnal hypoxemia, and incident hospitalized AF. RESULTS: In total, 8,256 subjects were included in this study. Their median age was 47 years, 62% were men; 28% had an AHI > 30 events per hour, and 6% spent > 30% of sleep time with oxygen saturation < 90%. Over a median follow-up of 10 years (interquartile range, 7-13 years), 173 participants (2.1%) were hospitalized with AF. Controlling for age, sex, alcohol consumption, smoking status, previous heart failure, COPD, and pulmonary embolism, nocturnal hypoxemia (but not AHI) was a significant predictor of incident AF: hazard ratio, 2.47 (95% CI, 1.64-3.71). After further controlling for BMI and hypertension, this association was attenuated but remained significant (hazard ratio, 1.77 [95% CI, 1.15-2.74]). CONCLUSIONS: In a large arrhythmia-free clinical cohort with suspected OSA, nocturnal hypoxemia was independently associated with a 77% increased hazard of incident hospitalized AF. These findings further support a relationship between OSA, nocturnal hypoxemia, and new-onset AF, and they may be used to enhance AF prevention in patients with OSA and severe nocturnal hypoxemia.

A clinical decision instrument to predict 30-day death and cardiovascular hospitalizations after an emergency department visit for atrial fibrillation: The Atrial Fibrillation in the Emergency Room, Part 2 (AFTER2) study.

BACKGROUND: In previous work, we derived and validated a tool that predicts 30-day mortality in emergency department atrial fibrillation (AF) patients. The objective of this study was to derive and validate a tool that predicts a composite of 30-day mortality and return cardiovascular hospitalizations. METHODS: This retrospective cohort study at 24 emergency departments in Ontario, Canada, included patients with a primary diagnosis of AF who were seen between April 2008 and March 2009. We assessed a composite outcome of 30-day mortality and subsequent hospitalizations for a cardiovascular reason, including stroke. RESULTS: Of 3,510 patients, 2,343 were randomly selected for the derivation cohort, leaving 1,167 in the validation cohort. The composite outcome occurred in 227 (9.7%) and 125 (10.7%) patients in the derivation and validation cohorts, respectively. Eleven variables were independently associated with the outcome: older age, not taking anticoagulation, HAS-BLED score of ≥3, 3 laboratory results (positive troponin, supratherapeutic international normalized ratio, and elevated creatinine), emergency department administration of furosemide, and 4 patient comorbidities (heart failure, chronic obstructive lung disease, cancer, dementia). In the validation cohort, the observed 30-day outcomes in the 5 risk strata that were defined using the derivation cohort were 2.0%, 6.6%, 10.7%, 12.5%, and 20.0%. The c statistic was 0.73 and 0.69 in the derivation and validation cohort, respectively. CONCLUSIONS: Using a population-based sample, we derived and validated a tool that predicts the risk of early death and rehospitalization for a cardiovascular reason in emergency department AF patients. The tool can offer information to managing physicians about the risk of death and rehospitalization for AF patients seen in the in emergency department, as well as identify patient groups for future targeted interventions aimed at preventing these outcomes.

Electrocardiograms in Low-Risk Patients Undergoing an Annual Health Examination.

Importance: Clinical guidelines advise against routine electrocardiograms (ECG) in low-risk, asymptomatic patients, but the frequency and impact of such ECGs are unknown. Objective: To assess the frequency of ECGs following an annual health examination (AHE) with a primary care physician among patients with no known cardiac conditions or risk factors, to explore factors predictive of receiving an ECG in this clinical scenario, and to compare downstream cardiac testing and clinical outcomes in low-risk patients who did and did not receive an ECG after their AHE. Design, Setting, and Participants: A population-based retrospective cohort study using administrative health care databases from Ontario, Canada, between 2010/2011 and 2014/2015 to identify low-risk primary care patients and to assess the subsequent outcomes of interest in this time frame. All patients 18 years or older who had no prior cardiac medical history or risk factors who received an AHE. Exposures: Receipt of an ECG within 30 days of an AHE. Main Outcomes and Measures: Primary outcome was receipt of downstream cardiac testing or consultation with a cardiologist. Secondary outcomes were death, hospitalization, and revascularization at 12 months. Results: A total of 3 629 859 adult patients had at least 1 AHE between fiscal years 2010/2011 and 2014/2015. Of these patients, 21.5% had an ECG within 30 days after an AHE. The proportion of patients receiving an ECG after an AHE varied from 1.8% to 76.1% among 679 primary care practices (coefficient of quartile dispersion [CQD], 0.50) and from 1.1% to 94.9% among 8036 primary care physicians (CQD, 0.54). Patients who had an ECG were significantly more likely to receive additional cardiac tests, visits, or procedures than those who did not (odds ratio [OR], 5.14; 95% CI, 5.07-5.21; P < .001). The rates of death (0.19% vs 0.16%), cardiac-related hospitalizations (0.46% vs 0.12%), and coronary revascularizations (0.20% vs 0.04%) were low in both the ECG and non-ECG cohorts. Conclusions and Relevance: Despite recommendations to the contrary, ECG testing after an AHE is relatively common, with significant variation among primary care physicians. Routine ECG testing seems to increase risk for a subsequent cardiology testing and consultation cascade, even though the overall cardiac event rate in both groups was very low.

"Presumed cardiac" arrest in children and young adults: A misnomer?

AIM: To use a novel methodology to assess the incidence and specific causes of Out-of-Hospital Cardiac Arrest (OHCA) within a young urban cohort. METHODS: All EMS attended OHCA patients in a large urban area, between 2009 and 2012, aged 2-45 years, treated or untreated, who died or survived, and that were designated as "no obvious cause" etiology by trained data abstractors were included. Using multisource (medical and coroner) records, an expert panel adjudicated the causes of the OHCAs as: confirmed cardiac causes, confirmed non- cardiac causes, and other causes. RESULTS: Of a total of 1993 cases EMS designated as "no obvious cause", only 29.9% (595/1993) were due to confirmed cardiac causes; the rest were due to other causes (non-cardiac etiologies): confirmed drug overdose (n=624), trauma (n=108), cancer (n=69), complex chronic care (n=65) and non-cardiac acute illness - mostly vascular, infectious, and metabolic (n=376). The annual incidence rate of "no obvious cause" OHCAs after initial field classification was 12.97/100,000 pt. years (95% CI 12.40, 13.50), compared to 3.87/100,000 pt. years (95% CI 3.56, 4.18) for the confirmed cardiac OHCAs after adjudication. The predominant underlying etiologies of confirmed cardiac OHCAs were coronary heart disease and structural heart disease. CONCLUSIONS: In young adults with OHCA, confirmed cardiac causes were responsible in a minority of cases, and they differed in presentation from those with confirmed non- cardiac causes. Establishing rigorous case ascertainment strategies with linkage to multiple data sources will facilitate a more reliable evaluation of the causes of these events.

Relationship between right and left ventricular function in candidates for implantable cardioverter defibrillator with low left ventricular ejection fraction.

BACKGROUND: Indications for the primary prevention of sudden death using an implantable cardioverter defibrillator (ICD) are based predominantly on left ventricular ejection fraction (LVEF). However, right ventricular ejection fraction (RVEF) is also a known prognostic factor in a variety of structural heart diseases that predispose to sudden cardiac death. We sought to investigate the relationship between right and left ventricular parameters (function and volume) measured by cardiovascular magnetic resonance (CMR) among a broad spectrum of patients considered for an ICD. METHODS: In this retrospective, single tertiary-care center study, consecutive patients considered for ICD implantation who were referred for LVEF assessment by CMR were included. Right and left ventricular function and volumes were measured. RESULTS: In total, 102 patients (age 62±14 years; 23% women) had a mean LVEF of 28±11% and RVEF of 44±12%. The left ventricular and right ventricular end diastolic volume index was 140±42 mL/m2 and 81±27 mL/m2, respectively. Eighty-six (84%) patients had a LVEF <35%, and 63 (62%) patients had right ventricular systolic dysfunction. Although there was a significant and moderate correlation between LVEF and RVEF (r=0.40, p<0.001), 32 of 86 patients (37%) with LVEF <35% had preserved RVEF, while 9 of 16 patients (56%) with LVEF ≥35% had right ventricular systolic dysfunction (Kappa=0.041). CONCLUSIONS: Among patients being considered for an ICD, there is a positive but moderate correlation between LVEF and RVEF. A considerable proportion of patients who qualify for an ICD based on low LVEF have preserved RVEF, and vice versa.

Long-term clinical outcomes and predictors for survivors of out-of-hospital cardiac arrest.

AIMS: Improvement in resuscitation efforts has translated to an increasing number of survivors after out-of-hospital cardiac arrest (OHCA). Our objectives were to assess the long-term outcomes and predictors of mortality for patients who survived OHCA. METHODS: We conducted a population-based cohort study linking the Toronto RescuNET cardiac arrest database with administrative databases in Ontario, Canada. We included patients with non-traumatic OHCA from December 1, 2005 to December 31, 2014. The primary outcomes were mortality at 1 year and 3 years. Cox proportional hazard models were constructed to evaluate the predictors of mortality. RESULTS: Among the 28,611 OHCA patients who received treatment at the scene of arrest, 1591 patients survived to hospital discharge. During hospitalization, 36% received coronary revascularizations and 27% received an implantable cardioverter defibrillator. At one year after discharge, 12.6% of patients had died and 37.3% were readmitted. At 3 years, mortality rate was 20% and all-cause readmission rate was 54.1%. Older age and a history of cancer were associated with higher risk of 3-year mortality. Shockable rhythm at presentation (hazard ratio [HR] 0.62, 95% CI 0.45-0.85), use of coronary revascularization (HR 0.37, 95% CI 0.28-0.51) or implantable cardioverter defibrillator (HR 0.28, 95% CI 0.20-0.41) was associated with substantially lower 3-year mortality. Prior cardiac conditions and other arrest characteristics were not associated with long-term mortality. CONCLUSIONS: Survivors of OHCA face significant morbidity and mortality after hospital discharge. Clinical trials are needed to evaluate the potential benefits of invasive cardiac procedures in OHCA survivors.

2016 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation.

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation (AF) Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in AF management. This 2016 Focused Update deals with: (1) the management of antithrombotic therapy for AF patients in the context of the various clinical presentations of coronary artery disease; (2) real-life data with non-vitamin K antagonist oral anticoagulants; (3) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (4) digoxin as a rate control agent; (5) perioperative anticoagulation management; and (6) AF surgical therapy including the prevention and treatment of AF after cardiac surgery. The recommendations were developed with the same methodology used for the initial 2010 guidelines and the 2012 and 2014 Focused Updates. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards, individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included in the Supplementary Material, and on the CCS Web site. The section on concomitant AF and coronary artery disease was developed in collaboration with the CCS Antiplatelet Guidelines Committee. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF Guidelines recommendations, from 2010 to the present 2016 Focused Update.

A Clinical Decision Instrument for 30-Day Death After an Emergency Department Visit for Atrial Fibrillation: The Atrial Fibrillation in the Emergency Room (AFTER) Study.

STUDY OBJECTIVE: The high volume of patients treated in an emergency department (ED) for atrial fibrillation is predicted to increase significantly in the next few decades. Currently, 11% of these patients die within a year. We sought to derive and validate a complex model and a simplified model that predicts mortality in ED patients with atrial fibrillation. METHODS: This population-based, retrospective cohort study included 3,510 adult patients with a primary diagnosis of atrial fibrillation who were treated at 24 hospital EDs in Ontario, Canada, between April 2008 and March 2009. The main outcome was 30-day all-cause mortality. RESULTS: In the derivation cohort (n=2,343; mean age 68.8 years), 2.6% of patients died within 30 days of the ED visit versus 2.7% in the validation cohort (n=1,167; mean age 68.3 years). Variables associated with mortality in the complex model included age, presenting pulse rate and systolic blood pressure, presence of chest pain, 2 laboratory results (positive troponin result and creatinine level greater than 200 µmol [2.26 mg/dL]), 4 comorbidities (smoking, chronic obstructive pulmonary disease, cancer, and dementia), an increased bleeding risk, and a second acute ED diagnosis (in addition to atrial fibrillation). Observed 30-day mortality in the 5 risk strata that were defined by the predicted probability of death were 0.44%, 0.41%, 0.23%, 1.61%, and 10.3%. The c statistics were 0.88 and 0.87 in the derivation and validation cohorts, respectively. The a priori-selected 6-variable model, TrOPs-BAC, included a positive Troponin result, Other acute ED diagnosis, Pulmonary disease (chronic obstructive pulmonary disease), Bleeding risk, Aged 75 years or older, and Congestive heart failure. The c statistic for the simplified model was 0.81 in both the derivation and validation cohorts. CONCLUSION: Using a population-based sample, we derived and validated both a complex and a simplified instrument that predicts mortality after an emergency visit for atrial fibrillation. These may aid clinicians in identifying high-risk patients for hospitalization while safely discharging more patients home.

Characterization of the ultrashort-TE (UTE) MR collagen signal.

Although current cardiovascular MR (CMR) techniques for the detection of myocardial fibrosis have shown promise, they nevertheless depend on gadolinium-based contrast agents and are not specific to collagen. In particular, the diagnosis of diffuse myocardial fibrosis, a precursor of heart failure, would benefit from a non-invasive imaging technique that can detect collagen directly. Such a method could potentially replace the need for endomyocardial biopsy, the gold standard for the diagnosis of the disease. The objective of this study was to measure the MR properties of collagen using ultrashort TE (UTE), a technique that can detect short T2* species. Experiments were performed in collagen solutions. Via a model of bi-exponential T2* with oscillation, a linear relationship (slope = 0.40 ± 0.01, R(2) = 0.99696) was determined between the UTE collagen signal fraction associated with these properties and the measured collagen concentration in solution. The UTE signal of protons in the collagen molecule was characterized as having a mean T2* of 0.75 ± 0.05 ms and a mean chemical shift of -3.56 ± 0.01 ppm relative to water at 7 T. The results indicated that collagen can be detected and quantified using UTE. A knowledge of the collagen signal properties could potentially be beneficial for the endogenous detection of myocardial fibrosis.

Increased atrial arrhythmia susceptibility induced by intense endurance exercise in mice requires TNFα.

Atrial fibrillation (AF) is the most common supraventricular arrhythmia that, for unknown reasons, is linked to intense endurance exercise. Our studies reveal that 6 weeks of swimming or treadmill exercise improves heart pump function and reduces heart-rates. Exercise also increases vulnerability to AF in association with inflammation, fibrosis, increased vagal tone, slowed conduction velocity, prolonged cardiomyocyte action potentials and RyR2 phosphorylation (CamKII-dependent S2814) in the atria, without corresponding alterations in the ventricles. Microarray results suggest the involvement of the inflammatory cytokine, TNFα, in exercised-induced atrial remodelling. Accordingly, exercise induces TNFα-dependent activation of both NFκB and p38MAPK, while TNFα inhibition (with etanercept), TNFα gene ablation, or p38 inhibition, prevents atrial structural remodelling and AF vulnerability in response to exercise, without affecting the beneficial physiological changes. Our results identify TNFα as a key factor in the pathology of intense exercise-induced AF.