The Importance of Nontraditional and Sex-Specific Risk Factors in Young Women With Vasomotor Nonobstructive vs Obstructive Coronary Syndromes.

Background: Heart disease is the leading cause of premature death for women in Canada. Ischemic heart disease 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 nontraditional ischemic heart disease risk factors and their relationships with (M)INOCA, compared to MI-CAD and non-MI-CAD in young women. Methods: This study investigated women who presented with premature (at age ≤ 55 years) 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 British Columbia (SAVEBC). Univariable and multivariable regression models were applied to investigate associations of risk factors with odds of (M)INOCA, MI-CAD, and non-MI-CAD. Results: A total of 254 women enrolled between 2015 and 2022 were analyzed, as follows: 77 with INOCA and 37 with MINOCA from the registry, and 66 with non-MI-CAD and 74 with MI-CAD from the study. Regression analyses demonstrated that migraines and preeclampsia or gestational hypertension were the most significant risk factors, with a higher likelihood of being associated with premature (M)INOCA, relative to obstructive CAD. Conversely, the presence of diabetes and a current or previous smoking history had the highest likelihood of being associated with premature CAD. Conclusions: The risk factor profiles of patients with premature (M)INOCA, compared to obstructive CAD, have significant differences.

Contexte: Au Canada, la cardiopathie est la principale cause de décès prématuré chez les femmes. La cardiopathie ischémique est catégorisée comme suit : infarctus du myocarde (IM) en l'absence de coronaropathie obstructive (MINOCA), ischémie sans obstruction des artères coronaires (INOCA) et athérosclérose coronaire obstructive accompagnée d'un IM ou sans IM. La présente étude vise à examiner la prévalence des facteurs de risque classiques et non classiques de cardiopathie ischémique et leurs liens avec le (M)INOCA, comparativement à l'athérosclérose coronaire obstructive accompagnée d'un IM ou sans IM chez les femmes jeunes. Méthodologie: Cette étude portait sur des femmes qui avaient prématurément (55 ans ou moins) souffert d'un (M)INOCA ou d'une coronaropathie obstructive confirmés par coronarographie et qui étaient inscrites au registre de la Leslie Diamond Women's Heart Health Clinic (WHC) ou qui participaient à l'étude visant à éviter les événements cardiovasculaires en Colombie-Britannique (Study toAvoid CardiovascularEvents inBC; SAVEBC). Des modèles de régression univariés et multivariés ont été utilisés pour explorer les associations entre les facteurs de risque et les probabilités de (M)INOCA, ainsi que d'athérosclérose coronaire obstructive accompagnée ou non d'un IM. Résultats: Au total, 254 femmes inscrites de 2015 à 2022 ont été recensées, soit 77 présentant une INOCA et 37, un MINOCA selon le registre WHC, et 66 présentant une athérosclérose coronaire obstructive sans IM et 74, une athérosclérose coronaire obstructive accompagnée d'un IM selon l'étude SAVEBC. Les analyses de régression ont démontré que les migraines et la prééclampsie ou l'hypertension gestationnelle étaient les facteurs de risque les plus importants associés à une probabilité la plus élevée de (M)INOCA comparativement à une coronaropathie obstructive. En revanche, la présence d'un diabète et d'un tabagisme actuel ou passé était associée à la probabilité la plus élevée de coronaropathie prématurée. Conclusions: Il existe d'importantes différences pour ce qui est des profils de facteurs de risque des patientes ayant prématurément souffert d'un (M)INOCA en comparaison d'une coronaropathie obstructive.

Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile.

BACKGROUND: An analytical benchmark for high-sensitivity cardiac troponin (hs-cTn) assays is to achieve a coefficient of variation (CV) of ≤ 10.0 % at the 99th percentile upper reference limit (URL) used for the diagnosis of myocardial infarction. Few prospective multicenter studies have evaluated assay imprecision and none have determined precision at the female URL which is lower than the male URL for all cardiac troponin assays. METHODS: Human serum and plasma matrix samples were constructed to yield hs-cTn concentrations near the female URLs for the Abbott, Beckman, Roche, and Siemens hs-cTn assays. These materials were sent (on dry ice) to 35 Canadian hospital laboratories (n = 64 instruments evaluated) participating in a larger clinical trial, with instructions for storage, handling, and monthly testing over one year. The mean concentration, standard deviation, and CV for each instrument type and an overall pooled CV for each manufacturer were calculated. RESULTS: The CVs for all individual instruments and overall were ≤ 10.0 % for two manufacturers (Abbott CVpooled = 6.3 % and Beckman CVpooled = 7.0 %). One of four Siemens Atellica instruments yielded a CV > 10.0 % (CVpooled = 7.7 %), whereas 15 of 41 Roche instruments yielded CVs > 10.0 % at the female URL of 9 ng/L used worldwide (6 cobas e411, 1 cobas e601, 4 cobas e602, and 4 cobas e801) (CVpooled = 11.7 %). Four Roche instruments also yielded CVs > 10.0 % near the female URL of 14 ng/L used in the United States (CVpooled = 8.5 %). CONCLUSIONS: The number of instruments achieving a CV ≤ 10.0 % at the female 99th-percentile URL varies by manufacturer and by instrument. Monitoring assay precision at the female URL is necessary for some assays to ensure optimal use of this threshold in clinical practice.

Atherosclerotic Coronary Plaque Regression and Risk of Adverse Cardiovascular Events: A Systematic Review and Updated Meta-Regression Analysis.

Importance: The association between changes in atherosclerotic plaque induced by lipid-lowering therapies (LLTs) and reduction in major adverse cardiovascular events (MACEs) remains controversial. Objective: To evaluate the association between coronary plaque regression assessed by intravascular ultrasound (IVUS) and MACEs. Data Sources: A comprehensive, systematic search of publications in PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science was performed. Study Selection: Clinical prospective studies of LLTs reporting change in percent atheroma volume (PAV) assessed by IVUS and describing MACE components were selected. Data Extraction and Synthesis: Reporting was performed in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The association between mean change in PAV and MACEs was analyzed by meta-regression using mixed-effects, 2-level binomial logistic regression models, unadjusted and adjusted for clinical covariates, including mean age, baseline PAV, baseline low-density lipoprotein cholesterol level, and study duration. Main Outcome and Measures: Mean PAV change and MACE in intervention and comparator arms were assessed in an updated systematic review and meta-regression analysis of IVUS trials of LLTs that also reported MACEs. Results: This meta-analysis included 23 studies published between July 2001 and July 2022, including 7407 patients and trial durations ranging from 11 to 104 weeks. Mean (SD) patient age ranged from 55.8 (9.8) to 70.2 (7.6) years, and the number of male patients from 245 of 507 (48.3%) to 24 of 26 (92.3%). Change in PAV across 46 study arms ranged from -5.6% to 3.1%. The number of MACEs ranged from 0 to 72 per study arm (17 groups [37%] reported no events, 9 [20%] reported 1-2 events, and 20 [43%] reported ≥3 events). In unadjusted analysis, a 1% decrease in mean PAV was associated with 17% reduced odds of MACEs (unadjusted OR, 0.83; 95% CI, 0.71-0.98; P = .03), and with a 14% reduction in MACEs in adjusted analysis (adjusted OR, 0.86; 95% CI, 0.75-1.00; P = .050). Further adjustment for cardiovascular risk factors showed a 19% reduced risk (adjusted OR, 0.81; 95% CI, 0.68-0.96; P = .01) per 1% decrease in PAV. A 1% reduction of PAV change between intervention and comparator arms within studies was also associated with a significant 25% reduction in MACEs (OR, 0.75; 95% CI, 0.56-1.00; P = .046). Conclusions and Relevance: In this meta-analysis, regression of atherosclerotic plaque by 1% was associated with a 25% reduction in the odds of MACEs. These findings suggest that change in PAV could be a surrogate marker for MACEs, but given the heterogeneity in the outcomes, additional data are needed.

One-Year Prospective Follow-up of Women With INOCA and MINOCA at a Canadian Women's Heart Centre.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Predictors of neurological outcome after out-of-hospital cardiac arrest: sex-based analysis: do males derive greater benefit from hypothermia management than females?

BACKGROUND: Previous studies of the effect of sex on after out-of-hospital cardiac arrest (OHCA) outcomes focused on survival to hospital discharge and 1-month survival. Studies on the effect of sex on neurological function after OHCA are still limited. The objective of this study was to identify the predictors of favorable neurological outcome and to examine the association between sex as a biological variable and favorable neurological outcome OHCA. METHODS: Retrospective analyses of clustered data from the Resuscitation Outcomes Consortium multi-center randomized controlled trial (2011-2015). We included adults with non-traumatic OHCA and EMS-attended OHCA. We used multilevel logistic regression to examine the association between sex and favorable neurological outcomes (modified Rankin Scale) and to identify the predictors of favorable neurological outcome. RESULTS: In total, 22,416 patients were included. Of those, 8109 (36.2%) were females. The multilevel analysis identified the following variables as significant predictors of favorable neurological outcome: younger age, shorter duration of EMS arrival to the scene, arrest in public location, witnessed arrest, bystander CPR, chest compression rate (CCR) of 100-120 compressions per minute, induction of hypothermia, and initial shockable rhythm. Two variables, insertion of an advanced airway and administration of epinephrine, were associated with poor neurological outcome. Our analysis showed that males have higher crude rates of survival with favorable neurological outcome (8.6 vs. 4.9%, p < 0.001). However, the adjusted rate was not significant. Further analyses showed that hypothermia had a significantly greater effect on males than females. CONCLUSIONS: Males had significantly higher crude rates of survival with favorable neurological outcome. However, the adjusted rate was not statistically significant. Males derived significantly greater benefit from hypothermia management than females, but this can possibly be explained by differences in arrest characteristics or in-hospital treatment. In-depth confirmatory studies on the hypothermia effect size by sex are required.

Long-term Mortality, Readmission, and Resource Utilization Among Hospital Survivors of Out-of-Hospital Cardiac Arrest.

BACKGROUND: Among patients with out-of-hospital cardiac arrest (OHCA), the influence of pre- and in-hospital factors on long-term survival, readmission, and resource utilization is ill-defined, mainly related to challenges combining disparate data sources. METHODS: Adult nontraumatic OHCA from the British Columbia Cardiac Arrest Registry (January 2009 to December 2016) were linked to provincial datasets comprising comorbidities, medications, cardiac procedures, mortality, and hospital admission and discharge. Among hospital-discharge survivors, the 3-year end point of mortality or mortality and all-cause readmission was examined with the use of the Kaplan-Meier method and multivariable Cox regression model for predictors. The use of publicly funded home care and community services within 1 year after discharge also was evaluated. RESULTS: Of the 10,674 linked, emergency medical services-treated adult OHCAs, 3230 were admitted to hospital and 1325 survived to hospital discharge. At 3 years after discharge, the estimated Kaplan-Meier survival rate was 84.1% (95% CI 81.7%-86.1%) and freedom from death or all-cause readmission was 31.8% (29.0%-34.7%). After exclusions, 26.6% (n = 315/1186) accessed residential or home care services within 1 year. Independent predictors of long-term outcomes included age and comorbidities, but also favourable arrest characteristics and in-hospital factors such as revascularization or receipt of an intracardiac defibrillator before discharge. CONCLUSIONS: Among OHCA hospital survivors, the long-term death or readmission risk persists and is modulated by both pre- and in-hospital factors. However, only 1 in 4 survivors required residential or home care after discharge. These results support efforts to improve care processes to increase survival to hospital discharge.

Sex Differences in the Management of Oral Anticoagulation and Outcomes for Emergency Department Presentation of Incident Atrial Fibrillation.

STUDY OBJECTIVE: To examine sex differences in oral anticoagulation management and outcomes among patients with incident nonvalvular atrial fibrillation presenting to the emergency department (ED). METHODS: 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. RESULTS: 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 range <65%) 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. CONCLUSION: 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.

Development of Acute Myocardial Infarction Mortality and Readmission Models for Public Reporting on Hospital Performance in Canada.

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.

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.

Premenopausal-aged females have no neurological outcome advantage after out-of-hospital cardiac arrest: A multilevel analysis of North American populations.

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 < 0.001) and older males (OR 0.52, 95% CI 0.39-0.69, p < 0.001) had a significantly lower odds of favourable neurological outcome than younger females. Among all groups, older females had the worst outcomes. CONCLUSIONS: We did not detect an association between premenopausal age and survival with good neurological outcome, suggesting females sex hormones do not impact OHCA outcomes. Our findings are not in line with results from other studies. Studies that rigorously evaluate menopausal status are required to definitively assess the impact of female sex hormones on outcomes.

Circulating levels of cell adhesion molecules and risk of cardiovascular events in obstructive sleep apnea.

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.

Impact of regionalizing ST-elevation myocardial infarction care on sex differences in reperfusion times and clinical outcomes.

BACKGROUND: Women with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention historically experience worse in-hospital outcomes compared to men. HYPOTHESIS: Implementation of a regional STEMI system will reduce care gaps in reperfusion times and in-hospital outcomes between women and men. METHODS: 1928 patients (413 women, 21.4%) presented with an acute STEMI between June 2007 and March 2016. The population was divided into an early cohort (n = 728 patients, 2007-May 2011), and a late cohort (n = 1200 patients, June 2011-2016). The primary endpoints evaluated were reperfusion times and in-hospital outcomes. RESULTS: Compared to men, women experienced significant delays in first medical contact (FMC) to arrival at the emergency room (26.0 vs. 22.0 min, p < 0.001) and FMC-to-device (109 vs. 101 min p = 0.001). Women had higher incidences of post-PCI heart failure and death compared to men (p < 0.05). Following multivariable adjustment, no mortality difference was observed for women versus men (adjusted OR; 0.82; 95% confidence interval [CI], 0.51-1.34; p = 0.433) or for early versus late cohorts (adjusted OR; 1.04; 95% CI, 0.68-1.60; p = 0.856). CONCLUSION: Following STEMI regionalization, women continued to experience significantly longer reperfusion times, although there was no difference in adjusted mortality. These results highlight the ongoing disparity of STEMI care between women and men, and suggest that regionalization alone is insufficient to close sex-based care gaps.

Association of "hypertriglyceridemic waist" with increased 5-year risk of subclinical atherosclerosis in a multi-ethnic population: a prospective cohort study.

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 (ß = 0.08 [0.04, 0.11], p < 0.001), total area (ß = 0.20 [0.07, 0.33], 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.

A feasibility study for CODE-MI: High-sensitivity cardiac troponin-Optimizing the diagnosis of acute myocardial infarction/injury in women.

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.

High-Sensitivity Cardiac Troponin-Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women (CODE-MI): Rationale and design for a multicenter, stepped-wedge, cluster-randomized trial.

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.

Examining Coronary Revascularization Practice Patterns for Diabetics: Perceived Barriers, Facilitators, and Implications for Knowledge Translation.

BACKGROUND: The FREEDOM trial provided robust evidence that coronary artery bypass grafting (CABG) was superior to percutaneous coronary intervention (PCI) for coronary revascularization in patients with diabetes mellitus (DM) and multivessel coronary artery disease (MV-CAD). The present study examined practice pattern changes and perceived barriers and facilitators to implementing FREEDOM trial evidence in British Columbia (BC). METHODS: Using a population-based database of cardiac procedures in BC, PCI:CABG ratios from 2007-2014 were compared before and after publication of the FREEDOM trial in the 4 tertiary cardiac centres that provided both CABG and PCI. Surveys of barriers and facilitators to implementation of evidence in practice were completed by 57 health care providers (HCPs) attending educational outreach sessions conducted in 2016-17 at 5 tertiary cardiac centres in BC. RESULTS: The overall PCI:CABG ratio declined from 1.59 (95% confidence interval [CI] 1.48-1.70, range 1.16-1.86) before publication to 0.88 (95% CI 0.75-1.01, range 0.56-0.82) after publication (P < 0.01). This decline from before to after publication was significant in 3 centres, but not in the fourth centre (from 1.62 to 1.49; P = 0.61). Barriers were identified at the levels of evidence (applicability, credibility), HCP (awareness/knowledge, practice behaviours), patient (knowledge/misconceptions, preferences), and systems (siloing of care, financial disincentives, resource limitations, geography). Facilitators were additional studies/guidelines, education/dissemination, shared decision making, a heart team approach, changes to remuneration models, and increased resources. CONCLUSIONS: Following publication of the FREEDOM trial, the proportion of patients with DM and MV-CAD undergoing CABG increased in BC; however, practice patterns varied across cardiac centres. HCPs attributed these practice variations to multilevel barriers and facilitators. Future knowledge translation strategies should be multifaceted and tailored to identified determinants.

Predictors of Cumulative Health Care Costs Associated With Transcatheter Aortic Valve Replacement in Severe Aortic Stenosis.

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 health care costs in TAVR. METHODS: Demographics, procedural details, in-hospital complications, and costs for all adults undergoing first-time TAVR from 2012 to 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 per 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 2009 first-time TAVR patients (mean age 81.7 ± 7.6, 45.9% female and Society of Thoracic Surgeons (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 to 360 days postprocedure. The referral phase median cost was $4527 (interquartile range [IQR]: 1708-12,594), 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 $6053 (IQR: 3320-17,048). 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 nontransfemoral access, complications of stroke, and pacemaker insertion. Predictors of higher cost in the third (stable) phase were predominantly nonmodifiable, 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.