A Feasibility Study for CODE-MI: High-Sensitivity Cardiac Troponin - Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women.

Objectives This feasibility study was conducted to inform the design and power evaluation of CODE-MI, a pan-Canadian trial evaluating 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 with symptoms suggestive for myocardial ischemia. Approach CODE-MI is a multi-center, stepped-wedge cluster randomized trial. The cohort and outcomes will be obtained from routinely collected administrative data. Using linked administrative data from 11 hospitals in Ontario from 2014/10 to 2017/09, this feasibility study obtained the following estimates: number of eligible patients, i.e., women presenting to the emergency department with symptoms suggestive of myocardial ischemia and a 24-hour peak hs-cTn value within the female-specific and overall thresholds (i.e. primary cohort); the rate of the 1-year composite outcome of all-cause mortality, re-admission for non-fatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization. Study power was evaluated via simulations. Results Overall, 2,073,849 emergency department 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. Conclusion Routinely collected administrative health data serve as a rich and essential resource for conducting pragmatic trials assessing process change, such as CODE-MI. We demonstrated the strength of using linked administrative health data to guide the design of pragmatic clinical trials and accurately evaluate the study power

Sex Differences in Mortality After Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis

ObjectivesThe aim of this study was to examine sex differences in outcome after transcatheter aortic valve replacement (TAVR) with real-world data from 2 large centers in Canada.BackgroundTranscatheter aortic valve replacement is an effective alternative to surgical valve replacement in symptomatic patients with severe aortic stenosis, but the impact of sex on outcomes remains unclear. The PARTNER (Placement of Aortic Transcatheter Valves) 1A trial demonstrated greater benefit of TAVR over surgery in women, but whether this was due to the poorer surgical outcome of women or better TAVR outcome, compared with men, is unknown.MethodsConsecutive patients (n = 641) undergoing TAVR in Vancouver and Quebec City, Canada, were evaluated. Differences in all-cause mortality were examined with Kaplan-Meier estimates, adjusted logistic regression, and proportional hazards models.ResultsWomen comprised 51.3% of the cohort. Balloon-expandable valves were used in 97% of cases, with transapical approach in 51.7 % women and 38.1% men. Women had more major vascular complications (12.4% vs. 5.4%, p = 0.003) and borderline significantly more major/life-threatening bleeds (21.6% vs. 15.8%, p = 0.08). At baseline, women had higher aortic gradients and worse renal function but better ejection fractions. Men had more comorbidities: prior myocardial infarction, prior revascularization, and chronic obstructive pulmonary disease. The adjusted odds ratio for 30-day all-cause mortality favored women, 0.39 (95% confidence interval: 0.19 to 0.80; p = 0.01), and this benefit persisted for 2 years, hazard ratio 0.60 (95% confidence interval: 0.41 to 0.88; p = 0.008).ConclusionsFemale sex is associated with better short- and long-term survival after TAVR. Added to the PARTNER 1A findings, these results suggest TAVR might be the preferred treatment option for elderly women with symptomatic severe aortic stenosis

Antibiotic use for prolongation of pregnancy in women with preterm labour or premature rupture of membranes

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Sex differences in acute myocardial infarction in younger adults

Background: Younger adults have been identified as an emerging ‘at-risk’ population with a rising prevalence of cardiac risk factors and hospitalization for acute myocardial infarction (AMI). Coupled with this is an unexplained excess early AMI mortality risk in younger women compared to younger men. Self-perceived health status (symptoms, physical function and disease perception) has been proposed as a contributing factor; however, not much is known about sex differences in health status outcomes of younger adults post AMI. The overarching goal of this thesis is to enhance our understanding of AMI in younger adults (20-55 years). The main objectives are: 1) to examine sex differences and 10-year trends in AMI hospitalization and early AMI mortality, and to determine whether the sex gap in early AMI mortality has changed in recent years, and 2) to examine the sex differences and changes in health status during the first year following AMI. Methods: The age- and sex-specific 10-year trends in AMI hospitalization and 30-day AMI mortality were based on population-based, administrative data in British Columbia (BC) and assessed using negative binomial and logistic regression, respectively. Sex differences and changes in health status were assessed using prospectively collected data on 286 younger AMI patients, in BC. Linear and generalized linear mixed models were used to assess health status changes. Results: Between 2000-2009, younger adults, particularly women, did not experience the same declining AMI hospitalization rates as older adults. Furthermore, for early AMI mortality, the observed sex differences among younger adults persisted, even after adjusting for comorbidities. While health status in both men and women diminished in the first month following AMI, driven by worse angina and physical function, it improved thereafter. Younger women consistently had significantly worse cardiac-related physical function, disease perception, and overall physical and mental health than younger men during the first year; however, the changes in health status were similar in men and women. Conclusions: The findings highlight a persistent sex difference in early mortality and health status following AMI among younger adults. The first month after AMI is a critical period to intensify support and treatment in order to improve outcomes.Medicine, Faculty ofPopulation and Public Health (SPPH), School ofGraduat