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Background: To retrospectively characterize and compare the dose of exercise training (ET) within a large cohort of patients demonstrating different levels of improvement in exercise capacity following a cardiac rehabilitation (CR) program., Methods: A total of 2310 patients who completed a 12-week, center-based, guidelines-informed CR program between January 2018 and December 2019 were included in the analysis. Peak metabolic equivalents (MET peak ) were determined pre- and post-CR during which total duration (ET time) and intensity [percent of heart rate peak (%HR peak )] of supervised ET were also obtained. Training responsiveness was quantified on the basis of changes in MET peak from pre- to post-CR. A cluster analysis was performed to identity clusters demonstrating discrete levels of responsiveness (i.e., negative, low, moderate, high, and very-high). These were compared for several baseline and ET-derived variables which were also included in a multivariable linear regression model., Results: At pre-CR, baseline MET peak was progressively lower with greater training responsiveness (F (4,2305)  = 44.2, P < 0.01, η 2 p  = 0.71). Likewise, average training duration (F (4,2305)  = 10.7 P < 0.01, η 2 p  = 0.02) and %HR peak (F (4,2305)  = 25.1 P < 0.01, η 2 p  = 0.042) quantified during onsite ET sessions were progressively greater with greater training responsiveness. The multivariable linear regression model confirmed that baseline MET peak , training duration and intensity during ET, BMI, and age (P < 0.001) were significant predictors of MET peak post-CR., Conclusions: Along with baseline MET peak , delta BMI, and age, the dose of ET (i.e., training duration and intensity) predicts MET peak at the conclusion of CR. A re-evaluation of current approaches for exercise intensity prescription is recommended to extend the benefits of completing CR to all patients., Competing Interests: Declaration of Competing Interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Evidence supports the benefit of managing atrial fibrillation (AF) specific risk factors in secondary prevention of AF. However, a comprehensive summary of the effect of multifactorial risk factor interventions on outcomes of patients with AF over long-term is lacking. We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL databases from inception to October 2021 for both randomized controlled trials (RCT) and observational studies comparing multifactorial risk factor interventions to usual care in patients with AF. Fifteen studies (10 RCT, 5 observational) with 3786 patients were included (mean age 63.8 years, 64.0% males). Follow-up ranged from 3 to 42 months. We found no significant effects of multifactorial risk factor interventions on AF recurrence [pooled relative risk (RR): 0.93, 95% CI: 0.74-1.16, P = 0.51, I 2  = 54%], AF-related rehospitalization at 12 months (RR: 0.69, 95% CI: 0.43-1.11, P= 0.13, I 2  = 0%), cardiovascular rehospitalization at 12 months (RR: 0.76, 95% CI: 0.53-1.09, P= 0.13, I 2  = 53%), or AF-related adverse events at 12 and 15 months. However, multifactorial interventions were associated with reduced AF-related symptoms and improved health-related quality of life (HRQoL) at all studied time points. Current evidence does not support consistent associations between multifactorial risk factor interventions and AF recurrence after rhythm control therapy or AF-related or cardiovascular hospitalization in patients with AF. However, these interventions are associated with clinically relevant improvement in AF-related symptoms and HRQoL. Additional randomized studies are required to evaluate the impact of multifactorial risk factor interventions on patient-centered health outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Patients with coronary artery disease (CAD) are at risk for developing atrial fibrillation (AF). Whether attending a cardiac rehabilitation (CR) program can attenuate this risk is unclear., Methods: This retrospective cohort study included patients who were free of pre-existing AF and referred to CR after coronary revascularization between April 2004 and March 2015 in Calgary, Canada. Patients with incident AF were identified using administrative data and the local electrocardiogram repository. Exposure variables and covariates were extracted from electronic medical records of a CR program and a clinical registry., Results: The study included 11,662 patients (mean age [standard deviation], 60.9 [10.9] years; male, 80.6%). In a median follow-up of 4.8 years, the cumulative incidence rate of AF was 1.04 per 100 person-years. There was no association between completion of CR and the risk of incident AF after adjusting for baseline characteristics (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.83-1.15). However, each higher metabolic equivalent (MET) of baseline cardiorespiratory fitness (CRF) and each MET gain in CRF following CR were independently associated with a 12% (95% CI, 6%-18%) and 18% (95% CI, 6%-28%) lower relative risk of incident AF, respectively. The risk of incident AF declined progressively, with the baseline CRF increasing up to 9.0 peak METs and with the 12-week CRF increasing up to 10.3 peak METs; beyond these peak MET levels, benefits plateaued., Conclusions: Completion of CR alone was not associated with a lower risk of incident AF. However, higher baseline CRF and greater CRF improvement had dose-dependent protective effects., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Despite expert recommendations advocating use of remote monitoring (RM) of cardiac implantable electronic devices, implementation in routine clinical practice remains modest due to inconsistent funding policies across health systems and uncertainty regarding the efficacy of RM to reduce adverse cardiovascular outcomes., Methods: We conducted a population-based cohort study of patients with de novo implantable cardioverter-defibrillators (ICDs) with or without cardiac resynchronization therapy (CRT-D), using administrative health data in Alberta, Canada, from 2010 to 2016. We assessed RM status as a predictor of all-cause mortality and cardiovascular (CV) hospitalization using Cox proportional hazards modelling, and direct health costs by generalized linear models. From this real-world data, we then constructed a decision-analytic Markov model to estimate the projected costs and benefits associated with RM compared with in-clinic visit follow-up alone., Results: Among 2799 ICD and CRT-D patients, 1830 (63.4%) were followed by RM for a mean follow-up of 50.3 months. After adjustment for age, sex, and comorbidities, RM was associated with a lower risk of death (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.36-0.52; P < 0.001) and CV hospitalization (HR 0.76, 95% CI 0.64-0.91; P = 0.002). In the economic model, cost savings were observed over 5 years with an estimated savings of $12,195 per person (95% CI -$21,818 to -$4,790). The model estimated a cost-savings associated with RM strategy in 99% of simulations., Conclusions: These population data support more widespread implementation of RM technology to facilitate better patient outcomes and improve health system efficiency., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Cardiac rehabilitation (CR) is a proven therapy for reducing cardiovascular death and hospitalization. Whether CR participation is associated with improved outcomes in patients with chronic kidney disease (CKD) is unknown., Methods: We obtained data on all adult patients in Calgary, Alberta, Canada with angiographically proven coronary artery disease from 1996 to 2016 referred to CR from The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease and TotalCardiology Rehabilitation. An estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m 2 or kidney replacement therapy defined CKD. Predictors of CR use were estimated with multinomial logistic regression. The association between starting versus not starting and completion versus noncompletion of CR and clinical outcomes were estimated using multivariable Cox proportional hazards models., Results: Of 23,215 patients referred to CR, 12,084 were eligible for inclusion. Participants with CKD (N = 1322) were older, had more comorbidity, lower exercise capacity on graded treadmill testing, and took longer to be referred and to start CR than those without CKD. CKD predicted not starting CR: odds ratio 0.73 (95% confidence interval [CI] 0.64-0.83). Over a median 1 year follow-up, there were 146 deaths, 40 (0.3%) from CKD and 106 (1.0%) not from CKD. Similar to those without CKD, the risk of death was lower in CR completers (hazard ratio [HR] 0.24 [95% CI 0.06-0.91) and starters (HR 0.56 [95% CI 0.29- 1.10]) with CKD., Conclusion: CR participation was associated with comparable benefits in people with moderate CKD as those without who survived to CR. Lower rates of CR attendance in this high-risk population suggest that strategies to increase CR utilization are needed., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Background: Hospitalization for nonvalvular atrial fibrillation (NVAF) is common and results in substantial cost burden. Current national data trends for the incidence, stroke risk profiles, and mortality of hospitalization for NVAF and atrial flutter (AFL) are sparse., Methods: The Canadian Institute of Health Information Discharge Abstract Database was used to identify patients ≥ 20 years with incident NVAF/AFL (NVAF, ICD-9 code 427.3 or ICD-10 I48) in any diagnosis field from 2006 to 2015 in Canada, except Québec. National and provincial trends in rate over time (rate ratio, 95% confidence interval [CI]) were calculated for age-sex standardized hospitalizations. Trends in stroke risk profiles and in-hospital mortality rates adjusted for stroke risk factors were also calculated., Results: A total of 578,947 patients were hospitalized with incident NVAF/AFL. The median age was 77 years (interquartile range: 68-84), 82% were ≥ 65 years, 54% were men, 54% had a CHADS2 ≥ 2, and 69% had a CHA2DS2-Vasc ≥ 3. The overall age- and sex-standardized rate of NVAF/AFL hospitalization was 315 per 100,000 population and declined by 2% per year (P < 0.001). There was an annual rate decline in NVAF/AFL hospitalizations in every province. The majority of hospitalized patients are at high risk of stroke, and this risk remained unchanged. The average adjusted in-hospital mortality was 8.80 per 100 patients 95% CI, 8.80-8.81 with a 2% annual decline in rate (P < 0.001)., Conclusion: Between 2006 and 2015, we found national and provincial hospitalization rates for incident NVAF/AFL are declining. The majority of patients are at high risk for stroke. In-hospital mortality has declined but remains substantial., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Acute myocardial infarction (AMI) recurrence is still high despite great progress in secondary prevention. Patients with recurrent AMI suffer worse prognosis compared to those with first AMI. The objective was to evaluate the effect of optimal medical therapy (OMT) on these patients with recurrent AMI., Methods and Results: Sub-analysis was performed including 13,343 patients with AMI from the international multicenter Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) registry. OMT was defined as the combination of aspirin, any P2Y12 inhibitor, statin, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. Among 1285 patients with prior AMI, 56.8% received OMT prescription. Patients receiving OMT suffered from less congestive heart failure, peripheral artery disease, malignancy, and bleeding history. Kaplan-Meier survival estimates revealed that OMT was strongly related to decreased in all-cause death (4.2% vs. 10.1%, p < .001) and the composite endpoint of death/re-AMI (11.1% vs. 16.9%, p = .005) at 1-year follow-up. OMT was the independent protect factor of primary endpoint even after adjusting for multiple possible confounders (HR, 0.46; 95% CI, 0.27-0.78; p = .004). However, no significant difference was observed regarding re-AMI between OMT and non-OMT groups. OMT also reduced all-cause death in patients with recurrent AMI after propensity score matching., Conclusions: The prescription of OMT was seriously insufficient in patients with recurrent AMI, especially high-risk patients, even though OMT was associated with improved prognosis. Further improvements in pharmacological therapy are needed to reduce subsequent recurrent events., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Infranodal conduction abnormalities, including right or left bundle branch block bifascicular block, and nonspecific intraventricular conduction block are common electrocardiogram (ECG) abnormalities with uncertain persistence and prognostic significance. We evaluated their trajectory and prognostic significance in patients undergoing coronary angiography., Methods: We linked an institutional ECG repository with the provincial coronary angiography registry and administrative databases. We included patients without severe left ventricular dysfunction who had an ECG within 180 days of angiography. Multivariable Cox models were used to assess associations between conduction abnormalities and a composite outcome, including all-cause mortality, heart failure hospitalizations, placement of a permanent pacemaker, and placement of an implantable cardiac defibrillator or cardiac resynchronization therapy defibrillator. Serial ECGs were used to model conduction disease as a time-dependent repeated measure., Results: We included 10,786 patients (mean age, 62.3 ± 12.4 years; 70.3% were male), of whom 2530 (23.4%) had baseline conduction abnormality. During a median follow-up of 3.5 years, conduction normalized in 885 patients (34.9%) and the composite outcome occurred in 1541 patients (14.3%). After multivariable adjustment, intraventricular conduction block (adjusted hazard ratio, 1.42; P = 0.001) and bifascicular block (adjusted hazard ratio, 1.59; P = 0.003) were associated with increased risk of the composite outcome. Left bundle branch block was not associated with the composite outcome., Conclusions: Regression of conduction abnormalities was frequent among patients undergoing coronary angiography, primarily for suspected acute coronary syndrome. After adjustment for important confounders including extent of coronary artery disease, infranodal conduction abnormalities were associated with a modest increase in cardiovascular risk., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Type 2 diabetes and cardiometabolic comorbidities manifesting as the metabolic syndrome (MetS) are highly prevalent in coronary heart disease (CHD) patients attending cardiac rehabilitation (CR). The study aimed to determine the prevalence of cardiometabolic derangements and MetS, and compare post-CR clinical responses in a large cohort of CHD patients with and without diabetes., Methods: Analyses were conducted on 3953 CHD patients [age: 61.1 ± 10.5 years; 741 (18.7%) with diabetes] that completed a representative 12-week CR program. A propensity model was used to match patients with diabetes (n = 731) to those without diabetes (n = 731) on baseline and clinical characteristics., Results: Diabetic patients experienced smaller improvements in metabolic parameters after completing CR, including abdominal obesity, and lipid profiles (all P ≤ .002), compared to non-diabetic patients. For both groups, there were similar improvement rates in peak metabolic equivalents ([METs]; P < .001); however, peak METs remained lower at 12-weeks in patients with diabetes than without diabetes. At baseline, the combined prevalence of insulin resistance (IR) and diabetes was 57.3%, whereas IR was present in 48.2% of non-diabetic patients, of which rates were reduced to 48.2% and 32.8% after CR, respectively. Accordingly, MetS prevalence decreased from 25.5% to 22.3% in diabetic versus 20.0% to 13.4% in non-diabetic patients (all P ≤ .004)., Conclusions: Completing CR appears to provide comprehensive risk reduction in cardio-metabolic parameters associated with diabetes and MetS; however, CHD patients with diabetes may require additional and more aggressive attention towards all MetS criteria over the course of CR in order to prevent future cardiovascular events., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cardiac rehabilitation (CR) is a guideline-indicated modality for reducing residual cardiovascular risk among patients undergoing coronary artery bypass grafting (CABG) surgery. However, many referred patients do not initiate or complete a CR program; even more patients are never even referred., Methods: All post-CABG patients in Calgary, Alberta, Canada, from January 1, 1996, to March 31, 2016, were included. Data were obtained from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease and TotalCardiology Rehabilitation databases. Automated referral to CR at discharge after CABG was instituted on July 1, 2007. We used interrupted time series analysis to evaluate the impact of automated referral on CR referral and completion rates and studied the association of these CR process markers with mortality., Results: A total of 8,118 patients underwent CABG surgery during the study period: 5,103 before automation and 3,015 after automation. Automation increased referral rates from 39.5% to 75.0% (P < 0.001). Automated referral was associated with a 7.2% increase in CR completion in the overall population (33.3% vs 26.1%; P < 0.001). In adjusted models, CR referral alone was not associated with reduced mortality (hazard ratio [HR] 0.84, 95% CI 0.64-1.11), but CR completion was (HR 0.43, 95% CI 0.31-0.61)., Conclusion: Automated referral in post-CABG patients resulted in modest improvement in CR program completion. Therefore, even when CR referral is automated to include all eligible patients, additional strategies to support CR program enrollment and completion remain necessary to achieve the desired health benefits., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Contrast-induced acute kidney injury (CI-AKI) is a common and serious complication of invasive cardiac procedures. Quality improvement programs have been associated with a lower incidence of CI-AKI over time, but there is a lack of high-quality evidence on clinical decision support for prevention of CI-AKI and its impact on processes of care and clinical outcomes., Methods: The Contrast-Reducing Injury Sustained by Kidneys (Contrast RISK) study will implement an evidence-based multifaceted intervention designed to reduce the incidence of CI-AKI, encompassing automated identification of patients at increased risk for CI-AKI, point-of-care information on safe contrast volume targets, personalized recommendations for hemodynamic optimization of intravenous fluids, and follow-up information for patients at risk. Implementation will use cardiologist academic detailing, computerized clinical decision support, and audit and feedback. All 31 physicians practicing in all 3 of Alberta's cardiac catheterization laboratories will participate using a cluster-randomized stepped-wedge design. The order in which they are introduced to this intervention will be randomized within 8 clusters. The primary outcome is CI-AKI incidence, with secondary outcomes of CI-AKI avoidance strategies and downstream adverse major kidney and cardiovascular events. An economic evaluation will accompany the main trial., Conclusions: The Contrast RISK study leverages information technology systems to identify patient risk combined with evidence-based protocols, audit, and feedback to reduce CI-AKI in cardiac catheterization laboratories across Alberta. If effective, this intervention can be broadly scaled and sustained to improve the safety of cardiac catheterization., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to compare the effectiveness of bucindolol with that of metoprolol succinate for the maintenance of sinus rhythm in a genetically defined heart failure (HF) population with atrial fibrillation (AF)., Background: Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta 1 -adrenergic receptor (ADRB1) Arg389Arg genotype., Methods: A total of 267 HFrEF patients with a left ventricular ejection fraction (LVEF) <0.50, symptomatic AF, and the ADRB1 Arg389Arg genotype were randomized 1:1 to receive bucindolol or metoprolol therapy and were up-titrated to target doses. The primary endpoint of AF or atrial flutter (AFL) or all-cause mortality (ACM) was evaluated by electrocardiogram (ECG) during a 24-week period., Results: The hazard ratio (HR) for the primary endpoint was 1.01 (95% confidence interval [CI]: 0.71 to 1.42), but trends for bucindolol benefit were observed in several subgroups. Precision therapeutic phenotyping revealed that a differential response to bucindolol was associated with the interval of time from the initial diagnoses of AF and HF to randomization and with the onset of AF relative to that of the initial HF diagnosis. In a cohort whose first AF and HF diagnoses were <12 years prior to randomization, in which AF onset did not precede HF by more than 2 years (n = 196), the HR was 0.54 (95% CI: 0.33 to 0.87; p = 0.011)., Conclusions: Pharmacogenetically guided bucindolol therapy did not reduce the recurrence of AF/AFL or ACM compared to that of metoprolol therapy in HFrEF patients, but populations were identified who merited further investigation in future phase 3 trials., (Copyright © 2019. Published by Elsevier Inc.)

Background: Peripheral arterial disease (PAD) is common in people referred for cardiac rehabilitation (CR). However, the associations between PAD diagnosis and CR attendance and mortality remain to be defined., Methods: All patients referred to a 12-week exercise-based CR program were included. Associations between PAD diagnosis and starting CR as well as between PAD diagnosis and completing CR were measured using multivariable logistic regression. Associations between CR completion and mortality were measured using adjusted Cox proportional hazards models, and a propensity-based matching sensitivity analysis was performed., Results: 23,215 patients (mean age 61.3 years; 21.6% female) were referred to CR; 1366 (5.9%) had PAD. Those with PAD were less likely to start CR (57.0% vs 68.2%, adjusted OR 0.81, 95%CI 0.72, 0.91) and complete CR if they started (70.6% vs 76.7%, adjusted OR 0.80, 95%CI 0.68, 0.94). Patients with PAD completing CR had lower exercise capacity at baseline (6.6 vs. 7.6 METs, p < 0.0001) and completion (7.5 vs 8.6 METs, p < 0.0001). There were 3510 deaths over follow-up; 10-year survival was lower in those with PAD (66.9 vs 84.5%; p < 0.0001). CR completion was associated with lower mortality for all (adjusted HR 0.62 (95%CI 0.57, 0.67)), and the magnitude of the association was independent of PAD status., Conclusions: Patients with PAD referred to CR had a higher mortality than those without, and were less likely to start and complete CR. Completion of CR was associated with improved fitness and survival for PAD patients. These data support broader use of CR by those with PAD., (Copyright © 2019. Published by Elsevier B.V.)

Background: Accurate 1-year bleeding risk estimation after hospital discharge for acute coronary syndrome (ACS) may help clinicians guide the type and duration of antithrombotic therapy. Currently there are no predictive models for this purpose. The aim of this study was to derive and validate a simple clinical tool for bedside risk estimation of 1-year post-discharge serious bleeding in ACS patients., Methods: The risk score was derived and internally validated in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry, an observational international registry involving 15,401 patients surviving admission for ACS and undergoing percutaneous coronary intervention (PCI) from 2003 to 2014, engaging 15 hospitals from 10 countries located in America, Europe and Asia. External validation was conducted in the SWEDEHEART population, with 96,239 ACS patients underwent PCI and 93,150 without PCI., Results: Seven independent predictors of bleeding were identified and included in the BleeMACS score: age, hypertension, vascular disease, history of bleeding, malignancy, creatinine and hemoglobin. The BleeMACS risk score exhibited a C-statistic value of 0.71 (95% CI 0.68-0.74) in the derivation cohort and 0.72 (95% CI 0.67-0.76) in the internal validation sample. In the SWEDEHEART external validation cohort, the C-statistic was 0.65 (95% CI 0.64-0.66) for PCI patients and 0.63 (95% CI 0.62-0.64) for non-PCI patients. The calibration was excellent in the derivation and validation cohorts., Conclusions: The BleeMACS bleeding risk score is a simple tool useful for identifying those ACS patients at higher risk of serious 1-year post-discharge bleeding. ClinicalTrials.govIdentifier: NCT02466854., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: The goal of this study was to assess associations between left ventricular (LV) mass, all-cause mortality, and need for revascularization in patients undergoing coronary angiography., Background: LV hypertrophy is associated with adverse cardiovascular outcomes in healthy subjects. However, its influence in those with known or suspected coronary artery disease is poorly understood., Methods: A total of 3,754 patients (mean age 59.3 ± 13.1 years) undergoing invasive coronary angiography and cardiac magnetic resonance (CMR) (mean interval 1.0 ± 1.5 months) were studied. LV mass and volumes were determined from cine images and indexed to body surface area. Analyses were adjusted for CMR variables, medical comorbidities, and severity of coronary artery disease (Duke Jeopardy Score) and were stratified to LV function., Results: At a median of 44.9 months, 315 patients (8.4%) died and 168 patients (4.5%) underwent revascularization. Multivariable analysis showed that each 10 g/m 2 increase in LV mass index was associated with a 6% greater risk of mortality (hazard ratio: 1.06; 95% confidence interval [CI]: 1.01 to 1.11; p = 0.02) and a 10% greater need for revascularization (hazard ratio: 1.10; 95% CI: 1.04 to 1.17; p < 0.01). According to pre-defined thresholds, moderate to severe hypertrophy was associated with a 1.7-fold risk of mortality (95% CI: 1.2 to 2.3) and 1.8-fold need for revascularization (95% CI: 1.18 to 2.67). These findings were predominantly observed in those with a left ventricular ejection fraction >35% with respective hazard ratios of 2.93 (95% CI: 1.92 to 4.47) and 2.20 (95% CI: 1.21 to 3.98)., Conclusions: LV mass index is an independent predictor of all-cause mortality and need for revascularization. This finding establishes relevance for LV mass measurements in clinical decision-making surrounding both the need and timing of revascularization in this population., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Left atrial appendage occlusion devices are an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation who are at risk of ischemic stroke. Thromboprophylaxis after implantation is recommended, but the optimal regimen is unknown. We report a clinicopathologic case in which thrombus adherent to an incompletely endothelialized WATCHMAN device (Boston Scientific, Marlborough, MA) resulted in multiple thromboembolic events, contributing to a fatal outcome. This case illustrates uncertainties regarding the device's endothelialization process., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

In 2010, the Canadian Cardiovascular Society embarked on an initiative to develop pan-Canadian quality indicators (QIs) and standardized data definitions with the ultimate goal of monitoring, comparing, and contrasting national cardiovascular care and its outcomes. One of the first working groups to be established was tasked with identifying and then defining a set of QIs for atrial fibrillation/flutter (AF/AFL). The Canadian Cardiovascular Society "Best Practices for Developing Cardiovascular Quality Indicators" methodology was used to develop an initial catalogue of 25 QIs intended to measure critical issues around access, process, and outcomes relating to AF/AFL management. This list was subsequently pared down to 5 QIs felt to have the greatest relative importance for quality assurance and measurability so as to facilitate early adoption. Three of these QIs were finally selected to assess the feasibility of their measurement using existing administrative datasets. These were the number of patients with a diagnosis of nonvalvular AF/AFL at high risk of stroke (75 years or older, or CHADS 2 ≥ 2) receiving an oral anticoagulant, and the rates of stroke and major haemorrhage in patients with nonvalvular AF/AFL according to CHA 2 DS 2 -VASc score and anticoagulant use. Despite their clear importance in assessing AF/AFL care, none of these 3 QIs were found to be readily measurable across Canada using existing national datasets. Investment in new medical data infrastructure is required to facilitate regular monitoring of QIs to improve cardiovascular care., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Registry-based randomized controlled trials are defined as pragmatic trials that use registries as a platform for case records, data collection, randomization, and follow-up. Recently, the application of registry-based randomized controlled trials has attracted increasing attention in health research to address comparative effectiveness research questions in real-world settings, mainly due to their low cost, enhanced generalizability of findings, rapid consecutive enrollment, and the potential completeness of follow-up for the reference population, when compared with conventional randomized effectiveness trials. However several challenges of registry-based randomized controlled trials have to be taken into consideration, including registry data quality, ethical issues, and methodological challenges. In this article, we summarize the advantages, challenges, and areas for future research related to registry-based randomized controlled trials., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Blood transfusions (BTs) may worsen the prognosis of patients affected by acute coronary syndromes (ACS), although few data detail their impact on short-term events according to clinical presentation (ST Segment Elevation Myocardial Infarction, STEMI vs. Non-ST Segment Elevation ACS, NSTE-ACS)., Methods: Patients undergoing percutaneous coronary intervention (PCI) for ACS, with data on BTs, were selected from the BleeMACS registry. The primary end point was the incidence of myocardial infarction during hospitalization (reAMI), the secondary end-points were 30-day mortality and the combined end-point of 30-day mortality and reAMI. Sensitivity analyses were performed according to clinical presentation (STEMI vs. NSTE-ACS)., Results: Overall, 13,975 patients were included: mean age was 64.1years, 10,651 (76.2%) were male and 7711 (55.2%) had STEMI. BTs were administered during hospitalization to 465 (3.3%) patients, who were older and presented a more relevant burden of risk factors. The primary end-point of reAMI occurred in 197 (1.4%) patients, of whom 102 (1.1%) with STEMI. After controlling for confounding variables, BTs independently predicted the primary end-point reAMI in patients admitted for STEMI (OR 4.059, 95% CI 2244-7.344) and not in those admitted for NSTE-ACS. Moreover, BTs independently related to 30-day mortality in STEMI and NSTE-ACS patients and to the composite of 30-day mortality and reAMI in STEMI patients., Conclusions: In patients undergoing PCI for ACS, BTs increase the risk of reAMI only in those admitted for STEMI, and not in those with NSTE-ACS. These results may help physicians to choose appropriate BT administration according to the admission diagnosis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Contemporary trends in the selection of and persistence with rate vs rhythm control for atrial fibrillation (AF) are not well studied, particularly in the context of multidisciplinary AF clinics., Methods: The initial arrhythmia management strategy in 1031 consecutive patients attending a multidisciplinary AF clinic from 2005-2012 was analyzed., Results: The 397 (38.5%) patients initially treated with rhythm control were younger (57.4 ± 14 years vs 65.6 ± 13 years; P < 0.0001) and more likely to be men (64.5% vs 56.9%; P = 0.019). They also had fewer comorbidities, lower CHADS 2 (Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack) scores, and greater symptom burden. The proportion treated with rhythm control declined from 46.9% in 2005-2006 to 28.4% in 2012 (P for trend < 0.0001). Compared with those initially selecting rate control, patients treated with rhythm control required more frequent clinic encounters (7 [interquartile range {IQR}, 3-12] vs 3 [IQR, 2-7]; P < 0.001) and longer follow-up (266 days [IQR, 84-548 days] vs 99 days [IQR, 0-313 days]; P < 0.001). Younger age, absence of diabetes and sleep apnea, earlier treatment year, higher symptom burden, and rural residence were independently associated with rhythm control. Persistence with the initial treatment strategy was reduced in the rhythm-control group (P = 0.003)., Conclusions: Use of rhythm control as the initial arrhythmia management strategy for AF in a specialty AF clinic is declining. Rhythm control requires more intensive follow-up and was more likely to lead to a change in arrhythmia management strategy., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: New York Heart Association (NYHA) functional class provides important prognostic information and is often used to select patients for cardiovascular therapies, yet, the effect of NYHA class on therapeutic efficacy has not been systematically studied., Methods: In this systematic review and meta-analysis we compared the relative and absolute mortality benefit of 5 common heart failure interventions (angiotensin-converting enzyme [ACE] inhibitors, β-blockers, mineralocorticoid receptor antagonists [MRAs], implantable cardioverter defibrillator [ICD], and cardiac resynchronization therapy [CRT]) across NYHA class. We included 26 randomized clinical trials of these interventions that reported all-cause mortality stratified according to baseline NYHA class in 36,406 patients., Results: Pooled relative risk for NYHA I/II vs. III/IV strata were similar for ACE inhibitors (0.90 vs. 0.88), β-blockers (0.72 vs. 0.79), MRA (0.79 vs. 0.75), and CRT (0.80 vs. 0.80), with all heterogeneity P > 0.8. Conversely, ICD efficacy was greater for class I/II (relative risk, 0.65 vs 0.86, heterogeneity P = 0.02). The pooled absolute risk difference was smaller for NYHA I/II vs III/IV with ACE inhibitors (-0.02 vs. -0.06, P = 0.12), β-blockers (-0.02 vs. -0.05, P = 0.047), MRA (-0.03 vs. -0.11, P = 0.001), and CRT (-0.01 vs. -0.04, P = 0.036), but was similar across NYHA class for the ICD (-0.07 vs. -0.05; P = 0.27)., Conclusions: Relative mortality reductions with most interventions were independent of baseline NYHA class. However, ICD efficacy was greater with NYHA I/II vs. III/IV limitation, and absolute benefit was greater with higher NYHA class. For interventions other than the ICD, there is little evidence supporting use of NYHA class as a rigid criterion for selecting heart failure therapies., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Conflicting data exist regarding the association between left ventricular (LV) lead position and benefit from cardiac resynchronization therapy. We evaluated the relationships between LV lead positions and the risk of death or hospitalization for heart failure (HF) in the cardiac resynchronization therapy arm of the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT)., Methods: LV lead position was categorized by site investigator (MD) and in a chest radiograph core laboratory (CXR) as "anterior," "lateral," or "posterior" in the short axis, and "basal," "mid," or "apical" in the long axis. Agreement between MD and CXR LV lead position classification was evaluated and the independent relationship between LV lead position and clinical outcome was assessed using Cox multivariable models., Results: Agreement between MD and CXR LV lead position was poor (κ ≤ 0.26). Over 39 ± 20 months, 140 of 447 (31.3%) patients met the RAFT primary end point (death or HF hospitalization). In adjusted analyses, neither MD-determined nor CXR-determined anterior or apical LV lead position was significantly associated with the primary outcome. However, CXR-defined apical LV lead position was associated with a higher risk of HF hospitalization (hazard ratio, 1.99; P = 0.004)., Conclusions: Poor agreement between implanting physician and core lab CXR-based categorizations of LV lead position was observed. Neither categorization method resulted in significant associations between apical or anterior LV lead position and the risk of the composite primary outcome of death or heart failure hospitalization. However, CXR-defined apical lead position was associated with increased risk of HF hospitalization., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The report from the 2nd Consensus Committee on BrS suggests that all patients with syncope without a "clear extracardiac cause" should have an implantable cardioverter-defibrillator (ICD). However, a clear extracardiac cause for syncope may be difficult to prove., Objective: The purpose of this study was to characterize syncope in patients with Brugada syndrome (BrS)., Methods: All patients diagnosed with BrS at our institution between 1999 and 2010 were enrolled in a prospective registry. Patients with suspected arrhythmic syncope (group 1) were compared to patients with nonarrhythmic syncope (group 2) and to patients with syncope of doubtful origin (group 3)., Results: Of 203 patients with BrS, 57 (28%; 44 male, age 46 ± 12 years) experienced at least 1 syncope. Group 1 consisted of 23 patients, all of whom received an ICD. In group 2 (17 patients), 3 received an ICD because of a positive electrophysiologic study. In group 3 (17 patients), 6 received an implantable loop recorder and 6 received an ICD. After mean follow-up of 65 ± 42 months, 14 patients in group 1 remained asymptomatic, 4 had recurrent syncope, and 6 had appropriate ICD therapy. In group 2, 9 patients remained asymptomatic and 7 had recurrent neurocardiogenic syncope. In group 3, 7 remained asymptomatic and 9 had recurrent syncope. One patient from each group died from a noncardiac cause., Conclusion: In the present study, syncope occurred in 28% of patients with BrS. The ventricular arrhythmia rate was 5.5% per year in group 1. In 30%, the etiology of the syncope was questionable. No sudden cardiac death occurred in groups 2 and 3., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: J waves are the hallmark of both inferolateral early repolarization (ER) and Brugada syndrome. While ajmaline, a class 1a antiarrhythmic drug, accentuates the J wave in Brugada syndrome, its effect on ER is unreported., Objective: To describe the effect of ajmaline on the electrocardiogram in ER., Methods: We analyzed electrocardiograms before and after the administration of intravenous ajmaline (1 mg/kg) in 31 patients with ER, 21 patients with Brugada type 1 electrocardiogram (Br), and 22 controls. ER was defined as J-point elevation of ≥1 mm with QRS slurring or notching in ≥2 inferolateral leads (I, aVL, II, III, aVF, V4-V6)., Results: Ajmaline decreased mean J-wave amplitude in the ER group from 0.2 ± 0.15 mV at baseline to 0.08 ± 0.09 mV (P < .001). The QRS width prolonged significantly in all 3 groups, but the prolongation was significantly less in the ER group (+21 ms) than in the Br group (+36 ms; P < .001) or controls (+28 ms; P = .010). Decrease in mean inferolateral R-wave amplitude was similar in all the groups (ER group -0.14 mV; Br group -0.11 mV; controls -0.13 mV; P = ns), but mean inferolateral S-wave amplitude increased significantly less in the ER group (ER group +0.14 mV; Br group +16 mV; controls +0.20 mV; P < .001)., Conclusions: Ajmaline significantly decreases the J-wave amplitude in ER and prolongs the QRS width significantly less than in patients with Br. This indicates a different pathogenesis for both disorders. The altered terminal QRS vector probably is responsible for the decrease in the J-wave amplitude in ER, although a specific effect of ajmaline on J waves cannot be excluded., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Whether patients with persistent atrial fibrillation (AF) obtain the same degree of benefit with cardiac resynchronization therapy (CRT) as those in sinus rhythm remains unclear., Methods: We enrolled 93 patients undergoing CRT implantation, 20 (22%) of whom had rate-controlled persistent AF. The primary endpoint was CRT response defined as 1 class improvement in Specific Activity Scale and 15% reduction in left ventricular end-systolic volume (LVESV) during 12 months. Other endpoints included changes in 6-minute walk distance, quality of life, B-type natriuretic peptide, and survival., Results: Baseline characteristics were similar in those with and without AF. Response to CRT was observed in 42% vs 54% of those with and without AF, respectively (P=0.3). Both groups had significant improvements in 6-minute walk distance, quality of life, and LVESV, but the improvement in LVESV was smaller in those with AF (13.7%±14.9% vs 27.7%±23.7%; P=0.02). During 2.8±1.4 years of follow-up, AF was associated with a 2.2-fold increased risk of death or transplantation (95% confidence interval, 1.2-3.9; P=0.01)., Conclusions: Compared with patients without rate-controlled persistent AF, those with rate-controlled persistent AF had similar rates of clinical improvement but less left ventricular reverse remodelling in the first year after CRT. AF was associated with a markedly higher risk of death or transplantation in long-term follow-up. Given these findings, randomized studies assessing CRT efficacy in those with AF are warranted., (Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Whether the benefits observed with cardiac resynchronization therapy (CRT) are similar in patients with versus those without atrial fibrillation (AF) is unclear. Furthermore, whether patients with AF receiving CRT should undergo atrioventricular nodal (AVN) ablation remains uncertain., Objective: The purpose of this study was to compare outcomes in patients with and those without AF receiving CRT and to evaluate the influence of AVN ablation on outcomes in patients with AF., Methods: A systematic review and meta-analysis was performed. Outcomes included death, CRT nonresponse, and changes in left ventricular (LV) remodeling, quality of life (QoL), and 6-minute hall walk distance (6MWD)., Results: Twenty-three observational studies were included and followed a total of 7,495 CRT recipients, 25.5% with AF, for a mean of 33 months. AF was associated with an increased risk of nonresponse to CRT (34.5% vs 26.7%; pooled relative risk [RR] 1.32; 95% confidence interval [CI] 1.12, 1.55; P = .001)) and all-cause mortality (10.8% vs 7.1% per year, pooled RR 1.50, 95% CI 1.08, 2.09; P = .015). The presence of AF was also associated with less improvement in QoL, 6-minute hall walk distance, and LV end-systolic volume but not LV ejection fraction. Among patients with AF, AVN ablation appeared favorable with a lower risk of clinical nonresponse (RR 0.40; 95% CI 0.28, 0.58; P <.001) and a reduced risk of death., Conclusion: The benefits of CRT appear to be attenuated in patients with AF. The presence of AF is associated with an increased risk of clinical nonresponse and death than in patients without AF. AVN ablation may improve CRT outcomes in patients with AF., (Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to use a candidate gene approach to identify common polymorphisms that are associated with resting sinus heart rate in a population without overt cardiovascular disease., Background: Increased resting heart rate is significantly associated with susceptibility to development of myocardial infarction, sudden cardiac death, and overall cardiac mortality., Methods: A longitudinal cohort of 1468 individuals (active and retired middle-aged Canadian firefighters) who were enrolled in the Firefighters and Their Endothelium (FATE) study was evaluated. Resting heart rate was recorded from the electrocardiogram (ECG) obtained at enrollment. Candidate genes were selected for their known roles in sinus node automaticity and/or its regulation, and single nucleotide polymorphisms (SNPs) with a minor allele frequency of > or =0.20 were targeted. A total of 53 SNPs in 46 genes were selected and analyzed in a screening sample, and 33 SNPs in 29 genes were evaluated in the full population., Results: Univariate analysis detected five putative associations between HR and SNPs. As expected, environmental covariates were identified. Three polymorphisms, ADRB1 G389R, SCN5a H558R, and CASQ1 intron 2, remained statistically significant and independent of covariates. Some alleles were associated with higher and some with lower heart rates. A stepwise increase in heart rate was observed that was dependent on the number of tachycardia-associated alleles with progressive increases in mean heart rate from 51 to 66 bpm., Conclusions: Common polymorphisms are associated with heart rate in a stepwise allele-dependent manner.