Uptake of SGLT2i and Outcomes in Patients with Diabetes and Heart Failure: A Population-Based Cohort and a Specialized Clinic Cohort.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are effective in adults with diabetes mellitus (DM) and heart failure (HF) based on randomized clinical trials. We compared SGLT2 inhibitor uptake and outcomes in two cohorts: a population-based cohort of all adults with DM and HF in Alberta, Canada and a specialized heart function clinic (HFC) cohort. METHODS: The population-based cohort was derived from linked provincial healthcare datasets. The specialized clinic cohort was created by chart review of consecutive patients prospectively enrolled in the HFC between February 2018 and August 2022. We examined the association between SGLT2 inhibitor use (modeled as a time-varying covariate) and all-cause mortality or deaths/cardiovascular hospitalizations. RESULTS: Of the 4,885 individuals from the population-based cohort, 64.2% met the eligibility criteria of the trials proving the effectiveness of SGLT2 inhibitors. Utilization of SGLT2 inhibitors increased from 1.2% in 2017 to 26.4% by January 2022. In comparison, of the 530 patients followed in the HFC, SGLT2 inhibitor use increased from 9.8% in 2019 to 49.1 % by March 2022. SGLT2 inhibitor use in the population-based cohort was associated with fewer all-cause mortality (aHR 0.51, 95%CI 0.41-0.63) and deaths/cardiovascular hospitalizations (aHR 0.65, 95%CI 0.54-0.77). However, SGLT2 inhibitor usage rates were far lower in HF patients without DM (3.5% by March 2022 in the HFC cohort). CONCLUSIONS: Despite robust randomized trial evidence of clinical benefit, the uptake of SGLT2 inhibitors in patients with HF and DM remains low, even in the specialized HFC. Clinical care strategies are needed to enhance the use of SGLT2 inhibitors and improve implementation.

Gestational diabetes: One size does not fit all-an observational study of maternal and neonatal outcomes by maternal glucose profile.

OBJECTIVES: To examine obstetrical and neonatal outcomes across maternal glucose profiles at the population level and to explore insulin sensitivity and beta-cell function across profiles in an independent, well-phenotyped cohort for potential pathophysiologic explanation. RESEARCH DESIGN AND METHODS: Observational cohort study of all pregnancies with gestational diabetes screening between October 2008 and December 2018 resulting in live singleton birth in Alberta, Canada (n = 436,773) were categorized into seven maternal glucose profiles: (1) normal 50 g-glucose challenge test (nGCT), (2) normal 75-g OGTT (nOGTT), (3) isolated elevated 1 h post-load glucose (ePLPG1), (4) isolated elevated 2 h post-load glucose (ePLPG2), (5) elevated 1 and 2 h post-load glucose (ePLPG12), (6) isolated elevated FPG (eFPG), and (7) elevated FPG + elevated 1-h and/or 2-h PLG (Combined). Primary outcomes were large for gestational age (LGA) and neonatal intensive care unit (NICU) admission rates. An independent observational cohort of 1451 women was examined for measures of beta-cell function (ISSI-2, insulinogenic index/HOMA-IR) and insulin sensitivity/resistance (Matsuda index, HOMA-IR) by similar maternal glucose profiles. RESULTS: Pregnancies with elevated FPG, either isolated or combined, had higher adverse events and lower insulin sensitivity. The combination of elevated FPG + elevated 1-h and/or 2-h PLG had the highest rates of LGA(20.9%), NICU admissions (14.7%), and lowest insulin sensitivity as measured by Matsuda index and HOMA-IR, and beta-cell function as measured by ISSI-2 and Insulinogenic index/HOMA-IR. CONCLUSIONS: Elevated fasting plasma glucose, either alone or combined with post-load glucose elevation is associated with worse outcomes than isolated post-load glucose elevation, possibly due to higher degrees of insulin resistance. Future work is needed to better understand these differences, and explore whether tailored treatment of GDM can improve neonatal outcomes.

Impact of a modified screening approach during the COVID-19 pandemic on the diagnosis and outcomes of gestational diabetes mellitus: A population-level analysis of 90,518 pregnant women.

AIMS: To provide real-world evidence on the uptake of and outcomes associated with the modified gestational diabetes mellitus (GDM) screening approach offered during the COVID-19 pandemic compared with the standard screening approach. METHODS: All pregnancies between 01 January 2020 and 31 December 2021, in Alberta, Canada, were included in the study. We examined GDM screening and diagnosis rates, and large-for-gestational-age (LGA) outcomes. RESULTS: Annual GDM screening rates were > 95% during the study time period. Overall, 84.7%, and 11.6% of the 92,505 pregnancies underwent standard and modified screening for GDM, respectively. The use of modified screening was the highest among deliveries in August 2020 (49.8%) which corresponded to the early first wave of the pandemic. GDM diagnosis rate was lower in the modified screening (7.4%) than in the standard screening (12.3%, p < 0.001) group. The LGA rates in the modified screening with GDM and the standard screening with GDM groups were 24.8% and 12.6%, respectively (p < 0.001). Women in the modified screening with GDM group were at a higher risk of having an LGA infant (adjusted odds ratio: 3.46; 95% confidence interval: 2.93, 4.08) compared to the standard screening with no GDM group. CONCLUSIONS: The COVID-19 epidemic had no impact on screening for GDM. Women who underwent modified screening, based on HbA1c/random plasma glucose, had lower rates of GDM cases.

Impact of inherited bleeding disorders on maternal bleeding and other pregnancy outcomes: A population-based cohort study.

INTRODUCTION: Increasing rate of postpartum haemorrhage (PPH) has been observed between 2003 and 2010 in Canada. Inherited bleeding disorders contribute to the risk of PPH. AIM: To identify the trend in PPH in the last decade, assess the impact of bleeding disorders on pregnancy outcomes and evaluate their coagulation workup during pregnancy. METHODS: We conducted a population-based retrospective cohort study using the Alberta Pregnancy Birth Cohort from 2010 to 2018. We included women with von Willebrand disease (VWD) and haemophilia, identified by previously validated algorithm and matched with controls. Logistic regression was used to compute odds of PPH and other pregnancy outcomes. RESULTS: We identified 311,330 women with a total of 454,400 pregnancies with live births. The rate of PPH did not change significantly from 10.13 per 100 deliveries (95% CI 10.10-10.16) in 2010-10.72 (95% CI 10.69-10.75) in 2018 (p for trend = .35). Women with bleeding disorders were significantly more likely to experience PPH (odds ratio [OR] 2.3; 95% CI 1.5-3.6), antepartum haemorrhage (OR 2.9; 95% CI 1.5-5.9) and red cell transfusion (OR 2.8; 95% CI 1.1-7.0). We observed a nonsignificant rise in the rate of PPH in women with VWD and haemophilia. Only 49.5% pregnancies with bleeding disorders had third trimester coagulation factor levels checked. Higher odds of PPH and antepartum haemorrhage were observed even with factor levels ≥0.50 IU/mL in third trimester. CONCLUSION: Despite comprehensive care in women with bleeding disorders, they are still at higher risk of adverse pregnancy outcomes compared to population controls.

Time trends in preeclampsia and gestational diabetes in Denmark and Alberta, Canada, 2005-2018-A population-based cohort study.

INTRODUCTION: Preeclampsia and gestational diabetes mellitus share risk factors such as obesity and increased maternal age, which have become more prevalent in recent decades. We examined changes in the prevalence of preeclampsia and gestational diabetes between 2005 and 2018 in Denmark and Alberta, Canada, and investigated whether the observed trends can be explained by changes in maternal age, parity, multiple pregnancy, comorbidity, and body mass index (BMI) over time. MATERIAL AND METHODS: This study was a register-based cohort study conducted using data from the Danish National Health Registers and the provincial health registers of Alberta, Canada. We included in the study cohort all pregnancies in 2005-2018 resulting in live-born infants and used binomial regression to estimate mean annual increases in the prevalence of preeclampsia and gestational diabetes in the two populations across the study period, adjusted for maternal characteristics. RESULTS: The study cohorts included 846 127 (Denmark) and 706 728 (Alberta) pregnancies. The prevalence of preeclampsia increased over the study period in Denmark (2.5% to 2.9%) and Alberta (1.7% to 2.5%), with mean annual increases of 0.03 (95% confidence interval [CI] 0.02-0.04) and 0.06 (95% CI 0.05-0.07) percentage points, respectively. The prevalence of gestational diabetes also increased in Denmark (1.9% to 4.6%) and Alberta (3.9% to 9.2%), with average annual increases of 0.20 (95% CI 0.19-0.21) and 0.44 (95% CI 0.42-0.45) percentage points. Changes in the distributions of maternal age and BMI contributed to increases in the prevalence of both conditions but could not explain them entirely. CONCLUSIONS: The prevalence of both preeclampsia and gestational diabetes increased significantly from 2005 to 2018, which portends future increases in chronic disease rates among affected women. Increasing demand for long-term follow up and care will amplify the existing pressure on healthcare systems.

Outrunning the grim reaper: longevity of the first 200 sub-4 min mile male runners.

OBJECTIVES: To determine the impact of running a sub-4 min mile on longevity. It was hypothesised that there would be an increase in longevity for runners who successfully completed a sub-4 min mile compared with the general population. METHODS: As part of this retrospective cohort study, the Sub-4 Alphabetic Register was used to extract the first 200 athletes to run a sub-4 min mile. Each runner's date of birth, date of their first successful mile attempt, current age (if alive) or age at death was compared with the United Nations Life Tables to determine the difference in each runner's current age or age at death with their country of origin-specific life expectancy. RESULTS: Of the first 200 sub-4 min mile runners (100% male), 60 were dead (30%) and 140 were still alive. Sub-4 min mile runners lived an average of 4.7 years beyond their predicted life expectancy (95% CI 4.7 to 4.8). When accounting for the decade of completion (1950s, 1960s or 1970s), the longevity benefits were 9.2 years (n=22; 95% CI 8.3 to 10.1), 5.5 years (n=88; 95% CI 5.3 to 5.7) and 2.9 years (n=90; 95% CI 2.7 to 3.1), respectively. CONCLUSION: Sub-4 min mile runners have increased longevity compared with the general population, thereby challenging the notion that extreme endurance exercise may be detrimental to longevity.

Lower Socioeconomic Status is Associated with an Increased Incidence and Spectrum of Major Congenital Heart Disease and Associated Extracardiac Pathology.

Several studies have suggested an inverse relationship between lower socioeconomic status (SES) and the incidence of congenital heart disease (CHD) among live births. We sought to examine this relationship further in a Canada-wide population study, exploring CHD subtypes, trends, and associated noncardiac abnormalities. Infants born in Canada (less Quebec) from 2008 to 2018 with CHD requiring intervention in the first year were identified using ICD-10 codes through the Canadian Institute for Health Information Discharge Abstract Database. Births of CHD patients were stratified by SES (census-based income quintiles) and compared against national birth proportions using X2 tests. Proportions with extracardiac defects (ED) and nonlethal genetic syndromes (GS) were also explored. From 2008 to 2018, 7711 infants born with CHD were included. The proportions of major CHD distributed across SES quintiles were 27.1%, 20.1%, 19.2%, 18.6%, and 15.0% from lowest to highest, with significant differences relative to national birth proportions (22.0%, 20.0%, 20.6%, 20.7%, and 16.7% from lowest (1) to highest (5)) (p < 0.0001). No temporal trends in the CHD proportions across SES categories were observed over the study period. The distribution across SES quintiles was different only for specific CHD subtypes (double-outlet right ventricle (n = 485, p = 0.03), hypoplastic left heart syndrome (n = 547, p = 0.006), heterotaxy (n = 224, p = 0.03), tetralogy of Fallot (n = 1007, p = 0.008), truncus arteriosus (n = 126, p < 0.0001), and ventricular septal defect (n = 1916, p < 0.0001)), with highest proportions observed in the lowest quintile. The proportion of the total population with ED but not GS was highest in lower SES quintiles (< 0.0001) commensurate with increased proportion of CHD. Our study suggests a negative association between SES and certain CHD lesions and ED.

Association Between Vaccination Status and Outcomes in Patients Admitted to the ICU With COVID-19.

OBJECTIVES: Although COVID-19 vaccines can reduce the need for intensive care unit admission in COVID-19, their effect on outcomes in critical illness remains unclear. We evaluated outcomes in vaccinated patients admitted to the ICU with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the association between vaccination and booster status on clinical outcomes. DESIGN: Retrospective cohort. SETTING AND PATIENTS: All patients were admitted to an ICU between January 2021 (after vaccination was available) and July 2022 with a diagnosis of COVID-19 based on a SARS-CoV-2 polymerase chain reaction test in Alberta, Canada. INTERVENTIONS: None. MEASUREMENT: The propensity-matched primary outcome of all-cause in-hospital mortality was compared between vaccinated and unvaccinated patients, and vaccinated patients were stratified by booster dosing. Secondary outcomes were mechanical ventilation (MV) duration ICU length of stay (LOS). MAIN RESULTS: The study included 3,293 patients: 743 (22.6%) were fully vaccinated (54.6% with booster), 166 (5.0%) were partially vaccinated, and 2,384 (72.4%) were unvaccinated. Unvaccinated patients were more likely to require invasive MV (78.4% vs 68.2%), vasopressor use (71.1% vs 66.6%), and extracorporeal membrane oxygenation (2.1% vs 0.5%). In a propensity-matched analysis, in-hospital mortality was similar (31.8% vs 34.0%, adjusted odds ratio [OR], 1.25; 95% CI, 0.97-1.61), but median duration MV (7.6 vs 4.7 d; p < 0.001) and ICU LOS (6.6 vs 5.2 d; p < 0.001) were longer in unvaccinated compared to fully vaccinated patients. Among vaccinated patients, greater than or equal to 1 booster had lower in-hospital mortality (25.5% vs 40.9%; adjusted OR, 0.50; 95% CI, 0.0.36-0.68) and duration of MV (3.8 vs 5.6 d; p = 0.025). CONCLUSIONS: Nearly one in four patients admitted to the ICU with COVID-19 after widespread COVID-19 vaccine availability represented a vaccine-breakthrough case. Mortality risk remains substantial in vaccinated patients and similar between vaccinated and unvaccinated patients after the onset of critical illness. However, COVID-19 vaccination is associated with reduced ICU resource utilization and booster dosing may increase survivability from COVID-19-related critical illness.

Kidney function monitoring and trajectories in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) and chronic kidney disease (CKD) frequently co-exist. The frequency of kidney monitoring and range of kidney function in patients with AF in clinical practice are uncertain. METHODS: All adult Albertans with AF between 2008 and 2017 were identified using ICD-9 and -10 codes 427.3 and I48. Kidney Disease Improving Global Outcomes (KDIGO) risk categories were defined using eGFR by the Chronic Kidney Disease Epidemiology Collaborative equation and albuminuria results within 6 months of eGFR measurement. eGFR trajectories were compared from baseline to maximum value within the following year. RESULTS: Among 105,946 patients with AF, 16.0% were KDIGO category G1 (eGFR ≥ 90), 49.0% G2 (60-89.9), 19.8% G3a (45-59.9), 11.4% G3b (30-44.9), and G4 3.8% (15-29.9). Albuminuria was normal/mild 83.4%, moderate 11.7%, and severe 4.9%. Kidney monitoring was more common among people with lower eGFR and worse albuminuria, from approximately twice annually for G1-2/A1-2 to 8 times annually in stage G4A3. Approximately 60-80% of patients received guideline-recommended monitoring, consistent across KDIGO stages. With lower baseline eGFR, annual change in eGFR decreased while the relative proportion of patients who worsened compared to improved increased: for baseline eGFR 60-89.9, 16.7% worsened vs 6.7% improved, but for eGFR 30-44.9, 8.8% worsened but only 1.0% improved. CONCLUSION: The frequency of kidney function monitoring in patients with AF increased with worsening KDIGO risk category and adhered to KDIGO guidelines in approximately three quarters of patients. A minority of patients had moderate to severe eGFR impairment, of whom most remained stable over 1 year.

Epidemiology of Worsening Heart Failure in a Population-based Cohort from Alberta, Canada: Evaluating Eligibility for Treatment With Vericiguat.

BACKGROUND: Patients with heart failure (HF) and a reduced ejection fraction (HFrEF) who experience worsening HF (WHF) events are at increased risk of adverse outcomes and experience significant morbidity and mortality. We herein describe the epidemiology of these patients and identify those potentially eligible for vericiguat therapy in this population-based study. METHODS AND RESULTS: This retrospective cohort study included hospitalized or emergency department patients with a primary diagnosis of HF and a left ventricular ejection fraction (LVEF) of less than 45% diagnosed between April 1, 2009, and March 31, 2019 in Alberta, Canada, with follow-up to March 31, 2020. Inclusion criteria from the VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection (VICTORIA) trial were applied to explore eligibility for vericiguat. Among 25,629 patients with HF and LVEF data, 9948 (38.8%) had HFrEF, of which 5259 (52.8%) experienced WHF at some point during a median 5.8 years of follow-up, and 38.3% of those met the vericiguat trial eligibility criteria. Compared with patients with HFrEF without WHF, those with WHF were older, with more comorbidities, worse renal function, and similar LVEF status, but greater use of HF medications at baseline. At the time of WHF, 27% of those with HFrEF and WHF were on triple therapy, 50.6% were on dual therapy, and 15.4% were on monotherapy. All-cause mortality and the composite outcome of all-cause mortality or cardiovascular hospitalization at 1-year of follow-up were higher in the HFrEF with WHF cohort compared with HFrEF without WHF (adjusted hazard ratios of 1.92 and 1.51, respectively, both P < .0001). CONCLUSIONS: Approximately one-half of patients with HFrEF experienced WHF over the long-term follow-up. Most were not on triple therapy, highlighting the underuse of the existing standard-of-care treatments and opportunities for application of newer therapies; more than one-third of patients with HFrEF may be eligible for vericiguat. LAY SUMMARY: Among patients with heart failure (HF), those who experience worsening HF (WHF) are at increased risk of adverse outcomes. A few new therapies, including vericiguat, have emerged recently for patients with HF and reduced ejection fraction. However, the epidemiology, treatment patterns, and outcomes of patients with WHF in large representative populations is unclear. In the current study, approximately one-half of the patients with HF and reduced ejection fraction experienced WHF and 38.3% were potentially eligible for vericiguat therapy. The guideline-recommended therapies were under-utilized among patients with WHF, which highlights the need for initiatives to address this care gap.

The Incidence and Prevalence of Cardiac Amyloidosis in a Large Community-Based Cohort in Alberta, Canada.

BACKGROUND: Despite the improved awareness of cardiac amyloidosis among clinicians, its incidence and prevalence is not well-described in a community setting. We sought to investigate the incidence and prevalence of cardiac amyloidosis in the community. METHODS AND RESULTS: In the adult population of Alberta, we examined 3 cohorts: (1) probable cases of cardiac amyloidosis: the presence of physician-assigned diagnosis of amyloidosis (International Classification of Diseases [ICD]-10 code E85; ICD-9 277.3) and 1 or more health care encounter for heart failure (HF) (ICD-10 I50; ICD-9 428); (2) possible cardiac amyloidosis: the presence of clinical phenotypes suggestive of amyloidosis; and (3) a comparator HF cohort without amyloidosis. Between 2004 and 2018, 982 of the 145,329 patients with HF were identified as probable cardiac amyloidosis. During the same period, the incidence rates of probable cardiac amyloidosis increased from 1.38 to 3.69 per 100,000 person-years and the prevalence rates increased from 3.42 to 14.85 per 100,000 person-years (Ptrend < .0001). Patients with probable cardiac amyloidosis were more likely to be male, have a higher comorbidity burden, greater health care use, and poorer outcomes as compared with patients with HF without amyloidosis. A much larger group of patients was identified as possible cardiac amyloidosis (n = 46,255), with similar increase in prevalence from 2004 to 2018 (from 416 to 850 per 100,000 person-years). CONCLUSIONS: The incidence and prevalence of cardiac amyloidosis has increased over the last decade. Given the advent of new therapies for cardiac amyloidosis and considering their high cost, it is imperative to devise strategies to screen, identify, and track patients with cardiac amyloidosis from administrative databases.

Association between maternal glucose and large for gestational outcomes: Real-world evidence to support Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) study findings.

AIMS: To compare large for gestational age (LGA) rates by maternal glucose levels in a real-world setting with those in the Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) study. To examine the association between fasting plasma glucose (FPG), 1- and 2-h on a 75-g oral glucose tolerance tests (OGTT) and LGA. METHODS: Pregnancies were categorized according to HAPO thresholds. Category-specific LGA rates were compared to those in HAPO. Categories with glucose thresholds below or above the diagnostic criteria for gestational diabetes mellitus (GDM) were labelled as lower and higher/GDM, respectively. GDM pregnancies were further stratified according to FPG or post-load elevations and logistic regression was used to examine their independent association with LGA. FINDINGS: In our cohort of 97,032 pregnancies, rates of LGA increased with increasing maternal glucose in lower categories of FPG, 1- and 2-h glucose (trend p < 0.01). However, LGA rates in higher/GDM categories were significantly lower in our study than those in HAPO for 1- and 2-h glucose, but not for FPG. Elevated FPG alone was associated with an almost twofold increase in risk of LGA, while elevated post-load glucose alone was associated with a 20% reduction in risk of LGA, compared to negative OGTT. CONCLUSIONS: Real-world data confirm the HAPO study findings at lower levels of maternal glycaemia. At higher levels, GDM diagnosis and treatment appear to be effective in reducing rates of LGA in pregnancies with post-load glucose elevations, but not elevated FPG. Elevated FPG is a stronger predictor of LGA than post-load glucose elevations.

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.

Is There a Sex Gap in Surviving an Acute Coronary Syndrome or Subsequent Development of Heart Failure?

BACKGROUND: We hypothesized that disparities between sexes in the management of myocardial infarction (MI) may have changed over time, and thus altered the prognoses after MI, especially the risk for the development of heart failure. METHODS: Using a large population-based cohort of patients with MI between April 1, 2002, and March 31, 2016, we examined the incidence, angiographic findings, treatment (including revascularization), and clinical outcomes of patients with a first-time MI. To elucidate the differences between sexes, a series of multivariable models were created to explore all MI and non-ST-segment-elevation MI (NSTEMI) versus ST-segment-elevation MI (STEMI) over time. RESULTS: Between 2002 and 2016, 45 064 patients (13 878 [30.8%] women) were hospitalized with a primary diagnosis of first-time MI (54.9% NSTEMI and 45.1% STEMI). Women were older (median age, 72 versus 61 years), had more comorbidities, and had lower rates of diagnostic angiography than did men (women, 74%, versus men, 87%). When angiography was performed, women had a lower proportion of left main, 2-vessel disease with proximal left anterior descending or 3-vessel disease compared with men (33.4% versus 40.9%, P<0.0001), and a higher frequency of 1-vessel disease or nonobstructive coronary artery disease (39.6% versus 29.1%, P<0.0001). Women had a higher unadjusted rate of in-hospital mortality than did men in both patients with STEMI (women, 9.4%, versus men, 4.5%) and patients with NSTEMI (women, 4.7%, versus men, 2.9%). After adjustment, this difference remained significant in STEMI (adjusted odds ratio, 1.42 [95% CI, 1.24-1.64]) but not in NSTEMI (adjusted odds ratio, 0.97 [95% CI, 0.83-1.13]). After discharge, women developed heart failure after STEMI (women, 22.5%, versus men, 14.9%) as well as after NSTEMI (women, 23.2%, versus men, 15.7%). The adjusted relative risk for women versus men of developing the outcomes of mortality and heart failure remained similar across years, although the differences were nonsignificantly attenuated over 5 years of follow-up. CONCLUSIONS: Although some attenuation of differences in clinical outcomes over time has occurred, women remain at higher risk than men of dying or developing heart failure in the subsequent 5 years after STEMI or NSTEMI, even after accounting for differences in angiographic findings, revascularization, and other confounders.

Validity of different dose reduction criteria for apixaban.

Reduced-dose apixaban is recommended in patients fulfilling 2 of 3 criteria: age ≥80 years, body weight ≤60 kg, and serum creatinine ≥1.5 mg/dL. However, patient weight is often not available in electronic health data. We examined the validity of alternative definitions based on age and renal function alone using an observational dataset of patients with atrial fibrillation and chronic kidney disease which included weight measurements.

Computing the polytomous discrimination index.

Polytomous regression models generalize logistic models for the case of a categorical outcome variable with more than two distinct categories. These models are currently used in clinical research, and it is essential to measure their abilities to distinguish between the categories of the outcome. In 2012, van Calster et al proposed the polytomous discrimination index (PDI) as an extension of the binary discrimination c-statistic to unordered polytomous regression. The PDI is a summary of the simultaneous discrimination between all outcome categories. Previous implementations of the PDI are not capable of running on "big data." This article shows that the PDI formula can be manipulated to depend only on the distributions of the predicted probabilities evaluated for each outcome category and within each observed level of the outcome, which substantially improves the computation time. We present a SAS macro and R function that can rapidly evaluate the PDI and its components. The routines are evaluated on several simulated datasets after varying the number of categories of the outcome and size of the data and two real-world large administrative health datasets. We compare PDI with two other discrimination indices: M-index and hypervolume under the manifold (HUM) on simulated examples. We describe situations where the PDI and HUM, indices based on multiple comparisons, are superior to the M-index, an index based on pairwise comparisons, to detect predictions that are no different than random selection or erroneous due to incorrect ranking.

Impact of Atrial Fibrillation Case Volume in the Emergency Department on Early and Late Outcomes of Patients With New Atrial Fibrillation.

STUDY OBJECTIVE: To define the association between atrial fibrillation case volume in the emergency department and death or all-cause hospitalization at 30 days and 1 year in patients with new atrial fibrillation. Secondary objectives examined repeat ED visits and the management of atrial fibrillation within 90 days. METHODS: We identified all adults presenting to an ED in Alberta, Canada, with a new primary diagnosis of atrial fibrillation/flutter between 2009 and 2015 using International Classification of Diseases, 10th Revision code I48. Volume was classified in tertiles weighted by annual ED number of atrial fibrillation cases. The association between volume and outcomes was evaluated using generalized linear mixed models, adjusting for prognostically important covariates as fixed effects and ED as a random effect to account for potential clustering within EDs. RESULTS: The tertiles consisted of 4 high, 9 medium, and 68 low atrial fibrillation volume EDs, with 4,217, 4,193, and 4,112 patients, respectively. Volume was not independently associated with the primary outcome or individual components. However, medium- and high-volume EDs had fewer repeat ED visits at 30 days (respective adjusted odds ratio [aOR] 0.75 [95% confidence interval {CI} 0.66 to 0.87] and 0.64 [0.52 to 0.79]) and 1 year (respective aOR 0.77 [95% CI 0.67 to 0.90] and 0.71 [0.56 to 0.90]). Fewer patients were admitted from medium- (37.1%) and high- (32.0%) compared with low-volume (39.5%) EDs. Patients attending medium- and high-volume EDs were more likely to be cardioverted (aOR 3.28 [95% CI 1.94 to 5.53] and 3.81 [1.39 to 10.48] for medium- and high-volume EDs, respectively). CONCLUSION: Treatment in higher volume EDs was associated with significantly lower admission rates and repeat ED visits but no difference in survival.

18F-Sodium Fluoride Imaging of Coronary Atherosclerosis in Ambulatory Patients With Diabetes Mellitus.

Objective- Although patients with diabetes mellitus (DM) are considered at high risk of cardiovascular events, there is growing evidence that this notion is incorrect. Atherosclerosis imaging may identify patients at risk. Approach and Results- We performed coronary atherosclerosis with 18F-sodium fluoride (NaF) positron emission tomography/computed tomography and gated chest computed tomography for coronary artery calcium in 88 consecutive ambulatory patients with DM on a stable medical regimen. NaF has been shown to localize avidly in culprit lesions of patients with acute coronary syndromes and may identify unstable plaques. NaF activity was measured as target (coronary arteries)-to-background (left ventricular pool) ratio (TBR). High TBR was defined as ≥1.5. The mean age of the cohort was 54±14 years, 55% had type 2 DM, 65% were men, the median HgbA1c (hemoglobin A1c) and LDL (low-density lipoprotein) cholesterol were 7.5% (interquartile range, 7.1-8.5) and 1.9 mmol/L (interquartile range, 1.5-2.6), respectively. Mean coronary artery calcium score was 374±773, and median TBR was 1.2. Coronary artery TBR ≥1.5 was detected in 13 (15%) patients. In univariable analyses, male sex ( P=0.0002), estimated glomerular filtration rate ( P=0.02), and total coronary artery calcium score ( P=0.04) were associated with TBR. In multivariable analyses, TBR >median was associated with male sex ( P=0.0001) and statin use ( P=0.042). Conclusions- In ambulatory patients with DM asymptomatic for cardiovascular disease, the prevalence of potentially vulnerable plaques detected with NaF was low, but in the absence of follow-up data at this stage, we cannot assess the import of this information. Future research will establish whether NaF imaging helps risk stratify patients with DM. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT03530176.

Impact of cardiology follow-up care on treatment and outcomes of patients with new atrial fibrillation discharged from the emergency department.

AIMS: The first presentation of atrial fibrillation (AF) is often to an emergency department (ED). We evaluated the association of subsequent specialist care with morbidity and mortality. METHODS AND RESULTS: Retrospective cohort study of all adults in Alberta, Canada, with a new primary diagnosis of AF treated and released during an index ED visit between 2009 and 2015. Types of physician follow-up within 3 months of ED visit was analysed using Cox proportional hazards models with time-varying covariates. Outcomes were evaluated at 1 year. Of 7986 patients, 476 (6.0%) had no physician follow-up within 3 months, whereas 2730 (34.2%) attended a non-specialist only, 1277 (16.0%) an internal medicine specialist, and 3503 (43.9%) cardiology. An increasing gradient of cardiac investigations occurred across these groups. Cardiology compared with non-cardiologist care was associated with approximately two-fold greater electrophysiology interventions and revascularization, and increased use of beta-blockers (48.9% vs. 43.0%, P < 0.0001), statins (31.4% vs. 26.7%, P < 0.0001), and oral anticoagulation in patients with CHADS2 scores ≥1 (53.7% vs. 43.6%, P < 0.0001). In the subsequent year, cardiology care was associated with fewer deaths [adjusted hazard ratio (aHR) 0.72, 95% confidence interval (CI) 0.55-0.93], strokes (aHR 0.60, 95% CI 0.37-0.96), or major bleeds (aHR 0.69, 95% CI 0.53-0.89). No differences in the risk of hospitalization or ED visits were associated with cardiology care. CONCLUSION: Cardiology care after an ED visit for symptomatic new-onset AF is associated with better prognosis. The benefit may be mediated through more intensive investigation, identification, and treatment of cardiovascular risk factors and disease.

Association between maternal diabetes, being large for gestational age and breast-feeding on being overweight or obese in childhood.

AIMS/HYPOTHESIS: This study aimed to examine the association of maternal diabetes, being large for gestational age (LGA) and breast-feeding with being overweight or obese in pre-school-aged children. METHODS: Data on height and weight at the time of their pre-school (age 4-6 years) immunisation visit between January 2009 and August 2017, as well as breast-feeding status in the first 5 months of life, for 81,226 children born between January 2005 and August 2013 were linked with maternal hospitalisation and outpatient records and birth registry data. Children were grouped into six categories based on maternal diabetes status during pregnancy (no diabetes, gestational diabetes or pre-existing diabetes) and birthweight (appropriate for gestational age [AGA] or LGA). WHO criteria were used to identify children who were overweight or obese. RESULTS: There were 69,506 children in the no diabetes/AGA group (control), 5926 in the no diabetes/LGA group, 4563 in the gestational diabetes/AGA group, 573 in the gestational diabetes/LGA group, 480 in the pre-existing diabetes/AGA group and 178 in the pre-existing diabetes/LGA group. The rate of being overweight/obese at pre-school age ranged from 20.5% in the control group to 42.9% in the gestational diabetes/LGA group. The adjusted attributable risk per cent for LGA alone (39.4%) was significantly higher than that for maternal gestational diabetes (16.0%) or pre-existing diabetes alone (15.1%); the risk for the combinations of gestational diabetes/LGA and pre-existing diabetes/LGA were 50.1% and 39.1%, respectively. Further stratification of the pre-existing diabetes groups found the prevalence of being overweight/obese was 21.2% in the type 1/AGA group, 31.4% in the type 1/LGA group (similar to those in the no diabetes groups), 26.7% in the type 2/AGA group and 42.5% in the type 2/LGA group. Breast-feeding was associated with a lower likelihood of being overweight/obese in childhood in all groups except gestational diabetes/LGA and pre-existing diabetes/LGA (both type 1 and type 2). CONCLUSION/INTERPRETATION: LGA is a stronger marker for risk of being overweight/obese in early childhood, compared with maternal diabetes during pregnancy. Rates of being overweight/obese in childhood were highest in LGA children born to mothers with gestational diabetes or pre-existing type 2 diabetes. Breast-feeding was associated with a lower risk of being overweight/obese in childhood in the majority of children; however, this association was not maintained in LGA children of mothers with diabetes.