Publications by authors named "Julia Cadrin-Tourigny"

40 Publications

International Evidence Based Reappraisal of Genes Associated With Arrhythmogenic Right Ventricular Cardiomyopathy Using the Clinical Genome Resource Framework.

Circ Genom Precis Med 2021 Jun 8;14(3):e003273. Epub 2021 Apr 8.

Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, the Netherlands (R.L.D., J.P.v.T.).

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by ventricular arrhythmias and progressive ventricular dysfunction. Genetic testing is recommended, and a pathogenic variant in an ARVC-associated gene is a major criterion for diagnosis according to the 2010 Task Force Criteria. As incorrect attribution of a gene to ARVC can contribute to misdiagnosis, we assembled an international multidisciplinary ARVC Clinical Genome Resource Gene Curation Expert Panel to reappraise all reported ARVC genes.

Methods: Following a comprehensive literature search, six 2-member teams conducted blinded independent curation of reported ARVC genes using the semiquantitative Clinical Genome Resource framework.

Results: Of 26 reported ARVC genes, only 6 (, , , , , and ) had strong evidence and were classified as definitive for ARVC causation. There was moderate evidence for 2 genes, and . The remaining 18 genes had limited or no evidence. was refuted as an ARVC gene since clinical data and model systems exhibited a catecholaminergic polymorphic ventricular tachycardia phenotype. In ClinVar, only 5 pathogenic/likely pathogenic variants (1.1%) in limited evidence genes had been reported in ARVC cases in contrast to 450 desmosome gene variants (97.4%).

Conclusions: Using the Clinical Genome Resource approach to gene-disease curation, only 8 genes (, , , , , , , and ) had definitive or moderate evidence for ARVC, and these genes accounted for nearly all pathogenic/likely pathogenic ARVC variants in ClinVar. Therefore, only pathogenic/likely pathogenic variants in these 8 genes should yield a major criterion for ARVC diagnosis. Pathogenic/likely pathogenic variants identified in other genes in a patient should prompt further phenotyping as variants in many of these genes are associated with other cardiovascular conditions.
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http://dx.doi.org/10.1161/CIRCGEN.120.003273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205996PMC
June 2021

Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect.

Nat Genet 2021 02 25;53(2):128-134. Epub 2021 Jan 25.

Department of Epidemiology and Biostatistics, Imperial College London, London, UK.

The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young, otherwise healthy, individuals. We conducted genome-wide association studies and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases) and nine left ventricular (LV) traits (19,260 UK Biobank participants with structurally normal hearts). We identified 16 loci associated with HCM, 13 with DCM and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased LV contractility with HCM risk. A polygenic risk score explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that polygenic risk score may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects.
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http://dx.doi.org/10.1038/s41588-020-00762-2DOI Listing
February 2021

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

Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Collaboration.

Circ Arrhythm Electrophysiol 2021 01 9;14(1):e008509. Epub 2020 Dec 9.

Department of Medicine, Division of Cardiology (J.C.-T., W.W., A.B., C.T., B.M., S.C., J.E.C., D.P.J., H.T., H.C., C.A.J.), Johns Hopkins Hospital, Baltimore, MD.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD.

Methods: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping.

Results: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism.

Conclusions: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.
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http://dx.doi.org/10.1161/CIRCEP.120.008509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834666PMC
January 2021

Pulmonary Vein Stenosis After Atrial Fibrillation Ablation: Insights From the ADVICE Trial.

Can J Cardiol 2020 12 3;36(12):1965-1974. Epub 2020 Nov 3.

Montreal Health Innovations Coordinating Center (MHICC), Montreal, Quebec, Canada.

Background: Pulmonary vein (PV) stenosis is a complication of atrial fibrillation (AF) ablation. The incidence of PV stenosis after routine post-ablation imaging remains unclear and is limited to single-centre studies. Our objective was to determine the incidence and predictors of PV stenosis following circumferential radiofrequency ablation in the multicentre Adenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination (ADVICE) trial.

Methods: Patients with symptomatic AF underwent circumferential radiofrequency ablation in one of 13 trial centres. Computed tomographic (CTA) or magnetic resonance (MRA) angiography was performed before ablation and 90 days after ablation. Two blinded reviewers measured PV diameters and areas. PVs with stenosis were classified as severe (> 70%), moderate (50%-70%), or mild (< 50%). Predictors of PV stenosis were identified by means of multivariable logistic regression.

Results: A total of 197 patients (median age 59.5 years, 29.4% women) were included in this substudy. PV stenosis was identified in 41 patients (20.8%) and 47 (8.2%) of 573 ablated PVs. PV stenosis was classified as mild in 42 PVs (7.3%) and moderate in 5 PVs (0.9%). No PVs had severe stenosis. Both cross-sectional area and diameter yielded similar classifications for severity of PV stenosis. Diabetes was associated with a statistically significant increased risk of PV stenosis (OR 4.91, 95% CI 1.45-16.66).

Conclusions: In the first systematic multicentre evaluation of post-ablation PV stenosis, no patient acquired severe PV stenosis. Although the results are encouraging for the safety of AF ablation, 20.8% of patients had mild or moderate PV stenosis, in which the long-term effects are unknown.
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http://dx.doi.org/10.1016/j.cjca.2020.10.013DOI Listing
December 2020

Keeping balance: Author's reply.

Europace 2021 Jan;23(1):157-158

Division of Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, 34 Utrecht University, Utrecht, the Netherlands.

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http://dx.doi.org/10.1093/europace/euaa259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842099PMC
January 2021

Missense variants in the spectrin repeat domain of DSP are associated with arrhythmogenic cardiomyopathy: A family report and systematic review.

Am J Med Genet A 2020 10 18;182(10):2359-2368. Epub 2020 Aug 18.

Cardiovascular Genetics Center, Montreal Heart Institute and Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.

Rare loss of function variants in DSP, which codes for the desmosomal protein desmoplakin, have been implicated in dilated and arrhythmogenic right ventricular cardiomyopathies. We present a family with arrhythmogenic cardiomyopathy associated with a novel missense variant in DSP (NM_004415.4): c.877G>A, p.(Glu293Lys). The phenotype is characterized by predominant involvement of the left ventricle with systolic dysfunction, fibrosis, and life-threatening arrhythmias. We performed a systematic review of literature collecting all cardiomyopathy cases with rare missense variants in DSP. We demonstrate that the distribution of missense variants across the protein domains in cardiomyopathy cases differs from that in gnomAD (p = .04), with a case enrichment of rare missense variants in the spectrin repeat domain (36/78 [46%] in cases vs. 449/1495 [30%] in gnomAD; p = .004). Our findings highlight the predominance of cardiac arrhythmia and left ventricular involvement in desmoplakin cardiomyopathy and pinpoint to a potential mutation hotspot in DSP thereby facilitating missense variant interpretation in the diagnostic setting.
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http://dx.doi.org/10.1002/ajmg.a.61799DOI Listing
October 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

Exercise restriction is protective for genotype-positive family members of arrhythmogenic right ventricular cardiomyopathy patients.

Europace 2020 08;22(8):1270-1278

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

Aims: In arrhythmogenic right ventricular cardiomyopathy (ARVC) patients, exercise worsens disease course, so exercise restriction is recommended. However, recommendations for genotype-positive ARVC family members is incompletely resolved. We aimed to provide evidence for exercise recommendations for genotype-positive ARVC family members.

Methods And Results: Arrhythmogenic right ventricular cardiomyopathy family members inheriting a pathogenic desmosomal variant were interviewed about exercise history from age 10. Exercise was characterized by duration, intensity, and dose (duration*intensity). Associations between exercise and (i) diagnosis by 2010 Task Force Criteria and (ii) development of sustained ventricular arrhythmias were examined. The study included 101 family members (age: 40.5 ± 19.3 years, male: 41%, Plakophilin-2 variant: 81%). Forty-four individuals (44%) met diagnostic criteria and 16 (16%) experienced sustained ventricular arrhythmia. Individuals who met diagnostic criteria had significantly higher average exercise duration and dose, but not peak intensity than those who did not. Only one individual who exercised below the American Heart Association recommended minimum (650 metabolic equivalent of task-hours/year) met diagnostic criteria or experienced sustained ventricular arrhythmia as opposed to 50% of individuals who exceeded it (adjusted odds ratio = 0.03, 95% confidence interval 0.003-0.26). The difference in exercise exposure between affected and unaffected individuals was more striking in females than in males. Females who had done high-dose exercise in adolescence had the worst survival free from diagnosis (P < 0.01).

Conclusions: In phenotype-negative ARVC family members with a pathogenic desmosomal variant, athletic activities should be limited, particularly exercise dose. Exercise may play a greater role in promoting disease in female family members.
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http://dx.doi.org/10.1093/europace/euaa105DOI Listing
August 2020

Infections Associated with Resterilized Pacemakers and Defibrillators.

N Engl J Med 2020 05;382(19):1823-1831

From the Montreal Heart Institute, Université de Montréal, Montreal (T.F.K., M.-A.L., C.V., R.C., D.R., M.T., M.D., B.T., P.G.G., L.R., K.D., B.M., R.T., J.C.-T., L.M., P.K.); Instituto Nacional de Cardiologia, Ignacio Chavez, Mexico City (S.N.); the Dominican Institute of Cardiology, Santo Domingo, Dominican Republic (F.V.B.); Clínicas Médicas las Américas, Guatemala City, Guatemala (F.S.O.); and Cardiología Hospital General del Sur, Choluteca (N.E.L.O.), and Instituto Nacional Cardiopulmonar (G.S.M.) and Medicina Interna-Programación de Marcapaso Definitivo, Instituto Nacional Cardiopulmonar, Tegucigalpa (C.A.C.) - all in Honduras.

Background: Access to pacemakers and defibrillators is problematic in places with limited resources. Resterilization and reuse of implantable cardiac devices obtained post mortem from patients in wealthier nations have been undertaken, but uncertainty around the risk of infection is a concern.

Methods: A multinational program was initiated in 1983 to provide tested and resterilized pacemakers and defibrillators to underserved nations; a prospective registry was established in 2003. Patients who received reused devices in this program were matched in a 1:3 ratio with control patients who received new devices implanted in Canada. The primary outcome was infection or device-related death, with mortality from other causes modeled as a competing risk.

Results: Resterilized devices were implanted in 1051 patients (mean [±SD] age, 63.2±18.5 years; 43.6% women) in Mexico (36.0%), the Dominican Republic (28.1%), Guatemala (26.6%), and Honduras (9.3%). Overall, 85% received pacemakers and 15% received defibrillators, with one (55.5%), two (38.8%), or three (5.7%) leads. Baseline characteristics did not differ between these patients and the 3153 matched control patients. At 2 years of follow-up, infections had occurred in 21 patients (2.0%) with reused devices and in 38 (1.2%) with new devices (hazard ratio, 1.66; 95% confidence interval, 0.97 to 2.83; P = 0.06); there were no device-related deaths. The most common implicated pathogens were and .

Conclusions: Among patients in underserved countries who received a resterilized and reused pacemaker or defibrillator, the incidence of infection or device-related death at 2 years was 2.0%, an incidence that did not differ significantly from that seen among matched control patients with new devices in Canada.
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http://dx.doi.org/10.1056/NEJMoa1813876DOI Listing
May 2020

Diagnosing arrhythmogenic right ventricular cardiomyopathy by 2010 Task Force Criteria: clinical performance and simplified practical implementation.

Europace 2020 05;22(5):787-796

Netherlands Heart Institute, Moreelsepark 1, 3511 EP Utrecht, the Netherlands.

Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is diagnosed by a complex set of clinical tests as per 2010 Task Force Criteria (TFC). Avoiding misdiagnosis is crucial to prevent sudden cardiac death as well as unnecessary implantable cardioverter-defibrillator implantations. This study aims to validate the overall performance of the TFC in a real-world cohort of patients referred for ARVC evaluation.

Methods And Results: We included patients consecutively referred to our centres for ARVC evaluation. Patients were diagnosed by consensus of three independent clinical experts. Using this as a reference standard, diagnostic performance was measured for each individual criterion as well as the overall TFC classification. Of 407 evaluated patients (age 38 ± 17 years, 51% male), the expert panel diagnosed 66 (16%) with ARVC. The clinically observed TFC was false negative in 7/66 (11%) patients and false positive in 10/69 (14%) patients. Idiopathic outflow tract ventricular tachycardia was the most common alternative diagnosis. While the TFC performed well overall (sensitivity and specificity 92%), signal-averaged electrocardiogram (SAECG, P = 0.43), and several family history criteria (P ≥ 0.17) failed to discriminate. Eliminating these criteria reduced false positives without increasing false negatives (net reclassification improvement 4.3%, P = 0.019). Furthermore, all ARVC patients met at least one electrocardiogram (ECG) or arrhythmia criterion (sensitivity 100%).

Conclusion: The TFC perform well but are complex and can lead to misdiagnosis. Simplification by eliminating SAECG and several family history criteria improves diagnostic accuracy. Arrhythmogenic right ventricular cardiomyopathy can be ruled out using ECG and arrhythmia criteria alone, hence these tests may serve as a first-line screening strategy among at-risk individuals.
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http://dx.doi.org/10.1093/europace/euaa039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203633PMC
May 2020

An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition.

Circulation 2020 02 16;141(6):429-439. Epub 2020 Jan 16.

European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (A.M., I.T., L.C., A.B., D.K., B.S., C.S., Y.D.W., S.D., A.A.M.W., E.R.B., J.T.-H., J.P.K., F.D., P.J.S., E.S.-B., S.G.P.).

Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare variants implicated in LQT5 was sought through an international multicenter collaboration.

Methods: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death.

Results: A total of 32 distinct rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, <0.001). ECG penetrance for heterozygous genotype positive family members was 20.7% (29/140). A definite arrhythmic event was experienced in 16.9% (15/89) of heterozygous probands in comparison with 1.4% (2/140) of family members (adjusted hazard ratio [HR] 11.6 [95% CI, 2.6-52.2]; =0.001). Event incidence did not differ significantly for Type 2 Jervell and Lange-Nielsen syndrome patients relative to the overall heterozygous cohort (10.5% [2/19]; HR 1.7 [95% CI, 0.3-10.8], =0.590). The cumulative prevalence of the 32 variants in the Genome Aggregation Database, which is a human database of exome and genome sequencing data from now over 140 000 individuals, was 238-fold greater than the anticipated prevalence of all LQT5 combined (0.238% vs 0.001%).

Conclusions: The present study suggests that putative/confirmed loss-of-function variants predispose to QT prolongation, however, the low ECG penetrance observed suggests they do not manifest clinically in the majority of individuals, aligning with the mild phenotype observed for Type 2 Jervell and Lange-Nielsen syndrome patients.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035205PMC
February 2020

Pharmacotherapy in inherited and acquired ventricular arrhythmia in structurally normal adult hearts.

Expert Opin Pharmacother 2019 Dec 30;20(17):2101-2114. Epub 2019 Sep 30.

Electrophysiology service, Montreal Heart Institute, Montreal, Quebec, Canada.

: Ventricular arrhythmias are often seen in association with structural heart disease. However, approximately a tenth of affected patients have apparently normal hearts, where such arrhythmias typically occur in young patients, are sometimes inherited and can occasionally lead to sudden cardiac death (SCD). Over the past two decades, increased understanding of the underlying pathophysiology resulted in improved targeted pharmacological therapy.: This article reviews current knowledge regarding drug therapy for inherited arrhythmia syndromes (Brugada, early repolarization, long QT and short QT syndromes, and catecholaminergic polymorphic ventricular tachycardia), and acquired arrhythmias (idiopathic ventricular fibrillation, short-coupled torsade de pointes, outflow tract ventricular tachycardia, idiopathic left, papillary muscle and annular ventricular tachycardias).: In inherited arrhythmia syndromes, appropriate clinical and genetic diagnoses followed by proper selection and dosing of antiarrhythmic drugs are of utmost importance to prevent SCD, most often without the need of implantable cardioverter-defibrillators. In acquired arrhythmias, appropriate pharmacotherapy in selected patients can also provide symptomatic relief and avoid the need for invasive therapy. Further research is needed to develop novel antiarrhythmic drugs or targeted therapy to increase efficacy and limit side effects.
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http://dx.doi.org/10.1080/14656566.2019.1669561DOI Listing
December 2019

Risk stratification for ventricular arrhythmias and sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy: an update.

Expert Rev Cardiovasc Ther 2019 Sep 21;17(9):645-651. Epub 2019 Aug 21.

Department of Medicine, Montreal Heart Institute , Montreal , Quebec , Canada.

: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined disease associated with a significant risk of ventricular arrhythmias and sudden cardiac death (SCD). Implantable cardioverter-defibrillators (ICDs) are the only effective preventive measure. Over the past 30 years, much effort has been invested in determining predictors of adverse arrhythmic events in these patients. : This review summarizes available evidence on risk stratification for ARVC, with an emphasis on recent research findings. While efforts are ongoing to define risk predictors, several recent publications have synthetized and built on this knowledge base. A recently published meta-analysis has clarified the strongest predictors of ventricular arrhythmias in ARVC, which vary depending on the population included. Three management guidelines/expert consensus documents have integrated the previously described risk predictors into proposed ICD recommendations. Furthermore, a risk prediction model has allowed the integration of multiple risk factors to provide individualized risk prediction and to inform shared-decision making regarding ICD implantation. : Over the past few years, knowledge of risk prediction in ARVC has been consolidated and refined. Further improvements may be made by the considering additional predictors such as exercise and by targeting more specific surrogate outcomes for SCD.
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http://dx.doi.org/10.1080/14779072.2019.1657831DOI Listing
September 2019

Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF): Methods and Design.

Can J Cardiol 2019 08 7;35(8):1069-1077. Epub 2019 May 7.

Department of Medicine, Université de Montréal, Montréal, Québec, Canada.

Background: Compelling evidence showing a link between atrial fibrillation (AF) and cognitive decline and dementia is accumulating.

Methods: Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF) is a prospective, multicentric, double-blind, randomized-controlled trial, recruiting patients with nonvalvular AF and a low risk of stroke. Patients with a high risk of bleeding will be excluded from the study. Participants will be randomized to receive either rivaroxaban (15 mg daily) or standard of care (placebo in patients without vascular disease or acetylsalicylic acid 100 mg daily in patients with vascular disease).

Results: The primary outcome is the composite of stroke, transient ischemic attack, and cognitive decline (defined by a decrease in the Montreal Cognitive Assessment score ≥ 3 at any follow-up visit after baseline). Approximately 3250 patients will be enrolled in approximately 130 clinical sites until 609 adjudicated primary outcome events have occurred.

Conclusions: BRAIN-AF determines whether oral anticoagulation therapy with rivaroxaban compared with standard of care reduces the risk of stroke, transient ischemic attack, or cognitive decline in patients with nonvalvular AF and a low risk of stroke.
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http://dx.doi.org/10.1016/j.cjca.2019.04.022DOI Listing
August 2019

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

Eur Heart J 2019 06;40(23):1850-1858

Department of Genetics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, The Netherlands.

Aims: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients.

Methods And Results: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001).

Conclusion: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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http://dx.doi.org/10.1093/eurheartj/ehz103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568197PMC
June 2019

Benefits of Multisite/Multipoint Pacing to Improve Cardiac Resynchronization Therapy Response.

Card Electrophysiol Clin 2019 03;11(1):99-114

Department of Cardiology, Montréal Heart Institute, University of Montréal, 5000 Bélanger Street, Montréal, Québec, H1T 1C8, Canada.

This article provides a general overview of the underlying mechanisms that support pacing from more discrete points and/or a wider vector (multisite and multipoint pacing) to improve left ventricular resynchronization. We performed a critical overview of the current literature and to identify some remaining knowledge gaps to spur further research. It was not our goal to provide a systematic review with a comprehensive bibliography, but rather to focus on selected publications that, in our opinion, have either expertly reviewed a specific aspect of cardiac resynchronization therapy or have been landmark studies in the field.
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http://dx.doi.org/10.1016/j.ccep.2018.11.016DOI Listing
March 2019

Subcutaneous Implantable Cardioverter-Defibrillator in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia: A Transatlantic Experience.

J Am Heart Assoc 2018 11;7(21):e008782

1 Division of Cardiology Department of Medicine Johns Hopkins Hospital Baltimore MD.

Background Despite growing use of the subcutaneous implantable cardioverter-defibrillator (S- ICD ), its clinical role in arrhythmogenic right ventricular cardiomyopathy/dysplasia ( ARVC /D) patients remains undefined. We aim to elucidate the cardiac phenotype, implant characteristics, and long-term efficacy regarding appropriate therapy and complications in ARVC /D patients with an S- ICD implant. Methods and Results A transatlantic cohort of ARVC /D patients who underwent S- ICD implantation was analyzed for clinical characteristics, S- ICD therapy, and long-term outcome including device-related complications. The cohort included 29 patients (52% male, 76% probands, 59% with ARVC /D-associated mutation, 59% primary prevention [no prior sustained ventricular arrhythmias], and 45% first-generation S- ICD devices). At implant, all inducible patients (27/29) had conversion of induced ventricular fibrillation. Two patients (7%) had superficial infections of the incision site that were treated conservatively. Over a median follow-up of 3.16 years (interquartile range: 2.21-4.51 years), all episodes (6 patients, 4% per year) of sustained ventricular arrhythmias were appropriately detected and treated. Six patients (21%) experienced 39 inappropriate shocks, with 3 requiring device explantation. Oversensing of noncardiac signal (n=4; especially myopotentials) and cardiac signal (n=4) was the most frequent etiology. No lead or device dislodgement, infection, skin erosion, or explantation related to need for antitachycardia pacing was noted. Conclusions S- ICD can effectively treat both induced and spontaneous ventricular arrhythmias in patients with ARVC /D. The rate of inappropriate shocks, although considerable, is comparable to that in ARVC /D patients treated with transvenous ICD s. When they occurred, inappropriate shocks were primarily due to cardiac and, uniquely, noncardiac oversensing. We suggest potential strategies for minimizing inappropriate therapy.
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http://dx.doi.org/10.1161/JAHA.118.008782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404172PMC
November 2018

Atrial fibrillation in young patients.

Expert Rev Cardiovasc Ther 2018 Jul 2;16(7):489-500. Epub 2018 Jul 2.

a Electrophysiology Service , Montreal Heart Institute, Université de Montréal , Montreal , Canada.

Introduction: Atrial fibrillation (AF) is the most frequent arrhythmia worldwide. While mostly seen in elderly, it can also affect young adults (≤ 45 years of age), older adolescent, and children. Areas covered: The aim of this review is to provide an overview of the current management of AF in young patients. Specific issues arise over diagnostic workup as well as antiarrhythmic and anticoagulation therapies. The future management and diagnostic strategies are also discussed. Expert commentary: Management of AF in the young adult is largely extrapolated from adult studies and guidelines. In this population, AF could reveal a genetic pathology (e.g. Brugada, Long QT or Short QT syndromes) or be the initial presentation of a cardiomyopathy. Therefore, thorough workup in the young population to eliminate potential malignant pathology.
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http://dx.doi.org/10.1080/14779072.2018.1490644DOI Listing
July 2018

Impact of Exercise Restriction on Arrhythmic Risk Among Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

J Am Heart Assoc 2018 06 16;7(12). Epub 2018 Jun 16.

Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD.

Background: Prior studies have shown a close link between exercise and development of arrhythmogenic right ventricular cardiomyopathy. How much exercise restriction reduces ventricular arrhythmia (VA), how genotype modifies its benefit, and whether it reduces risk sufficiently to defer implantable cardioverter-defibrillator (ICD) placement in arrhythmogenic right ventricular cardiomyopathy are unknown.

Methods And Results: We interviewed 129 arrhythmogenic right ventricular cardiomyopathy patients (age: 34.0±14.8 years; male: 60%) with ICDs (36% primary prevention) about exercise participation. Exercise change was defined as annual exercise duration and dose in the 3 years before clinical presentation minus that after presentation. The primary outcome was appropriate ICD therapy for VA. During the 5.1 years (interquartile range: 2.7-10.8 years) after presentation, 74% (95/129) patients reduced exercise dose and 85 (66%) patients experienced the primary outcome. In multivariate analyses, top tertile reduction in exercise duration and dose were both associated with less VA (duration: hazard ratio: 0.23 [95% confidence interval, 0.07-0.81]; dose: hazard ratio: 0.14 [95% confidence interval, 0.04-0.44]). Greater reduction in exercise dose conferred greater reduction in VA (=0.01 for trend). Patients without desmosomal mutations and those with primary-prevention ICDs benefited more from exercise reduction (=0.16 and =0.06 for interaction); however, 58% (18/31) of athletes who reduced exercise dose by >80% still experienced VA.

Conclusions: Exercise restriction should be recommended to all arrhythmogenic right ventricular cardiomyopathy patients with ICDs. Patients who are "gene-elusive" and those with primary-prevention devices may particularly benefit. Exercise reduction is unlikely to reduce arrhythmia sufficiently in high-risk patients to alter decision-making regarding ICD implantation.
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http://dx.doi.org/10.1161/JAHA.118.008843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220537PMC
June 2018

Arrhythmic outcome of arrhythmogenic right ventricular cardiomyopathy patients without implantable defibrillators.

J Cardiovasc Electrophysiol 2018 10 27;29(10):1396-1402. Epub 2018 Jun 27.

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

Background: Implantable defibrillators (ICD) are an important therapy for arrhythmogenic right ventricular cardiomyopathy (ARVC) patients at high risk of sudden death. Given the high appropriate ICD therapy rate, some have argued that the mere act of implanting an ICD inflates the malignant arrhythmia rate in ARVC.

Objective: To report the arrhythmic course of ARVC patients without ICDs at the fulfillment of the 2010 Task Force Criteria and explore predictors of malignant ventricular arrhythmias.

Methods: We included 131 definite ARVC patients (age 32 ± 15 years, male 39%, proband 50%) either without ICDs (N  =  47) or receiving an ICD at least 6 months after the fulfillment of the diagnostic criteria. The primary outcome was a composite of cardiac arrest (both resuscitated successfully and unsuccessfully) and sustained ventricular tachyarrhythmias (cycle length< 600 milliseconds, at least 30 seconds or requiring an intervention for termination).

Results: At the fulfillment of the diagnostic criteria, ICDs were not recommended to 59 (45%) patients and declined by 22 (17%) patients. Forty (31%) patients were not recognized as having ARVC by the treating physicians. Over 8 (interquartile interval: 3-12) years, 38 (29%) patients had primary outcomes (8 cardiac arrests [3 died] and 30 sustained ventricular arrhythmias) while not having ICDs. The 1-year and 5-year event-free survival was 92% and 72%. Spontaneous sustained ventricular arrhythmias, cardiac syncope, men, proband, and inducibility in electrophysiology study were significantly associated with the primary outcome.

Conclusion: In a contemporary cohort, a considerable risk of malignant arrhythmias existed in ARVC when ICDs were not implanted.
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http://dx.doi.org/10.1111/jce.13668DOI Listing
October 2018

Predicting arrhythmic risk in arrhythmogenic right ventricular cardiomyopathy: A systematic review and meta-analysis.

Heart Rhythm 2018 07 3;15(7):1097-1107. Epub 2018 Feb 3.

Netherlands Heart Institute, Utrecht, The Netherlands; Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands; Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland. Electronic address:

While many studies evaluate predictors of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC), a systematic review consolidating this evidence is currently lacking. Therefore, we searched MEDLINE and Embase for studies analyzing predictors of ventricular arrhythmias (sustained ventricular tachycardia/fibrillation (VT/VF), appropriate implantable cardioverter-defibrillator therapy, or sudden cardiac death) in patients with definite ARVC, patients with borderline ARVC, and ARVC-associated mutation carriers. In the case of multiple publications on the same cohort, the study with the largest population was included. This yielded 45 studies with a median cohort size of 70 patients (interquartile range 60 patients) and a median follow-up of 5.0 years (interquartile range 3.3 - 6.7 years). The average proportion of arrhythmic events observed was 10.6%/y in patients with definite ARVC, 10.0%/y in patients with borderline ARVC, and 3.7%/y with mutation carriers. Predictors of ventricular arrhythmias were population dependent: consistently predictive risk factors in patients with definite ARVC were male sex, syncope, T-wave inversion in lead >V, right ventricular dysfunction, and prior (non)sustained VT/VF; in patients with borderline ARVC, 2 additional predictors-inducibility during electrophysiology study and strenuous exercise-were identified; and with mutation carriers, all aforementioned predictors as well as ventricular ectopy, multiple ARVC-related pathogenic mutations, left ventricular dysfunction, and palpitations/presyncope determined arrhythmic risk. Most evidence originated from small observational cohort studies, with a moderate quality of evidence. In conclusion, the average risk of ventricular arrhythmia ranged from 3.7 to 10.6%/y depending on the population with ARVC. Male sex, syncope, T-wave inversion in lead >V, right ventricular dysfunction, and prior (non)sustained VT/VF consistently predict ventricular arrhythmias in all populations with ARVC.
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http://dx.doi.org/10.1016/j.hrthm.2018.01.031DOI Listing
July 2018

Loss-of-Function Variants: True Monogenic Culprits of Long-QT Syndrome or Proarrhythmic Variants Requiring Secondary Provocation?

Circ Arrhythm Electrophysiol 2017 Aug;10(8)

For author affiliations, please see the Appendix.

Background: Insight into type 6 long-QT syndrome (LQT6), stemming from mutations in the -encoded voltage-gated channel β-subunit, is limited. We sought to further characterize its clinical phenotype.

Methods And Results: Individuals with reported pathogenic mutations identified during arrhythmia evaluation were collected from inherited arrhythmia clinics and the Rochester long-QT syndrome (LQTS) registry. Previously reported LQT6 cases were identified through a search of the MEDLINE database. Clinical features were assessed, while reported mutations were evaluated for genotype-phenotype segregation and classified according to the contemporary American College of Medical Genetics guidelines. Twenty-seven probands possessed reported pathogenic mutations, while a MEDLINE search identified 17 additional LQT6 cases providing clinical and genetic data. Sixteen probands had normal resting QTc values and only developed QT prolongation and malignant arrhythmias after exposure to QT-prolonging stressors, 10 had other LQTS pathogenic mutations, and 10 did not have an LQTS phenotype. Although the remaining 8 subjects had an LQTS phenotype, evidence suggested that the variant was not the underlying culprit. The collective frequency of variants implicated in LQT6 in the Exome Aggregation Consortium database was 1.4%, in comparison with a 0.0005% estimated clinical prevalence for LQT6.

Conclusions: On the basis of clinical phenotype, the high allelic frequencies of LQT6 mutations in the Exome Aggregation Consortium database, and absence of previous documentation of genotype-phenotype segregation, our findings suggest that many variants, and perhaps all, have been erroneously designated as LQTS-causative mutations. Instead, variants may confer proarrhythmic susceptibility when provoked by additional environmental/acquired or genetic factors, or both.
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http://dx.doi.org/10.1161/CIRCEP.117.005282DOI Listing
August 2017

Decreased Mortality With Beta-Blockers in Patients With Heart Failure and Coexisting Atrial Fibrillation: An AF-CHF Substudy.

JACC Heart Fail 2017 02 11;5(2):99-106. Epub 2017 Jan 11.

Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada; Montreal Health Innovations Coordinating Center, Université de Montréal, Montreal, Quebec, Canada. Electronic address:

Objectives: The impact of beta-blockers on mortality and hospitalizations was assessed in the largest randomized trial of patients with both atrial fibrillation (AF) and heart failure with a reduced ejection fraction (HFrEF): the Atrial Fibrillation-Congestive Heart Failure trial.

Background: Although beta-blockers are the cornerstone of therapy for HFrEF, a recent patient-level meta-analysis cast doubt on their efficacy in patients with coexisting AF.

Methods: From a total of 1,376 subjects randomized in the AF-CHF trial, those without beta-blockers at baseline were propensity matched to a maximum of 2 exposed patients. All absolute standardized differences after matching were ≤10%. Primary analyses respected the intention-to-treat principle. In on-treatment sensitivity analyses, beta-blocker status was modeled as a time-dependent covariate.

Results: Baseline characteristics were comparable among the matched cohorts (mean age 70 ± 11 years, 81% male, and mean left ventricular ejection fraction 27 ± 6%). During a median follow-up of 37 months, beta-blockers were associated with significantly lower all-cause mortality (hazard ratio [HR]: 0.721, 95% confidence interval [CI]: 0.549 to 0.945; p = 0.0180) but not hospitalizations (HR: 0.886; 95% CI: 0.715 to 1.100; p = 0.2232). Similar results were obtained in sensitivity analyses that modeled beta-blockers as a time-dependent variable (HR: 0.668 for all-cause mortality; 95% CI: 0.511 to 0.874; p = 0.0032; HR: 0.814 for hospitalizations; 95% CI: 0.653 to 1.014; p = 0.0658). There were no significant interactions between beta-blockers and patterns (i.e., persistent vs. paroxysmal) or burden of AF with respect to mortality or hospitalizations.

Conclusions: In propensity-matched analyses, beta-blockers were associated with significantly lower mortality but not hospitalizations in patients with HFrEF and AF, irrespective of the pattern or burden of AF. These results support current evidence-based recommendations for beta-blockers in patients with HFrEF, whether or not they have associated AF.
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http://dx.doi.org/10.1016/j.jchf.2016.10.015DOI Listing
February 2017

Predictors of Ventricular Arrhythmias and Sudden Death in a Québec Cohort With Brugada Syndrome.

Can J Cardiol 2016 11 31;32(11):1355.e1-1355.e7. Epub 2016 Mar 31.

Department of Medicine, Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada; Montréal Health Innovations Coordinating Center (MHICC), Montréal Heart Institute, Montréal, Québec, Canada.

Background: Patients with Brugada syndrome (BrS) are at risk for ventricular arrhythmias (VAs) and sudden death. Identification of high-risk individuals beyond those with syncope or resuscitated sudden death remains a major challenge.

Methods: We assessed the value of clinical, electrophysiological, and electrocardiographic (ECG) features, including depolarization and repolarization metrics, in predicting arrhythmic events and sudden death in consecutive patients with BrS diagnosed between 2002 and 2013 in Quebec, Canada. Qualifying electrocardiograms with the highest type 1 ST-segment elevations were reviewed and analyzed by 2 electrophysiologists who were blinded to clinical history. Survival analyses were adjusted for Firth bias correction and left truncation.

Results: A total of 105 patients, 79.8% of whom were men, were diagnosed with BrS at a mean age of 46.2 ± 13.3 years and were followed for 59.6 ± 16.4 months. Ten (9.5%) had a history of cardiac arrest, 37 (35.2%) had syncope, and 7 (6.7%) experienced 20 arrhythmic events during follow-up, all consisting of appropriate ICD therapy (7 antitachycardia pacing; 13 shocks). In multivariate Cox regression analyses, a spontaneous type 1 electrocardiographic (ECG) pattern (hazard ratio [HR], 10.80; 95% confidence interval [CI], 1.03-113.87; P = 0.0476), maximal T peak-end (T) duration ≥ 100 ms (HR, 29.73; 95% CI, 1.33-666.37; P = 0.0325), and QRS duration in lead V > 110 ms (HR, 15.27; 95% CI, 1.07-217.42; P = 0.0443) were independently associated with VAs or aborted sudden cardiac death.

Conclusions: In a multicentre cohort with BrS from Quebec, Canada, VAs and sudden death were independently associated with standard 12-lead ECG features, including a spontaneous type 1 pattern, depolarization (QRS in lead V), and repolarization (maximal T duration) criteria.
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http://dx.doi.org/10.1016/j.cjca.2016.03.012DOI Listing
November 2016

ECG Features Associated With Adverse Cardiovascular Outcomes in Patients With Atrial Fibrillation: A Combined AFFIRM and AF-CHF Analysis.

J Cardiovasc Electrophysiol 2016 Apr 25;27(4):404-13. Epub 2016 Feb 25.

Electrophysiology Service, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.

Background: The association between standard parameters from a simple 12-lead ECG (i.e., QRS duration and PR, JT, and QT intervals) and adverse cardiovascular outcomes (cardiovascular mortality, all-cause mortality, arrhythmic mortality, and hospitalizations) in patients with a history of atrial fibrillation (AF) has not been previously studied.

Methods And Results: A pooled analysis of patient-level data was conducted on 5,436 patients, age 68.2 ± 8.3 years, 34.8% female, with a history of non-permanent AF randomized in AFFIRM and AF-CHF trials. The predictive value of ECG parameters was assessed in AF and sinus rhythm in multivariate Cox regression models. During a follow-up of 40.8 ± 16.3 months, QRS duration >120 milliseconds was independently associated with all-cause mortality (hazard ratio [HR] 1.46, 95% confidence interval [CI; 1.21-1.76] in AF, P < 0.001), cardiovascular mortality (HR 1.75, 95% CI (1.15-2.65) in sinus rhythm, P = 0.009; HR 1.56, 95% CI [1.27-1.93] in AF, P < 0.001), arrhythmic mortality (HR 1.90, 95% CI [1.09-3.32] in sinus, P = 0.024; HR 1.84, 95% CI [1.35-2.51] in AF, P < 0.001), any hospitalization (HR 1.15, 95% CI [1.02-1.29] in AF, P = 0.027), and cardiovascular hospitalization (HR 1.21, 95% CI [1.06-1.37] in AF; P = 0.004). Increased PR interval (>200 milliseconds) was independently associated with cardiovascular (HR 1.56, 95% CI [1.11-2.21], P = 0.010) and arrhythmic (HR 1.91, 95% CI [1.14-3.18], P = 0.004) mortality. The JT and QTc intervals were not predictive of mortality.

Conclusions: Simple parameters from standard ECGs are significantly and independently associated with adverse cardiovascular outcomes in patients with a history of AF.
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http://dx.doi.org/10.1111/jce.12934DOI Listing
April 2016