Publications by authors named "Jeffrey S Healey"

81 Publications

Variant Re-interpretation in Survivors of Cardiac Arrest with Preserved Ejection Fraction (CASPER Registry) by Clinicians and Clinical Commercial Laboratories.

Circ Genom Precis Med 2021 May 7. Epub 2021 May 7.

Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

- Following an unexplained cardiac arrest, clinical genetic testing is increasingly becoming standard of care. Periodic review of variant classification is required, as re-interpretation can change the diagnosis, prognosis, and management of patients and their relatives. - This study aimed to develop and validate a standardized algorithm to facilitate clinical application of the 2015 American College of Medical Genetics and Association for Molecular Pathology (ACMG-AMP) guidelines for the interpretation of genetic variants. The algorithm was applied to genetic results in the Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER), to assess the rate of variant re-classification over time. Variant classifications were then compared to the classifications of two commercial laboratories to determine the rate and identify sources of variant interpretation discordance. - Thirty-one percent of participants (40/131) had at least one genetic variant with a clinically significant reclassification over time. Variants of uncertain significance were more likely to be downgraded (73%) to benign than upgraded to pathogenic (27%, p= 0.03). For the second part of the study, 50% (70/139) of variants had discrepant interpretations (excluding benign variants), provided by at least one team. - Periodic review of genetic variant classification is a key component of follow-up care given rapidly changing information in the field. There is potential for clinical care gaps with discrepant variant interpretations, based in the interpretation and application of current guidelines. The development of gene and disease specific guidelines and algorithms may provide an opportunity to further standardize variant interpretation reporting in the future.
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http://dx.doi.org/10.1161/CIRCGEN.120.003235DOI Listing
May 2021

Post-operative pain following cardiac implantable electronic device implantation: insights from the BRUISE CONTROL trials.

Europace 2020 Dec 28. Epub 2020 Dec 28.

Division of Cardiology, Department of Medicine, University of Calgary, Libin Cardiovascular Institute, Calgary, AB, Canada.

Aims : Post-operative pain following cardiac implantable electronic device (CIED) insertion is associated with patient dissatisfaction, emotional distress, and emergency department visits. We sought to identify factors associated with post-operative pain and develop a prediction score for post-operative pain.

Methods And Results : All patients from the BRUISE CONTROL-1 and 2 trials were included in this analysis. A validated Visual Analogue Scale (VAS) was used to assess the severity of pain related to CIED implant procedures. Patients were asked to grade the most severe post-operative pain, average post-operative pain, and pain on the day of the first post-operative clinic. Multivariable regression analyses were performed to identify predictors of significant post-operative pain and to develop a pain-prediction score. A total of 1308 patients were included. Multivariable regression analysis found that the presence of post-operative clinically significant haematoma {CSH; P value < 0.001; odds ratio (OR) 3.82 [95% confidence interval (CI): 2.37-6.16]}, de novo CIED implantation [P value < 0.001; OR 1.90 (95% CI: 1.47-2.46)], female sex [P value < 0.001; OR 1.61 (95% CI: 1.22-2.12)], younger age [<65 years; P value < 0.001; OR 1.54 (95% CI: 1.14-2.10)], and lower body mass index [<20 kg/m2; P value < 0.05; OR 2.05 (95% CI: 0.98-4.28)] demonstrated strong and independent associations with increased post-operative pain. An 11-point post-operative pain prediction score was developed using the data.

Conclusion : Our study has identified multiple predictors of post-operative pain after CIED insertion. We have developed a prediction score for post-operative pain that can be used to identify individuals at risk of experiencing significant post-operative pain.
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http://dx.doi.org/10.1093/europace/euaa349DOI Listing
December 2020

The Hearts in Rhythm Organization: A Canadian National Cardiogenetics Network.

CJC Open 2020 Nov 29;2(6):652-662. Epub 2020 May 29.

Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Background: The Hearts in Rhythm Organization (HiRO) is a team of Canadian inherited heart rhythm and cardiomyopathy experts, genetic counsellors, nurses, researchers, patients, and families dedicated to the detection of inherited arrhythmias and cardiomyopathies, provision of best therapies, and protection from the tragedy of sudden cardiac arrest.

Methods: Recently, existing disease-specific registries were merged into the expanded National HiRO Registry, creating a single common data set for patients and families with inherited conditions that put them at risk for sudden death in Canada. Eligible patients are invited to participate in the registry and optional biobank from 20 specialized cardiogenetics clinics across Canada.

Results: Currently, there are 4700 participants enrolled in the National HiRO Registry, with an average of 593 participants enrolled annually over the past 5 years. The capacity to enable knowledge translation of research findings is built into HiRO's organizational infrastructure, with 3 additional working groups (HiRO Clinical Care Committee, HiRO Active Communities Committee, and HiRO Annual Symposium Committee), supporting the organization's current goals and priorities as set alongside patient partners.

Conclusion: The National HiRO Registry aims to be an integrated research platform to which researchers can pose novel research questions leading to a better understanding, detection, and clinical care of those living with inherited heart rhythm and cardiomyopathy conditions and ultimately to prevent sudden cardiac death.
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http://dx.doi.org/10.1016/j.cjco.2020.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710951PMC
November 2020

Remote Ambulatory Cardiac Monitoring Before and After Transcatheter Aortic Valve Replacement.

CJC Open 2020 Sep 25;2(5):416-419. Epub 2020 Apr 25.

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

Remote ambulatory cardiac monitoring (rACM) could identify high-grade atrioventricular block (AVB) before and after transcatheter aortic valve replacement (TAVR). Retrospective analysis of patients undergoing TAVR, with 14-day rACM before and after TAVR, was performed. Of 62 patients undergoing TAVR, 41 patients had rACM before TAVR. Three patients had asymptomatic AVB leading to planned pacemaker (PM) implant. After TAVR, 23 patients had rACM, with 1 patient requiring a PM implant for asymptomatic AVB. Five patients underwent unplanned PM after TAVR. Using rACM, almost half of PM implants in TAVR recipients were identified electively. High-grade AVB requiring PM was identified in nearly 10% of patients before TAVR.
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http://dx.doi.org/10.1016/j.cjco.2020.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499381PMC
September 2020

Global variations in the prevalence, treatment, and impact of atrial fibrillation in a multi-national cohort of 153,152 middle-aged individuals.

Cardiovasc Res 2020 Aug 10. Epub 2020 Aug 10.

Independent University, Bangladesh.

Aims: To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine anti-thrombotic use and clinical outcomes.

Methods And Results: Baseline ECGs were collected in 153,152 middle-aged participants (ages 35 to 70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow up of 7.4 years) were available in one cohort. Cross sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p < 0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs)(p < 0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received anti-thrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke (hazard ratio [HR: 2.29; 95% confidence interval [CI] 1.49-3.52) and death (HR: 2.97; 95% CI 2.25-3.93); with similar rates in different country income levels.

Conclusions: Large variations in AF prevalence occur in different regions and country income settings, but this is only partially explained by traditional AF risk factors. Anti-thrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF.

Translational Perspective: We examined atrial fibrillation (AF) prevalence in 153,152 middle-aged participants spanning 20 countries. Age and sex-standardized prevalence of AF varied by as much as 12-fold between regions; highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p < 0.001); and by as much as 11-fold between groups of countries at different income levels (p < 0.001). Global variations were poorly explained by traditional AF risk factors. Future studies are needed to understand the predominant determinants driving the variation in AF burden across different regions of the world.
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http://dx.doi.org/10.1093/cvr/cvaa241DOI Listing
August 2020

Population-Based Screening for Atrial Fibrillation.

Circ Res 2020 06 18;127(1):143-154. Epub 2020 Jun 18.

From the Cardiovascular Research Center (S.K., S.A.L.), Massachusetts General Hospital, Boston.

Atrial fibrillation (AF) is a common and morbid arrhythmia. Stroke is a major hazard of AF and may be preventable with oral anticoagulation. Yet since AF is often asymptomatic, many individuals with AF may be unaware and do not receive treatment that could prevent a stroke. Screening for AF has gained substantial attention in recent years as several studies have demonstrated that screening is feasible. Advances in technology have enabled a variety of approaches to facilitate screening for AF using both medical-prescribed devices as well as consumer electronic devices capable of detecting AF. Yet controversy about the utility of AF screening remains owing to concerns about potential harms resulting from screening in the absence of randomized data demonstrating effectiveness of screening on outcomes such as stroke and bleeding. In this review, we summarize current literature, present technology, population-based screening considerations, and consensus guidelines addressing the role of AF screening in practice.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.316341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388078PMC
June 2020

Mortality Risk Increases With Clustered Ventricular Arrhythmias in Patients With Implantable Cardioverter-Defibrillators.

JACC Clin Electrophysiol 2020 03 29;6(3):327-337. Epub 2020 Jan 29.

Division of Cardiology, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.

Objectives: This study sought to examine the adverse prognosis associated with ventricular arrhythmia clusters that falls outside the current electrical storm definition.

Background: Electrical storm is most frequently defined as a cluster of ≥3 episodes of ventricular arrhythmia (VA) in a 24-h period. This definition has been associated with adverse cardiovascular outcomes and mortality, but the effect of lesser and greater clustering of arrhythmias has not been described.

Methods: Among all patients in the Resynchronization in Ambulatory Heart Failure trial, 14,515 implantable cardioverter-defibrillator-detected events with data available were rigorously adjudicated in blinded fashion. Arrhythmia incidence was examined for clustering, defined as 2 or more VA events occurring within 3 months. The prognostic importance of clustering was analyzed by varying the cluster length and number of events used to define a cluster. Mortality rates of groups with clustered arrhythmias were compared to patients with no arrhythmia or with unclustered arrhythmia.

Results: The trial included 1,764 patients, among whom 465 patients had two or more VA episodes within 3 months, whereas 406 had unclustered arrhythmias. Compared to patients with no arrhythmia, patients experiencing unclustered VA had increased risk of death (hazard ratio [HR]: 1.45; 95% confidence interval [CI]: 1.09 to 1.93; p = 0.011), whereas the risk was even higher in patients with clustered arrhythmia (HR: 2.68; 95% CI: 2.13 to 3.36; p < 0.0001). Mortality risk increased with higher VA burden (number of VAs in a cluster) and shorter cluster length. This was observed in all groups tested, including the cluster with the least VA burden in the longest cluster length tested (2 VA episodes occurring within 3 months) (mortality HR: 2.85; 95% CI: 1.95 to 4.17; p < 0.0001). Although clustered arrhythmias terminated with antitachycardia pacing were associated with increased mortality, clusters terminated with implantable cardioverter-defibrillator shocks were associated with still higher mortality risk.

Conclusions: Significant adverse prognostic association of clustered VAs is observable with even 2 VA events within 3 months and increases with higher cluster density.
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http://dx.doi.org/10.1016/j.jacep.2019.11.012DOI Listing
March 2020

Searching for Atrial Fibrillation Poststroke: A White Paper of the AF-SCREEN International Collaboration.

Circulation 2019 11 25;140(22):1834-1850. Epub 2019 Nov 25.

Edinburgh Napier University, United Kingdom (L.N.).

Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non-vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non-vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.040267DOI Listing
November 2019

Comparison of Ajmaline and Procainamide Provocation Tests in the Diagnosis of Brugada Syndrome.

JACC Clin Electrophysiol 2019 04 27;5(4):504-512. Epub 2019 Mar 27.

Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Objectives: The authors studied the response rates and relative sensitivity of the most common agents used in the sodium-channel blocker (SCB) challenge.

Background: A type 1 Brugada electrocardiographic pattern precipitated by an SCB challenge confers a diagnosis of Brugada syndrome.

Methods: Patients undergoing an SCB challenge were prospectively enrolled across Canada and the United Kingdom. Patients with no prior cardiac arrest and family histories of sudden cardiac death or Brugada syndrome were included.

Results: Four hundred twenty-five subjects underwent SCB challenge (ajmaline, n = 331 [78%]; procainamide, n = 94 [22%]), with a mean age of 39 ± 15 years (54% men). Baseline non-type 1 Brugada ST-segment elevation was present in 10%. A total of 154 patients (36%) underwent signal-averaged electrocardiography, with 41% having late potentials. Positive results were seen more often with ajmaline than procainamide infusion (26% vs. 4%, p < 0.001). On multivariate analysis, baseline non-type 1 Brugada ST-segment elevation (odds ratio [OR]: 6.92; 95% confidence interval [CI]: 3.15 to 15.2; p < 0.001) and ajmaline use (OR: 8.76; 95% CI: 2.62 to 29.2; p < 0.001) were independent predictors of positive results to SCB challenge. In the subgroup undergoing signal-averaged electrocardiography, non-type 1 Brugada ST-segment elevation (OR: 9.28; 95% CI: 2.22 to 38.8; p = 0.002), late potentials on signal-averaged electrocardiography (OR: 4.32; 95% CI: 1.50 to 12.5; p = 0.007), and ajmaline use (OR: 12.0; 95% CI: 2.45 to 59.1; p = 0.002) were strong predictors of SCB outcome.

Conclusions: The outcome of SCB challenge was significantly affected by the drug used, with ajmaline more likely to provoke a type 1 Brugada electrocardiographic pattern compared with procainamide. Patients undergoing SCB challenge may have contrasting results depending on the drug used, with potential clinical, psychosocial, and socioeconomic implications.
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http://dx.doi.org/10.1016/j.jacep.2019.01.026DOI Listing
April 2019

Early Repolarization Pattern Inheritance in the Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER).

JACC Clin Electrophysiol 2018 11 29;4(11):1473-1479. Epub 2018 Aug 29.

University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Objectives: This study explored early repolarization (ER) pattern inheritance between survivors of unexplained cardiac arrest (UCA) and their first-degree relatives.

Background: ER is considered a factor that confers an increased risk of sudden death. A monogenic explanation for ER is seldom evident after cascade screening.

Methods: UCA survivors and their first-degree relatives enrolled in the CASPER (Cardiac Arrest Survivors With Preserved Ejection Fraction Registry) were included in the study. ER was defined and characterized according to accepted criteria. Logistic regression was performed to explore the association between ER status in the UCA survivor and first-degree relative groups based on the presence of an ER pattern in their related family members after adjusting for age, sex, and ethnicity.

Results: A total of 289 patients from 14 Canadian sites were studied (age: 43.0 ± 15.9 years; 148 women), and 945 electrocardiograms were analyzed. Seventy-five patients had the ER pattern. There was a significantly higher prevalence of the ER pattern in UCA survivors who had first-degree relatives with the ER pattern (adjusted odds ratio: 5.79; 95% confidence intervals [CIs]: 1.79 to 18.7). There was also a nonsignificant higher prevalence of the ER pattern in first-degree relatives of UCA survivors with the ER pattern (OR: 2.43; 95% CI: 0.70 to 8.43). The highest prevalence of the ER pattern was seen in first-degree relatives of UCA survivors with ER syndrome (29%).

Conclusions: The ER pattern appeared to be more common among UCA survivors and first-degree relatives whose related family members had similar changes on electrocardiography, which suggested that genetically complex factors contribute to electrocardiographic patterns that predispose to cardiac arrest.
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http://dx.doi.org/10.1016/j.jacep.2018.07.001DOI Listing
November 2018

Is Screening for Atrial Fibrillation in Canadian Family Practices Cost-Effective in Patients 65 Years and Older?

Can J Cardiol 2018 11 21;34(11):1522-1525. Epub 2018 Jun 21.

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

We present an economic evaluation of a recently completed cohort study in which 2054 seniors were screened for atrial fibrillation (AF) in 22 Canadian family practices. Using a Markov model, trial and literature data were used to project long-term outcomes and costs associated with 4 AF screening strategies for individuals aged 65 years or older: no screening, screen with 30-second radial manual pulse check (pulse check), screen with a blood pressure machine with AF detection (BP-AF), and screen with a single-lead electrocardiogram (SL-ECG). Costs and outcomes were discounted at 1.5% and the model used a lifetime horizon from a public payer perspective. Compared with no screening, screening for AF in Canadian family practice offices using pulse check or screen with a blood pressure machine with AF detection is the dominant strategy whereas screening with SL-ECG is a highly cost-effective strategy with an incremental cost per quality-adjusted life-year (QALY) gained of CAD$4788. When different screening strategies were compared, screening with pulse check had the lowest expected costs ($202) and screening with SL-ECG had the highest expected costs ($222). The no-screening arm resulted in the lowest number of QALYs (8.74195) whereas pulse check and SL-ECG resulted in the highest expected QALYs (8.74362). Probabilistic analysis confirmed that pulse check had the highest probability of being cost-effective (63%) assuming a willingness to pay of $50,000 per QALY gained. Screening for AF in seniors during routine appointments with Canadian family physicians is a cost-effective strategy compared with no screening. Screening with a pulse check is likely to be the most cost-effective strategy.
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http://dx.doi.org/10.1016/j.cjca.2018.05.016DOI Listing
November 2018

Diagnostic accuracy and yield of screening tests for atrial fibrillation in the family practice setting: a multicentre cohort study.

CMAJ Open 2018 Jul-Sep;6(3):E308-E315. Epub 2018 Aug 2.

Libin Cardiovascular Institute of Alberta (Quinn), University of Calgary, Calgary, Alta.; Division of Neurology (Gladstone), Sunnybrook Health Sciences Centre and Sunnybrook Research Institute, and Department of Medicine, University of Toronto, Toronto, Ont.; Department of Family and Community Medicine (Ivers), Women's College Hospital - University of Toronto, Toronto, Ont.; University of Alberta (Sandhu), Edmonton, Alta.; Department of Family Medicine (Dolovich), McMaster University, Hamilton, Ont.; Population Health Research Institute (Ling, Nakamya, Ramasundarahettige, Healey), McMaster University, Hamilton, Ont.; Mount Dennis Weston Health Centre (Frydrych), Toronto, Ont.; SKDS Research Inc. (Henein), Newmarket, Ont.; Ken Ng Family Practice (Ng), Markham, Ont.; Foothills Family Medical Centre (Congdon), Black Diamond, Alta.; Department of Family Medicine (Birtwhistle), Queen's University, Kingston, Ont.; Crowfoot Village Family Practice (Ward), Calgary, Alta.

Background: Detection of undiagnosed or undertreated ("actionable") atrial fibrillation could increase the use of appropriate oral anticoagulant therapy and reduce the risk of stroke. We sought to compare newer screening technologies with a pulse-check for the detection of atrial fibrillation and to determine whether the detection of actionable atrial fibrillation increases the use of oral anticoagulant agents.

Methods: This prospective multicentre cohort study involved 22 primary care clinics. We recruited participants aged 65 years and older who were attending routine appointments. Each participant underwent 3 methods of screening: a 30-second radial pulse-check; single-lead electrocardiogram; and screening by blood pressure machine with atrial fibrillation detection algorithms. Participants who received a positive result on 1 or more test underwent 12-lead electrocardiogram with or withour 24-hour Holter. Screening tests were compared using the McNemar test. Participants with confirmed atrial fibrillation received follow-up at 90 days.

Results: The mean age of participants was 73.7 (± 6.9) years, and 53.4% of participants were female. Of 2171 patients, we had data from all 3 screening tests for 2054 patients. Both single-lead electrocardiogram and the blood pressure device showed superior specificity compared with pulse-check ( < 0.001 for each). Fifty-six patients (2.7%) had confirmed atrial fibrillation: 12 patients had newly detected atrial fibrillation (none of the patients were using anticoagulation agents), and 44 patients had previously diagnosed atrial fibrillation (42 patients were receiving anticoagulant therapy, 2 were not). Thus, 14 patients had actionable atrial fibrillation (0.7%). By 90 days, 77% of patients with actionable atrial fibrillation had started anticoagulant therapy.

Interpretation: Newer screening technologies showed superior specificity compared with a pulse-check. Screening detected undiagnosed or undertreated atrial fibrillation in 0.7% of participants, and 77% started appropriate anticoagulant therapy.

Trial Registration: ClinicalTrials.gov, no. NCT02262351.
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http://dx.doi.org/10.9778/cmajo.20180001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182120PMC
August 2018

Cost Effectiveness of Ventricular Tachycardia Ablation Versus Escalation of Antiarrhythmic Drug Therapy: The VANISH Trial.

JACC Clin Electrophysiol 2018 05 28;4(5):660-668. Epub 2018 Mar 28.

Department of Medicine, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Canada. Electronic address:

Objectives: This analysis uses the data from the randomized controlled trial to assess the cost effectiveness of catheter ablation (n = 132) versus escalated antiarrhythmic therapy (n = 127).

Background: For survivors of myocardial infarction with implantable cardioverter-defibrillator shocks despite antiarrhythmic drugs, the VANISH (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) trial demonstrated improved clinical outcomes with catheter ablation compared with more aggressive antiarrhythmic pharmacotherapy.

Methods: Health care resource use and quality-of-life data were used to determine the cost effectiveness of catheter ablation. Published references were used to estimate costs (in 2015 Canadian dollars). The analysis was over 3 years, with a 5% discount rate. Adjustment was made for censoring and baseline utilities.

Results: Ablation resulted in greater quality-adjusted life-years (QALYs) than escalated drug therapy did (1.63 vs. 1.49; difference: 0.14; 95% confidence interval [CI]: -0.20 to 0.46) and higher cost ($65,126 vs. $60,269; difference: $4,857; 95% CI: -$19,757 to $27,106); with an incremental cost per QALY gained for ablation versus escalated drug therapy of $34,057 primarily due to the initial costs of ablation, which were partially offset by the costs of subsequent ablations and adverse outcomes in the escalated drug therapy arm. For patients with amiodarone-refractory ventricular tachycardia, ablation dominated escalated drug therapy, with greater QALYs (1.48 vs. 1.26; difference: 0.22; 95% CI: -0.19 to 0.59) and lower costs ($67,614 vs. $68,383; difference: -$769; 95% CI: -$35,330 to $27,092). For those with sotalol-refractory ventricular tachycardia, ablation resulted in similar QALYs (1.90 vs. 1.90; difference: -0.00; 95% CI: -0.59 to 0.62) and higher costs ($60,455 vs. $45,033; difference: $15,422; 95% CI: -$10,968 to $48,555).

Conclusions: For the total trial population, results are suggestive that ablation is cost effective compared with escalation of drug therapy. This result was only manifest for the subgroup of patients whose qualifying arrhythmia occurred despite amiodarone.
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http://dx.doi.org/10.1016/j.jacep.2018.01.007DOI Listing
May 2018

Propensity score matched comparison of subcutaneous and transvenous implantable cardioverter-defibrillator therapy in the SIMPLE and EFFORTLESS studies.

Europace 2018 09;20(FI2):f240-f248

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

Aims: Comparison of outcomes between subcutaneous and transvenous implantable cardioverter-defibrillator (S-ICD and TV-ICD) therapy is hampered by varying patient characteristics and complication definitions. The aim of this analysis is to compare clinical outcomes of S-ICD and TV-ICD therapy in a matched cohort.

Methods And Results: Patients implanted with de novo implantable cardioverter-defibrillators without need for pacing were selected from two studies: SIMPLE (n = 1091 single and n = 553 dual chamber TV-ICDs) and EFFORTLESS (n = 798 S-ICDs). Subcutaneous implantable cardioverter-defibrillator patients were 1:1 matched on propensity score to TV-ICD patients. Propensity scores were calculated using 15 baseline characteristics including diagnosis. The Kaplan-Meier estimates for complications requiring invasive intervention, appropriate shocks, and inappropriate shocks were calculated at 3 years follow-up. The primary analysis yielded 391 patients pairs with balanced baseline characteristics, with mean age 55 ± 14 years, 49% ischaemic cardiomyopathy, mean left ventricular ejection fraction 40%, 71% primary prevention, and 89% of TV-ICDs were single chamber. Follow-up was mean 2.9 years in the S-ICD arm vs. 3.3 in the TV-ICD arm. All-cause complications occurred in 9.0% of S-ICD vs. 6.5% of TV-ICD patients, P = 0.29. Appropriate shocks occurred in 9.9% of S-ICD vs. 13.8% in TV-ICD patients, P = 0.03 and inappropriate shocks in 11.9% in S-ICD vs. 8.9% in TV-ICD patients (P = 0.07). Total shock burden (20 vs. 31, P = 0.05) and appropriate shock burden per 100 patients years (9 vs. 18, P = 0.02) were lower for S-ICD patients, while inappropriate shock burden was equal (11 vs. 13, P = 0.56).

Conclusion: The earliest experience of the S-ICD demonstrates similar outcomes as contemporary TV-ICD therapy in a matched comparison with predominately single-chamber devices at 3 years follow-up.
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http://dx.doi.org/10.1093/europace/euy083DOI Listing
September 2018

Differentiating Ventricular From Supraventricular Arrhythmias Using the Postpacing Interval After Failed Antitachycardia Pacing.

Circ Arrhythm Electrophysiol 2018 04;11(4):e005921

Heart Rhythm Service, University of British Columbia, Vancouver, Canada (M.T.B., J.G.A., A.D.K.); University of Toronto, Ontario, Canada (N.L.); Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada (J.S., R.P., M.G.); Hamilton Health Sciences Center, Ontario, Canada (J.S.H.); Montreal Heart Institute, Quebec, Canada (B.T.); Royal Jubilee Hospital, Victoria, British Columbia, Canada (L.S.); McGill, Montreal, Quebec, Canada (V.E.); University of Ottawa, Ontario, Canada (D.B., P.N.); University of Alberta, Edmonton, Canada (S.S.); University of Western Ontario, London, Ontario, Canada (A.T.).

Background: Implantable cardioverter defibrillator arrhythmia discrimination algorithms often are unable to discriminate ventricular from supraventricular arrhythmias. We sought to evaluate whether the response to antitachycardia pacing (ATP) in patients with an implantable cardioverter defibrillator could further discriminate ventricular from supraventricular arrhythmias in patients receiving ATP.

Methods And Results: All episodes of ventricular or supraventricular tachycardia where ATP was delivered in patients enrolled in RAFT (Cardiac-Resynchronization Therapy for Mild-to-Moderate Heart Failure Trial) were included. RAFT randomized 1798 patients with New York Heart Association class II/III heart failure, left ventricular ejection fraction ≤30%, and QRS duration of ≥120 ms to a implantable cardioverter defibrillator±cardiac resynchronization therapy. The tachycardia cycle lengths (TCLs) before and after the delivery of ATP and the postpacing intervals were assessed. Overall, 10 916 ATP attempts were reviewed for 8150 tachycardia episodes in 924 patients. After excluding tachycardias where ATP terminated the episode or where the specific mechanism of the tachycardia was uncertain, we analyzed 3676 ATP attempts delivered for 2046 tachycardia episodes in 541 patients. A shorter difference between postpacing interval and TCL (PPI-TCL) was more likely to be associated with ventricular tachycardia than with supraventricular tachyarrhythmia (138.1±104.2 versus 277.4±126.9 ms; <0.001). Analysis of the receiver operator curve for the PPI-TCL revealed an area under the curve of 0.803 (<0.001; 95% confidence interval, 0.784-0.822). The majority of tachycardias with a PPI-TCL >360 ms were supraventricular with a PPI-TCL value of ≤360 ms having a sensitivity of 97.4% and specificity of 28.3% for ventricular tachycardia.

Conclusions: The ATP response, specifically the PPI-TCL, can further discriminate ventricular from supraventricular arrhythmias in patients with implantable cardioverter defibrillators when the currently available discriminators fail.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00251251.
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http://dx.doi.org/10.1161/CIRCEP.117.005921DOI Listing
April 2018

Quality of life with ablation or medical therapy for ventricular arrhythmias: A substudy of VANISH.

J Cardiovasc Electrophysiol 2018 03 30;29(3):421-434. Epub 2018 Jan 30.

Department of Medicine, QEII Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada.

Background/objective: We compared health-related quality of life (HRQoL) in patients randomized to escalated therapy and those randomized to ablation for ventricular tachycardia in the VANISH trial.

Methods: HRQoL was assessed among VANISH patients at baseline and 3-, 6-, and 12-month follow-up visits. Four validated instruments were used: the SF-36, the implanted cardioverter defibrillator (ICD) Concerns questionnaire (ICDC), the Hospital Anxiety and Depression Scale (HADS), and the EuroQol five dimensions questionnaire (EQ-5D). Linear mixed-effects modeling was used for repeated measures with SF-36, HADS, ICDC, and EQ-5D as dependent variables. In a second model, treatment was subdivided by amiodarone use prior to enrollment.

Results: HRQoL did not differ significantly between those randomized to ablation or escalated therapy. On subgroup analysis, improvement in SF-36 measures was seen at 6 months in the ablation group for social functioning (63.5-69.3, P = 0.03) and energy/fatigue (43.0-47.9, P = 0.01). ICDC measures showed a reduction in ICD concern in the ablation group at 6 months (10.4-8.7, P = 0.01) and a reduction in ICD concern in the escalated therapy group at 6 months (10.9-9.4, P = 0.04). EQ-5D measures showed a significant improvement in overall health in ablation patients at 6 months (63.4-67.3, P = 0.04).

Conclusion: Patients in the VANISH study randomized to ablation did not have a significant change in quality of life outcomes compared to those randomized to escalated therapy. Some subgroup findings were significant, as those randomized to ablation showed persistent improvement in SF-36 energy/fatigue and ICD concern, and transient improvement in SF-36 social functioning and EQ-5D overall health.
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http://dx.doi.org/10.1111/jce.13419DOI Listing
March 2018

Rationale and design of the Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation (ARTESiA) trial.

Am Heart J 2017 Jul 24;189:137-145. Epub 2017 Apr 24.

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

Background: Device-detected subclinical atrial fibrillation (AF) refers to infrequent, short-lasting, asymptomatic AF that is detected only with long-term continuous monitoring. Subclinical AF is common and associated with an increased risk of stroke; however, the risk of stroke with subclinical AF is lower than for clinical AF, and very few patients with subclinical AF alone have been included in large AF anticoagulation trials. The net benefit of anticoagulation in patients with subclinical AF is unknown.

Design: ARTESiA is a prospective, multicenter, double-blind, randomized controlled trial, recruiting patients with subclinical AF detected by an implanted pacemaker, defibrillator, or cardiac monitor, and who have additional risk factors for stroke. Patients with clinical AF documented by surface electrocardiogram will be excluded from the study. Participants will be randomized to receive either apixaban (according to standard AF dosing) or aspirin 81mg daily. The primary outcome is the composite of stroke, transient ischemic attack with diffusion-weighted magnetic resonance imaging evidence of cerebral infarction, and systemic embolism. Approximately 4,000 patients will be enrolled from around 230 clinical sites, with an anticipated mean follow-up of 36months until 248 adjudicated primary outcome events have occurred.

Summary: ARTESiA will determine whether oral anticoagulation therapy with apixaban compared with aspirin reduces the risk of stroke or systemic embolism in patients with subclinical AF and additional risk factors.
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http://dx.doi.org/10.1016/j.ahj.2017.04.008DOI Listing
July 2017

Genetic Testing in the Evaluation of Unexplained Cardiac Arrest: From the CASPER (Cardiac Arrest Survivors With Preserved Ejection Fraction Registry).

Circ Cardiovasc Genet 2017 Jun;10(3)

Background: Unexplained cardiac arrest may be because of an inherited arrhythmia syndrome. The role of genetic testing in cardiac arrest survivors without a definite clinical phenotype is unclear.

Methods And Results: The CASPER (Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) is a large registry of cardiac arrest survivors where initial assessment reveals normal coronary arteries, left ventricular function, and resting ECG. Of 375 cardiac arrest survivors in CASPER from 2006 to 2015, 174 underwent genetic testing. Patients were classified as phenotype-positive (n=72) or phenotype-negative (n=102). Genetic testing was performed at treating physicians' discretion in line with contemporary guidelines and availability. All genetic variants identified from original laboratory reports were reassessed by the investigators in line with modern criteria. Pathogenic variants were identified in 29 (17%) patients (60% channelopathy-associated and 40% cardiomyopathy-associated genes) and 70 variants of unknown significance were identified in 32 (18%) patients. Prior syncope (odds ratio, 4.0; 95% confidence interval, 1.6-9.7) and a family history of sudden death (odds ratio, 3.2; 95% confidence interval, 1.1-9.4) were independently associated with the presence of a pathogenic variant. In phenotype-negative patients, broad multiphenotype genetic testing led to higher yields (21% versus 8%; =0.04) but was associated with more variants of unknown significance (55% versus 5%; <0.01).

Conclusions: Genetic testing identifies a pathogenic variant in a significant proportion of unexplained cardiac arrest survivors. Prior syncope and family history of sudden death are predictors of a positive genetic test. Both arrhythmia and cardiomyopathy genes are implicated. Broad, multiphenotype testing revealed the highest frequency of pathogenic variants in phenotype-negative patients.

Clinical Trial Registration: https://www.clinicaltrials.gov. Unique Identifier: NCT00292032.
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http://dx.doi.org/10.1161/CIRCGENETICS.116.001686DOI Listing
June 2017

Screening for Atrial Fibrillation: A Report of the AF-SCREEN International Collaboration.

Circulation 2017 05;135(19):1851-1867

From Heart Research Institute, Charles Perkins Centre, and Concord Hospital Cardiology, University of Sydney, Australia (B.F.); St Georges Hospital, London, UK (J.C.); Johns Hopkins University, Baltimore, MD (H.C.); Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (J.S.H., D.C.); Karolinska Institute, Stockholm, Sweden (M.R., J.E., L.F., E.S.); The Shanghai Institute of Hypertension, Ruijin Hospital, Jiaotong University School of Medicine, China (J.W.); Brigham and Womens Hospital, Harvard Medical School, Boston, MA (C.M.A.); The George Institute for Global Health, Sydney, Australia (C.S.A.); Barts Health NHS Trust, London, UK (S.A.); National Heart, Lung, and Blood Institute and Boston University's Framingham Heart Study, MA (E.J.B.); University of Modena and Reggio Emilia, Italy (G.B.); Klinikum Coburg, Germany (J.B.); Odense University Hospital, Denmark (A.B.); Cardiovascular Research Centre, National Yang-Ming University, Taipei, Taiwan (T.- F.C.); University Hospital, Basel, Switzerland (D.C.); Université François Rabelais, Tours, France (L.F.); University of Birmingham, UK (D.A.F.); Mayo Clinic College of Medicine, Rochester, MN (B.J.G.); University of Toronto, Ontario, Canada (D.J.G., A.V.); Hackensack University Medical Centre, NJ (T.V.G.); Poche Centre, University of Sydney, Australia (K.G.); University of Western Australia, Perth (G.J.H.); Trinity College, Dublin, Ireland (J.H.); Royal Perth Hospital, University of Western Australia (G.S.H.); StopAfib.org, Dallas, TX (M.T.H.); Weill Cornell Medical College, New York (H.K.); Institute of Cardiovascular Sciences, University of Birmingham, UK (P.K.); SWBH and UHB NHS trusts, Birmingham, UK (P.K.); AFNET, Muenster, Germany (P.K.); Lankenau Institute for Medical Research, Wynnewood, OK (P.R.K.); University Hospital of Zurich, Switzerland (D.K.); Chinese University of Hong Kong (V.W.Y.L., B.P.Y.); University of Linköping, Sweden (L.-A.L.); University of Birmingham, UK; Aalborg University, Denmark (G.Y.H.L.); Arrhythmia Alliance, London, UK (T.L.); Charles Perkins Centre, University of Sydney, Australia (N.L.); Cliniques du Sud Luxembourg, Arlon, Belgium (G.H.M.); Institute for Epidemiology Statistics and Informatics, Frankfurt, Germany (C.M.); Edinburgh Napier University, UK (L.N.); Charles Perkins Centre, University of Sydney, Australia (J.O.); Duke University, Durham, NC (J.P.P.); University of Auckland, New Zealand (K.P.); University of Belgrade, Serbia (T.S.P.); KH der Elisabethinen, Ordensklinikum Linz, Austria (H.P.); University of Groningen, University Medical Centre Groningen, The Netherlands (M.R.); University of Alberta, Edmonton, Canada (R.K.S.); University Heart Centre, Hamburg, Germany (R.B.S.); The University of Hong Kong (C.-W.S.); Scripps Translational Science Institute, San Diego, CA (S.S.); Rigshospitalet, The Heart Centre, University of Copenhagen, Denmark (J.H.S.); Ospedale dell'Angelo Venice-Mestre, Venice, Italy (S.T.); Martini Hospital, Groningen, The Netherlands (R.G.T.); Stanford University, CA (M.P.T.); VA Palo Alto Health Care System, CA (M.P.T.); The Department of Medical Research, Bærum Hospital, Rud, Norway (A.T.); Department of General Practice, Academic Medical Center, Amsterdam, The Netherlands (S.B.U.); University of Groningen, University Medical Centre Groningen, The Netherlands (I.C.V.G.); and University of Göttingen, Germany (R.W.).

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.026693DOI Listing
May 2017

Cardiac Resynchronization Therapy Reduces Ventricular Arrhythmias in Primary but Not Secondary Prophylactic Implantable Cardioverter Defibrillator Patients: Insight From the Resynchronization in Ambulatory Heart Failure Trial.

Circ Arrhythm Electrophysiol 2017 Mar;10(3)

From the Department of Medicine, Division of Cardiology, Dalhousie University, Halifax, NS, Canada (J.L.S., R.P., M.J.G.); Department of Medicine (G.A.W.), Cardiovascular Research Methods Centre (E.Y.), and Department of Medicine, Division of Cardiology (D.B., P.B.N.), University of Ottawa Heart Institute, ON, Canada; Department of Medicine, Division of Cardiology, Population Health Research Institute, Hamilton, ON, Canada (J.S.H.); Department of Medicine, Montreal Heart Institute, QC, Canada (B.T.); Department of Medicine, Division of Cardiology, Royal Jubilee Hospital, Victoria, BC, Canada (L.D.S.); Department of Medicine, Division of Cardiology, University of Alberta, Edmonton, Canada (S.S.); Department of Medicine, Division of Cardiology, McGill University Health Centre and Hopital Sacre Coeur de Montreal, Quebec, Canada (V.E.); Department of Medicine, Division of Cardiology, University of Toronto, ON, Canada (P.D.); and Division of Cardiology, Department of Medicine, Western University, London, Canada (A.S.L.T.).

Background: The RAFT (Resynchronization in Ambulatory Heart Failure Trial) demonstrated that cardiac resynchronization therapy (CRT) reduced both mortality and heart failure hospitalizations in patients with functional class II or III heart failure and widened QRS. We examined the influence of CRT on ventricular arrhythmias in patients with primary versus secondary prophylaxis defibrillator indications.

Methods And Results: All ventricular arrhythmias among RAFT study participants were downloaded and adjudicated by 2 blinded reviewers with an overreader for disagreements and committee review for remaining discrepancies. Incidence of ventricular arrhythmias among patients randomized to CRT-D versus implantable cardioverter defibrillator (ICD) were compared within the groups of patients treated for primary prophylaxis and for secondary prophylaxis. Of 1798 enrolled patients, 1764 had data available for adjudication and were included. Of these, 1531 patients were implanted for primary prophylaxis, while 233 patients were implanted for secondary prophylaxis; 884 patients were randomized to ICD and 880 to CRT-D. During 5953.6 patient-years of follow-up, there were 11 278 appropriate ICD detections of ventricular arrhythmias. In the primary prophylaxis group, CRT-D significantly reduced incidence ventricular arrhythmias in comparison to ICD (hazard ratio, 0.86; 95% confidence interval, 0.74-0.99; =0.044). This effect was not seen in the secondary prophylaxis group (hazard ratio, 1.14; 95% confidence interval, 0.82-1.58; =0.45). CRT-D was not associated with significant differences in overall ventricular arrhythmia burden in either group.

Conclusions: CRT reduced the rate of onset of new ventricular arrhythmias detected by ICDs in patients without a history of prior ventricular arrhythmias. This effect was not observed among patients who had prior ventricular arrhythmias.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00251251.
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http://dx.doi.org/10.1161/CIRCEP.116.004875DOI Listing
March 2017

Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation: A Randomized, Open-Label Clinical Trial (SMAC-AF [Substrate Modification With Aggressive Blood Pressure Control]).

Circulation 2017 May 22;135(19):1788-1798. Epub 2017 Feb 22.

From Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, Nova Scotia, Canada (R.P., J.L.S., C.G., M.G.); University of Ottawa Heart Institute, Ontario, Canada, (G.A.W.); Population Health Research Institute, Hamilton, Ontario, Canada (J.S.H.); Montreal Heart Institute, Quebec, Canada (J.-C.T., L.R.); Centre Hospitalier de L'Universite de Montreal, Quebec, Canada (I.G.); Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada (J.-F.R.); University of Western Ontario, London, Canada (L.G., A.S.L.T.); Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Canada (I.N.); Royal Jubilee Hospital, Victoria, British Columbia, Canada (P.N.); Ottawa Heart Institute, Ontario, Canada (D.B.); University Health Network, Toronto, Ontario, Canada (A.H.); Libin Cardiovascular Institute of Alberta, Calgary, Canada (S.B.W.); and St. Michael's Hospital, Toronto, Ontario, Canada (I.M.).

Background: Radiofrequency catheter ablation for atrial fibrillation has become an important therapy for AF; however, recurrence rates remain high. We proposed to determine whether aggressive blood pressure (BP) lowering prevents recurrent atrial fibrillation (AF) after catheter ablation in patients with AF and a high symptom burden.

Methods: We randomly assigned 184 patients with AF and a BP >130/80 mm Hg to aggressive BP (target <120/80 mm Hg) or standard BP (target <140/90 mm Hg) treatment before their scheduled AF catheter ablation. The primary outcome was symptomatic recurrence of AF/atrial tachycardia/atrial flutter lasting >30 seconds, determined 3 months beyond catheter ablation by a blinded end-point evaluation.

Results: The median follow-up was 14 months. At 6 months, the mean systolic BP was 123.2±13.2 mm Hg in the aggressive BP treatment group versus 135.4±15.7 mm Hg (<0.001) in the standard treatment group. The primary outcome occurred in 106 patients, 54 (61.4%) in the aggressive BP treatment group compared with 52 (61.2%) in the standard treatment group (hazard ratio=0.94; 95% confidence interval, 0.65-1.38; =0.763). In the prespecified subgroup analysis of the influence of age, patients ≥61 years of age had a lower primary outcome event rate with aggressive BP (hazard ratio=0.58; 95% confidence interval, 0.34-0.97; =0.013). There was a higher rate of hypotension requiring medication adjustment in the aggressive BP group (26% versus 0%).

Conclusions: In this study, this duration of aggressive BP treatment did not reduce atrial arrhythmia recurrence after catheter ablation for AF but resulted in more hypotension.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00438113.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.026230DOI Listing
May 2017

Cardiac Abnormalities in First-Degree Relatives of Unexplained Cardiac Arrest Victims: A Report From the Cardiac Arrest Survivors With Preserved Ejection Fraction Registry.

Circ Arrhythm Electrophysiol 2016 09;9(9)

For the author affiliations, please see the Appendix.

Background: Unexplained cardiac arrest (UCA) may be explained by inherited arrhythmia syndromes. The Cardiac Arrest Survivors With Preserved Ejection Fraction Registry prospectively assessed first-degree relatives of UCA or sudden unexplained death victims to screen for cardiac abnormalities.

Methods And Results: Around 398 first-degree family members (186 UCA, 212 sudden unexplained death victims' relatives; mean age, 44±17 years) underwent extensive cardiac workup, including ECG, signal averaged ECG, exercise testing, cardiac imaging, Holter-monitoring, and selective provocative drug testing with epinephrine or procainamide. Genetic testing was performed when a mutation was identified in the UCA survivor or when the diagnostic workup revealed a phenotype suggestive of a specific inherited arrhythmia syndrome. The diagnostic strength was classified as definite, probable, or possible based on previously published definitions. Cardiac abnormalities were detected in 120 of 398 patients (30.2%) with 67 of 398 having a definite or probable diagnosis (17%), including Long-QT syndrome (13%), catecholaminergic polymorphic ventricular tachycardia (4%), arrhythmogenic right ventricular cardiomyopathy (4%), and Brugada syndrome (3%). The detection yield was similar for family members of UCA and sudden unexplained death victims (31% versus 27%; P=0.59). Genetic testing was performed more often in family members of UCA patients (29% versus 20%; P=0.03). Disease-causing mutations were identified in 20 of 398 relatives (5%). The most common pathogenic mutations were RyR2 (2%), SCN5A (1%), and KNCQ1 (0.8%).

Conclusions: Cardiac screening revealed abnormalities in 30% of first-degree relatives of UCA or sudden unexplained death victims, with a clear working diagnosis in 17%. Long-QT, arrhythmogenic right ventricular cardiomyopathy, and catecholaminergic polymorphic ventricular tachycardia were the most common diagnoses. Systematic cascade screening and genetic testing in asymptomatic individuals will lead to preventive lifestyle and medical interventions with potential to prevent sudden cardiac death.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032.
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http://dx.doi.org/10.1161/CIRCEP.115.004274DOI Listing
September 2016

The Canadian Arrhythmogenic Right Ventricular Cardiomyopathy Registry: Rationale, Design, and Preliminary Recruitment.

Can J Cardiol 2016 12 21;32(12):1396-1401. Epub 2016 Apr 21.

QEII Health Sciences Center, Halifax, Nova Scotia, Canada.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a complex and clinically heterogeneous arrhythmic condition. Incomplete penetrance and variable expressivity are particularly evident in ARVC, making clinical decision-making challenging.

Methods: Pediatric and adult cardiologists, geneticists, genetic counsellors, ethicists, nurses, and qualitative researchers are collaborating to create the Canadian ARVC registry using a web-based clinical database. Biological samples will be banked and systematic analysis will be performed to examine potentially causative mutations, variants, and biomarkers. Outcomes will include syncope, ventricular arrhythmias, defibrillator therapies, heart failure, and mortality.

Results: Preliminary recruitment has enrolled 365 participants (aged 42.7 ± 17.1 years; 50% women), including 129 probands and 236 family members. Previous cardiac arrest occurred in 28 (8%) participants, syncope occurred in 43 (12%) participants, and 46% of probands had a family history of sudden death. Overall yield of genetic testing was 36% for a disease-causing mutation and 20% for a variant of unknown significance. Target enrollment is 1000 affected patients and 500 unaffected family member controls over 7 years. The cross-sectional and longitudinal data collected in this manner will allow a robust assessment of the natural history and clinical course of genetic subtypes.

Conclusions: The Canadian ARVC Registry will create a population-based cohort of patients and their families to inform clinical decisions regarding patients with ARVC.
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http://dx.doi.org/10.1016/j.cjca.2016.04.004DOI Listing
December 2016

Is It Time to Systematically Replace Warfarin With a New Oral Anticoagulant for Higher-Risk Patients With Nonvalvular Atrial Fibrillation?

Can J Cardiol 2016 10 24;32(10):1203.e9-1203.e11. Epub 2016 Mar 24.

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

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http://dx.doi.org/10.1016/j.cjca.2016.03.011DOI Listing
October 2016

Frequency and Outcomes of Postrandomization Atrial Tachyarrhythmias in the Resynchronization/Defibrillation in Ambulatory Heart Failure Trial.

Circ Arrhythm Electrophysiol 2016 May;9(5)

From the Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada (S.B.W., D.V.E., D.G.W.); University of Ottawa Heart Institute, University of Ottawa, Ottawa, Ontario, Canada (E.Y., G.W.); Department of Medicine, Western University, London, United Kingdom (A.S.L.T.); and Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (J.S.H.).

Background: Whether adding cardiac resynchronization therapy (CRT-D) to an implanted cardioverter-defibrillator alters the risk of atrial fibrillation or other atrial tachyarrhythmias (AF/AT), or if postimplantation AF/AT modulate the benefits of CRT-D, remain unknown.

Methods And Results: We studied 972 Resynchronization/Defibrillation in Ambulatory Heart Failure Trial (RAFT) participants without permanent AF, who were randomized to CRT-D (n=495) versus nonresynchronization defibrillator (implanted cardioverter-defibrillator; n=477) within the predefined stratum eligible for an atrial lead. Occurrence of postrandomization AF/AT was prospectively assessed, and Cox models were used to test the independent association between the postrandomization AF/AT and the RAFT primary composite outcome of all-cause mortality or hospitalization for heart failure. Over 41 (±19) months, postrandomization AF/AT occurred in 216 (45.3%) patients randomized to implanted cardioverter-defibrillator and 249 (50.3%) randomized to CRT-D. After adjusting for competing risk of death, randomization to CRT-D increased risk of postrandomization AF/AT (hazard ratio, 1.20; 95% confidence interval, 1.00-1.42; P=0.045). Postrandomization AF/AT, which remained paroxysmal in 69.5%, did not reduce biventricular pacing percentage. In adjusted models, postrandomization AF/AT was not associated with the primary outcome (hazard ratio, 1.04; 95% confidence interval, 0.84-1.30). However, AF/AT was associated with a borderline decreased risk of mortality (hazard ratio, 0.75; 95% confidence interval, 0.58-1.00) but increased risk of heart failure hospitalization (hazard ratio, 1.43; 95% confidence interval, 1.08-1.90).

Conclusions: In RAFT, nearly half of the patients developed postrandomization AF/AT, and those randomized to CRT-D had borderline significant higher risk. Postrandomization AF/AT was associated with risk of heart failure hospitalization, but not with the primary composite outcome.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00251251.
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http://dx.doi.org/10.1161/CIRCEP.115.003807DOI Listing
May 2016

Delayed AICD therapy and cardiac arrest resulting from undersensing of ventricular fibrillation in a subject with hypertrophic cardiomyopathy-A case report.

Indian Pacing Electrophysiol J 2015 Mar-Apr;15(2):121-4. Epub 2015 Jul 29.

Arrhythmia Service, Division of Cardiology, University of Ottawa Heart Institute, 40 Ruskin Ave, Ottawa, Ontario K1Y 4W7, Canada.

Defibrillation testing is no longer routinely performed after automatic implantable cardioverter-defibrillator (AICD) implantation. However, certain subjects undergoing AICD implantation may be at higher risk of undersensing of ventricular arrhythmias resulting in potentially fatal outcomes. We present the case of a 30-year-old woman with hypertrophic cardiomyopathy (HCM; 'asymmetric septal hypertophy' morphologic variant) and prophylactic AICD who experienced an out of hospital cardiac arrest. AICD interrogation revealed undersensing as a result of intermittent high amplitude electrograms during an episode of ventricular fibrillation (VF). The subject underwent replacement and repositioning of the AICD lead along with pulse generator replacement (that utilized a different VF sensing algorithm) with appropriate sensing of VF and successful defibrillation testing. The presence of intermittent high amplitude electrograms during episodes of VF in AICDs using the AGC function should be recognized as a situation that may necessitate interventions to prevent undersensing and consequent delay in therapy.
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http://dx.doi.org/10.1016/j.ipej.2015.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750165PMC
March 2016

A New, Simplified Measure of Anticoagulation Control With Warfarin: Potential Role in the Direct Oral Anticoagulant Era.

Can J Cardiol 2016 10 2;32(10):1203.e5-1203.e7. Epub 2015 Dec 2.

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

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October 2016

Outcome of Apparently Unexplained Cardiac Arrest: Results From Investigation and Follow-Up of the Prospective Cardiac Arrest Survivors With Preserved Ejection Fraction Registry.

Circ Arrhythm Electrophysiol 2016 Jan;9(1):e003619

From the Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada (A.R.M.H., C.C., K.G., M.T.B., C.S., M.J., S.C., A.D.K.); Department of Cardiovascular Sciences, Libin Cardiovascular Institute, University of Calgary, Calgary, AB, Canada (B.G.); Division of Cardiology, Department of Medicine, Queen's University, Kingston, ON, Canada (C.S.S.); University of Ottawa Heart Institute, Ottawa, ON, Canada (D.H.B.); Division of Cardiology, Department of Medicine, Western University, London, ON, Canada (G.J.K., R.Y.); Department of Medicine, Quebec Heart and Lung Institute, Quebec City, QC, Canada (J.C.); Division of Cardiology, Department of Medicine, Population Health Research Institute, Hamilton, ON, Canada (J.S.H.); Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada (M.T.); Division of Cardiology, Department of Medicine, QEII Health Sciences Center, Halifax, NS, Canada (M.G.); Division of Cardiology, Department of Medicine, University Health Network, Toronto, ON, Canada (M.H.G., V.S.C.); Division of Cardiology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada (P.A.); Division of Cardiology, Department of Medicine, Royal Jubilee Hospital, Victoria, BC, Canada (R.L.); and Division of Cardiology, Department of Pediatrics, BC Children's Hospital, Vancouver, BC, Canada (S.S.).

Background: The Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER) enrolls patients with apparently unexplained cardiac arrest and no evident cardiac disease to identify the pathogenesis of cardiac arrest through systematic clinical testing. Exercise testing, drug provocation, advanced cardiac imaging, and genetic testing may be useful when a cause is not apparent.

Methods And Results: The first 200 survivors of unexplained cardiac arrest from 14 centers across Canada were evaluated to determine the results of investigation and follow-up (age, 48.6±14.7 years, 41% female). Patients were free of evidence of coronary artery disease, left ventricular dysfunction, or evident repolarization syndromes. Advanced testing determined a diagnosis in 34% of patients at baseline, with a diagnosis emerging during follow-up in 7% of patients. Of those who were diagnosed, 28 (35%) had an underlying structural condition and 53 (65%) had a primary electric disease. During a mean follow-up of 3.15±2.34 years, 23% of patients had either a shock or an appropriate antitachycardia pacing from their implantable cardioverter defibrillator, or both. The implantable cardioverter defibrillator appropriate intervention rate was 8.4% at 1 year and 18.1% at 3 years, with no clear difference between diagnosed and undiagnosed subjects, or between those diagnosed with a primary electric versus structural pathogenesis.

Conclusions: Obtaining a diagnosis in previously unexplained cardiac arrest patients requires systematic clinical testing and regular follow-up to unmask the cause. Nearly half of apparently unexplained cardiac arrest patients ultimately received a diagnosis, allowing for improved treatment and family screening. A substantial proportion of patients received appropriate implantable cardioverter defibrillator therapy during medium-term follow-up.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032.
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http://dx.doi.org/10.1161/CIRCEP.115.003619DOI Listing
January 2016

Clinical Risk Stratification for Primary Prevention Implantable Cardioverter Defibrillators.

Circ Heart Fail 2015 Sep 29;8(5):927-37. Epub 2015 Jul 29.

From the Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada (D.S.L., J.H., X.W., P.C.A., J.V.T.); Peter Munk Cardiac Centre (D.S.L., K.N.) and Joint Department of Medical Imaging (D.S.L.), University Health Network (D.S.L., K.N.), Institute for Health Policy, Management and Evaluation (D.S.L., P.C.A., J.V.T.), Division of Cardiology, Department of Medicine, Sunnybrook Health Sciences Centre (E.C., J.V.T.), and Division of Cardiology, Department of Medicine, St. Michael's Hospital (I.M., P.D.), University of Toronto, Toronto, Ontario, Canada; Division of Cardiology, Department of Medicine, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada (R.Y.); Division of Cardiology, Department of Medicine, Hamilton Health Sciences Centre, McMaster University, Hamilton, Ontario, Canada (J.S.H.); Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.B.); Kingston General Hospital, Queen's University, Kingston, Ontario, Canada (C.S.S.); and Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada (A.D.K.).

Background: A conceptualized model may be useful for understanding risk stratification of primary prevention implantable cardioverter defibrillators considering the competing risks of appropriate implantable cardioverter defibrillator shock versus mortality.

Methods And Results: In a prospective, multicenter, population-based cohort with left ventricular ejection fraction ≤35% referred for primary prevention implantable cardioverter defibrillator, we developed dual risk stratification models to determine the competing risks of appropriate defibrillator shock versus mortality using a Fine-Gray subdistribution hazard model. Among 7020 patients referred, 3445 underwent defibrillator implant (79.7% men, median, 66 years [25th, 75th: 58-73]). During 5918 person-years of follow-up, appropriate shock occurred in 204 patients (3.6 shocks/100 person-years) and 292 died (4.9 deaths/100 person-years). Competing risk predictors of appropriate shock included nonsustained ventricular tachycardia, atrial fibrillation, serum creatinine concentration, digoxin or amiodarone use, and QRS duration near 130-ms peak. One-year cumulative incidence of appropriate shock was 0.9% in the lowest risk category, and 1.7%, 2.5%, 4.9%, and 9.3% in low, intermediate, high, and highest risk groups, respectively. Hazard ratios for appropriate shock ranged from 4.04 to 7.79 in the highest 3 deciles (all P≤0.001 versus lowest risk). Cumulative incidence of 1-year death was 0.6%, 1.9%, 3.3%, 6.2%, and 17.7% in lowest, low, intermediate, high, and highest risk groups, respectively. Mortality hazard ratios ranged from 11.48 to 36.22 in the highest 3 deciles (all P<0.001 versus lowest risk).

Conclusions: Simultaneous estimation of risks of appropriate shock and mortality can be performed using clinical variables, providing a potential framework for identification of patients who are unlikely to benefit from prophylactic implantable cardioverter defibrillator.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.115.002414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568903PMC
September 2015