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BackgroundHeart disease is the leading cause of premature death for women in Canada. Ischemic heart disease (IHD) is categorized as myocardial infarction (MI) with no obstructive coronary artery disease (MINOCA), ischemia with no obstructive coronary arteries (INOCA), and atherosclerotic obstructive coronary artery disease (CAD) with MI (MI-CAD) or without MI (non-MI CAD). This study aims to study the prevalence of traditional and non-traditional IHD risk factors and their relationships with (M)INOCA compared to MI-CAD and non-MI CAD in young women.MethodsThis study investigated women who presented with premature (≤55 years old) vasomotor entities of (M)INOCA or obstructive CAD confirmed by coronary angiography, who are currently enrolled in either the Leslie Diamond Women’s Heart Health Clinic Registry (WHC) or the Study to Avoid cardioVascular Events in BC (SAVEBC). Univariable and multivariable regression models were applied to investigate associations of risk factors with odds of (M)INOCA, MI-CAD or non-MI CAD.ResultsA total of 254 women enrolled between 2015-2022 were analyzed: 77 INOCA and 37 MINOCA from the WHC and 66 with non-MI CAD and 74 MI-CAD from SAVEBC. Regression analyses demonstrated that migraines and preeclampsia/gestational hypertension were the most significant risk factors with higher likelihood to associate with premature (M)INOCA relative to obstructive CAD. Conversely, the presence of diabetes and a current or previous smoking history had the highest likelihood to associate with premature CAD.ConclusionThere are significant differences in the risk factor profiles of patients with premature (M)INOCA compared to obstructive CAD.

In a CODE-MI sub-study, six troponin assays were evaluated over 12 months using 3-samples (normal, female and male 99th-percentile levels; n=2,142 results from 67 instruments). Mean differences varied per assay with maximum values being ±4, ±8 and ±9 ng/L at the normal and sex-specific 99th-percentiles, respectively. A pragmatic approach, combining all assays, established maximum differences of ±3 ng/L or ±30%.

Background Hypertriglyceridemic waist (HTGW), which incorporates measures of waist circumference and levels of triglyceride in blood, could act as an early-stage predictor to identify the individuals at high-risk for subclinical atherosclerosis. Previous studies have explored the cross-sectional association between HTGW and atherosclerosis; however, understanding how this association might change over time is necessary. This study will assess the association between HTGW with 5-year subclinical carotid atherosclerosis. Methods 517 participants of Aboriginal, Chinese, European, and South Asian ethnicities were examined for baseline HTGW and 5-year indices of subclinical atherosclerosis (intima media thickness (mm), total area (mm2), and plaque presence). Family history of cardiovascular disease, sociodemographic measures (age, sex, ethnicity, income level, maximum education), and traditional risk factors (systolic blood pressure, smoking status, total cholesterol, high-density lipoprotein cholesterol, body mass index) were incorporated into the models of association. These models used multiple linear regression and logistic regression. Results Baseline HTGW phenotype is a statistically significant and clinically meaningful predictor of 5-year intima media thickness (β = 0.08 [0.04, 0.11], p p = 0.002), and plaque presence (OR = 2.17 [1.13, 4.19], p = 0.02) compared to the non-HTGW group independent of sociodemographic factors and family history. However, this association is no longer significant after adjusting for the traditional risk factors of atherosclerosis (p = 0.27, p = 0.45, p = 0.66, respectively). Moreover, change in status of HTGW phenotype does not correlate with change in indices of atherosclerosis over 5 years. Conclusions Our results suggest that when the traditional risk factors of atherosclerosis are known, HTGW may not offer additional value as a predictor of subclinical atherosclerosis progression over 5 years.

Many women with cardiac chest pain and ischemia or myocardial infarction have no obstructive coronary artery disease (INOCA or MINOCA). Studies suggest that these patients have a decreased quality of life and are at increased risk of cardiovascular events. Our study reports 1-year quality of life, frequency of angina, and outcomes following entry into a multidisciplinary Women's Heart Centre (WHC).Patients with INOCA and MINOCA completed questionnaires on baseline demographics and clinical presentation. At 1-year, frequency of chest pain, quality of life, depression and anxiety symptoms, and cardiovascular outcomes were reported and compared with baseline.A total of 154 women with nonobstructive coronary artery disease were included in this study (112 patients with INOCA and 42 with MINOCA). Median age was 59 years, and the most common referral was for chest pain (94% in INOCA and 66% in MINOCA). At baseline, 64% of patients with INOCA and 43% of patients with MINOCA did not have specific diagnoses. Following investigations in the WHC, 71.4% of patients with INOCA established a new or a changed diagnosis (most common was coronary microvascular dysfunction at 68%), whereas 60% of patients with MINOCA established new or changed diagnoses (the most common of which was coronary vasospasm at 60%). At 1-year, participants had significantly decreased chest pain, improved quality of life, and improved mental health.A multidisciplinary WHC significantly increases the yield of a specific diagnosis in patients with INOCA and MINOCA. Further, attending a WHC could significantly improve the clinical and psychological outcomes of women with INOCA and MINOCA.

Background There is wide variation in hospitalization costs for transcatheter aortic valve replacement (TAVR), suggesting inefficiency in care delivery. Our goal was to identify drivers of healthcare costs in TAVR. Methods Demographics, procedural details, in-hospital complications, and costs for all adults undergoing first-time TAVR from 2012-2016 in Ontario, Canada, were obtained through linkages of clinical/administrative databases. Total costs included were from initial referral to the first of either death or 1-year post-TAVR. Phase-based costing was performed to empirically estimate the presence, duration and cost/patient for each phase up to 1-year or death. Multivariable regression was used to identify drivers of cost accumulation per phase. Results We identified 2,009 first-time TAVR patients (mean age 81.7±7.6, 45.9% female and STS-score of 7.2±5.8). Phases of cost were identified with an early high cost period within 60-days of referral, a second phase from the procedure to 60-days, and a stable phase from 60-360 days post-procedure. The referral phase median cost was $4,527 (Interquartile range [IQR]: 1,708-12,594), the procedure to 60-days phase median cost was $29,518 (IQR: 24,842-40,279) and the post 60-day stable phase median cost was $6,053 (IQR: 3,320-17,048). Predictors of higher cost in the referral phase were in-hospital wait-location, dialysis dependence, and heart failure status. In the second (procedural) phase, predictors were non-transfemoral access, complications of stroke and pacemaker insertion. Predictors of higher cost in the third (stable) phase were predominantly non-modifiable, such as frailty. Conclusions This analysis shows that there are 3 distinct phases of cost accumulation from referral to post-TAVR with some potentially modifiable cost drivers in each phase.

To examine sex differences in oral anticoagulation management and outcomes among patients with incident nonvalvular atrial fibrillation presenting to the emergency department (ED).We identified patients older than 20 years presenting to the ED with incident nonvalvular atrial fibrillation between April 1, 2012, and March 30, 2019, using linked administrative databases in Alberta, Canada. We assessed the use of and adherence to oral anticoagulants at 1 year using the proportion of days covered for direct oral anticoagulants and time in therapeutic range for warfarin. Outcomes included stroke, heart failure, and all-cause mortality at 1 year.Of the 28,886 patients with nonvalvular atrial fibrillation presenting to ED, 44% were females. After adjustment, the rate of oral anticoagulant use was 5% lower in females with a guideline indication than that in males (adjusted hazard ratio 0.95, 95% confidence interval [CI] 0.91 to 0.99) discharged home, and there was no difference among admitted patients (adjusted hazard ratio 1.00, 95% CI 0.96 to 1.05). Females had high adherence to direct oral anticoagulants (≥80% proportion of days covered) compared to males (discharged: 77.7% versus 74.0%; admitted: 80.0% versus 76.7%; adjusted odds ratio for females: 1.15, 95% CI 1.02 to 1.29). More than half of the females and males had poor warfarin control (time in therapeutic range65%) regardless of discharge status. In multivariable analyses, there was no sex difference in outcomes except a 1.48-fold (95% CI 1.14 to 1.92) higher risk of stroke in females.Females with incident nonvalvular atrial fibrillation discharged from the ED are less likely to receive oral anticoagulants than males. When oral anticoagulant treatment is initiated, females have high adherence to direct oral anticoagulants, and both the sexes have poor warfarin control. At 1 year, females were at a significantly higher risk of developing stroke.

Background: Given changes in the care and outcomes of acute myocardial infarction (AMI) patients over the past several decades, we sought to develop prediction models that could be used to generate accurate risk-adjusted mortality and readmission outcomes for hospitals in current practice across Canada. Methods: A Canadian national expert panel was convened to define appropriate AMI patients for reporting and develop prediction models. Preliminary candidate variable evaluation was conducted using Ontario patients hospitalized with a most responsible diagnosis of AMI from April 1, 2015 to March 31, 2018. National data from the Canadian Institute for Health Information was used to develop AMI prediction models. The main outcomes were 30-day all-cause in-hospital mortality and 30-day urgent all-cause readmission. Discrimination of these models (measured by c-statistics) was compared with that of existing Canadian Institute for Health Information models in the same study cohort. Results: The AMI mortality model was assessed in 54,240 Ontario AMI patients and 153,523 AMI patients across Canada. We observed a 30-day in-hospital mortality rate of 6.3%, and a 30-day all-cause urgent readmission rate of 10.7% in Canada. The final Canadian AMI mortality model included 12 variables and had a c-statistic of 0.834. For readmission, the model had 13 variables and a c-statistic of 0.679. Discrimination of the new AMI models had higher c-statistics compared with existing models (c-statistic 0.814 for mortality; 0.673 for readmission). Conclusions: In this national collaboration, we developed mortality and readmission models that are suitable for profiling performance of hospitals treating AMI patients in Canada. RÉSUMÉ: Contexte: Compte tenu des changements apportés au cours des dernières décennies aux soins des patients ayant subi un infarctus aigu du myocarde (IAM) et aux issues d'un tel événement, nous avons voulu élaborer des modèles prédictifs pouvant servir à calculer de façon précise les résultats relatifs à la mortalité et aux réadmissions, ajustés selon les risques, pour les hôpitaux dans la pratique actuelle au Canada. Méthodologie: Un groupe national d'experts canadiens a été mis sur pied et a reçu le mandat de définir les critères appropriés applicables aux patients ayant subi un IAM aux fins de déclaration des cas et d’élaborer des modèles prédictifs. L’évaluation préliminaire des variables proposées a été effectuée à partir de patients hospitalisés en Ontario entre le 1er avril 2015 et le 31 mars 2018 chez lesquels l'IAM était le diagnostic principal à l'origine de l'hospitalisation. Les données à l’échelle nationale de l'Institut canadien d'information sur la santé (ICIS) ont été utilisées pour élaborer des modèles prédictifs d'IAM. Les deux principales issues évaluées étaient la mortalité hospitalière toutes causes confondues à 30 jours et la réadmission urgente toutes causes confondues à 30 jours. Le pouvoir discriminant de ces modèles (mesuré par la statistique C) a été comparé à celui des modèles existants de l'ICIS dans la même cohorte de l’étude. Résultats: Le modèle de mortalité par IAM a été évalué auprès de patients ayant subi un IAM, dont 54 240 en Ontario et 153 523 dans l'ensemble du Canada. Nous avons observé un taux de mortalité hospitalière à 30 jours de 6,3 % et un taux de réadmission urgente à 30 jours toutes causes confondues de 10,7 % au Canada. Le modèle canadien final de prédiction de la mortalité par IAM était constitué de 12 variables et avait une statistique C de 0,834. Pour la réadmission, le modèle comportait 13 variables et présentait une statistique C de 0,679. Le pouvoir discriminant des nouveaux modèles d'IAM présentait une statistique C supérieure à celle des modèles existants (statistique C de 0,814 pour la mortalité et de 0,673 pour la réadmission). Conclusions: Dans le cadre de cette collaboration nationale, nous avons élaboré des modèles prédictifs de la mortalité et de la réadmission hospitalière qui permettent d’établir un profil des résultats obtenus par les hôpitaux traitant des patients ayant subi un IAM au Canada.

Health administrative data are routinely used to assess disease burden, quality of care, and outcomes for atrial fibrillation (AF). Governments, administrators, and researchers define cohorts differently, based on 3 key factors: the case definition algorithm to identify AF, inclusion/exclusion of transient AF, and the lookback period to identify cases. We assessed the impact of varying these key factors on estimates of the use of guideline-indicated oral anticoagulation (OAC). Hospitalization, ED, and outpatient claim databases were linked in British Columbia. AF was defined by ICD-9 or 10 codes 427.3x or I48.x. We examined a specific (1 hospital or 1 ED or 2 outpatient) vs a sensitive (1 hospital or ED or outpatient) algorithm; inclusion/exclusion of AF associated with open-heart surgery; and lookback periods of 1 to 10 years. We found the more specific AF definition increased OAC utilization by 5% (58.7% vs 53.4%); excluding AF associated with open-heart surgery increased OAC utilization by 0.7% to 2.3%; and each additional lookback year identified more prevalent cases but reduced OAC utilization by approximately 1%. In 40 scenarios, generated by varying all 3 key factors, OAC utilization ranged from 52% to 72%. Assuming a ceiling of 90%, the estimated "treatment gap" therefore varied from 18% to 38%. The 2-fold variation in the OAC treatment gap was based entirely on cohort definition. This has significant implications for health policy and quality indicators.

Patients with obstructive sleep apnea (OSA) are at increased risk of cardiovascular and cerebrovascular disease (CVD) but it is unclear who are at greatest risk. We determined whether the inflammatory marker, C-reactive protein (CRP), could be a useful prognostic biomarker. Adult patients referred for polysomnography (PSG) with OSA were studied. Serum CRP levels were measured using ELISA the morning after PSG. Validated CV events within 4 years of PSG were ascertained by linking to provincial research datasets. 155 patients with OSA (AHI ≥ 5/h) had CRP measured. Median age was 53 and median AHI was 21/h. 10 patients (7.1%) suffered at least one event, but rates varied substantially by CRP (0/35 patients in the lowest quartile, and 7/39 in the highest CRP quartile). In the unadjusted analysis, patients in the highest CRP quartile (≥ 2.38 mg/L) were significantly more likely to suffer an event (odds ratio = 9.72 (95% CI 2.43–38.84), p = 0.001). CRP continued to be a significant predictor after controlling for multiple confounders. OSA severity and desaturation were not significantly associated with prospective events. In this small preliminary study, OSA patients with an elevated CRP were significantly more likely to suffer a CVD event in the 4 years after PSG. Although these findings need to be confirmed in larger prospective cohorts, CRP may be useful in risk stratifying OSA patients to guide therapy or to identify patients that might be most appropriate for clinical trials of CVD prevention.

A number of clinical trials have examined the effect of canola oil (CO) on body composition in recent years; however, the results have been inconsistent. The present investigation aims to examine the effect of CO on body weight (BW) and body composition using a systematic review and meta-analysis of controlled clinical trials. Online databases including PubMed, Scopus, and Google Scholar were searched up to February, 2018 for randomized controlled clinical trials that examined the effect of CO on anthropometric measures and body composition indexes in adults. The Cochrane Collaboration's tool was used to assess the risk of bias in individual studies. A random-effects model was used to evaluate the effect of CO consumption on several outcomes: BW, body mass index, waist circumference, hip circumference, waist-to-hip ratio, android-to-gynoid ratio, and body lean and fat mass. In total, 25 studies were included in the systematic review. The meta-analysis revealed that CO consumption reduces BW [weighted mean difference (WMD) = −0.30 kg; 95% CI: −0.52, −0.08 kg, P = 0.007; n = 23 effect sizes], particularly in participants with type 2 diabetes (WMD = −0.63 kg; 95% CI: −1.09, −0.17 kg, P = 0.007), in studies with a parallel design (WMD = −0.49 kg; 95% CI: −0.85, −0.14 kg, P = 0.006), in nonfeeding trials (WMD = −0.32 kg; 95% CI: −0.55, −0.09 kg, P = 0.006), and when compared with saturated fat (WMD = −0.40 kg; 95% CI: −0.74, −0.06 kg, P = 0.019). CO consumption did not significantly affect any other anthropometric measures or body fat markers (P > 0.05). Although CO consumption results in a modest decrease in BW, no significant effect was observed on other adiposity indexes. Further well-constructed clinical trials that target BW and body composition as their primary outcomes are needed.

AIM We investigated the impact of premenopausal age on neurological function at hospital discharge in patients with out-of-hospital cardiac arrest (OHCA). We hypothesized that premenopausal-aged females (18-47 years of age) with OHCA would have a higher probability of survival with favourable neurological function at hospital discharge compared with males of the same age group, older males, and older females (>53 years of age). METHODS Retrospective analyses of data from the Resuscitation Outcomes Consortium multi-center randomized controlled trial (June 2011-May 2015). We included adults with non-traumatic OHCA treated by emergency medical service. We stratified the cohort into four groups by age and sex: premenopausal-aged females (18-47 years of age), older females (≥53 years old), younger males (18-47 years of age), and older male. We used multilevel logistic regression to examine the association between age-sex and favourable neurological outcomes (modified Rankin Scale ≤ 3). RESULTS In total, 23,725 patients were included: 1050 (4.5%) premenopausal females; 1930 (8.1%) younger males; 7569 (31.9%) older females; and 13,176 (55.5%) older males. The multilevel analysis showed no difference in neurological outcome between younger males and younger females (OR 0.95, 95% CI 0.69-1.32, p = 0.75). Both older females (OR 0.36, 95% CI 0. 0.26-0.48, p

Objectives: We evaluated the effect of sex and age on out-of-hospital cardiac arrest (OHCA) outcomes in a Canadian population. Methods: This study was a retrospective analysis of the British Columbia (BC) Cardiac Arrest Registry (2011–16). We included adult, non-traumatic, EMS-treated OHCA. We stratified the cohort into four groups by age and sex: younger females (18–47 years of age), younger males (18–47 years of age), older females, and older males (>53 years old). We used logistic regression to examine the effect of sex and interaction effect of sex and age on ROSC and survival to hospital discharge. Results: We included 8115 patients; 31.4% were females. Females had a lower proportion of OHCA in public locations, bystander witnessed arrests, and with initial shockable rhythms. Overall, females had greater adjusted odds of ROSC (OR 1.29, 95% CI 1.15–1.42, p < 0.001). The ROSC advantage was significant in females with non-shockable rhythms (OR 1.48, 95% CI 1.24–1.78, p < 0.001) and females of premenopausal age. However, there was no significant difference in survival to hospital discharge between females and males overall or by sex-age groups. Both younger females and younger males have higher odds of survival to hospital discharge compared to older females and males. Older females had the lowest survival rate among all other sex-age groups. Conclusions: Female sex was associated with ROSC but not survival to hospital discharge. In the post-arrest phase, females, specifically those in the older age group, had a higher death rate, demonstrating the need for sex- and age-specific research in pre-and-post-OHCA care.

Gender refers to the socially constructed roles, behaviours, expressions and identities of girls, women, boys, men and gender diverse people. Gender-related factors are seldom assessed as determinants of health outcomes, despite their powerful contribution. The Gender Outcomes INternational Group: to Further Well-being Development (GOING-FWD) project developed a standard five-step methodology applicable to retrospectively identify gender-related factors and assess their relationship to outcomes across selected cohorts of non-communicable chronic diseases from Austria, Canada, Spain, Sweden. Step 1 (identification of gender-related variables): Based on the gender framework of the Women Health Research Network (ie, identity, role, relations and institutionalised gender), and available literature for a certain disease, an optimal ‘wish-list’ of gender-related variables was created and discussed by experts. Step 2 (definition of outcomes): Data dictionaries were screened for clinical and patient-relevant outcomes, using the International Consortium for Health Outcome Measurement framework. Step 3 (building of feasible final list): a cross-validation between variables per database and the ‘wish-list’ was performed. Step 4 (retrospective data harmonisation): The harmonisation potential of variables was evaluated. Step 5 (definition of data structure and analysis): The following analytic strategies were identified: (1) local analysis of data not transferable followed by a meta-analysis combining study-level estimates; (2) centrally performed federated analysis of data, with the individual-level participant data remaining on local servers; (3) synthesising the data locally and performing a pooled analysis on the synthetic data and (4) central analysis of pooled transferable data. The application of the GOING-FWD multistep approach can help guide investigators to analyse gender and its impact on outcomes in previously collected data.

Background Patients with severe, symptomatic aortic stenosis derive substantial 30-day quality of life (QOL) benefit from transcatheter aortic valve replacement (TAVR). Whether the QOL benefit of TAVR emerges earlier is unknown. We used data from the Multimodality, Multidisciplinary but Minimalist (3M) TAVR study to assess early changes in QOL after transfemoral (TF) TAVR. Methods Health status was assessed at baseline, 2-weeks, 30-days, and 1-year after TAVR using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Medical Outcomes Study Short-Form 12 (SF-12). The KCCQ overall summary (KCCQ-OS) score (range 0–100; higher scores = better health) was the primary health status outcome. Linear mixed effects models were used to describe trajectories of QOL scores over time. A good outcome was defined as being “alive and well”, with a KCCQ-OS score ≥ 60 points with no decrease from baseline ≥10 points. Results A total of 358 patients (87.1%) completed the baseline and at least one follow-up survey. Between baseline and 2-weeks, the KCCQ-OS increased by 21.3 points (95% confidence interval [CI]: 19.3–23.2). This improvement was sustained over time with only slight further improvement between 2-weeks and 1-month (3.4 points; 95% CI: 1.4 to 5.5) and no significant change between 1-month and 1-year (1.9 points; 95% CI: −0.2 to 4.1). Scores for the KCCQ subscales and SF-12 physical and mental component summary scales showed a similar pattern. Most patients (74.4%) were “alive and well” at 2 weeks with similar rates at 1-month and 1-year (79.5% and 77.3%, respectively). Conclusions Among patients undergoing TF-TAVR, both disease-specific and generic health status improved substantially within the first 2 weeks, with only minimal further improvement thereafter.

Background CODE-MI is a pan-Canadian, multicentre, stepped-wedge, cluster randomized trial that evaluates the impact of using the female-specific 99th percentile threshold for high-sensitivity cardiac troponin (hs-cTn) on the diagnosis, treatment and outcomes of women presenting to the emergency department (ED) with symptoms suggestive for myocardial ischemia. A feasibility study was conducted to estimate the number of eligible patients, the rate of the study's primary outcome under control conditions, and the statistical power to detect a clinically important difference in the primary outcome. Methods Using linked administrative data from 11 hospitals in Ontario, Canada, from October 2014 to September 2017, the following estimates were obtained: number of women presenting to the ED with symptoms suggestive of myocardial ischemia and a 24-hour peak hs-cTn value within the female-specific and overall thresholds (ie, primary cohort); the rate of the 1-year composite outcome of all-cause mortality, re-admission for nonfatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization. Study power was evaluated via simulations. Results Overall, 2,073,849 ED visits were assessed. Among women, chest pain (with or without cardiac features) and shortness of breath were the most common complaints associated with a diagnosis of acute coronary syndrome. An estimated 7.7% of women with these complaints are eligible for inclusion in the primary cohort. The rate of the 1-year outcome in the primary cohort varied significantly across hospitals with a median rate of 12.2% (95%CI: 7.9%-17.7%). With 30 hospitals, randomized at 5-month intervals in 5 steps, approximately 19,600 women are expected to be included in CODE-MI, resulting in >82% power to detect a 20% decrease in the odds of the primary outcome at a 0.05 significance level. Conclusions This feasibility study greatly enhanced the design of CODE-MI, allowed accurate evaluation of the study power, and demonstrated the strength of using linked administrative health data to guide the design of pragmatic clinical trials.

Background A significant proportion of patients with spontaneous coronary artery dissection (SCAD) have ongoing chronic chest pain despite healing of their dissection. We sought to determine whether coronary microvascular dysfunction contributes to post‐SCAD chronic chest pain by performing coronary reactivity testing in the cardiac catheterization laboratory. Methods and Results Eighteen patients consented to coronary reactivity testing at least 3 months post‐SCAD. Coronary flow reserve (CFR) and index of microcirculatory resistance were measured in the previously affected SCAD artery and 1 non‐SCAD artery. CFR 25 units. Seventeen women underwent coronary reactivity testing (1 had chronic dissection and was excluded). All presented with myocardial infarction and 2 underwent coronary stenting during the initial SCAD event. Fibromuscular dysplasia was present in 70.6% upon screening renal, iliac, and cerebrovascular arteries. Twelve patients (70.6%) had CFR 25 in at least 1 artery. There was no difference in the frequency of a low CFR measurement between SCAD and non‐SCAD arteries. Conclusions Among patients with chronic chest pain after an SCAD event, >70% had coronary microvascular dysfunction as indicated by abnormal CFR or index of microcirculatory resistance in at least 1 coronary artery on invasive coronary reactivity testing. Presence of coronary microvascular dysfunction in both SCAD and non‐SCAD arteries suggests that underlying microvascular abnormalities from vasculopathies such as coronary fibromuscular dysplasia may be the underlying etiology.

Background Despite evidence that high-sensitivity cardiac troponin (hs-cTn) levels in women are lower than in men, a single threshold based on the 99th percentile upper reference limit of the overall reference population is commonly used to diagnose myocardial infarction in clinical practice. This trial aims to determine whether the use of a lower female-specific hs-cTn threshold would improve the diagnosis, treatment, and outcomes of women presenting to the emergency department with symptoms suggestive of myocardial ischemia. Methods/Design CODE-MI (hs-cTn—Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women) is a multicenter, stepped-wedge, cluster-randomized trial of 30 secondary and tertiary care hospitals across 8 Canadian provinces, with the unit of randomization being the hospital. All adults (≥20 years of age) presenting to the emergency department with symptoms suggestive of myocardial ischemia and at least 1 hs-cTn test are eligible for inclusion. Over five, 5-month intervals, hospitals will be randomized to implement lower female hs-cTn thresholds according to the assay being used at each site. Men will continue to be assessed using the overall thresholds throughout. Women with a peak hs-cTn value between the female-specific and the overall thresholds will form our primary cohort. The primary outcome, a 1-year composite of all-cause mortality or readmission for nonfatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization, will be compared before and after the implementation of female thresholds using mixed-effects logistic regression models. The cohort and outcomes will be obtained from routinely collected administrative data. The trial is designed to detect a 20% relative risk difference in the primary outcome, or a 2.2% absolute difference, with 82% power. Conclusions This pragmatic trial will assess whether adopting lower female hs-cTn thresholds leads to appropriate assessment of women with symptoms suggestive of myocardial infarction, thereby improving treatment and outcomes.

Aim While public access automated external defibrillator (AED) programs appear to improve outcomes in out-of-hospital cardiac arrest (OHCA) it is unclear if men and women benefit equally. We examined gender-based differences in OHCA location to determine what proportion were potentially eligible for public access AED application, and if patient gender was associated with AED utilization. Methods We analyzed data from the Resuscitation Outcomes Consortium registry (2011–2015). We compared differences in OHCA locations by gender. We fit multivariate logistic regression models, restricted to public location OHCAs and public-location cases with bystander intervention, to calculate the association between gender and public access AED application. Results Among 61 473 cases, 34% were female and 50% had bystander resuscitation. The incidence of public OHCA was 8.8% for women and 18% for men (risk difference 9.2%, 95% CI 8.7–9.7%). Women had significantly fewer OHCAs on roadways, in public buildings, places of recreation, and farms, but more in homes, non-acute healthcare facilities, and residential institutions. Female gender was associated with a lower odds of AED application in public OHCA (adjusted OR 0.76, 95% CI 0.64–0.90) and public-location cases with bystander interventions (adjusted OR 0.83, 95% CI 0.71–0.99). Conclusion Women had fewer OHCA in public locations that may have public access AEDs. Even among public location OHCA with bystander interventions, women were less likely to have public access AED applied. Initiatives to optimize AED locations and to engage the public with gender-specific resuscitation training may improve outcomes in women with OHCA.

Appropriate intake of micronutrient, such as electrolyte minerals is critical for the well-being of the cardiovascular health system. However, there are some debates regarding the impacts of dietary and/or supplemental intake of these minerals, on the risk of cardiovascular events and associated risk factors. High sodium intake is adversely associated with the risk of hypertension. Although many reports refered to the positive association of Na intake and cardiovascular events and all-cause mortality, however, other studies indicated that low Na intake is related to higher risk of all-cause mortality and HF-related events. By contrast, dietary potassium, magnesium and calcium have an inverse correlation with cardiovascular events and risk factors, especially with blood pressure. There are some controversies about cardiovascular effects and all-cause mortality of high Ca intake, including no effect, preventive or adverse effect with or without vitamin D. Calcium supplementation might be beneficial for prevention of cardiovascular events and all-cause mortality only in individuals with low intake. Moreover, calcium intake showed a J- or U-shaped association with the risk of cardiovascular diseases. Due to the controversies of the effect of electrolyte minerals especially sodium and calcium intake on cardiovascular events, large scale, well-designed long-term randomized clinical trials are required to evaluate the effect of minerals intake on cardiovascular events and all-cause mortality. In this review, we discuss the role of dietary and or supplemental sodium, potassium, magnesium, calcium, in cardiovascular health, as well as their clinical applications, benefits, and risks for the primary prevention of cardiovascular disease, in general population.

Background Obstructive sleep apnea (OSA) patients are at increased risk of cardiovascular disease (CVD). Cell adhesion molecules (CAM) are increased in OSA and CAM are also implicated in the development of CVD. Research question Do CAM (ICAM-1, VCAM-1 and E-selectin) have prognostic value in identifying risk of cardiovascular events in OSA? Study design and methods Patients with suspected OSA referred for a polysomnogram provided a fasting blood sample. Plasma levels of ICAM-1, VCAM-1 and E-selectin were determined by multiplex Luminex Assay (Milliporesigma ON, Canada). Cardiovascular events were determined by deterministic linkage to provincial health databases. Results 418 patients were included in the analysis. Mostly male (68.2%), mean age of 50.7 yrs, median AHI 16.5 events/hour, and mean BMI of 31.7 kg/m2. 36 cardiovascular events occurred in 8-yrs of follow up. Higher levels of ICAM-1 were associated with developing CVD (HR = 3.65 95% CI 1.40–9.53, 2nd and 3rd tertiles vs. 1st tertile), including in patients with OSA (HR = 3.1 95% CI 1.16–8.25). E-selectin was significantly associated with cardiovascular events in patients with moderate to severe OSA (HR = 3.31 95% CI 0.94–11.72, 2nd and 3rd tertiles vs. 1st tertile) but not in patients without moderate to severe OSA (HR = 0.67 95% CI 0.19–2.38), p-value for interaction = 0.07. Interpretation In a suspected OSA cohort, patients with higher levels of ICAM-1 (>816 ng/ml) were significantly more likely to experience a cardiovascular event within 8 years after PSG. In moderate to severe OSA patients, a higher E-selectin (>36.4 ng/ml) was significantly associated with cardiovascular events.

Patients with acute myocardial infarction (MI) and nonobstructive coronary artery disease (CAD) have an elevated cardiac event rate, suggesting that these patients may benefit from cardiac medication.We evaluated the rates of cardiac medication use 3 months before angiography and 3 months following clinically indicated angiography for MI in patients with no CAD, nonobstructive CAD, and obstructive CAD. We also examined the sex differences in cardiac medication use 3 months following angiography in patients by extent of angiographic CAD.We studied patients ≥20 years old with MI undergoing coronary angiography in British Columbia, Canada, from January 1, 2008, to March 31, 2010 (n = 3,841). No CAD, nonobstructive CAD, and obstructive CAD were defined as 0%, 1% to 49%, and ≥50% luminal narrowing in any epicardial coronary artery, respectively. Medication use, 3 months before and 3 months following angiography, was obtained through British Columbia PharmaNet for angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), beta-blockers, statins, and antiplatelet agents. Optimal medical therapy (OMT) was defined as filled prescriptions for all three: ACE-Is/ARBs, beta-blockers, and statins.Following angiography, in all medication categories except CCBs, patients with no CAD and nonobstructive CAD had significantly lower rates of prescriptions filled than patients with obstructive CAD (all p 0.001). After adjusting for age and prior medication use, patients with nonobstructive CAD were still less likely to receive these medications than patients with obstructive CAD, including OMT with an odds ratio = 0.25 (95% confidence interval: 0.18-0.36). There were no significant sex differences in medication use 3 months postangiography.In post-MI patients, medication use following angiography is significantly lower in nonobstructive CAD than obstructive CAD at 3 months. While sex was not an independent predictor of medication use 3 months post-catheterization, future studies should explore methods of improving medication use in both females and males with nonobstructive CAD post-MI.

Treatment of patients with stable angina and nonobstructive coronary artery disease (CAD) has not been well characterized. We comparatively evaluated medication use in males and females with stable angina with no CAD, nonobstructive CAD, and obstructive CAD.We studied all patients ≥20 years old with stable angina undergoing coronary angiography in British Columbia (BC), Canada, from January 2008 to March 2010 (n = 7,535). No CAD, nonobstructive CAD, and obstructive CAD were defined as 0%, 1%-49%, and ≥50% luminal narrowing in any epicardial coronary artery, respectively. Medication use, 3 months before and 3 months following angiography, was obtained through BC PharmaNet for angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), beta-blockers, statins, antiplatelet agents, and prescriptions for all three ACE-I/ARBs, beta-blockers, and statins (combination therapy).Following angiography, patients with no and nonobstructive CAD had significantly lower rates of prescription use of all medications, including combination therapy, than patients with obstructive CAD (p 0.001). Use of ACE-I/ARBs, beta-blockers, statins, and combination therapy did not differ by sex, but females had higher use of CCB in all CAD groups, and clopidogrel in nonobstructive and obstructive CAD groups, compared to males.In patients with stable angina, medication use following angiography is low in nonobstructive CAD with only 58.9% prescribed a statin and 19.4% on combination therapy at 3 months. There are no important sex differences in medication use in any CAD category post-angiography. Future studies should explore methods of improving quality of care in patients with nonobstructive CAD.

Background Spontaneous coronary artery dissection (SCAD) is underdiagnosed and an important cause of myocardial infarction (MI), especially in young women. Long-term cardiovascular outcomes, including recurrent SCAD, are inadequately reported. Objectives This study sought to describe the acute and long-term cardiovascular outcomes and assess the predictors of recurrent SCAD. Methods Nonatherosclerotic SCAD patients were prospectively followed at Vancouver General Hospital systematically to ascertain baseline, predisposing and precipitating stressors, angiographic features, revascularization, use of medication, and in-hospital and long-term cardiovascular events. Clinical predictors for recurrent de novo SCAD were tested using univariate and multivariate Cox regression models. Results The authors prospectively followed 327 SCAD patients. Average age was 52.5 ± 9.6 years, and 90.5% were women (56.9% postmenopausal). All presented with MI; 25.7% had ST-segment elevation MI, 74.3% had non–ST-segment elevation MI, and 8.9% had ventricular tachycardia/ventricular fibrillation. Precipitating emotional stressors were reported in 48.3% and physical stressors in 28.1%. Fibromuscular dysplasia was present in 62.7%, connective tissue disorder in 4.9%, and systemic inflammatory disease in 11.9%. The majority (83.1%) were initially treated medically, with only 16.5% or 2.2% undergoing in-hospital percutaneous coronary intervention or coronary artery bypass graft surgery, respectively. The majority of SCAD patients were taking aspirin and beta-blocker therapy at discharge and at follow-up. Median hospital stay was 3.0 days, and the overall major adverse event rate was 7.3%. Median long-term follow-up was 3.1 years, and overall major adverse cardiac event rate was 19.9% (death rate: 1.2%; recurrent MI: 16.8%; stroke/transient ischemic attack: 1.2%; revascularization: 5.8%). Recurrent SCAD occurred in 10.4% of patients. In multivariate modeling, only hypertension increased (hazard ratio: 2.46; p = 0.011) and beta-blocker use diminished (hazard ratio: 0.36; p = 0.004) recurrent SCAD. Conclusions In our large prospectively followed SCAD cohort, long-term cardiovascular events were common. Hypertension increased the risk of recurrent SCAD, whereas beta-blocker therapy appeared to be protective.

Background Progression from paroxysmal to persistent atrial fibrillation (AF) has important clinical implications and is relevant to the management of patients with AF. Objective The purpose of this study was to define the long-term rate of progression from paroxysmal to persistent AF and the relevant clinical variables. Methods The Canadian Registry of Atrial Fibrillation enrolled patients after a first electrocardiographic diagnosis of paroxysmal AF. Associations between baseline characteristics and clinical outcomes were evaluated using a multivariable Cox proportional hazard model and a competing risk model accounting for death as a competing risk, where appropriate. Results We enrolled 755 patients (61.7% men) aged between 14 and 91 years (mean age 61.2 ± 14.2 years). The median follow-up was 6.35 years (interquartile range 2.93–10.04 years), with a rate of progression to persistent AF at 1, 5, and 10 years was 8.6%, 24.3%, and 36.3%, respectively. All-cause mortality was 30.3% at 10 years. Factors associated with AF progression were increasing age (hazard ratio [HR] 1.40; 95% confidence interval [CI] 1.23–1.60, for each 10-year increment), mitral regurgitation (HR 1.87; 95% CI 1.28–2.73), left atrial dilatation (HR 3.01; 95% CI 2.03–4.47), aortic stenosis (HR 2.40; 95% CI 1.05–5.48), and left ventricular hypertrophy (HR .47; 95% CI 1.04–2.08). Factors associated with a lower rate of progression were a faster heart rate during AF (HR 0.94; 95% CI 0.92–0.96 per 5-beat/min increment) and angina (HR 0.54; 95% CI 0.38–0.77). After accounting for death as a competing risk, left ventricular hypertrophy and aortic stenosis were no longer significant. Conclusion Within 10 years of presenting with paroxysmal AF, >50% of patients will progress to persistent AF or be dead. Increasing age, mitral regurgitation, aortic stenosis, left ventricular hypertrophy, and left atrial dilatation were associated with progression to persistent AF.

Introduction Out-of-hospital cardiac arrest (OHCA) is common among females and males alike; however, previous studies reported differences in outcomes between sexes in different regions. To investigate possible explanations for this disparity, we examined sex differences in resuscitation interventions in the province of British Columbia (BC). Methods We performed an observational analysis of the BC Cardiac Arrest Registry (2011–16). We included adults with non-traumatic and EMS-treated OHCA. We examined sex differences in bystander CPR, chest compression rate, and intra-arrest transport using chi-square tests, student’s t-test, multivariable linear and logistic regressions. Results In total, 7398 patients were eligible for the bystander CPR analysis; 31% were female. More males received bystander CPR (54% vs. 50%); however, male sex was not associated with bystander CPR after adjustment for confounders (adjusted OR male vs. female: 1.07, 95% CI 0.96, 1.18). There was no difference in the chest compression rate for males and females in unadjusted or adjusted analyses. Among subjects who did not achieve prehospital ROSC (n = 5225, 32% females), 64% were pronounced dead at the scene with the remaining transported to hospital. Males more often underwent intra-arrest transport than females (36.7% vs. 34.0%). After adjustment, males had 1.2 greater odds of being transported to hospital than females (95% CI 1.04, 1.37). Conclusions We did not detect an association between sex and bystander CPR or chest compression rate. In those who did not achieve prehospital ROSC, males had 1.2-fold greater odds of being transported to hospital compared to females.

Background In patients with severe calcific aortic stenosis, transcatheter aortic valve replacement (TAVR) has been shown to significantly improve quality of life (QOL). However, changes in QOL at early follow-up ( Methods A total of 411 patients at 13 centers were enrolled in the Multimodality, Multidisciplinary but Minimalist TAVR (3M TAVR) study in 2015–2017. QOL was evaluated using the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) in participants with a baseline score and at least one score at 2 weeks, 30 days and 1 year. Study endpoints were change in (1) KCCQ-Overall Summary Score (KCCQ-OS) and (2) minimal clinically important differences (MCID). Mixed effects models were used to explore patterns of change from baseline, with fixed terms for time, status at 1-year and their interaction terms, and a random intercept for subject to account for within subject correlation. Descriptive statistics were used to report MCID. Results Data were available for 358 (87.1%) participants. 216 (60.3%) were men with a median age 84.0 and STS 5.0 There was significant increase in QOL 2 weeks after TAVR (p≤0.01), and further significant improvement at the 1-month timepoint (p0.05). In the first 2 weeks, moderate (10–20 points) and large (>20 points) improvements were observed in 19.9% and 49.0% of the surviving patients, respectively; at 1-year, similar MCID were seen in 14.6% and 64.0% respectively. Figure 1 Conclusion This is the first study to report significant increase in QOL 2 weeks after TAVR, with sustained improvement during the first year in patients treated with the Vancouver TAVR Clinical Pathway with a goal of next-day discharge. Further studies are necessary to determine whether alternative TAVR clinical pathways yield similar findings. Acknowledgement/Funding Investigator-initiated unrestricted research grant, Edwards

Spontaneous coronary artery dissection (SCAD) is gaining recognition as an important cause of myocardial infarction, especially in young women. There has been a surge in the diagnosis of SCAD in recent years, presumably due to an increased use of coronary angiography, and the clinical availability and application of high-resolution intracoronary imaging. The improved recognition and diagnosis, together with increased publications and attention through social media, have considerably raised awareness of this condition, which was once believed to be very rare. Recent publications of moderate to large contemporary case series have helped elucidate the early natural history, presenting characteristics (clinical and angiographic), underlying etiology, management, and cardiovascular outcomes with this condition, thus providing observations and important clinical insights of value to clinicians managing this challenging and perplexing patient cohort. The aim of our review is to provide a comprehensive contemporary update of SCAD to aid health care professionals in managing these patients in both the acute and chronic settings.

Transcatheter aortic valve replacement (TAVR) has become the standard of care for patients with hemodynamically severe aortic stenosis who are symptomatic but deemed too high risk for surgery. Recent reports suggest that sex differences exist in outcomes following TAVR and in the diagnostic imaging evaluation of patients being considered for TAVR. In this review, the authors explore the differences between men and women in baseline characteristics and outcomes following TAVR, as well as sex differences in the imaging findings of severe aortic stenosis (AS) including the diagnostic challenges in the hemodynamic assessment of severe AS in elderly women, differences in aortic valvular calcification and in the associated myocardial response to severe AS. Additionally, sex differences in imaging findings as they relate to post-TAVR complications including coronary obstruction, annular rupture and prosthesis-patient mismatch are also discussed.

Background “Gender” reflects social norms for women and men, whereas “sex” defines biological characteristics. Gender-related characteristics explain some differences in access to care for premature acute coronary syndrome (ACS); whether they are associated with cardiovascular outcomes is unknown. Objectives This study estimated associations between gender and sex with recurrent ACS and major adverse cardiac events (MACE) (e.g., ACS, cardiac mortality, revascularization) over 12 months in patients with ACS. Methods We studied 273 women and 636 men age 18 to 55 years from GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-Premature Acute Coronary SYndrome), a prospective observational cohort study, who were hospitalized for ACS between January 2009 and April 2013. Gender-related characteristics (e.g., social roles) were assessed using a self-administered questionnaire, and a composite measure of gender was derived. Outcomes included recurrent ACS and MACE over 12 months. Results Feminine roles and personality traits were associated with higher rates of recurrent ACS and MACE compared with masculine characteristics. This difference persisted for recurrent ACS, after multivariable adjustment (hazard ratio from score 0 to 100: 4.50; 95% confidence interval: 1.05 to 19.27), and was a nonstatistically significant trend for MACE (hazard ratio: 1.54; 95% confidence interval: 0.90 to 2.66). A possible explanation is increased anxiety, the only condition that was more prevalent in patients with feminine characteristics and that rendered the association between gender and recurrent ACS nonstatistically significant (hazard ratio: 3.56; 95% confidence interval: 0.81 to 15.61). Female sex was not associated with outcomes post-ACS. Conclusions Younger adults with ACS with feminine gender are at an increased risk of recurrent ACS over 12 months, independent of female sex.

Objectives This study sought to describe the development of a multicenter, transcatheter aortic valve replacement program and regional systems of care intended to optimize coordinated, efficient, and appropriate delivery of this new therapy. Background Transcatheter aortic valve replacement (TAVR) has become an accepted treatment option for patients with severe aortic stenosis who are at high surgical risk. Regional systems of care have led to improvements in outcomes for patients undergoing intervention for myocardial infarction, cardiac arrest, and stroke. We implemented a regional system of care for patients undergoing TAVR in British Columbia, Canada. Methods We describe a prospective observational cohort of 583 patients who underwent TAVR in British Columbia between 2012 and 2014. Regionalization of TAVR care in British Columbia refers to a centrally coordinated, funded, and evaluated program led by a medical director and a multidisciplinary advisory group that oversees planning, access to care, and quality of outcomes at the 4 provincial sites. Risk-stratified case selection for transfemoral TAVR is performed by heart teams at each site on the basis of consensus provincial indications. Referrals for lower volume and more complicated TAVR, including nontransfemoral access and valve-in-valve procedures, are concentrated at a single site. In-hospital and 30-day outcomes are reported. Results The median age was 83 years (interquartile range [IQR]: 78 to 87 years) and median STS score was 6% (IQR: 4% to 8%). Transfemoral access was performed in 499 (85.6%) cases and nontransfemoral in 84 (14.4%). Transcatheter valve-in-valve procedures in for failed bioprosthetic valves were performed in 43 patients (7.4%). A balloon-expandable valve was inserted in 386 (66.2%) and a self-expanding valve in 189 (32.4%). All-cause 30-day mortality was 3.5%. All-cause in-hospital mortality and disabling stroke occurred in 3.1% and 1.9%, respectively. Median length of stay was 3 days (IQR: 3 to 6 days), with 92.8% of patients discharged directly home. Conclusions This experience demonstrates the potential benefits of a regional system of care for TAVR. Excellent outcomes were demonstrated: most patients had short in-hospital stays and were discharged directly home.

Objectives: Despite advances in screening and prevention, rates of premature coronary artery disease (CAD) have been stagnant. The goals of this study were to investigate the barriers to early risk detection and preventive treatment in patients with premature CAD. In particular, we: 1) assessed the performance of the latest versions of major international guidelines in detection of risk of premature CAD and eligibility for preventive treatment; and, 2) investigated real-life utilization of primary prevention with lipid-lowering therapies in these patients. Methods: We included patients in the Study to Avoid cardioVascular Events in British Columbia (SAVE BC), an observational study of patients with premature (males ​≤ ​50 years, females ​≤ ​55 years) angiographically confirmed CAD. Eligibility for primary prevention and treatment received were assessed retrospectively based on information recorded prior to or at the index presentation with CAD. Results: Of 417 patients (28.1% females) who met the criteria, 94.3% had at least one major cardiovascular risk factor. In the retrospective risk assessment, 41.7%, 61.4%, and 34.3% (p ​

Elevated cardiac troponin (cTn), with signs/symptoms of ischemia, is a key element in a diagnosis of myocardial infarction (MI). Underdiagnosis of MI in women has been attributed to atypical symptoms, inconsistent ECG findings, and less diagnostic testing. We sought to determine if there are sex differences in cTn testing following presentation to the emergency department (ED) with a chief complaint of ischemic chest pain (CP) and if presentation affects diagnostic assessment.All adults presenting to six hospital EDs in the Vancouver, Canada with a chief complaint of ischemic CP from 2009 to 2013 were included. The highest cTn level within 24 hours of ED presentation was used. CP was classified into cardiac- or respiratory dominant based on standard Canadian Emergency Department Triage and Acuity Scale coding. Chi-square testing was used to test for sex differences in CP categories and cTn testing within 24 hours. Logistic regression models were used to examine the association between sex, cTn testing, and CP categories.Of 27,063 patients with ischemic CP, cardiac presentation was more common in men than women, irrespective of age. Among cardiac CP, 24.7% of men were50 years compared to 18.2% of women; however, more women (19.9%) than men (11.6%) were80 years. Overall, women were 1.8% less likely to have cTn testing; in patients50 years, testing was markedly lower in women compared to men [odds ratio, OR (95% confidence intervals, CI) 0.78 (0.70-0.87)]. The odds of cardiac catheterization within 90 days of ED presentation were lower in women [OR, (95% CI) 0.52 (0.44-0.63)]. Even with cardiac CP, 17.7% of women versus 32.7% of men had cardiac catheterization.In men and women presenting to the ED with ischemic CP, cTn testing overall is similar except among young women under 50 years old, where it is markedly lower. Women undergo less cardiac catheterization, irrespective of CP type.