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Background: Atrial fibrillation (AF) represents a global epidemic. Although international AF practice guidelines indicate weight loss for patients with AF and comorbid obesity (BMI ≥ 30 kg/m2) to alleviate symptom burden and improve prognosis, few cardiac rehabilitation (CR) programs include targeted weight loss treatment. Aims: This RCT protocol will evaluate the efficacy of a "Small Changes" behavioral weight loss treatment (BWLT) to produce clinically relevant (≥ 10%) weight loss among patients with AF and obesity undergoing CR, relative to CR alone. Secondary aims are to establish efficacy of CR + BWLT for improving AF symptoms, AF risk factors, and health-related quality of life. Methods: Adults (18 +) with AF and obesity will be recruited and randomized to receive CR + BWLT (intervention) or CR-only (control). Controls will receive CR consisting of supervised exercise and risk factor self-management for 12 weeks. The intervention group will receive CR plus BWLT (12 weekly, group-based virtual sessions, followed by 12 weeks of follow-up support). Weight and AF-risk factors will be assessed at pre-randomization, 12 weeks, 24 weeks, and 52 weeks. AF burden will be assessed using 30-s ECGs recorded bidaily and with AF symptoms. The primary endpoint of weight loss will be calculated from baseline to 52 weeks as a percentage of starting weight. Intention-to-treat analyses will compare the proportion in each group achieving ≥ 10% weight loss. Assuming success rates of 5% and 30% among controls and intervention groups, respectively, and a 30% loss to follow-up, 120 patients (60 per group) will provide 80% power to detect a difference using a two-sided independent test of proportions (alpha = 5%). Impact: This clinical trial will be the first to demonstrate that adding BWLT to CR promotes clinically meaningful weight loss among patients with AF and comorbid obesity. Findings will inform design and execution of a large efficacy trial of long-term (e.g., 5-year) clinical endpoints (e.g., AF severity, mortality). Implementing weight control interventions designed to target the AF substrate in CR could dramatically reduce morbidity and enhance quality of life among patients living with AF in Canada. Trial registration: ClinicalTrials.gov registration number: NCT05600829. Registered October 31, 2022. [ABSTRACT FROM AUTHOR]

Purpose: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models. Methods: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics. Results: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease. Conclusion: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models' Type I error and statistical power for identifying covariates associated with DIF. [ABSTRACT FROM AUTHOR]

Purpose: Patients with coronary artery disease (CAD) experience significant angina symptoms and lifestyle changes. Revascularization procedures can result in better patient-reported outcomes (PROs) than optimal medical therapy (OMT) alone. This study evaluates the impact of response shift (RS) on changes in PROs of patients with CAD across treatment strategies. Methods: Data were from patients with CAD in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease (APPROACH) registry who completed the 16-item Canadian version of the Seattle Angina Questionnaire at 2 weeks and 1 year following a coronary angiogram. Multi-group confirmatory factor analysis (MG-CFA) was used to assess measurement invariance across treatment groups at week 2. Longitudinal MG-CFA was used to test for RS according to receipt of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical therapy (OMT) alone. Results: Of the 3116 patients included in the analysis, 443 (14.2%) received CABG, 2049(65.8%) PCI, and the remainder OMT alone. The MG-CFA revealed a partial-strong invariance across the treatment groups at 2 weeks (CFI = 0.98, RMSEA [90% CI] = 0.05 [0.03, 0.06]). Recalibration RS was detected on the Angina Symptoms and Burden subscale and its magnitude in the OMT, PCI, and CABG groups were 0.32, 0.28, and 0.53, respectively. After adjusting for RS effects, the estimated target changes were largest in the CABG group and negligible in the OMT group. Conclusion: Adjusting for RS is recommended in studies that use SAQ-CAN to assess changes in patients with CAD who have received revascularization versus OMT alone. [ABSTRACT FROM AUTHOR]

Aims Prior studies suggest that sodium–glucose cotransporter-2 inhibitors (SGLT2is) may decrease the incidence of atrial fibrillation (AF). However, it is unknown whether SGLT2i can attenuate the disease course of AF among patients with pre-existing AF and Type II diabetes mellitus (DM). In this study, our objective was to examine the association between SGLT2i prescription and arrhythmic outcomes among patients with DM and pre-existing AF. Methods and results We conducted a population-based cohort study of adults with DM and AF between 2014 and 2019. Using a prevalent new-user design, individuals prescribed SGLT2i were matched 1:1 to those prescribed dipeptidyl peptidase-4 inhibitors (DPP4is) based on time-conditional propensity scores. The primary endpoint was a composite of AF-related healthcare utilization (i.e. hospitalization, emergency department visits, electrical cardioversion, or catheter ablation). Secondary outcome measures included all-cause mortality, heart failure (HF) hospitalization, and ischaemic stroke or transient ischaemic attack (TIA). Cox proportional hazard models were used to examine the association of SGLT2i with the study endpoint. Among 2242 patients with DM and AF followed for an average of 3.0 years, the primary endpoint occurred in 8.7% (n = 97) of patients in the SGLT2i group vs. 10.0% (n = 112) of patients in the DPP4i group [adjusted hazard ratio 0.73 (95% confidence interval 0.55–0.96; P = 0.03)]. Sodium–glucose cotransporter-2 inhibitors were associated with significant reductions in all-cause mortality and HF hospitalization, but there was no difference in the risk of ischaemic stroke/TIA. Conclusion Among patients with DM and pre-existing AF, SGLT2is are associated with decreased AF-related health resource utilization and improved arrhythmic outcomes compared with DPP4is. [ABSTRACT FROM AUTHOR]

Background: High-density (HD) mapping of the pulmonary vein (PVs) has been hypothesized to improve the detection of conduction gaps in the radiofrequency ablation lesions set after pulmonary vein isolation (PVI) for the treatment of atrial fibrillation (AF). We aimed to compare the incidence of gaps after PVI with a standard 20-pole circumferential mapping catheter (CMC-20) and an HD mapping catheter (HD Grid). Methods: This prospective study included patients scheduled for high-power short-duration PVI. Acute PVI was defined as an entrance and exit block using the CMC-20 after ≥ 20 min waiting period. The left atrium was then remapped using the HD Grid high-density mapping catheter to identify residual conduction gaps in the PVI lines by voltage and activation criteria. The primary endpoint was the number of gaps identified per patient by the HD Grid catheter. Results: A total of 20 patients were included (mean age 59.9 ± 10.8 years, 15% female, 70% paroxysmal AF). The new map with the HD Grid identified 6 gaps in 4 patients (20%) or 0.3 ± 0.7 gaps per patient (p = 0.055 when compared to CMC-20). Five gaps (83%) were located at the right PVs. There was no difference in mapping time (CMC-20 12.2 ± 2.6 min vs HD Grid 11.7 ± 3.4 min, p = 0.452); however, the number of points was significantly higher in the HD Grid map (1662.7 ± 366.1 vs 1171.6 ± 313.6, p < 0.001). Conclusions: HD mapping during AF ablation identified PVI gaps in 1 out of 5 patients. Therefore, HD mapping may have the potential to improve AF ablation success rates in the long term. Trial registration: ClinicalTrials.gov NCT04850508 on April 20, 2021. [ABSTRACT FROM AUTHOR]

Background: Patients with previous acute coronary syndrome (ACS) are at high risk of recurrent adverse cardiovascular events. Recently, prolonged dual antiplatelet therapy (DAPT) and oral anticoagulation therapy (OAT) have been shown to reduce recurrent ischemic events to the expense of an increase in bleeding events. The number of patients potentially eligible for these therapies in real life remains to be determined. Methods: Among ACS patients from five registries and one randomized controlled trial, we assessed the proportion of patients eligible for the PEGASUS strategy only and the proportion of patients eligible for the COMPASS strategy only, and set out the proportion of patients with an overlap between the strategies. Findings: Among the 10,048 evaluable patients, we found that 5373 (53.4%) were eligible for the PEGASUS strategy and 3841 (38.2%) were eligible for the COMPASS strategy, with a group of 3444 (34.4%) overlapping between the two strategies. The number of patients eligible for the PEGASUS strategy only was 1929 (19.2%) and the number eligible for the COMPASS strategy only was 397 (4.0%); 4278 (42.6%) were eligible for neither a PEGASUS strategy nor a COMPASS strategy. Interpretation: In a large cohort of ACS patients, one in three patients was eligible for either a prolonged DAPT with ticagrelor 60 mg and low-dose aspirin or a dual pathway inhibition approach with rivaroxaban 2.5 mg and low-dose aspirin. [ABSTRACT FROM AUTHOR]

Background: Atrial Fibrillation (AF) is a major cause of stroke. Oral anticoagulation can reduce the risk of AF-associated stroke by 65% but it remains underused. Stroke prevention therapy in patients with AF has been considered a good target for shared decision making with patient decision aids as it is a long-term, preference-sensitive decision with known risk-benefit trade-offs. The aim of this systematic review was to summarize published literature on the effectiveness of patient decision aids on the choice of and adherence to stroke prevention therapy in individuals with AF. Methods: We conducted a structured literature search for prospective studies evaluating decision aids for AF stroke prevention therapy in adult patients with nonvalvular AF. We included studies that compared those exposed to a decision aid with a control condition for outcomes including choice of therapy, adherence, decisional conflict and patient knowledge. Quantitative meta-analysis was not feasible due to excessive between-study heterogeneity. Results: Eight studies met inclusion and exclusion criteria. Six studies were randomized clinical trials and two were pre-post comparisons. Of the 8 studies, each evaluated a different decision aid, with only three including all contemporary oral anticoagulant drugs. All decision aids improved AF knowledge compared to baseline or control and decision aids reduced decisional conflict in four of six studies. However, there were inconsistent effects of the studied decision aids on initiation of oral anticoagulation. Adherence to initial stroke prevention therapy choice appeared to benefit from decision aid use in 2 studies that addressed this issue. Conclusions: Decision aids for stroke prevention increased AF patients' knowledge and decisional confidence but had variable impacts on choice of and adherence to stroke prevention therapy. The results highlight the need for well-designed decision aids that present patients with all contemporary therapeutic options. [ABSTRACT FROM AUTHOR]

Importance: Contrast-associated acute kidney injury (AKI) is a common complication of coronary angiography and percutaneous coronary intervention (PCI) that has been associated with high costs and adverse long-term outcomes.Objective: To determine whether a multifaceted intervention is effective for the prevention of AKI after coronary angiography or PCI.Design, Setting, and Participants: A stepped-wedge, cluster randomized clinical trial was conducted in Alberta, Canada, that included all invasive cardiologists at 3 cardiac catheterization laboratories who were randomized to various start dates for the intervention between January 2018 and September 2019. Eligible patients were aged 18 years or older who underwent nonemergency coronary angiography, PCI, or both; who were not undergoing dialysis; and who had a predicted AKI risk of greater than 5%. Thirty-four physicians performed 7820 procedures among 7106 patients who met the inclusion criteria. Participant follow-up ended in November 2020.Interventions: During the intervention period, cardiologists received educational outreach, computerized clinical decision support on contrast volume and hemodynamic-guided intravenous fluid targets, and audit and feedback. During the control (preintervention) period, cardiologists provided usual care and did not receive the intervention.Main Outcomes and Measures: The primary outcome was AKI. There were 12 secondary outcomes, including contrast volume, intravenous fluid administration, and major adverse cardiovascular and kidney events. The analyses were conducted using time-adjusted models.Results: Of the 34 participating cardiologists who were divided into 8 clusters by practice group and center, the intervention group included 31 who performed 4327 procedures among 4032 patients (mean age, 70.3 [SD, 10.7] years; 1384 were women [32.0%]) and the control group included 34 who performed 3493 procedures among 3251 patients (mean age, 70.2 [SD, 10.8] years; 1151 were women [33.0%]). The incidence of AKI was 7.2% (310 events after 4327 procedures) during the intervention period and 8.6% (299 events after 3493 procedures) during the control period (between-group difference, -2.3% [95% CI, -0.6% to -4.1%]; odds ratio [OR], 0.72 [95% CI, 0.56 to 0.93]; P = .01). Of 12 prespecified secondary outcomes, 8 showed no significant difference. The proportion of procedures in which excessive contrast volumes were used was reduced to 38.1% during the intervention period from 51.7% during the control period (between-group difference, -12.0% [95% CI, -14.4% to -9.4%]; OR, 0.77 [95% CI, 0.65 to 0.90]; P = .002). The proportion of procedures in eligible patients in whom insufficient intravenous fluid was given was reduced to 60.8% during the intervention period from 75.1% during the control period (between-group difference, -15.8% [95% CI, -19.7% to -12.0%]; OR, 0.68 [95% CI, 0.53 to 0.87]; P = .002). There were no significant between-group differences in major adverse cardiovascular events or major adverse kidney events.Conclusions and Relevance: Among cardiologists randomized to an intervention including clinical decision support with audit and feedback, patients undergoing coronary procedures during the intervention period were less likely to develop AKI compared with those treated during the control period, with a time-adjusted absolute risk reduction of 2.3%. Whether this intervention would show efficacy outside this study setting requires further investigation.Trial Registration: ClinicalTrials.gov Identifier: NCT03453996. [ABSTRACT FROM AUTHOR]

Background: Assessment of potential geographic variation in quality indicators of atrial fibrillation care may identify opportunities for improvement in the quality of atrial fibrillation care. The objective of this study was to assess for potential geographic variation in the quality of atrial fibrillation care in Alberta, Canada. Methods: In a population-based cohort of adults (age ≥ 18 yr) with incident nonvalvular atrial fibrillation (NVAF) diagnosed between Apr. 1, 2008, and Mar. 31, 2016, in Alberta, we investigated the variation in national quality indicators of atrial fibrillation care developed by the Canadian Cardiovascular Society. Specifically, we assessed the geographic and temporal variation in the proportion of patients with initiation of oral anticoagulant therapy, persistence with therapy, ischemic stroke and major bleeding outcomes 1 year after atrial fibrillation diagnosis using linked administrative data sets. We defined stroke risk using the CHADS2 score. We assessed geographic variation using small-area variation statistics and geospatial data analysis. Results: Of the 64 093 patients in the study cohort (35 019 men [54.6%] and 29 074 women [45.4%] with a mean age of 69 [standard deviation 15.9] yr), 36 199 were at high risk for stroke and 14 411 were at moderate risk. Within 1 year of NVAF diagnosis, 20 180 patients (55.7%) in the high-risk group and 6448 patients (44.7%) in the moderate-risk group were prescribed anticoagulation. A total of 2187 patients (3.4%) had an ischemic stroke, and 2996 patients (4.7%) experienced a major bleed. There was substantial regional variation observed in initiation of oral anticoagulant therapy but not in the proportion of patients with ischemic stroke or major bleeding. Among the 64 Health Status Areas in Alberta, therapy initiation rates ranged from 22.6% to 71.2% among patients at high stroke risk and from 22.7% to 55.8% among those at moderate stroke risk, with clustering of lower therapy initiation rates in rural northern regions. Interpretation: The rate of initiation of oral anticoagulant therapy among adults with incident atrial fibrillation was less than 60% in patients in whom oral anticoagulant therapy would be considered guideline-appropriate care. The large geographic variation in oral anticoagulant prescribing warrants additional study into patient, provider and health care system factors that contribute to variation and drive disparities in high-quality, equitable atrial fibrillation care. [ABSTRACT FROM AUTHOR]

Low estradiol status is associated with increased cardiovascular risk. We sought to determine the association between heart rate variability (HRV), a marker of cardiovascular risk, at baseline and in response to stressor as a function of menopausal status, menstrual cycle phase and estradiol level. Forty‐one healthy women (13 postmenopausal, 28 premenopausal) were studied. Eleven premenopausal women were additionally studied in the high and low estradiol phases of the menstrual cycle. HRV was calculated by spectral power analysis (low Frequency (LF), high frequency (HF) and LF:HF) at baseline and in response to graded Angiotensin II (AngII) infusion. The primary outcomes were differences in HRV at baseline and in response to AngII. Compared to premenopausal women in the low estradiol phase, postmenopausal women demonstrated lower baseline LF (p = 0.01) and HF (p < 0.001) measures, which were not significant after adjustment for age and BMI. In response to AngII, a decrease in cardioprotective HRV (ΔHF = −0.43 ± 0.46 ln ms2, p = 0.005 vs. baseline) was observed in postmenopausal women versus premenopausal women. Baseline HRV parameters did not differ by menstrual phase in premenopausal women. During the low estradiol phase, no differences were observed in the HRV response to AngII challenge. In contrast, women in the high estradiol phase were unable to maintain HRV (ΔLF = −0.07 ± 0.46 ln ms2, p = 0.048 response vs. baseline, ΔHF = −0.33 ± 0.74 ln ms2, p = 0.048 response vs. baseline). No association was observed between any measure of HRV and estradiol level. Menopausal status and the high estradiol phase in premenopausal women were associated with reduced HRV, a marker of cardiovascular risk. Understanding the role of estradiol in the modulation of cardiac autonomic tone may help guide risk reduction strategies in women. [ABSTRACT FROM AUTHOR]

Purpose: The Seattle Angina Questionnaire (SAQ) is a widely used patient-reported measure of health status in patients with coronary artery disease. Comparisons of SAQ scores amongst population groups and over time rely on the assumption that its factorial structure is invariant. This study evaluates the measurement invariance of the SAQ across different demographic and clinical groups and over time. Methods: Data were obtained from the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry, a registry of patients who received coronary angiogram in Alberta, Canada. The study cohort consists of adult patients who completed the paper-based version of the 16-item Canadian version of the SAQ (SAQ-CAN) 2 weeks and 1-year post-coronary angiogram between 2009 and 2016. Multi-group confirmatory factor analysis was used to assess configural, weak, strong, and strict measurement invariance across age groups, sex, angina type, treatment, and over time. Model fit was assessed using the comparative fit index and root mean square error of approximation. Results: Of the 8101 patients included in these analysis, 1300 (16.1%) were at least 75 years old, while 1755 (21.7%) were female, 5154 (63.6%) were diagnosed with acute coronary syndrome, 1177 (14.5%) received coronary artery bypass graft treatment, and 3279 had complete data on the SAQ-CAN at both occasions. There was evidence of strict invariance across age, sex, and angina type, and treatment groups, but partial strict invariance was established over time. Conclusion: SAQ-CAN can be used to compare the health status of coronary artery disease patients across population groups and over time. [ABSTRACT FROM AUTHOR]

Purpose: Higher risk of bleeding with ticagrelor over clopidogrel in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) has been suggested. We assessed the incidence of major bleedings (MB), reinfarction (re-MI), and all-cause death to evaluate safety and efficacy of ticagrelor versus clopidogrel in such population. Methods: Real-world registries RENAMI and BleeMACS were merged. The pooled cohort was divided into two groups, clopidogrel versus ticagrelor. Statistical analysis considered patients <75 versus ≥75 years old. Endpoints were BARC 3–5 MB, re-MI, and all-cause death at 1-year follow-up. The study included 16,653 patients (13,153 < 75 and 3500 ≥ 75 years). Ticagrelor was underused in elderly patients (16.3% versus 20.8%, P < 0.001). Using propensity score matching (PSM), two treatment groups of 1566 patients were included in the final analysis. Results: Ticagrelor was able to prevent re-MI (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.2–0.6; P < 0.001) and all-cause death (HR, 0.60; 95% CI, 0.4–0.9; P = 0.026) irrespective of age. In patients ≥75 years, ticagrelor reduced all-cause death (HR, 0.32; 95% CI, 0.1–0.8; P = 0.012) and re-MI (HR, 0.25; 95% CI, 0.1–1.1, P = 0.072). Moreover, even with the limit of the low number of events, ticagrelor did not significantly increase the incidence of MB (HR, 1.49; 95% CI, 0.70–3.0; P = 0.257). At multiple Cox regression, age (HR, 1.03; 95% CI, 1.02–1.05; P < 0.001) resulted an independent risk factor for bleeding. Conclusion: In our study, reflecting the results from two large retrospective, real-world registries, Ticagrelor did not significantly increase MB compared with clopidogrel in elderly patients with ACS treated with PCI, while significantly improving 1-year survival. Further studies on elderly patients are suggested. [ABSTRACT FROM AUTHOR]

Objectives: Despite advances in medical therapy, reperfusion, and mechanical support, cardiogenic shock remains associated with excess morbidity and mortality. Accurate risk stratification may improve patient management. We compared the accuracy of established risk scores for cardiogenic shock. Methods: Patients admitted to tertiary care center cardiac care units in the province of Alberta in 2015 were assessed for cardiogenic shock. The Acute Physiology and Chronic Health Evaluation-II (APACHE-II), CardShock, intra-aortic balloon pump (IABP) Shock II, and sepsis-related organ failure assessment (SOFA) risk scores were compared. Receiver operating characteristic curves were used to assess discrimination of in-hospital mortality and compared using DeLong's method. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. Results: The study included 3021 patients, among whom 510 (16.9%) had cardiogenic shock. Patients with cardiogenic shock had longer median hospital stays (median 11.0 vs 4.1 days, P < .001) and were more likely to die (29.0% vs 2.5%, P < .001). All risk scores were adequately calibrated for predicting hospital morality except for the APACHE-II score (Hosmer-Lemeshow P < .001). Discrimination of in-hospital mortality with the APACHE-II (area under the curve [AUC]: 0.72, 95% confidence interval [CI]: 0.66-0.76) and IABP-Shock II (AUC: 0.73, 95% CI: 0.68-0.77) scores were similar, while the CardShock (AUC: 0.76, 95% CI: 0.72-0.81) and SOFA (AUC: 0.76, 95%CI: 0.72-0.81) scores had better discrimination for predicting in-hospital mortality. Conclusions: In a real-world population of patients with cardiogenic shock, existing risk scores had modest prognostic accuracy, with no clear superior score. Further investigation is required to improve the discriminative abilities of existing models or establish novel methods. [ABSTRACT FROM AUTHOR]

Background Young women with end-stage kidney disease (ESKD) have early menopause compared with women in the general population and the highest mortality among the dialysis population. We hypothesized that low estrogen status was associated with death in women with ESKD. Methods We measured estradiol and sex hormone levels in female ESKD patients initiating hemodialysis from 2005 to 2012 in four Canadian centers. We divided women into quintiles based on estradiol levels and tested for associations between the estradiol level and cardiovascular (CV), non-CV and all-cause mortality. Participants were further dichotomized by age. Results A total of 482 women (60 ± 15 years of age, 53% diabetic, estradiol 116 ± 161 pmol/L) were followed for a mean of 2.9 years, with 237 deaths (31% CV). Estradiol levels were as follows (mean ± standard deviation): Quintile 1: 19.3 ± 0.92 pmol/L; Quintile 2: 34.6 ± 6.6 pmol/L; Quintile 3: 63.8 ± 10.6 pmol/L; Quintile 4: 108.9 ± 19.3; Quintile 5: 355 ± 233 pmol/L. Compared with Quintile 1, women in Quintiles 4 and 5 had significantly higher adjusted all-cause mortality {hazard ratio [HR] 2.12 [95% confidence interval (CI) 1.38–3.25] and 1.92 [1.19–3.10], respectively}. Similarly, compared with Quintile 1, women in Quintile 5 had higher non-CV mortality [HR 2.16 (95% CI 1.18–3.96)]. No associations were observed between estradiol levels and CV mortality. When stratified by age, higher quintiles were associated with greater all-cause mortality (P for trend <0.001) and non-CV mortality (P for trend = 0.02), but not CV mortality in older women. Conclusions In women with ESKD treated with hemodialysis, higher estradiol levels were associated with greater all-cause and non-CV mortality. Further studies are required to determine the mechanism for the observed increased risk. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease (CKD) and heart disease face challenging treatment decisions. We sought to explore the perceptions of patients and physicians about shared decision-making for coronary procedures for people with CKD, as well as opinions about strategies and tools to improve these decisions. Methods: We partnered with 4 patients with CKD and 1 caregiver to design and conduct a qualitative descriptive study using semi-structured interviews and content analysis. Patient participants with CKD and either acute coronary syndrome or cardiac catheterization in the preceding year were recruited from a provincial cardiac registry, cardiology wards and clinics in Calgary between March and September 2018. Cardiologists from the region also participated in the study. Data analysis emphasized identifying, organizing and describing themes found within the data. Results: Twenty patients with CKD and 10 cardiologists identified several complexities related to bidirectional information exchange needed for shared decision-making. Themes identified by both patients and physicians included challenges synthesizing best evidence, variable patient knowledge seeking, timeliness in the acute care setting and influence of roles on decision-making. Themes identified by physicians related to processes and tools to help support shared decision-making in this setting included personalization to reflect the variability of risks and heterogeneity of patient preferences as well as allowing for physicians to share their clinical judgment. Interpretation: There are complexities related to bidirectional information exchange between patients with CKD and their physicians for shared decision-making about coronary procedures. Processes and tools to facilitate shared decision-making in this setting require personalization and need to be time sensitive. [ABSTRACT FROM AUTHOR]

Background: In studies showing associations between ambient air pollution and myocardial infarction (MI), data have been lacking on the inherent spatial variability of air pollution. The aim of this study was to determine whether the long-term spatial distribution of air pollution influences short-term temporal associations between air pollution and admission to hospital for MI. Methods: We identified adults living in Calgary who were admitted to hospital for an MI between 2004 and 2012. We evaluated associations between short-term exposure to air pollution (ozone [O3], nitrogen dioxide [NO2], sulfur dioxide [SO2], carbon monoxide [CO], particulate matter < 10 μm in diameter [PM10] and particulate matter < 2.5 μm in diameter [PM2.5]), and hospital admissions for MI using a time-stratified, case-crossover study design. Air Quality Health Index (AQHI) scores were calculated from a composition of O3, NO2 and PM2.5. Conditional logistic regression models were stratified by low, medium and high levels of neighbourhood NO2 concentrations derived from land use regression models; results of these analyses are presented as odds ratios (ORs) with 95% confidence intervals (CIs). Results: From 2004 to 2012, 6142 MIs were recorded in Calgary. Individuals living in neighbourhoods with higher long-term air pollution concentrations were more likely to be admitted to hospital for MI after short-term elevations in air pollution (e.g., 5-day average NO2: OR 1.20, 95% CI 1.03–1.40, per interquartile range [IQR]) as compared with regions with lower air pollution (e.g., 5-day average NO2: OR 0.90, 95% CI 0.78–1.04, per IQR). In high NO2 tertiles, the AQHI score was associated with MI (e.g., 5-day average OR 1.13, 95% CI 1.02–1.24, per IQR; 3-day average OR 1.13, 95% CI 1.04–1.23, per IQR). Interpretation: Our results show that the effect of air pollution on hospital admissions for MI was stronger in areas with higher NO2 concentrations than that in areas with lower NO2 concentrations. Individuals living in neighbourhoods with higher traffic-related pollution should be advised of the health risks and be attentive to special air quality warnings. [ABSTRACT FROM AUTHOR]

Aims Left ventricular hypertrophy (LVH) is the most common form of myocardial remodelling and predicts adverse outcomes in patients with coronary artery disease (CAD). However, sex-specific prevalence and prognostic significance of LVH patterns are poorly understood. We investigated the sex-specific influence of LVH pattern on clinical outcomes in patients undergoing cardiovascular magnetic resonance (CMR) and coronary angiography following adjustment for co-morbidities including CAD burden. Methods and results Patients undergoing CMR and coronary angiography between 2005 and 2013 were included. Volumetric measurements of left ventricular (LV) mass with classification of concentric vs. eccentric remodelling patterns were determined from CMR cine images. Multivariable Cox analysis was performed to assess independent associations with the primary outcome of all-cause mortality. In total, 3754 patients were studied (mean age 59.3 ± 13.1 years), including 1039 (27.7%) women. Women were more likely to have concentric remodelling (8.1% vs. 2.1%, P  < 0.001), less likely to have eccentric hypertrophy (15.1% vs. 26.8%, P  < 0.001) and had a similar prevalence of concentric hypertrophy (6.1 vs. 5.2%, P  = 0.296) compared to men. At a median follow-up of 3.7 years, 315 (8.4%) patients died. Following adjustment including CAD burden, concentric hypertrophy was associated with increased all-cause mortality in women [adjusted hazard ratio (HR) 3.48, P  < 0.001] and men (adjusted HR 2.57, P  < 0.001). Eccentric hypertrophy was associated with all-cause mortality only in women (adjusted HR 1.78, P  = 0.047). Conclusion Patterns of LV remodelling differ by sex and LVH and provides prognostic information in both men and women. Our findings support the presence of sex-specific factors influencing LV remodelling. [ABSTRACT FROM AUTHOR]

Background: We developed and validated laboratory test--based risk scores (i.e., lab risk scores) to reclassify mortality risk among patients undergoing their first coronary catheterization. Methods: Patients were catheterized between 2009 and 2015 in Calgary, Alberta, Canada (n=14 135, derivation cohort), and in Edmonton, Alberta, Canada (n=12 143, validation cohort). Logistic regression with group LASSO (least absolute shrinkage and selection operator) penalty was used to select quintiles of the last laboratory tests (red blood cell count, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, mean corpuscular volume, red cell distribution width, platelet count, total white blood cell count, plasma sodium, potassium, chloride, CO2, international normalized ratio, estimated glomerular filtration rate) performed <30 days before catheterization and by age and sex that were significantly associated with death ≤60 and >60 days after catheterization. Follow-up was until 2016. Risk scores were developed from significant tests, internally validated in Calgary among bootstrap samples and externally validated in Edmonton after recalibration using coefficients developed in Calgary. Interaction tests were performed, and net reclassification improvement vs conventional demographic and clinical risk factors was determined. Results: Lab risk scores were strongly associated with mortality (29-40x for top vs bottom quintile, P for trends <0.01), had good discrimination and were well calibrated in Calgary (C=0.80-0.85, slope=0.99-1.01) and Edmonton (C=0.80-0.82; slope=1.02-1.05)--similar to demographic and clinical risk factors alone. Associations were attenuated by several comorbidities; however, scores appropriately reclassified 11%-20% of deaths (both follow-up periods) and 6%-9% of survivors (>60 days) after catheterization vs demographic and clinical risk factors. [ABSTRACT FROM AUTHOR]

Introduction: Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks. Methods: A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents. Results: A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3–5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3–5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3–5 events. Conclusion: In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events. [ABSTRACT FROM AUTHOR]

The association between prior stroke/transient ischemic attack (TIA) and clinical outcomes in patients with acute coronary syndrome (ACS) has not been well explored. We evaluated the impact of prior stroke/TIA on this specific patient population. We conducted an international multicenter study including 15 401 patients with ACS from the Bleeding Complications in a Multicenter Registry of Patients Discharged With Diagnosis of Acute Coronary Syndrome registry. They were divided into 2 groups: patients with and without prior stroke/TIA. The primary end point was death at 1-year follow-up. Prior stroke/TIA was associated with higher rate of 1-year death (8.7% vs 3.4%; P <.001). It was an independent predictor of 1-year death even after adjustment for confounding variables (odds ratio, 1.705; 95% confidence interval, 1.046-2.778; P =.032). Besides, patients with prior stroke/TIA had significantly increased 1-year reinfarction (5.6% vs 3.8%, P =.015), in-hospital bleeding (8.7% vs 5.8%, P <.001), and 1-year bleeding (5.2% vs 3.0%, P <.001). No difference of antithrombotic therapies or dual antiplatelet therapy (DAPT) types on outcomes was observed in patients with prior stroke/TIA. Prior stroke/TIA was associated with higher 1-year death for patients with ACS who underwent percutaneous coronary intervention. No benefits or harms were observed with different antithrombotic therapies or DAPT types in these patients. [ABSTRACT FROM AUTHOR]

Background: Characterization of left atrial (LA) hemodynamics in paroxysmal atrial fibrillation (PAF) may provide valuable insights for thromboembolic risk.Purpose: To evaluate LA vortex formation and velocity distributions by 4D flow MRI and identify associations with age, LA/LV (left ventricle) function, and established risk scores.Study Type: Prospective clinical.Population: Patients with PAF (n = 45, 46 ± 14 years) and healthy controls (n = 15, 54 ± 9 years) were enrolled.Mri Sequences: 3T standardized cardiac MRI protocol inclusive of 4D flow MRI.Assessment: Flow analysis planes were prescribed at each pulmonary vein. Velocity distribution analysis and vortex size quantification by the Lambda2 (λ2 ) method were performed in the LA.Statistics: Pearson or Spearman's correlation coefficients, r, were calculated to identify relationships between 4D flow-derived LA parameters and age, LA/LV function, and CHA2 DS2 -VASc stroke risk score. Univariate and multivariate determinants of stroke risk were assessed using linear regressions. To compare parameters within multiple groups, one-way analysis of variance or Kruskal-Wallis was used.Results: LA vortice sizes were observed in all subjects using λ2 showing inverse correlations with peak pulmonary vein inflow velocities (P < 0.05), and positive correlations with LA volume (P < 0.05). Vortex size was elevated in PAF at all phases of the cardiac cycle, being most prominent at end early diastole (3.98 ± 1.84 cm3 vs. 6.93 ± 3.11 cm3 , P = 0.001). Velocity distribution analysis showed a greater incidence of flow stasis among patients with PAF (P < 0.05). In univariate regression, vortex size was associated with the CHA2 DS2 -VASc risk score at peak systole (0.457 ± 0.038, P ≤ 0.001). However, in multivariate regression age was the dominant determinant of stroke risk (0.348 ± 0.012, P = 0.006).Data Conclusion: This study demonstrated that LA vortex size is increased among low-risk patients with PAF and is associated with the CHA2 DS2 -VASc risk score. Age remained the dominant determinant of stroke risk.Level Of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:871-884. [ABSTRACT FROM AUTHOR]

Purpose: Perceived social support is known to be an important predictor of health outcomes in patients with acute coronary syndrome (ACS). This study investigates patterns of longitudinal trajectories of patient-reported perceived social support in individuals with ACS.Methods: Data are from 3013 patients from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry who had their first cardiac catheterization between 2004 and 2011. Perceived social support was assessed using the 19-item Medical Outcomes Study Social Support Survey (MOS) 2 weeks, 1 year, and 3 years post catheterization. Group-based trajectory analysis based on longitudinal multiple imputation model was used to identify distinct subgroups of trajectories of perceived social support over a 3-year follow-up period.Results: Three distinct social support trajectory subgroups were identified, namely: "High" social support group (60%), "Intermediate" social support group (30%), and "Low" social support subgroup (10%). Being female (OR = 1.67; 95% CI = [1.18-2.36]), depression (OR = 8.10; 95% CI = [4.27-15.36]) and smoking (OR = 1.70; 95% CI = [1.23-2.35]) were predictors of the differences among these trajectory subgroups.Conclusion: Although the majority of ACS patients showed increased or fairly stable trajectories of social support, about 10% of the cohort reported declining social support. These findings can inform targeted psycho-social interventions to improve their perceived social support and health outcomes. [ABSTRACT FROM AUTHOR]

Background: Comorbidity indexes derived from administrative databases are essential tools of research in global health. We sought to develop and validate a novel cardiac-specific comorbidity index, and to compare its accuracy with the generic Charlson-Deyo and Elixhauser comorbidity indexes.Methods: We derived the cardiac-specific comorbidity index from consecutive patients who were admitted to hospital at a tertiary-care cardiology hospital in Quebec. We used logistic regression analysis and incorporated age, sex and 22 clinically relevant comorbidities to build the index. We compared the cardiac-specific comorbidity index with refitted Charlson-Deyo and Elixhauser comorbidity indexes using the C-statistic and net reclassification improvement to predict in-hospital death, and the Akaike information criterion to predict length of stay. We validated our findings externally in an independent cohort obtained from a provincial registry of coronary disease in Alberta.Results: The novel cardiac-specific comorbidity index outperformed the refitted generic Charlson-Deyo and Elixhauser comorbidity indexes for predicting in-hospital mortality in the derivation population (n = 10 137): C-statistic 0.95 (95% confidence interval [CI] 0.94-0.9) v. 0.81 (95% CI 0.77-0.84) and 0.86 (95% CI 0.82-0.89), respectively. In the validation population (n = 17 877), the cardiac-specific comorbidity index was similarly better: C-statistic 0.92 (95% CI 0.89-0.94) v. 0.76 (95% CI 0.71-0.81) and 0.82 (95% CI 0.78-0.86), respectively, and also numerically outperformed the Charlson-Deyo and Elixhauser comorbidity indexes for predicting 1-year mortality (C-statistic 0.78 [95% CI 0.76-0.80] v. 0.75 [95% CI 0.73-0.77] and 0.77 [95% CI 0.75-0.79], respectively). Similarly, the cardiac-specific comorbidity index showed better fit for the prediction of length of stay. The net reclassification improvement using the cardiac-specific comorbidity index for the prediction of death was 0.290 compared with the Charlson-Deyo comorbidity index and 0.192 compared with the Elixhauser comorbidity index.Interpretation: The cardiac-specific comorbidity index predicted in-hospital and 1-year death and length of stay in cardiovascular populations better than existing generic models. This novel index may be useful for research of cardiology outcomes performed with large administrative databases. [ABSTRACT FROM AUTHOR]

A number of clinical studies have reported that diabetes mellitus (DM) is an independent risk factor for Atrial fibrillation (AF). After adjustment for other known risk factors including age, sex, and cardiovascular risk factors, DM remains a significant if modest risk factor for development of AF. The mechanisms underlying the increased susceptibility to AF in DM are incompletely understood, but are thought to involve electrical, structural, and autonomic remodeling in the atria. Electrical remodeling in DM may involve alterations in gap junction function that affect atrial conduction velocity due to changes in expression or localization of connexins. Electrical remodeling can also occur due to changes in atrial action potential morphology in association with changes in ionic currents, such as sodium or potassium currents, that can affect conduction velocity or susceptibility to triggered activity. Structural remodeling in DM results in atrial fibrosis, which can alter conduction patterns and susceptibility to re-entry in the atria. In addition, increases in atrial adipose tissue, especially in Type II DM, can lead to disruptions in atrial conduction velocity or conduction patterns that may affect arrhythmogenesis. Whether the insulin resistance in type II DM activates unique intracellular signaling pathways independent of obesity requires further investigation. In addition, the relationship between incident AF and glycemic control requires further study. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to evaluate prognostic value of beta-blocker (BB) administration in acute coronary syndromes (ACS) patients in the percutaneous coronary intervention (PCI) era.Methods and Results: The BleeMACS project is a multicenter, observational, retrospective registry enrolling patients with ACS worldwide in 15 hospitals. Patients discharged with BB therapy were compared to those discharged without a BB before and after propensity score with matching. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints included in-hospital reinfarction, in-hospital heart failure, 1-year myocardial infarction, 1-year bleeding and 1-year composite of death and recurrent myocardial infarction. After matching, 2935 patients for each group were enrolled. The primary endpoint of 1-year death was significantly lower in the group on BB therapy (4.5 vs 7%, p < 0.05), while only a trend was noted for recurrent acute myocardial infarction (4.5 vs 4.9%, p = 0.54). These results were consistent for patients older than 80 years of age, for ST-elevation myocardial infarction (STEMI) patients, and for those discharged with complete versus incomplete revascularization, but not for non-STEMI/unstable angina patients.Conclusions: BB therapy was related to 1-year lower risk of all-cause mortality, independently from completeness of revascularization, admission diagnosis, age and ejection fraction. Randomized controlled trials for patients treated with PCI for ACS should be performed. [ABSTRACT FROM AUTHOR]

Background: Surveys of patients suggest many want to be actively involved in treatment decisions for acute coronary syndromes. However, patient experiences of their engagement and participation in early phase decision-making have not been well described.Methods: We performed a patient led qualitative study to explore patient experiences with decision-making processes when admitted to hospital with non-ST elevation acute coronary syndrome. Trained patient-researchers conducted the study via a three-phase approach using focus groups and semi-structured interviews and employing grounded theory methodology.Results: Twenty patients discharged within one year of a non-ST elevation acute coronary syndrome participated in the study. Several common themes emerged. First, patients characterized the admission and early treatment of ACS as a rapidly unfolding process where they had little control. Participants felt they played a passive role in early phase decision-making. Furthermore, participants described feeling reduced capacity for decision-making owing to fear and mental stress from acute illness, and therefore most but not all participants were relieved that expert clinicians made decisions for them. Finally, once past the emergent phase of care, participants wanted to retake a more active role in their treatment and follow-up plans.Conclusions: Patients admitted with ACS often do not take an active role in initial clinical decisions, and are satisfied to allow the medical team to direct early phase care. These results provide important insight relevant to designing patient-centered interventions in ACS and other urgent care situations. [ABSTRACT FROM AUTHOR]

Background: Although sudden cardiac death (SCD) is recognized as a distinct cause of death in patients with end stage renal disease (ESRD), its incidence has not been well summarized.Methods: We performed a systematic review and meta-analysis of the literature based on a protocol developed a priori. We searched MEDLINE and EMBASE (inception to March 2015) for randomized controlled trials and cohort studies reporting the incidence of SCD in adult patients with ESRD on hemodialysis or peritoneal dialysis. We collected data on number of SCD as well as the definition of SCD for each individual study. A random-effects model was used to summarize the incidence of SCD. We conducted subgroup analyses to explore sources of heterogeneity.Results: Forty two studies (n = 80,382 patients) were included in the meta-analysis. The incidence of SCD among adults with ESRD ranged from 0.4 to 10.04 deaths per 100 person-years. The definitions and assessment of SCD varied across the included studies. There was evidence of significant heterogeneity (I(2) = 98; p < 0.001), which was not explained by subgroup analyses stratified by mean age, proportion of hypertensive or diabetic patients, follow-up time, study size, or type of cohort studied.Conclusion: Current estimates of the incidence of SCD among adults with ESRD vary widely. There is a need for further studies to more accurately estimate the incidence of SCD in patients with ESRD. [ABSTRACT FROM AUTHOR]