Publications by authors named "Jeff S Healey"

251 Publications

Detection of atrial fibrillation in asymptomatic at-risk individuals.

Int J Cardiol 2021 Apr 28. Epub 2021 Apr 28.

Bristol Myers Squibb, Montréal, Canada. Electronic address:

Background: Undiagnosed atrial fibrillation (AF) exposes unsuspecting patients to elevated stroke risks. The optimal algorithm for identifying patients who should be screened for AF remains undetermined. The objective of this study is to determine the AF burden in an asymptomatic, at-risk population. We also sought to investigate potential predictors of undiagnosed AF.

Methods: This registry is a prospective observational study assessing continuous ECG monitoring in screening for AF using a wearable single lead 7-day continuous monitoring device. Patients included were asymptomatic individuals, at risk for AF as determined by either 1) ≥65 years of age with ≥1 high risk factor or; 2) ≥75 years of age and ≥2 moderate risk factors. A multivariable logistic regression was used to explore the predictive value of certain patient characteristics in identifying patients susceptible to have undiagnosed AF.

Results: Among the 942 patients included, 25 patients (2.7%) had evidence of AF detected. Only 8 patients had AF duration ≥24 h. History of perioperative AF (OR: 3.25, 95%CI: 1.08-9.79, p = 0.036), age over 85 (OR: 4.71, 95%CI: 1.31-16.92, p = 0.017) and absence of cardiovascular disease (CVD) (OR: 0.27, 95%CI: 0.10-0.76, p = 0.013) were found to be predictive of undiagnosed AF.

Conclusion: This study demonstrates the feasibility of office-based AF screening in at-risk population. The low rate of AF detection suggests that the optimal algorithm for identifying asymptomatic patients who would benefit from continuous screening remains unclear. Advanced age, history of perioperative AF and absence of CVD are variables that could be explored further.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.048DOI Listing
April 2021

Antidiabetic drugs for preventing atrial fibrillation: A new revolution?

Heart Rhythm 2021 Apr 8. Epub 2021 Apr 8.

McMaster University and Population Health Research Institute, Hamilton, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2021.03.046DOI Listing
April 2021

Outcomes and Safety of Fluoroless Catheter Ablation for Atrial Fibrillation.

CJC Open 2021 Mar 13;3(3):303-310. Epub 2020 Nov 13.

Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.

Background: Intracardiac echocardiography and 3D mapping systems allow catheter ablation for atrial fibrillation (AF) to be conducted without fluoroscopy; however, the safety and effectiveness of fluoroless AF ablation are not well defined.

Methods: We examined consecutive radiofrequency AF catheter ablations at a large academic teaching hospital from November 2017 to July 2019. Outcomes for fluoroscopy-guided (N = 176) and fluoroless (N = 147) ablations were compared. Cases were designated as fluoroless at the outset of the procedure.

Results: Mean age was 59.5 ± 10 years, 66.9% were male, 71.8% had paroxysmal AF, and the mean CHADS-VASc score was 1.7 ± 1.4. There were no differences in patient baseline characteristics. In the fluoroless group, minimal fluoroscopy was used in 17 patients (median, 3 seconds; interquartile range, 1.2-4.8). Mean procedure time, fluoroscopy time, and radiation dose (± standard deviation) were greater in the fluoroscopy group compared with the fluoroless group (194 ± 56 vs 176 ± 46 minutes,  = 0.0021; 10.7 ± 6.6 vs 0.008 ± 0.03 minutes, < 0.0001; 2759.2 ± 1911 vs 5.4 ± 24 μGy m, < 0.0001). In multivariable linear regression models, fluoroless AF ablation was independently associated with reduced procedure times (ß = -16.5 minutes,  = 0.01). Acute procedural success (95.5% vs 98.6%,  = 0.1), complication rates (4.5% vs 2.0%,  = 0.24), and 1-year AF recurrence rates (28.7% vs 27.1%, log-rank  = 0.69) were similar between fluoroscopy and fluoroless groups. Excluding the 17 patients receiving fluoroscopy in the fluoroless group did not impact our results ( = 0.013). After exclusion of redo cases, fluoroless AF ablation was no longer associated with reduced procedure times (ß = -11.4 minutes,  = 0.106).

Conclusions: Fluoroless radiofrequency AF ablation had similar effectiveness and safety compared with conventional fluoroscopy-guided AF ablation.
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http://dx.doi.org/10.1016/j.cjco.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984996PMC
March 2021

Single-dose oral anti-arrhythmic drugs for cardioversion of recent-onset atrial fibrillation: a systematic review and network meta-analysis of randomized controlled trials.

Europace 2021 Mar 16. Epub 2021 Mar 16.

Population Health Research Institute, McMaster University, 20 Copeland Ave, Hamilton, ON, L8L2X2, Canada.

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.
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http://dx.doi.org/10.1093/europace/euab014DOI Listing
March 2021

Who is at risk of atrial fibrillation?

Heart Rhythm 2021 Feb 24. Epub 2021 Feb 24.

Vancouver Stroke Program, University of British Columbia, XXXX, British Columbia, Canada.

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http://dx.doi.org/10.1016/j.hrthm.2021.02.019DOI Listing
February 2021

Screening for Atrial Fibrillation in the Older Population: A Randomized Clinical Trial.

JAMA Cardiol 2021 May;6(5):558-567

Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

Importance: Atrial fibrillation (AF) is a major cause of preventable strokes. Screening asymptomatic individuals for AF may increase anticoagulant use for stroke prevention.

Objective: To evaluate 2 home-based AF screening interventions.

Design, Setting, And Participants: This multicenter randomized clinical trial recruited individuals from primary care practices aged 75 years or older with hypertension and without known AF. From April 5, 2015, to March 26, 2019, 856 participants were enrolled from 48 practices.

Interventions: The control group received standard care (routine clinical follow-up plus a pulse check and heart auscultation at baseline and 6 months). The screening group received a 2-week continuous electrocardiographic (cECG) patch monitor to wear at baseline and at 3 months, in addition to standard care. The screening group also received automated home blood pressure (BP) machines with oscillometric AF screening capability to use twice-daily during the cECG monitoring periods.

Main Outcomes And Measures: With intention-to-screen analysis, the primary outcome was AF detected by cECG monitoring or clinically within 6 months. Secondary outcomes included anticoagulant use, device adherence, and AF detection by BP monitors.

Results: Of the 856 participants, 487 were women (56.9%); mean (SD) age was 80.0 (4.0) years. Median cECG wear time was 27.4 of 28 days (interquartile range [IQR], 18.4-28.0 days). In the primary analysis, AF was detected in 23 of 434 participants (5.3%) in the screening group vs 2 of 422 (0.5%) in the control group (relative risk, 11.2; 95% CI, 2.7-47.1; P = .001; absolute difference, 4.8%; 95% CI, 2.6%-7.0%; P < .001; number needed to screen, 21). Of those with cECG-detected AF, median total time spent in AF was 6.3 hours (IQR, 4.2-14.0 hours; range 1.3 hours-28 days), and median duration of the longest AF episode was 5.7 hours (IQR, 2.9-12.9 hours). Anticoagulation was initiated in 15 of 20 patients (75.0%) with cECG-detected AF. By 6 months, anticoagulant therapy had been prescribed for 18 of 434 participants (4.1%) in the screening group vs 4 of 422 (0.9%) in the control group (relative risk, 4.4; 95% CI, 1.5-12.8; P = .007; absolute difference, 3.2%; 95% CI, 1.1%-5.3%; P = .003). Twice-daily AF screening using the home BP monitor had a sensitivity of 35.0% (95% CI, 15.4%-59.2%), specificity of 81.0% (95% CI, 76.7%-84.8%), positive predictive value of 8.9% (95% CI, 4.9%-15.5%), and negative predictive value of 95.9% (95% CI, 94.5%-97.0%). Adverse skin reactions requiring premature discontinuation of cECG monitoring occurred in 5 of 434 participants (1.2%).

Conclusions And Relevance: In this randomized clinical trial, among older community-dwelling individuals with hypertension, AF screening with a wearable cECG monitor was well tolerated, increased AF detection 10-fold, and prompted initiation of anticoagulant therapy in most cases. Compared with continuous ECG, intermittent oscillometric screening with a BP monitor was an inferior strategy for detecting paroxysmal AF. Large trials with hard clinical outcomes are now needed to evaluate the potential benefits and harms of AF screening.

Trial Registration: ClinicalTrials.gov Identifier: NCT02392754.
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http://dx.doi.org/10.1001/jamacardio.2021.0038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905702PMC
May 2021

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

Can J Anaesth 2021 Feb 23. Epub 2021 Feb 23.

Population Health Research Institute, McMaster University, Hamilton, ON, Canada.

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.
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http://dx.doi.org/10.1007/s12630-021-01944-0DOI Listing
February 2021

Dynamic risk assessment to improve quality of care in patients with atrial fibrillation: the 7th AFNET/EHRA Consensus Conference.

Europace 2021 Mar;23(3):329-344

Atrial Fibrillation NETwork (AFNET), Münster, Germany.

Aims: The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes.

Methods And Results: This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence.

Conclusion: The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.
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http://dx.doi.org/10.1093/europace/euaa279DOI Listing
March 2021

The Optimal Timing of Primary Prevention Implantable Cardioverter-Defibrillator Referral in the Rapidly Changing Medical Landscape.

Can J Cardiol 2021 Apr 4;37(4):644-654. Epub 2021 Feb 4.

Population Health Research Institute, Hamilton, Ontario, Canada; Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.

The use of implantable cardioverter-defibrillators (ICDs) significantly reduces the risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Current guidelines, which are based on seminal clinical trials published nearly 2 decades ago, recommend that patients be on optimal medical therapy for HF for a minimum of 3 months before referral for prophylactic ICD. This waiting period allows for left ventricular reverse remodelling and improvement in HF symptoms, which may render primary prevention ICD implantation unnecessary. However, medical therapy for HFrEF has significantly evolved since the publication of these landmark trials. Given the plethora of medical therapy options now available for HFrEF, it is appropriate to reassess the duration of this waiting period. In the present review, we examine the landmark randomised trials in primary prevention of sudden cardiac death in patients with HFrEF, summarise the novel medical therapies (sacubitril-valsartan, sodium-glucose cotransporter 2 inhibitors, ivabradine, vericiguat, and omecamtiv mecarbil) that have emerged since the publication of those trials, discuss the optimal timing of ICD referral, and review subtypes of nonischemic cardiomyopathy where timing of ICD insertion is guided by alternative criteria. With the steps now needed to optimise medical therapy for HFrEF, in terms of both classes of drugs and doses of each agent, it can easily take up to 6 months to achieve optimisation. Following that, waiting periods of 3 months for ischemic cardiomyopathy and 6 months for nonischemic cardiomyopathy may be required to allow adequate reverse remodelling before reevaluating for ICD implantation.
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http://dx.doi.org/10.1016/j.cjca.2021.01.024DOI Listing
April 2021

Is Screening for Atrial Fibrillation and Its Risk Factors Useful and Cost-Effective?

Card Electrophysiol Clin 2021 03 8;13(1):235-241. Epub 2021 Jan 8.

Population Health Research Institute, McMaster University, 237 Barton Street, C3-121, Hamilton, Ontario L8L 2X2, Canada. Electronic address:

Atrial fibrillation (AF) is a major, preventable cause of stroke, whose prevalence is increasing with the aging of the population. There are safe and effective anticoagulation therapies to prevent stroke and new technologies that can identify AF in asymptomatic individuals. Ongoing research will determine if AF screening is cost-effective and will define the best screening strategies. The effectiveness of AF screening can be enhanced by simultaneously screening for the cardiovascular conditions that predispose to the development and progression of AF and its complications. Future studies evaluating an integrated screening program on outcomes, health care utilization, and cost are needed.
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http://dx.doi.org/10.1016/j.ccep.2020.10.009DOI Listing
March 2021

Remote-only monitoring for patients with cardiac implantable electronic devices: a before-and-after pilot study.

CMAJ Open 2021 Jan-Mar;9(1):E53-E61. Epub 2021 Jan 25.

QEII Health Sciences Centre, Dalhousie University (Sapp, AbdelWahab, Parkash), Halifax, NS; Department of Cardiac Sciences (Gillis, Raj), University of Calgary, Calgary, Alta.; Institut universitaire de cardiologie and pneumologie de Quebec (Nault, Philippon), Université Laval, Québec, Que.; University of Ottawa Heart Institute (Nery, Wells), Ottawa, Ont.; Hamilton Health Sciences (Healey), McMaster University, Hamilton, Ont.; CK Hui Heart Centre (Lockwood), Edmonton, Alta.; Vancouver Island Health Authority (Sterns), Victoria, BC; East Carolina University (Sears), Greenville, NC; London Health Sciences Centre (Yee, Tang), University of Western Ontario, London, Ont.

Background: Outcomes for patients with cardiac implantable electronic devices are better when follow-up incorporates remote monitoring technology in addition to in-clinic visits. For patients with implantable devices, we sought to determine the feasibility, safety and associated health care utilization of remote-only follow-up, along with its effects on patients' quality of life and costs.

Methods: This multicentre before-and-after pilot study involved patients with new or existing pacemakers or implantable cardioverter defibrillators. The "before" phase of the study spanned the period October 2015 to February 2017; the "after" phase spanned the period October 2016 to February 2018. The exposure was remote-only follow-up in combination with Remote View, a service that facilitates access to device data, allowing device settings to be viewed remotely to facilitate remote programming. Outcomes at 12 months were feasibility (adherence to remote monitoring), safety (rate of adverse events) and health care utilization (remote and in-clinic appointments). We also assessed quality of life, using 3 validated scales, and costs, taking into account both health care system and patient costs.

Results: A total of 176 patients were enrolled. Adherence (defined as at least 1 successful remote transmission during follow-up) was 87% over a mean follow-up of 11.7 (standard deviation 2.2) months. There was a reduction in in-clinic visits at specialized sites among patients with both implantable defibrillators (26 v. 5, < 0.001, = 48) and pacemakers (42 v. 10, < 0.001, = 51). There was no significant change in visits to community sites for patients with defibrillators (13 v. 17, = 0.3, = 48). The composite rate of death, stroke, cardiovascular hospitalization and device-related hospitalization was 7% ( = 164). No adverse events were linked to the intervention. There was no change in quality-of-life scales between baseline and 12 months. Health care costs were reduced by 31% for patients with defibrillators and by 44% for those with pacemakers.

Interpretation: This pilot study showed the feasibility of remote-only follow-up, with no increase in adverse clinical outcomes and no effect on quality of life, but with reductions in costs and health care utilization. These results support progression to a larger-scale study of whether superior effectiveness and reduced cost can be achieved, with preservation of safety, through use of remote-only follow-up.

Trial Registration: ClinicalTrials.gov, no. NCT02585817.
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http://dx.doi.org/10.9778/cmajo.20200041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843075PMC
January 2021

Research Priorities in Atrial Fibrillation Screening: A Report From a National Heart, Lung, and Blood Institute Virtual Workshop.

Circulation 2021 Jan 25;143(4):372-388. Epub 2021 Jan 25.

Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (R.D.L., J.P.P., S.M.A.-K.).

Clinically recognized atrial fibrillation (AF) is associated with higher risk of complications, including ischemic stroke, cognitive decline, heart failure, myocardial infarction, and death. It is increasingly recognized that AF frequently is undetected until complications such as stroke or heart failure occur. Hence, the public and clinicians have an intense interest in detecting AF earlier. However, the most appropriate strategies to detect undiagnosed AF (sometimes referred to as subclinical AF) and the prognostic and therapeutic implications of AF detected by screening are uncertain. Our report summarizes the National Heart, Lung, and Blood Institute's virtual workshop focused on identifying key research priorities related to AF screening. Global experts reviewed major knowledge gaps and identified critical research priorities in the following areas: (1) role of opportunistic screening; (2) AF as a risk factor, risk marker, or both; (3) relationship between AF burden detected with long-term monitoring and outcomes/treatments; (4) designs of potential randomized trials of systematic AF screening with clinically relevant outcomes; and (5) role of AF screening after ischemic stroke. Our report aims to inform and catalyze AF screening research that will advance innovative, resource-efficient, and clinically relevant studies in diverse populations to improve the diagnosis, management, and prognosis of patients with undiagnosed AF.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047633DOI Listing
January 2021

A randomized ablation-based atrial fibrillation rhythm control versus rate control trial in patients with heart failure and high burden atrial fibrillation: The RAFT-AF trial rationale and design.

Am Heart J 2021 04 17;234:90-100. Epub 2021 Jan 17.

Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.

Heart failure (HF) and atrial fibrillation (AF) are 2 cardiac conditions that are increasing in prevalence and incidence. The 2 conditions frequently coexist, and are associated with increased morbidity and mortality. Catheter ablation of AF has been successfully performed in patients with HF, with an improvement in HF and AF, when compared to amiodarone, but further data is required to compare this to rate control. OBJECTIVES: The primary objective is to determine whether AF treated by catheter ablation, with or without antiarrhythmic drugs reduces all-cause mortality and hospitalizations for HF as compared with rate control in patients with HF and a high burden AF. METHODS: This is a multi-center prospective randomized open blinded endpoint (PROBE) study. Patients with NYHA class II-III HF (HF with reduced ejection fraction (<35%) or HF with preserved ejection fraction), and high burden AF are included in the trial. Patients are randomized to either rate control or catheter ablation-based AF rhythm control in a 1:1 ratio. Patients in the rate control group receive optimal HF therapy and rate control measures to achieve a resting hazard ratio (HR) < 80 bpm and 6-minute walk HR < 110 bpm. Patients randomized to catheter ablation-based AF rhythm control group receive optimal HF therapy and one or more aggressive catheter ablation, which include PV antral ablation and LA substrate ablation with or without adjunctive antiarrhythmic drug. The primary outcome is a composite of all-cause mortality and hospitalization for heart failure defined as an admission to a health care facility. The sample size is 600. Enrolment has been completed.
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http://dx.doi.org/10.1016/j.ahj.2021.01.012DOI Listing
April 2021

High-Sensitivity Estimate of the Incidence of New-Onset Atrial Fibrillation in Critically Ill Patients.

Crit Care Explor 2021 Jan 8;3(1):e0311. Epub 2021 Jan 8.

Population Health Research Institute, McMaster University, Hamilton, ON, Canada.

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.
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http://dx.doi.org/10.1097/CCE.0000000000000311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803666PMC
January 2021

Stroke risk prediction in patients with atrial fibrillation with and without rheumatic heart disease.

Cardiovasc Res 2021 Jan 2. Epub 2021 Jan 2.

Population Health Research Institute, McMaster University, Hamilton, Canada.

Aims: Patients with atrial fibrillation (AF) and rheumatic heart disease (RHD), especially mitral stenosis, are assumed to be at high risk of stroke, irrespective of other factors. We aimed to re-evaluate stroke risk factors in a contemporary cohort of AF patients.

Methods And Results: We analyzed data of 15,400 AF patients presenting to an emergency department and who were enrolled in the global RE-LY AF registry, representing 47 countries from all inhabited continents. Follow-up occurred at 1 year after enrollment. A total of 1,788 (11.6%) patients had RHD. These patients were younger (51.4 ± 15.7 vs. 67.8 ± 13.6 years), more likely to be female (66.2% vs. 44.7%) and had a lower mean CHA2DS2-VASc score (2.1 ± 1.7 vs. 3.7 ± 2.2) as compared to patients without RHD (all p < 0.001). Significant mitral stenosis (average mean transmitral gradient 11.5 ± 6.5 mmHg) was the predominant valve lesion in those with RHD (59.6%). Patients with RHD had a higher baseline rate of anticoagulation use (60.4% vs. 45.2%, p < 0.001). Unadjusted stroke rates at 1 year were 2.8% and 4.1% for patients with and without RHD, respectively. The performance of the CHA2DS2-VASc score was modest in both groups (stroke at 1 year, c-statistics 0.69, 95% confidence interval [CI] 0.60-0.78 and 0.63, 95% CI 0.61-0.66, respectively). In the overall cohort, advanced age, female sex, prior stroke, tobacco use and non-use of anticoagulation were predictors for stroke (all p < 0.05). Mitral stenosis was not associated with stroke risk (adjusted odds ratio 1.07, 95% CI 0.67-1.72, p = 0.764).

Conclusions: The performance of the CHA2DS2-VASc score was modest in AF patients both with and without RHD. In this cohort, moderate-to-severe mitral stenosis was not an independent risk factor for stroke.

Translational Perspective: Based on studies conducted several decades ago, the presence of moderate-to-severe mitral stenosis has been associated with a very high risk of stroke in patients with AF. Our results, based on a large, global sample of contemporary patients with AF that contained a significant proportion of individuals with RHD, challenge the assumption that mitral stenosis is a major, independent risk factor for stroke. The performance of the widely used CHA2DS2-VASc score was modest in both patients with and without RHD. At least one ongoing randomized trial is evaluating the optimal antithrombotic strategy in patients with AF and RHD.
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http://dx.doi.org/10.1093/cvr/cvaa344DOI Listing
January 2021

Differences in Healthcare Use Between Patients With Persistent and Paroxysmal Atrial Fibrillation Undergoing Catheter-Based Atrial Fibrillation Ablation: A Population-Based Cohort Study From Ontario, Canada.

J Am Heart Assoc 2021 Jan 31;10(1):e016071. Epub 2020 Dec 31.

Department of Medicine University of Toronto Ontario Canada.

Background Patients with persistent atrial fibrillation (AF) undergoing catheter-based AF ablation have lower success rates than those with paroxysmal AF. We compared healthcare use and clinical outcomes between patients according to their AF subtypes. Methods and Results Consecutive patients undergoing AF ablation were prospectively identified from a population-based registry in Ontario, Canada. Via linkage with administrative databases, we performed a retrospective analysis comparing the following outcomes between patients with persistent and paroxysmal AF: healthcare use (defined as AF-related hospitalizations/emergency room visits), periprocedural complications, and mortality. Multivariable Poisson modeling was performed to compare the rates of AF-related and all-cause hospitalizations/emergency room visits in the year before versus after ablation. Between April 2012 and March 2016, there were 3768 consecutive patients who underwent first-time AF ablation, of whom 1040 (27.6%) had persistent AF. The mean follow-up was 1329 days. Patients with persistent AF had higher risk of AF-related hospitalization/emergency room visits (hazard ratio [HR], 1.21; 95% CI, 1.09-1.34), mortality (HR, 1.74; 95% CI, 1.15-2.63), and periprocedural complications (odds ratio, 1.36; 95% CI, 1.02-1.75) than those with paroxysmal AF. In the overall cohort, there was a 48% reduction in the rate of AF-related hospitalization/emergency room visits in the year after versus before ablation (rate ratio [RR], 0.52; 95% CI, 0.48-0.56). This reduction was observed for patients with paroxysmal (RR, 0.45; 95% CI, 0.41-0.50) and persistent (RR, 0.74; 95% CI, 0.63-0.87) AF. Conclusions Although patients with persistent AF had higher risk of adverse outcomes than those with paroxysmal AF, ablation was associated with a favorable reduction in downstream AF-related healthcare use, irrespective of AF type.
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http://dx.doi.org/10.1161/JAHA.120.016071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955473PMC
January 2021

Stroke Prevention in Atrial Fibrillation: Looking Forward.

Circulation 2020 Dec 14;142(24):2371-2388. Epub 2020 Dec 14.

Division of Neurology, McMaster University and Population Health Research Institute, Hamilton Health Sciences, Canada (A.H.K., R.G.H.).

Ischemic strokes related to atrial fibrillation are highly prevalent, presenting with severe neurologic syndromes and associated with high risk of recurrence. Although advances have been made in both primary and secondary stroke prevention for patients with atrial fibrillation, the long-term risks for stroke recurrence and bleeding complications from antithrombotic treatment remain substantial. We summarize the major advances in stroke prevention for patients with atrial fibrillation during the past 30 years and focus on novel diagnostic and treatment approaches currently under investigation in ongoing clinical trials. Non-vitamin K antagonist oral anticoagulants have been proven to be safer and equally effective compared with warfarin in stroke prevention for patients with nonvalvular atrial fibrillation. Non-vitamin K antagonist oral anticoagulants are being investigated for the treatment of patients with atrial fibrillation and rheumatic heart disease, for the treatment of patients with recent embolic stroke of undetermined source and indirect evidence of cardiac embolism, and in the prevention of vascular-mediated cognitive decline in patients with atrial fibrillation. Multiple clinical trials are assessing the optimal timing of non-vitamin K antagonist oral anticoagulant initiation after a recent ischemic stroke and the benefit:harm ratio of non-vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation and history of previous intracranial bleeding. Ongoing trials are addressing the usefulness of left atrial appendage occlusion in both primary and secondary stroke prevention for patients with atrial fibrillation, including those with high risk of bleeding. The additive value of prolonged cardiac monitoring for subclinical atrial fibrillation detection through smartphone applications or implantable cardiac devices, together with the optimal medical management of individuals with covert paroxysmal atrial fibrillation, is a topic of intensive research interest. Colchicine treatment and factor XIa inhibition constitute 2 novel pharmacologic approaches that might provide future treatment options in the secondary prevention of cardioembolic stroke attributable to atrial fibrillation.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.049768DOI Listing
December 2020

Device-Detected Atrial Fibrillation Before and After Hospitalisation for Noncardiac Surgery or Medical Illness: Insights From ASSERT.

Can J Cardiol 2021 May 1;37(5):803-809. Epub 2020 Dec 1.

Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

Background: Atrial fibrillation (AF) is often detected during hospitalisation for surgery or medical illness and is often assumed to be due to the acute condition.

Methods: The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) study enrolled patients ≥ 65 years old without AF. Pacemakers or implantable cardioverter-defibrillators recorded device-detected AF. We identified participants who were hospitalised and compared the prevalence of AF before and after hospitalisation.

Results: Among 2580 participants, 436 (16.9%) had a surgical or medical hospitalisation. In the 30 days following a first hospitalisation, 43 participants (9.9%, 95% confidence interval [CI] 7.2%-13.1%) had > 6 minutes of device-detected AF; 20 (4.6%, 95% CI 2.8%-7.0%) had > 6 hours. More participants had AF > 6 minutes in the 30 days following hospitalisation compared with the period 30-60 days before hospitalisation (9.9% vs 4.4%; P < 0.001). Similar results were observed for episodes > 6 hours (4.6% vs 2.3%, P = 0.03). Roughly half of participants with device-detected AF in the 30 days following hospitalisation had at least 1 episode of the same duration in the 6 months before (50% [95% CI 31.3%-68.7%] for > 6 min; 68.8% [95% CI 41.3%-89.0%] for > 6 h). Those with AF in the 30 days following hospitalisation were more likely to have had AF in the past (adjusted odds ratio [OR] 7.2, 95% CI 3.2-15.8 for > 6 min; adjusted OR 32.6, 95% CI 10.3-103.4 for > 6 h).

Conclusions: The prevalence of device-detected AF increases around the time of hospitalisation for noncardiac surgery or medical illness. About half of patients with AF around the time of hospitalisation previously had similar episodes.
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http://dx.doi.org/10.1016/j.cjca.2020.11.012DOI Listing
May 2021

The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation.

Can J Cardiol 2020 12 22;36(12):1847-1948. Epub 2020 Oct 22.

Institut de Cardiologie de Montréal, Université de Montréal, Montréal, Québec, Canada.

The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, since 2010 a large number of developments had accumulated in a wide range of areas, motivating the committee to complete a thorough guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to evaluate recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.
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http://dx.doi.org/10.1016/j.cjca.2020.09.001DOI Listing
December 2020

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

Pacing Clin Electrophysiol 2020 11 28;43(11):1373-1381. Epub 2020 Oct 28.

Division of Cardiology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

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.
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http://dx.doi.org/10.1111/pace.14091DOI Listing
November 2020

Long-Term Treatment with Apixaban in Patients with Atrial Fibrillation: Outcomes during the Open-Label Extension following AVERROES.

Thromb Haemost 2021 Apr 4;121(4):518-528. Epub 2020 Oct 4.

Population Health Research Institute, Hamilton, Ontario, Canada.

Background:  AVERROES, a randomized controlled trial in high-risk patients with atrial fibrillation, unsuitable for vitamin K antagonist therapy, demonstrated efficacy and safety of apixaban compared with aspirin. At the conclusion of the double-blind phase, an open-label extension was initiated to allow study participants to receive apixaban until it became locally available. This study reports outcomes of patients on apixaban during the open-label extension.

Methods:  Rates of stroke or systemic embolism, hemorrhagic stroke, major bleeding, and other outcomes during the open-label extension are reported.

Results:  Of the 5,599 participants enrolled in AVERROES, 3,275 (58.5%) received apixaban during the open-label extension. Median (interquartile range) follow-up in the open-label extension was 3.0 (2.5-3.5) years. The rate of stroke or systemic embolism during the open-label extension was 1.0% per year, and the annual rates of hemorrhagic stroke and major bleeding were 0.3 and 1.2%, respectively. After adjustment for imbalances in patient variables, event rates in patients on apixaban during the open-label extension were similar to those of patients receiving apixaban during AVERROES. Additional analyses in all patients who received apixaban, at any time from the start of AVERROES to the end of the open-label extension, were performed. This cohort ( = 4,414) showed annual event rates of 1.1% for stroke or systemic embolism, 0.3% for hemorrhagic stroke, and 1.2% for major bleeding.

Conclusion:  During the open-label extension, annual rates of stroke or systemic embolism, hemorrhagic stroke, and major bleeding remained as low as those observed during apixaban treatment in AVERROES. These data support the long-term efficacy and safety of apixaban in patients with atrial fibrillation.
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http://dx.doi.org/10.1055/s-0040-1717115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982299PMC
April 2021

Rate, Time Course, and Predictors of Implantable Cardioverter Defibrillator Infections: An Analysis From the SIMPLE Trial.

CJC Open 2020 Sep 25;2(5):354-359. Epub 2020 Apr 25.

Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

Background: The number of implantable cardioverter defibrillator (ICD) infections is increasing due to an increased number of ICD implants, higher-risk patients, and more frequent replacement procedures, which carry a higher risk of infection. Reducing the morbidity, mortality, and cost of ICD-related infections requires an understanding of the current rate of this complication and its predictors.

Methods: The hock ant valuation Trial (SIMPLE) trial randomized 2500 ICD recipients to defibrillation testing or not. Over an average of 3.1 years, patients were seen every 6 months and examined for evidence of ICD infection, which was defined as requiring device removal and/or intravenous antibiotics.

Results: Within 24 months, 21 patients (0.8%) developed infection. Fourteen patients (67%) with infection presented within 30 days, 20 patients by 12 months, and only 1 patient beyond 12 months. Univariate analysis demonstrated that patients with primary electrical disorders (3 patients,  = 0.009) and those with a secondary prevention indication (13 patients,  = 0.0009) were more likely to develop infection. Among the 2.2% of patients who developed an ICD wound hematoma, 10.4% developed an infection. Among the 8.3% of patients requiring an ICD reintervention, 1.9% developed an infection.

Conclusions: This cohort of ICD recipients at high-volume centres have a low risk of device-related infection. However; strategies to reduce wound hematoma and the need for ICD reintervention could further reduce the rate of infection.
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http://dx.doi.org/10.1016/j.cjco.2020.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499364PMC
September 2020

Consumer-led screening for atrial fibrillation using consumer-facing wearables, devices and apps: A survey of health care professionals by AF-SCREEN international collaboration.

Eur J Intern Med 2020 12 12;82:97-104. Epub 2020 Sep 12.

AF-SCREEN International Collaboration; Heart Research Institute, Sydney Australia; Charles Perkins Centre and Concord Hospital Cardiology, University of Sydney, Sydney, Australia.

Aim: A variety of consumer-facing wearables, devices and apps are marketed directly to consumers to detect atrial fibrillation (AF). However, their management is not defined. Our aim was to explore their role for AF screening via a survey.

Methods And Results: An anonymous web-based survey was undertaken by 588 health care professionals (HCPs) (response rate 23.7%). Overall, 57% HCPs currently advise wearables/apps for AF detection in their patients: this was much higher for electrophysiologists and nurses/allied health professionals (74-75%) than cardiologists (57%) or other physicians (34-38%). Approximately 46% recommended handheld (portable) single-lead dedicated ECG devices, or, less frequently, wristband ECG monitors with similar differentials between HCPs . Only 10-15% HCPs advised photoplethysmographic wristband monitors or smartphone apps. In over half of the HCP consultations for AF detected by wearables/apps, the decision to screen was entirely the patient's. About 45% of HCPs perceive a potential role for AF screening in people aged >65 years or in those with risk factors. Almost 70% of HCPs believed we are not yet ready for mass consumer-initiated screening for AF using wearable devices/apps, with patient anxiety, risk of false positives and negatives, and risk of anticoagulant-related bleeding perceived as potential disadvantages, and perceived need for appropriate management pathways.

Conclusions: There is a great potential for appropriate use of consumer-facing wearables/apps for AF screening. However, it appears that there is a need to better define suitable individuals for screening and an appropriate mechanism for managing positive results before they can be recommended by HCPs.
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http://dx.doi.org/10.1016/j.ejim.2020.09.005DOI Listing
December 2020

Atrial Arrhythmias in Clinically Manifest Cardiac Sarcoidosis: Incidence, Burden, Predictors, and Outcomes.

J Am Heart Assoc 2020 09 20;9(17):e017086. Epub 2020 Aug 20.

Division of Cardiology University of Ottawa Heart Institute Ottawa ON Canada.

Background Recent data have suggested a substantial incidence of atrial arrhythmias (AAs) in cardiac sarcoidosis (CS). Our study aims were to first assess how often AAs are the presenting feature of previously undiagnosed CS. Second, we used prospective follow-up data from implanted devices to investigate AA incidence, burden, predictors, and response to immunosuppression. Methods and Results This project is a substudy of the CHASM-CS (Cardiac Sarcoidosis Multicenter Prospective Cohort Study; NCT01477359). Inclusion criteria were presentation with clinically manifest cardiac sarcoidosis, treatment-naive status, and implanted with a device that reported accurate AA burden. Data were collected at each device interrogation visit for all patients and all potential episodes of AA were adjudicated. For each intervisit period, the total AA burden was obtained. A total of 33 patients met the inclusion criteria (aged 56.1±7.7 years, 45.5% women). Only 1 patient had important AAs as a part of the initial CS presentation. During a median follow-up of 49.1 months, 11 of 33 patients (33.3%) had device-detected AAs, and only 2 (6.1%) had a clinically significant AA burden. Both patients had reduced burden after CS was successfully treated and there was no residual fluorodeoxyglucose uptake on positron emission tomography scan. Conclusions First, we found that AAs are a rare presenting feature of clinically manifest cardiac sarcoidosis. Second, AAs occurred in a minority of patients at follow-up; the burden was very low in most patients. Only 2 patients had clinically significant AA burden, and both had a reduction after CS was treated. Registration URL: https://www.clini​caltr​ials.gov; unique identifier NCT01477359.
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http://dx.doi.org/10.1161/JAHA.120.017086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660760PMC
September 2020

Active-Fixation Atrial Leads and the Risk of Atrial Fibrillation: Insights From ASSERT.

Circ Arrhythm Electrophysiol 2020 09 23;13(9):e008655. Epub 2020 Jul 23.

Population Health Research Institute, Hamilton, Ontario, Canada (A.P.B., J.W., W.F.M., J.A.W., S.J.C., J.S.H.).

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http://dx.doi.org/10.1161/CIRCEP.120.008655DOI Listing
September 2020

Health-Related Quality of Life in Patients With Atrial Fibrillation Treated With Catheter Ablation or Antiarrhythmic Drug Therapy: A Systematic Review and Meta-analysis.

CJC Open 2020 Jul 2;2(4):286-295. Epub 2020 Apr 2.

School of Nursing, McMaster University, Hamilton, Ontario, Canada.

Background: Catheter ablation (CA) is performed in patients with atrial fibrillation (AF) to reduce symptoms and improve health-related quality of life (HRQL).

Methods: This systematic review and meta-analysis of randomized controlled trials (RCTs) evaluated CA of any energy modality compared with antiarrhythmic drugs (AADs) using inverse-variance random-effects models. We searched for RCTs reporting HRQL and AF-related symptoms at 3, 6, 12, 24, 48, and 60 months after treatment as well as the number of repeat ablations.

Results: Of 15,878 records, we included 13 RCTs of CA vs AADs for the analyses of HRQL, 7 RCTs for the analyses of AF-related symptoms, and 13 RCTs for the number of repeat ablations. For the HRQL analyses at 3 months, there were significant increases in both the Physical Component Summary score (3 months' standardized mean difference = 0.58 [0.39-0.78]; < 0.00001,  = 6%, 3 trials, n = 443) and the Mental Component Summary score (3 months' standardized mean difference = 0.57 [0.37-0.77]; < 0.00001,  = 0%, 3 trials, n = 443), favouring CA over AADs. These differences were sustained at 12 months but not >24 months after randomization. Similar results were seen for AF-related symptoms. The number of repeat ablations and success rates after procedure varied considerably across trials.

Conclusions: Evidence from few trials suggests that CA improves physical and mental health and AF-related symptoms in the short term, but these benefits decrease with time. More trials, reporting both HRQL and AF-related symptoms, at consistent time points are needed to assess the effectiveness of CA for the treatment of AF.
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http://dx.doi.org/10.1016/j.cjco.2020.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365832PMC
July 2020

An International Multicenter Evaluation of Inheritance Patterns, Arrhythmic Risks, and Underlying Mechanisms of -Catecholaminergic Polymorphic Ventricular Tachycardia.

Circulation 2020 Sep 22;142(10):932-947. Epub 2020 Jul 22.

Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, ON, Canada (K.N., J.W., A.S.T., A.C.S., J.M., J.D.R.).

Background: Genetic variants in calsequestrin-2 () cause an autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia (CPVT), although isolated reports have identified arrhythmic phenotypes among heterozygotes. Improved insight into the inheritance patterns, arrhythmic risks, and molecular mechanisms of -CPVT was sought through an international multicenter collaboration.

Methods: Genotype-phenotype segregation in -CPVT families was assessed, and the impact of genotype on arrhythmic risk was evaluated using Cox regression models. Putative dominant missense variants and the established recessive CASQ2-p.R33Q variant were evaluated using oligomerization assays and their locations mapped to a recent CASQ2 filament structure.

Results: A total of 112 individuals, including 36 CPVT probands (24 homozygotes/compound heterozygotes and 12 heterozygotes) and 76 family members possessing at least 1 presumed pathogenic variant, were identified. Among homozygotes and compound heterozygotes, clinical penetrance was 97.1% and 26 of 34 (76.5%) individuals had experienced a potentially fatal arrhythmic event with a median age of onset of 7 years (95% CI, 6-11). Fifty-one of 66 heterozygous family members had undergone clinical evaluation, and 17 of 51 (33.3%) met diagnostic criteria for CPVT. Relative to heterozygotes, homozygote/compound heterozygote genotype status in probands was associated with a 3.2-fold (95% CI, 1.3-8.0; =0.013) increased hazard of a composite of cardiac syncope, aborted cardiac arrest, and sudden cardiac death, but a 38.8-fold (95% CI, 5.6-269.1; <0.001) increased hazard in genotype-positive family members. In vitro turbidity assays revealed that p.R33Q and all 6 candidate dominant missense variants evaluated exhibited filamentation defects, but only p.R33Q convincingly failed to dimerize. Structural analysis revealed that 3 of these 6 putative dominant negative missense variants localized to an electronegative pocket considered critical for back-to-back binding of dimers.

Conclusions: This international multicenter study of -CPVT redefines its heritability and confirms that pathogenic heterozygous variants may manifest with a CPVT phenotype, indicating a need to clinically screen these individuals. A dominant mode of inheritance appears intrinsic to certain missense variants because of their location and function within the CASQ2 filament structure.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.045723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484339PMC
September 2020

Atrial Cardiopathy in the Absence of Atrial Fibrillation Increases Risk of Ischemic Stroke, Incident Atrial Fibrillation, and Mortality and Improves Stroke Risk Prediction.

J Am Heart Assoc 2020 06 20;9(11):e013227. Epub 2020 May 20.

Institute for Clinical Evaluative Sciences Toronto Ontario Canada.

Background Atrial fibrillation (AF) is a major, often undetected, cardiac cause of stroke. Markers of atrial cardiopathy, including left atrial enlargement (LAE) or excessive atrial ectopy (EAE) increase the risk of AF and have shown associations with stroke. We sought to determine whether these markers improve stroke risk prediction beyond traditional vascular risk factors (eg CHADS-VASc score). Methods and Results Retrospective longitudinal cohort of 32 454 consecutive community-dwelling adults aged ≥65 years referred for outpatient echocardiogram or Holter in Ontario, Canada (2010-2017). Moderate-severe LAE was defined as men >47 mm and women >43 mm, and EAE was defined as >30 APBs per hour. Cause-specific competing risks Cox proportional hazards used to estimate risk of ischemic stroke (primary), incident AF, and death (secondary). C-statistics, incremental discrimination improvement and net reclassification were used to compare CHADS-VASc with LAE and EAE to CHADS-VASc alone. Each 10 mm increase in left atrial diameter increased 2- and 5-year adjusted cause-specific stroke hazard almost 2-fold (LAE: 2-year hazard ratio (HR), 1.72; =0.007; 5-year HR, 1.87; <0.0001), while EAE showed no significant associations with stroke (2-year HR, 1.00; =0.99; 5-year HR, 1.08, =0.70), adjusting for incident AF. Stroke risk estimation improved significantly at 2 (C-statistics=0.68-0.75, 0.008) and 5 years (C-statistics=0.70-0.76, =0.003) with LAE and EAE. Conclusions LAE was independently associated with an increased risk of ischemic stroke in the absence of AF and both LAE and EAE improved stroke risk prediction. These findings have implications for stroke risk stratification, AF screening, and stroke prevention before the onset of AF.
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http://dx.doi.org/10.1161/JAHA.119.013227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428995PMC
June 2020

Clinical outcomes in patients with systolic heart failure. Are atrial high rate episodes a common marker of disease progression?

Int J Cardiol 2020 10 5;316:184-185. Epub 2020 May 5.

Population Health Research Institute, Mc Master University, Hamilton, Ontario, Canada.

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http://dx.doi.org/10.1016/j.ijcard.2020.04.077DOI Listing
October 2020

Guidance on Minimizing Risk of Drug-Induced Ventricular Arrhythmia During Treatment of COVID-19: A Statement from the Canadian Heart Rhythm Society.

Can J Cardiol 2020 06 8;36(6):948-951. Epub 2020 Apr 8.

University of British Columbia, Vancouver, British Columbia, Canada.

The COVID-19 pandemic has led to efforts at rapid investigation and application of drugs which may improve prognosis but for which safety and efficacy are not yet established. This document attempts to provide reasonable guidance for the use of antimicrobials which have uncertain benefit but may increase risk of QT interval prolongation and ventricular proarrhythmia, notably, chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir. During the pandemic, efforts to reduce spread and minimize effects on health care resources mandate minimization of unnecessary medical procedures and testing. We recommend that the risk of drug proarrhythmia be minimized by 1) discontinuing unnecessary medications that may also increase the QT interval, 2) identifying outpatients who are likely to be at low risk and do not need further testing (no history of prolonged QT interval, unexplained syncope, or family history of premature sudden cardiac death, no medications that may prolong the QT interval, and/or a previous known normal corrected QT interval [QTc]), and 3) performing baseline testing in hospitalized patients or those who may be at higher risk. If baseline electrocardiographic testing reveals a moderately prolonged QTc, optimization of medications and electrolytes may permit therapy. If the QTc is markedly prolonged, drugs that further prolong it should be avoided, or expert consultation may permit administration with mitigating precautions. These recommendations are made while there are no known effective treatments for COVID-19 and should be revisited when further data on efficacy and safety become available.
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http://dx.doi.org/10.1016/j.cjca.2020.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195336PMC
June 2020