Publications by authors named "Allan C Skanes"

196 Publications

Thromboembolic events following cardioversion of acute atrial fibrillation and flutter: a systematic review and meta-analysis.

CJEM 2021 Mar 14. Epub 2021 Mar 14.

Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada.

Background: Recent studies have presented concerning data on the safety of cardioversion for acute atrial fibrillation and flutter. We conducted this meta-analysis to evaluate the effect of oral anticoagulation use on thromboembolic events post-cardioversion of low-risk acute atrial fibrillation and flutter patients of < 48 h in duration.

Methods: We searched MEDLINE, Embase, and Cochrane from inception through February 6, 2020 for studies reporting thromboembolic events post-cardioversion of acute atrial fibrillation and flutter. Main outcome was thromboembolic events within 30 days post-cardioversion. Primary analysis compared thromboembolic events based on oral anticoagulation use versus no oral anticoagulation use. Secondary analysis was based on baseline thromboembolic risk. We performed meta-analyses where 2 or more studies were available, by applying the DerSimonian-Laird random-effects model. Risk of bias was assessed with the Quality in Prognostic Studies tool.

Results: Of 717 titles screened, 20 studies met inclusion criteria. Primary analysis of seven studies with low risk of bias demonstrated insufficient evidence regarding the risk of thromboembolic events associated with oral anticoagulation use (RR = 0.82 where RR < 1 suggests decreased risk with oral anticoagulation use; 95% CI 0.27 to 2.47; I = 0%). Secondary analysis of 13 studies revealed increased risk of thromboembolic events with high baseline thromboembolic risk (RR = 2.25 where RR > 1 indicates increased risk with higher CHADS or CHADS-VASc scores; 95% CI 1.25 to 4.04; I = 0%).

Conclusion: Primary analysis revealed insufficient evidence regarding the effect of oral anticoagulation use on thromboembolic events post-cardioversion of low-risk acute atrial fibrillation and flutter, though the event rate is low in contemporary practice. Our findings can better inform patient-centered decision-making when considering 4-week oral anticoagulation use for acute atrial fibrillation and flutter patients.
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http://dx.doi.org/10.1007/s43678-021-00103-0DOI Listing
March 2021

Enrichment of loss-of-function and copy number variants in ventricular cardiomyopathy genes in 'lone' atrial fibrillation.

Europace 2021 Jun;23(6):844-850

Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, ON, Canada.

Aims: Atrial fibrillation (AF) is a complex heritable disease whose genetic underpinnings remain largely unexplained, though recent work has suggested that the arrhythmia may develop secondary to an underlying atrial cardiomyopathy. We sought to evaluate for enrichment of loss-of-function (LOF) and copy number variants (CNVs) in genes implicated in ventricular cardiomyopathy in 'lone' AF.

Methods And Results: Whole-exome sequencing was performed in 255 early onset 'lone' AF cases, defined as arrhythmia onset prior to 60 years of age in the absence of known clinical risk factors. Subsequent evaluations were restricted to 195 cases of European genetic ancestry, as defined by principal component analysis, and focused on a pre-defined set of 43 genes previously implicated in ventricular cardiomyopathy. Bioinformatic analysis identified 6 LOF variants (3.1%), including 3 within the TTN gene, among cases in comparison with 4 of 503 (0.80%) controls [odds ratio: 3.96; 95% confidence interval (CI): 1.11-14.2; P = 0.033]. Further, two AF cases possessed a novel heterozygous 8521 base pair TTN deletion, confirmed with Sanger sequencing and breakpoint validation, which was absent from 4958 controls (P = 0.0014). Subsequent cascade screening in two families revealed evidence of co-segregation of a LOF variant with 'lone' AF.

Conclusion: 'Lone' AF cases are enriched in rare LOF variants from cardiomyopathy genes, findings primarily driven by TTN, and a novel TTN deletion, providing additional evidence to implicate atrial cardiomyopathy as an AF genetic sub-phenotype. Our results also highlight that AF may develop in the context of these variants in the absence of a discernable ventricular cardiomyopathy.
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http://dx.doi.org/10.1093/europace/euaa421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184224PMC
June 2021

Role of Common Genetic Variation in Lone Atrial Fibrillation.

Circ Genom Precis Med 2021 Feb 1;14(1):e003179. Epub 2021 Feb 1.

Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (A.C.S., L.J.G., A.S.T., J.D.R.), Western University, London, Ontario, Canada.

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http://dx.doi.org/10.1161/CIRCGEN.120.003179DOI Listing
February 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 01 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

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

Para-Hisian Pacing During Sinus Rhythm: Establishing Threshold Values to Distinguish Nodal From Septal Pathway Conduction.

JACC Clin Electrophysiol 2020 10 12;6(10):1246-1252. Epub 2020 Aug 12.

London Heart Rhythm Program, Western University, London, Ontario, Canada.

Objectives: This study sought to identify minimum threshold values below which conduction over the atrioventricular (AV) node would be unexpected.

Background: Para-Hisian pacing is used to evaluate for the presence of a septal accessory pathway (AP); however, threshold values to differentiate nodal from AP conduction are unknown.

Methods: The authors performed high- and low-output para-Hisian pacing during sinus rhythm to capture the His and para-Hisian ventricular myocardium (H+V) and para-Hisian ventricular myocardium (V) alone, respectively. The change in stimulation (stim)-to-atrial electrogram interval after loss of His bundle capture in patients with (AP+) and without (AP-) a septal AP was evaluated. Stim-to-proximal coronary sinus (PCS) and stim-to-high right atrium (HRA) intervals were measured and within-patient differences (△) for V and H+V capture were calculated.

Results: A total of 23 AP+ and 45 AP- patients were evaluated. The difference in stimulus to earliest atrial signal in the high right atrial catheter seen with the loss of His bundle capture (△-stim-HRA) (21 ms; interquartile range [IQR]: 3 to 43 ms vs. 64 ms; IQR: 56 to 73 ms; p < 0.001) and difference in stimulus to earliest atrial signal in the proximal coronary sinus catheter seen with the loss of His Bundle capture (△-stim-PCS) (11 ms; IQR: 0 to 30 ms vs. 61 ms; IQR: 52 to 72 ms; p < 0.001) were shorter in AP+ patients. The shortest △-stim-PCS and △-stim-HRA in AP- patients were 37 ms and 32 ms, respectively, whereas the longest corresponding intervals in AP+ patients were 51 ms and 75 ms, respectively.

Conclusions: A △-stim-PCS <37 ms or △-stim-HRA <32 ms confirmed the presence of a septal AP, whereas a value >51 ms for △-stim-PCS or >75 ms for △-stim-HRA excluded it. Alternatively, the minimum △-stim-PCS with loss of His capture compatible with AV nodal conduction in isolation was 37 ms, and a △-stim-PCS >51 ms effectively ruled out the presence of a septal AP.
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http://dx.doi.org/10.1016/j.jacep.2020.05.012DOI Listing
October 2020

A simple maneuver to determine if septal accessory pathway ablation requires a left atrial approach.

J Cardiovasc Electrophysiol 2020 12 24;31(12):3207-3214. Epub 2020 Sep 24.

Division of Cardiology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

Introduction: Septal accessory pathway (AP) ablation can be challenging due to the complex anatomy of the septal region. The decision to access the left atrium (LA) is often made after failure of ablation from the right. We sought to establish whether the difference between ventriculo-atrial (VA) time during right ventricular (RV) apical pacing versus the VA during tachycardia would help establish the successful site for ablation of septal APs.

Methods: Intracardiac electrograms of patients with orthodromic reciprocating tachycardia (ORT) using a septal AP with successful catheter ablation were reviewed. The ∆VA was the difference between the VA interval during RV apical pacing and the VA interval during ORT. The difference in the VA interval during right ventricular entrainment and ORT (StimA-VA) was also measured.

Results: The median ∆VA time was significantly less in patients with a septal AP ablated on the right side compared with patients with a septal AP ablated on the left side (12 ± 19 vs. 56 ± 10 ms, p < .001). The StimA-VA was significantly different between the two groups (22 ± 14 vs. 53 ± 9 ms, p < .001). The ∆VA and StimA-VA were always 40 ms in patients with non-decremental septal APs ablated from the right side and always greater than 40 ms in those with septal APs ablated from the left.

Conclusion: ΔVA and StimA-VA values identified with RV apical pacing in the setting of ORT involving a septal AP predict when left atrial access will be necessary for successful ablation.
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http://dx.doi.org/10.1111/jce.14745DOI Listing
December 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

Eliminating the effects of motion during radiofrequency lesion delivery using a novel contact-force controller.

J Cardiovasc Electrophysiol 2019 09 7;30(9):1652-1662. Epub 2019 Aug 7.

Robarts Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada.

Introduction: Catheter-tissue contact force is a determinant of radiofrequency (RF) ablation lesion effectiveness. However, ablation on a beating heart is subject to force variability, making it difficult to optimally deliver consistently durable and transmural lesions. This work evaluates improvements in contact force stability and lesion reproducibility by using a catheter contact-force controller (CFC) during lesion delivery in vitro and in vivo.

Methods And Results: Using a sheath and force-sensing catheter, an experienced operator attempted to maintain a constant force of 20 g at targets within the atria and left ventricle of a pig manually and using the CFC; the average force and contact-force variation (CFV) achieved using each approach were compared. Ablation lesions (20 W, 30 seconds, 17 mL/min irrigation) were created in bovine tissue samples mounted on a platform programmed to reproduce clinically relevant motion. CFC-assisted lesions were delivered to stationary and moving tissue with forces of 5 to 35  g. Mimicking manual intervention, lesions were also delivered to moving tissue while the CFC was disabled. Resultant lesion volumes were compared using two-way analysis of variance. When using the CFC, the average force was within 1 g of the set level, with a CFV less than 5 g, during both in vitro and in vivo experiments. Reproducible and statistically identical (P = .82) lesion volumes proportional to the set force were achieved in both stationary and moving tissue when the CFC was used.

Conclusions: CFC assistance maintains constant force in vivo and removes effect of motion on lesion volume during RF lesion delivery.
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http://dx.doi.org/10.1111/jce.14093DOI Listing
September 2019

Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy.

J Clin Invest 2019 07 2;129(8):3171-3184. Epub 2019 Jul 2.

Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Arrhythmogenic cardiomyopathy (ACM) is an inherited arrhythmia syndrome characterized by severe structural and electrical cardiac phenotypes, including myocardial fibrofatty replacement and sudden cardiac death. Clinical management of ACM is largely palliative, owing to an absence of therapies that target its underlying pathophysiology, which stems partially from our limited insight into the condition. Following identification of deceased ACM probands possessing ANK2 rare variants and evidence of ankyrin-B loss of function on cardiac tissue analysis, an ANK2 mouse model was found to develop dramatic structural abnormalities reflective of human ACM, including biventricular dilation, reduced ejection fraction, cardiac fibrosis, and premature death. Desmosomal structure and function appeared preserved in diseased human and murine specimens in the presence of markedly abnormal β-catenin expression and patterning, leading to identification of a previously unknown interaction between ankyrin-B and β-catenin. A pharmacological activator of the WNT/β-catenin pathway, SB-216763, successfully prevented and partially reversed the murine ACM phenotypes. Our findings introduce what we believe to be a new pathway for ACM, a role of ankyrin-B in cardiac structure and signaling, a molecular link between ankyrin-B and β-catenin, and evidence for targeted activation of the WNT/β-catenin pathway as a potential treatment for this disease.
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http://dx.doi.org/10.1172/JCI125538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668697PMC
July 2019

Atrial Fibrillation and Heart Failure: Untangling a Modern Gordian Knot.

Can J Cardiol 2018 11 20;34(11):1437-1448. Epub 2018 Aug 20.

London Heart Rhythm Program, Western University, London, Ontario, Canada.

Heart failure (HF) and atrial fibrillation (AF) share common risk factors and frequently coexist. Both are highly prevalent in our aging population, and mortality associated with the combination is significantly higher than for each alone. An intricate link exists between AF and HF, including interrelated mechanisms and pathophysiology. Asymptomatic left ventricular systolic or diastolic dysfunction can exacerbate or be exacerbated by AF, resulting in HF with reduced ejection fraction or preserved ejection fraction. A number of treatment strategies have improved symptoms, exercise tolerance, and quality of life for patients with HF, but few have resulted in alteration in prognosis. Sinus rhythm, achieved pharmacologically, has not altered important outcomes, including cardiovascular or total mortality in patients with HF. In recent studies, catheter ablation to achieve sinus rhythm seems to have a significant impact on symptoms, heart function, and possibly mortality. Until future studies can confirm or clarify the impact of catheter ablation on outcomes, the field remains cautious but optimistic that better treatment strategies for patients with HF with reduced ejection fraction or preserved ejection fraction are within reach.
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http://dx.doi.org/10.1016/j.cjca.2018.07.483DOI Listing
November 2018

Elevated Incidence of Atrial Fibrillation and Stroke in Patients With Atrial Flutter-A Population-Based Study.

Can J Cardiol 2018 06 6;34(6):774-783. Epub 2018 Jan 6.

Institute for Clinical Evaluative Sciences, Western University, London, Ontario, Canada.

Background: The risk of stroke from atrial flutter and its relationship with progression to atrial fibrillation (AF) is unclear. This study describes the incidence of AF and stroke in patients with atrial flutter, and whether atrial flutter ablation attenuates the incidence of AF and stroke.

Methods: We performed a population-based retrospective cohort study of adults with typical atrial flutter with no AF history. Using linked health administrative databases we defined 3 cohorts: (1) adult patients diagnosed with new isolated atrial flutter; (2) a contemporary, 1-to-1 matched cohort from the Ontario population; and (3) patients with isolated atrial flutter who underwent atrial flutter ablation.

Results: A total of 9339 new typical atrial flutter patients were identified and 7248 were matched to general population subjects. Over the 3-year follow-up, AF occurred in 40.4% of patients with atrial flutter, and 3.3% of the matched general population (rate ratio, 12.2; P < 0.001). Stroke occurred in 4.1% of patients with atrial flutter and 1.2% of the general population cohort (rate ratio, 3.4; P < 0.001). Among 218 patients who had an atrial flutter ablation, AF occurred in 47 (21.6%) over the following 3 years, and incidence of stroke was between 0 and 2.3%.

Conclusions: Patients with isolated atrial flutter develop AF and stroke at a higher rate than the general population. Catheter ablation reduces but does not eliminate future AF incidence and stroke risk and continued anticoagulation after successful atrial flutter ablation might therefore be warranted.
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http://dx.doi.org/10.1016/j.cjca.2018.01.001DOI Listing
June 2018

Measuring the Impact of Guideline Concordance: The More Things Change, the More They Stay the Same.

Circ Arrhythm Electrophysiol 2017 11;10(11)

From the London Heart Rhythm Program, Division of Cardiology, Department of Medicine, Western University, London, Ontario, Canada.

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http://dx.doi.org/10.1161/CIRCEP.117.005838DOI Listing
November 2017

Interpatient Variation in Rivaroxaban and Apixaban Plasma Concentrations in Routine Care.

Can J Cardiol 2017 08 24;33(8):1036-1043. Epub 2017 Apr 24.

Division of Clinical Pharmacology, Department of Medicine, London Health Sciences Centre, Western University, London, Ontario, Canada; Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. Electronic address:

Background: Direct-acting oral anticoagulants (DOACs) are widely prescribed for stroke prevention in patients with atrial fibrillation (AF). An important advantage of DOACs is that routine monitoring of an anticoagulation response is not necessary. Nevertheless, because of their mechanism of action, a DOAC anticoagulation effect can be inferred based on the observed plasma concentration. However, there is a paucity of data relating to observed interpatient variation in DOAC plasma concentrations in the postmarket clinical setting.

Methods: We determined rivaroxaban and apixaban plasma concentrations in patients with AF during routine clinic visits.

Results: Among 243 patients (rivaroxaban, n = 94; apixaban, n = 149) enrolled in this study, a 60- and 50-fold interpatient variation in plasma concentration was observed for rivaroxaban and apixaban, respectively. Approximately 12% of patients receiving rivaroxaban and 13% of patients receiving apixaban exceeded the 95th percentile for predicted maximum plasma concentration observed in clinical trials.

Conclusions: In this routine-care setting, rivaroxaban and apixaban plasma concentrations tended to be more variable than those observed in clinical trials. Identification of additional clinical and molecular determinants that more fully predict patients at risk for excessively high or low DOAC concentrations may enable a more precise DOAC dosing regimen for the individual patient.
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http://dx.doi.org/10.1016/j.cjca.2017.04.008DOI Listing
August 2017

Ventricular pacing site separation by cardiac computed tomography: validation for the prediction of clinical response to cardiac resynchronization therapy.

Int J Cardiovasc Imaging 2017 Sep 29;33(9):1433-1442. Epub 2017 Mar 29.

Stephenson Cardiac Imaging Centre, Libin Cardiovascular Institute, Calgary, AB, Canada.

Cardiac Resynchronization Therapy (CRT) fails to provide benefit in up to one-third of patients. Maximizing the geographic separation of right and left ventricular pacing lead sites has been suggested as one way to improve response. Cardiac CT provides an opportunity to explore 3-dimensional inter-lead distance (ILD) measures for the prediction of CRT response. The objective of this study was to investigate associations between standardized measures of ILD by cardiac CT and echocardiographic response to CRT. Forty-two consecutive patients undergoing CRT had serial clinical and echocardiographic evaluations performed in addition to a post-procedural cardiac-gated CT with blinded measurement of direct and circumferential (via the myocardium) ILD measures. Clinical response to CRT, the primary clinical outcome, was defined as a ≥15% reduction in LVESV using echocardiography at 6-months. The mean age and ejection fraction was 63.6 ± 8.9 years and 25.2 ± 7.8%, respectively. The primary outcome occurred in 35 of 42 patients (83%). Both direct and circumferential CT-based ILD measures were associated with the primary outcome by univariate analysis. Receiver Operator Characteristic analysis identified Circumferential ILD to have the strongest predictive accuracy (AUC 0.78). Inter- and intra-observer reproducibility of CT-derived ILD measures was excellent. Circumferential ILD measures on cardiac CT are predictive of clinical response to CRT. Incorporation of these measures into the selection of optimal pacing targets, particularly from pre-procedural CT coronary vein imaging may be of therapeutic benefit and warrants further investigation.
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http://dx.doi.org/10.1007/s10554-017-1120-4DOI Listing
September 2017

Design and Evaluation of a Catheter Contact-Force Controller for Cardiac Ablation Therapy.

IEEE Trans Biomed Eng 2016 11 4;63(11):2301-2307. Epub 2016 Feb 4.

Goal: Maintaining a constant contact force (CF) of an ablation catheter during cardiac catheter ablation therapy is clinically challenging due to inherent myocardial motion, often resulting in poor ablation of arrhythmogenic substrates. To enable a prescribed contact force to be applied during ablation, a catheter contact force controller (CCFC) was developed.

Methods: The system includes a hand-held device attached to a commercial catheter and steerable sheath. A compact linear motor assembly attaches to an ablation catheter and autonomously controls its relative position within the shaft of the steerable sheath. A closed-loop control system is implemented within embedded electronics to enable real-time catheter-tissue contact force control. To evaluate the performance of the CCFC, a linear motion phantom was used to impose a series of physiological CF profiles; lesion CF was controlled at prescribed levels ranging from 15 to 40 g.

Results: For a prescribed CF of 25 g, the CCFC was able to regulate the CF with a root mean squared error of 3.7 ± 0.7 g. The ability of the CCFC to retract the catheter upon sudden changes in tissue motion, which may have caused tissue damage, was also demonstrated. Finally, the device was able to regulate the CF for a predetermined amount of time according to a force-time integral model.

Conclusion: The developed CCFC is capable of regulating catheter-tissue CF in a laboratory setting that mimics clinical ablation therapy.

Significance: Catheter-tissue CF control promises to improve the precision and success of ablation lesion delivery.
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http://dx.doi.org/10.1109/TBME.2016.2525929DOI Listing
November 2016

Effect of Left Atrial Wall Thickness on Radiofrequency Ablation Success.

J Cardiovasc Electrophysiol 2016 Nov 16;27(11):1298-1303. Epub 2016 Sep 16.

Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada.

Introduction: Radiofrequency (RF) ablation in thicker regions of the left atrium (LA) may require increased ablation energy in order to achieve effective transmural lesions. Consequently, many cases of recurrent atrial fibrillation (AF) postablation may be due to thicker-than-normal atrial tissue. The aim of this study was to test the hypotheses that patients with recurrent AF have thicker tissue overall and that electrical reconnection is more likely in regions of thicker tissue.

Methods And Results: Retrospective analysis was performed on 86 CT images acquired preoperatively from a cohort of 119 patients who had undergone RF ablation for AF. Of these, 33 patients experienced recurrence of AF within 1 year of initial treatment and 29 returned for a repeat ablation. For each patient, LA wall thickness (LAWT) was measured from the images in 12 anatomical regions using custom software. Patients with recurrent AF had larger LAWT compared to successfully treated patients (1.6 ± 0.6 mm vs. 1.5 ± 0.5 mm, P < 0.001) and reconnection was found to be at regions of thicker tissue (1.6 ± 0.6 mm, P = 0.038) compared to nonreconnected regions (1.5 ± 0.5 mm). The superior right posterior wall of the LA was significantly related to both recurrence (P = 0.048) and reconnection (P = 0.014).

Conclusion: Increased LAWT has a small but significant effect on postablation recurrence and reconnection. Measures of LAWT may facilitate appropriate dosing of RF energy, but other factors will be critical in transmural lesion formation and ablation success.
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http://dx.doi.org/10.1111/jce.13065DOI Listing
November 2016

Aerobic Fitness and Risk of Ventricular Arrhythmia Following Physical Exertion.

Can J Cardiol 2016 Apr 28;32(4):533-8. Epub 2015 Dec 28.

Department of Epidemiology and Biostatistics, Schulich Medicine and Dentistry, Western University, London, Ontario, Canada; Division of Cardiology, Western University, London, Ontario, Canada. Electronic address:

Background: Brief episodes of physical exertion are associated with an immediately greater risk of cardiovascular events. Previous studies on the risk of ventricular arrhythmia (VA) shortly after exertion have not assessed if this risk differs according to the level of aerobic fitness or sedentary behaviour. Therefore, we conducted a prospective cohort study of patients with implantable cardioverter-defibrillators (ICDs) with a nested case-crossover analysis to examine the risk of VA shortly after exertion and whether this risk is modified by aerobic fitness and sedentary behaviour.

Methods: Ninety-seven consecutive patients were recruited at the time of ICD implantation and 30 confirmed events occurred among patients who completed interviews about physical exertion preceding ICD therapy. We compared the frequency of exertion within an hour of ICD discharge to each patient's usual frequency of exertion reported at the time of ICD implantation.

Results: Within an hour of episodes of exertion, the risk of VA was 5.3 (95% confidence interval [CI], 2.7-10.6) times greater compared with periods of rest. The association was higher among patients with aerobic fitness below the median (relative risk [RR] = 17.5; 95% CI, 5.2-58.5) than for patients with aerobic fitness above the median (RR, 1.2; 95% CI, 0.4-4.2; P homogeneity = 0.002) and higher among patients who were sedentary (RR, 52.8; 95% CI, 10.1-277) compared with individuals who were not sedentary (RR, 3.2; 95% CI, 1.3-7.6; P homogeneity = 0.0002).

Conclusions: Within 1 hour of episodes of exertion, there is an increased risk of VA, especially among individuals with lower levels of aerobic fitness and with sedentary behaviour.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087593PMC
http://dx.doi.org/10.1016/j.cjca.2015.12.026DOI Listing
April 2016

Atrial flutter and atrial fibrillation ablation - sequential or combined? A cost-benefit and risk analysis of primary prevention pulmonary vein ablation.

Heart Rhythm 2016 07 2;13(7):1441-8. Epub 2016 Mar 2.

Arrhythmia Service, University Hospital, Western University, London, Canada.

Background: Recent studies have tested the hypothesis that preventive pulmonary vein isolation (PVI) at time of atrial flutter ablation in patients who have not had atrial fibrillation (AF) will reduce future incidence of AF.

Objective: To model relative procedural costs, risks, and benefits of sequential versus combined ablation strategies.

Methods: The decision model compares a sequential ablation strategy of atrial flutter ablation, followed by future PVI if necessary, with an initial combined flutter and preventive PVI ablation strategy. Assumptions are AF incidence 20% per year, PVI success rate 70%, PVI complication rate 4%, atrial flutter complication rate 1%, and costs $13,056 for PVI and $8,466 for atrial flutter ablation.

Results: The sequential ablation strategy is less expensive, at 1.4 vs 1.6 expected flutter ablation equivalents (FAE) ($11,852 vs $13,545) per patient, and entails less average risk, at 2% vs 4%. A combined ablation strategy is more expensive if the relative cost of PVI is more than 24.6% higher than atrial flutter ablation. A combined ablation strategy has higher total risk if PVI procedural risk is 24.6% more than atrial flutter ablation.

Conclusions: Under base case assumptions of relative cost of PVI to flutter ablation 1.5 and relative risk 4, a sequential ablation approach has less total expected cost and less expected risk. There appears to be no compelling reason to adopt a combined ablation approach into standard practice. Nomograms are presented to allow the reader to assess which strategy is preferred according to local relative costs and risk.
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http://dx.doi.org/10.1016/j.hrthm.2016.02.018DOI Listing
July 2016

Values and Preferences of Physicians and Patients With Nonvalvular Atrial Fibrillation Who Receive Oral Anticoagulation Therapy for Stroke Prevention.

Can J Cardiol 2016 06 10;32(6):747-53. Epub 2015 Nov 10.

Department of Cardiology, Memorial University of Newfoundland, St John's, Newfoundland and Labrador, Canada.

Background: Real-world data on patients' and physicians' values related to the use of oral anticoagulant (OAC) therapy for stroke prevention in patients with nonvalvular atrial fibrillation are currently lacking. We sought to assess the values, preferences, and experience of patients who receive OAC therapy, and of physicians who prescribe OAC therapy.

Methods: A national survey of randomly selected patients (n = 266) and physicians (n = 178) was conducted between May and September 2014. Each was asked to evaluate the importance of individual OAC attributes and identify which of 2 medication profiles they would prefer (individual attributes were progressively modified to determine which were the most valued and/or influenced treatment choice). Medication adherence and prescription practice was also assessed.

Results: The preferences of patients and physicians regarding OAC therapy differed but largely focused on characteristics related to safety and, to a lesser extent, efficacy. When based solely on the basis of the attribute profile (blinded to the specific agent), physicians were more likely to select apixaban (61%), whereas patients showed no significant preference among apixaban, rivaroxaban, and warfarin. Despite this, 49% of physicians spontaneously stated rivaroxaban as their preferred agent (vs 25% apixaban). Patients prescribed and taking once daily medications (rivaroxaban or warfarin) showed better compliance with their OAC therapy (approximately 30% of twice daily medications being taken once daily, with significantly more missed doses compared with once daily medications).

Conclusions: Real-world prescriptions do not reflect reported values, which suggests that other factors influence patient-physician decision-making around OAC therapy. Data on self-reported adherence to OAC therapy and discordance in the use of OACs from prescribed regimens are concerning and warrant further investigation.
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http://dx.doi.org/10.1016/j.cjca.2015.09.023DOI Listing
June 2016

Pulmonary Vein Isolation With Incomplete Antral Ablation Lines: Is More Ablation Necessary? Results of a Randomized Trial.

J Cardiovasc Electrophysiol 2016 Mar 18;27(3):298-302. Epub 2015 Dec 18.

Arrhythmia Service, University Hospital, Western University, London, Ontario, Canada.

Background: A full circumferential set of antral lesions is not always required for bidirectional pulmonary vein conduction block. It is unknown whether a partial lesion set that isolates the veins will have clinical success rates similar to a full circumferential lesion set, and if procedural times or procedural risk will be affected.

Methods: We performed a prospective, randomized clinical trial to test the hypothesis that a partial lesion set that isolates the pulmonary veins has comparable clinical success rate and shorter procedure times compared to a strategy of completing the circumferential lesion set once the veins are isolated.

Results: A total of 119 patients were enrolled, 59 randomized to circumferential ablation, and 60 to segmental. Mean age was 58.3 ± 10.1, 77% male. Mean procedure time was 221.0 ± 46.9 minutes in circumferential and 224.7 ± 51.3 in segmental (P = 0.68). Twelve-month freedom from AF recurrence was 61.3% overall, 64.4% in circumferential, and 58.3% in segmental (P = 0.50). Among 25 segmental patients with AF recurrence, 23 underwent second ablation. Among 33 areas of conduction recovery, 23 (70%) occurred in segments ablated at first procedure and 10 (30%) in segments not previously ablated, suggesting reversible conduction block from edema.

Conclusion: No difference in AF recurrence or procedure time is detectable in a sample of 119 patients randomized to segmental or circumferential antral ablation to achieve pulmonary vein isolation. Second ablation procedures confirmed that some antral sites do not require ablation. A segmental approach results in unacceptably high rates of untargeted or recovered antral sites to make this approach feasible.
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http://dx.doi.org/10.1111/jce.12876DOI Listing
March 2016

Design, development and evaluation of a compact telerobotic catheter navigation system.

Int J Med Robot 2016 Sep 3;12(3):442-52. Epub 2015 Nov 3.

Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.

Background: Remote catheter navigation systems protect interventionalists from scattered ionizing radiation. However, these systems typically require specialized catheters and extensive operator training.

Methods: A new compact and sterilizable telerobotic system is described, which allows remote navigation of conventional tip-steerable catheters, with three degrees of freedom, using an interface that takes advantage of the interventionalist's existing dexterity skills. The performance of the system is evaluated ex vivo and in vivo for remote catheter navigation and ablation delivery.

Results: The system has absolute errors of 0.1 ± 0.1 mm and 7 ± 6° over 100 mm of axial motion and 360° of catheter rotation, respectively. In vivo experiments proved the safety of the proposed telerobotic system and demonstrated the feasibility of remote navigation and delivery of ablation.

Conclusion: The proposed telerobotic system allows the interventionalist to use conventional steerable catheters; while maintaining a safe distance from the radiation source, he/she can remotely navigate the catheter and deliver ablation lesions. Copyright © 2015 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/rcs.1711DOI Listing
September 2016

Electrophysiology testing and catheter ablation are helpful when evaluating asymptomatic patients with Wolff-Parkinson-White pattern: the con perspective.

Card Electrophysiol Clin 2015 Sep 7;7(3):377-83. Epub 2015 Jul 7.

Arrhythmia Services, University Hospital, Western University, 339 Windermere Road, London, Ontario N6A 5A5, Canada.

The association between asymptomatic Wolff-Parkinson-White (WPW) syndrome and sudden cardiac death (SCD) has been well documented. The inherent properties of the accessory pathway determine the risk of SCD in WPW, and catheter ablation essentially eliminates this risk. An approach to WPW syndrome is needed that incorporates the patient's individualized considerations into the decision making. Patients must understand that there is a trade-off of a small immediate risk of an invasive approach for elimination of a small lifetime risk of the natural history of asymptomatic WPW. Clinicians can minimize the invasive risk by only performing ablation for patients with at-risk pathways.
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http://dx.doi.org/10.1016/j.ccep.2015.05.002DOI Listing
September 2015

Finding the optimal ablation site in ventricular tachycardia through a single electrogram: Is it too good to be true?

Heart Rhythm 2015 Aug 29;12(8):1745-6. Epub 2015 May 29.

Arrhythmia Service, Division of Cardiology, Schulich School of Medicine, Western University, London, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2015.05.033DOI Listing
August 2015

A detailed description and assessment of outcomes of patients with hospital recorded QTc prolongation.

Am J Cardiol 2015 Apr 15;115(7):907-11. Epub 2015 Jan 15.

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

Corrected QT (QTc) interval prolongation has been shown to be an independent predictor of mortality in many clinical settings and is a common finding in hospitalized patients. The causes and outcomes of patients with extreme QTc interval prolongation during a hospital admission are poorly described. The aim of this study was to prospectively identify patients with automated readings of QTc intervals >550 ms at 1 academic tertiary hospital. One hundred seventy-two patients with dramatic QTc interval prolongation (574 ± 53 ms) were identified (mean age 67.6 ± 15.1 years, 48% women). Most patients had underlying heart disease (60%), predominantly ischemic cardiomyopathy (43%). At lease 1 credible and presumed reversible cause associated with QTc interval prolongation was identified in 98% of patients. The most common culprits were QTc interval-prolonging medications, which were deemed most responsible in 48% of patients, with 25% of these patients taking ≥2 offending drugs. Two patients were diagnosed with congenital long-QT syndrome. Patients with electrocardiograms available before and after hospital admission demonstrated significantly lower preadmission and postdischarge QTc intervals compared with the QTc intervals recorded in the hospital. In conclusion, in-hospital mortality was high in the study population (29%), with only 4% of patients experiencing arrhythmic deaths, all of which were attributed to secondary causes.
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http://dx.doi.org/10.1016/j.amjcard.2015.01.016DOI Listing
April 2015

Postoperative atrial fibrillation is not pulmonary vein dependent: results from a randomized trial.

Heart Rhythm 2015 Apr 13;12(4):699-705. Epub 2015 Jan 13.

Medicine, Western University, London Health Sciences Centre, University Hospital, Ivey Cardiac Centre, London, Ontario, Canada.

Background: Although often short-lived and self-limiting, postoperative atrial fibrillation (POAF) is a well-recognized postoperative complication of cardiac surgery and is associated with a 2-fold increase in cardiovascular mortality and morbidity.

Objective: Our aim was to determine whether intraoperative bilateral pulmonary vein radiofrequency ablation decreases the incidence of POAF in patients undergoing coronary artery bypass grafting (CABG).

Methods: A total of 175 patients undergoing CABG was prospectively randomized to undergo adjuvant bilateral radiofrequency pulmonary vein ablation in addition to CABG (group A; n = 89) or CABG alone (group B; n = 86). Intraoperative pulmonary vein isolation was confirmed by the inability to pace the heart via the pulmonary veins after ablation. All patients received postoperative β-blocker.

Results: There was no difference in the incidence of POAF in the treatment group who underwent adjuvant pulmonary vein ablation (group A; 37.1%) compared with the control group who did not (group B; 36.1%) (P = .887). There were no differences in postoperative inotropic support, antiarrhythmic drug use, need for oral anticoagulation, and complication rates. The mean length of postoperative hospital stay was 8.2 ± 6.5 days in the ablation group and 6.7 ± 4.6 days in the control group (P < .001).

Conclusion: Adjuvant pulmonary vein isolation does not decrease the incidence of POAF or its clinical impact but increases the mean length of stay in the hospital. The mechanism of POAF does not appear to depend on the pulmonary veins.
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http://dx.doi.org/10.1016/j.hrthm.2015.01.014DOI Listing
April 2015

Modeling and estimation of tip contact force for steerable ablation catheters.

IEEE Trans Biomed Eng 2015 May 9;62(5):1404-15. Epub 2015 Jan 9.

Objective: The efficacy of catheter-based cardiac ablation procedures can be significantly improved if real-time information is available concerning contact forces between the catheter tip and cardiac tissue. However, the widely used ablation catheters are not equipped for force sensing. This paper proposes a technique for estimating the contact forces without direct force measurements by studying the changes in the shape of the deflectable distal section of a conventional 7-Fr catheter (henceforth called the "deflectable distal shaft," the "deflectable shaft," or the "shaft" of the catheter) in different loading situations.

Method: First, the shaft curvature when the tip is moving in free space is studied and based on that, a kinematic model for the deflectable shaft in free space is proposed. In the next step, the shaft shape is analyzed in the case where the tip is in contact with the environment, and it is shown that the curvature of the deflectable shaft provides useful information about the loading status of the catheter and can be used to define an index for determining the range of contact forces exerted by the ablation tip.

Results: Experiments with two different steerable ablation catheters show that the defined index can detect the range of applied contact forces correctly in more than 80% of the cases. Based on the proposed technique, a framework for obtaining contact force information by using the shaft curvature at a limited number of points along the deflectable shaft is constructed.

Conclusion: The proposed kinematic model and the force estimation technique can be implemented together to describe the catheter's behavior before contact, detect tip/tissue contact, and determine the range of contact forces.

Significance: This study proves that the flexibility of the catheter's distal shaft provides a means of estimating the force exerted on tissue by the ablation tip.
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http://dx.doi.org/10.1109/TBME.2015.2389615DOI Listing
May 2015