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Background: Data are limited data on the prevalence of cardiovascular disease (CVD) and multimorbidity in contemporary cohorts of high-cost users (HCUs) in Canada.We examined the following: (i) the prevalence of CVD, with a comparison of total healthcare costs among HCUs with vs without CVD; (ii) the contribution of other comorbidities to costs among HCUs with CVD; and (iii) the trajectory of healthcare costs in the years before and after becoming an HCU. Methods: The study included adult Alberta patients in the Canadian Institutes of Health Research/Canadian Institute for Health Information Dynamic Cohort of Complex, High System Users from 2011-2012 through 2014-2015. We examined total healthcare costs, including hospital, ambulatory care, physician services, and drugs. Results: Among 88,536 HCUs, 23.4% had no CVD, 28.9% were hospitalized with a primary diagnosis of CVD, and 47.7% were hospitalized with a secondary diagnosis of CVD. Total healthcare costs were $2.0 billion (20.4% non-hospital costs), $2.8 billion (24.1% non-hospital costs), and $4.9 billion (19.8% non-hospital costs), respectively, in the 3 groups. Many HCUs with CVD were frail (74.2%) and many had diabetes (33.8%) or chronic obstructive pulmonary disease (27.9%), which contributed to higher costs and mortality. Healthcare expenditures in HCUs with CVD were several times higher than per capita health expenditures in the years prior to, and following, their inclusion in the dynamic HCU cohort. Conclusions: CVD is very common in HCUs of healthcare. HCUs with CVD have high rates of frailty and multimorbidity. Further research is needed to identify and intervene earlier, in order to flatten the cost curve in these complex patients. Résumé: Introduction: Les données sur la prévalence des maladies cardiovasculaires (MCV) et de la multimorbidité au sein des cohortes contemporaines de grands utilisateurs (GU) du Canada sont limitées. Nous avons examiné ce qui suit : (i) la prévalence des MCV en comparant les coûts totaux des soins de santé entre les GU atteints de MCV et les GU non atteints de MCV; (ii) la contribution des autres comorbidités aux coûts liés aux GU atteints de MCV; (iii) la trajectoire des coûts des soins de santé dans les années avant et après avoir été considérés comme un GU. Méthodes: L’étude portait sur des patients adultes de l’Alberta de la Cohorte dynamique de grands utilisateurs du système de santé aux besoins complexes de 2011-2012 à 2014-2015 des Instituts de recherche en santé du Canada et de l’Institut canadien d’information sur la santé. Nous avons examiné les coûts totaux des soins de santé, notamment les coûts hospitaliers, les coûts des soins ambulatoires, des services médicaux et des médicaments. Résultats: Parmi les 88 536 GU, 23,4 % n’avaient pas de MCV, 28,9 % étaient hospitalisés et avaient un diagnostic principal de MCV, et 47,7 % étaient hospitalisés et avaient un diagnostic secondaire de MCV. Les coûts totaux des soins de santé des 3 groupes étaient respectivement de 2,0 G$ (20,4 % de coûts non hospitaliers), 2,8 G$ (24,1 % de coûts non hospitaliers) et 4,9 G$ (19,8 % de coûts non hospitaliers). Plusieurs GU atteints de MCV étaient fragiles (74,2 %) et beaucoup avaient le diabète (33,8 %) ou une maladie pulmonaire obstructive chronique (27,9 %), qui contribuaient à des coûts et à une mortalité plus élevés. Les dépenses de santé par personne liées aux GU atteints de MCV étaient beaucoup plus élevées que les dépenses de santé par personne dans les années qui précédaient ou suivaient leur inclusion dans la cohorte dynamique de GU atteints de MCV. Conclusions: Les GU de soins de santé sont très fréquemment atteints de MCV. Les GU atteints de MCV présentent des taux de fragilité et de multimorbidité élevés. D’autres recherches sont nécessaires pour cerner et intervenir plus tôt afin d’aplatir la courbe des coûts chez ces patients aux besoins complexes.

Several specialties treat thoracic aortic disease, resulting in multiple patient care pathways. This study aimed to characterize these varied care models to guide health policy.A 57-question e-survey was sent to staff cardiac surgeons, cardiologists, interventional radiologists, and vascular surgeons at 7 Canadian medical societies.For 914 physicians, the response rate was 76% (86 of 113) for cardiac surgeons, 40% (58 of 146) for vascular surgeons, 24% (34 of 140) for radiologists, and 14% (70 of 515) for cardiologists. Several services admitted type B dissections (vascular 37%, cardiology 31%, cardiac 18%, other 7%), and care was heterogeneous. Ownership of disease management was overestimated relative to the perspective of the other specialties. Type A dissection admissions and treatment were more uniform, but emergent call coverage varied. A 24/7 aortic specialist on-call schedule was present only 4% of the time. "Aortic" case rounds promoted attendance by a broader aortic specialty contingency relative to rounds that were specialty specific. Although 89% of respondents felt an aortic team was best for patient care, only 54% worked at an institution with an aortic team present, and only 28% utilized an aortic clinic. Questions designed to define an aortic team derived 63 different combinations.Thoracic aortic disease follows a network of undefined and variable care pathways, despite its high-risk population in need of complex treatment considerations. Multidisciplinary aortic teams and clinics exist in low volume, and the "aortic team" remains an obscure construct. A multispecialty initiative to define the aortic team and outline standardized navigation pathways within the health systems hospitals is advocated.La prise en charge de la maladie de l'aorte thoracique peut faire appel à plusieurs spécialités, ce qui a pour effet de multiplier les trajectoires de soins des patients. Cette étude visait à caractériser ces différents modèles de soins afin d'éclairer l'élaboration des politiques de santé.Un sondage électronique de 57 questions a été envoyé aux chirurgiens cardiaques, aux cardiologues, aux radiologistes interventionnels et aux chirurgiens vasculaires membres de 7 associations médicales canadiennes.Sur un total de 914 médecins, le taux de réponse a été de 76 % (86 sur 113) chez les chirurgiens cardiaques, de 40 % (58 sur 146) chez les chirurgiens vasculaires, de 24 % (34 sur 140) chez les radiologistes et de 14 % (70 sur 515) chez les cardiologues. Plusieurs services avaient admis des cas de dissection aortique de type B (chirurgie vasculaire 37 %, cardiologie 31 %, chirurgie cardiaque 18 %, autre 7 %) et les soins étaient hétérogènes. Les spécialistes surestimaient leur responsabilité de la prise en charge des cas par rapport à celle des autres spécialistes. Les admissions de cas de dissection de type A et leur traitement étaient plus uniformes, mais la présence de spécialistes de garde pouvant traiter les cas urgents était variable. La présence continue d'un spécialiste de l'aorte de garde n'était observée que pendant 4 % du temps. Les séances de discussion de cas « aortiques » favorisaient la participation par une gamme plus large de spécialistes de l'aorte que les discussions axées sur une spécialité donnée. Si 89 % des répondants estimaient qu'une équipe « aortique » était la meilleure option pour les soins aux patients, ils n'étaient que 54 % à travailler dans un établissement disposant d'une telle équipe et 28 % à utiliser les services d'une clinique de l'aorte. En réponse aux questions portant sur les éléments constitutifs d'une équipe aortique, 63 combinaisons différentes de spécialités ont été proposées.La prise en charge de la maladie de l'aorte thoracique emprunte un dédale de trajectoires de soins non définies et variables, alors que sa population à haut risque a besoin de traitements complexes. Les équipes multidisciplinaires et les cliniques spécialisées dans le traitement de l'aorte sont rares, et la notion d' « équipe aortique » demeure un concept obscur. Nous préconisons une initiative réunissant des spécialistes de différents domaines pour définir les éléments constitutifs d'une équipe aortique et établir des trajectoires de navigation normalisées au sein des hôpitaux du système de santé.

Background: A previous review of sex, gender, and equity within cardiovascular (CV) medicine, surgery, and science in Canada has revealed parity during medical and graduate school training. The purpose of this study was to explore sex and gendered experiences within the Canadian CV landscape, and their impact on career training and progression. Methods: An environmental scan was conducted of the Canadian CV landscape, which included an equity survey using Qualtrics software. Results: The environmental scan revealed that women remain underrepresented within CV training programs as trainees (12%–30%), program directors (33%), in leadership roles at the divisional level (21%), and in other professional or career-related activities (< 30%). Our analysis also showed improvements of career engagement at these levels of women at over time. The thematic analysis of the equity survey responses (n = 71 respondents; 83% female; 9.7% response rate among female Canadian Cardiovascular Society members) identified the following themes reported within the socio-ecological framework: desire to report inequities vs staying the course (individual level); desire for social support and mentorship and challenges of dual responsibilities (interpersonal level); concerns over exclusionary cliques and desire for respect and opportunity (organizational level); and increasing awareness and actions to overcome institutional barriers and accountability (societal level). Conclusions: Although women face challenges and remain underrepresented in CV medicine, surgery, and science, this study highlights potential opportunities for improving access of female medical, surgical, and research trainees and professionals to specialized cardiovascular training, career advancement, leadership, and research. Résumé: Contexte: Une étude antérieure portant sur le sexe, le genre et l'équité en médecine, chirurgie et sciences cardiovasculaires (CV) au Canada a révélé une parité au cours de la formation médicale et des études supérieures. L'objectif de cette étude était d’évaluer les expériences liées au sexe et au genre dans le paysage canadien du domaine CV, et leur impact sur la formation et la progression de carrière. Méthodes: Une analyse de l'environnement du paysage canadien dans le domaine CV a été réalisée, incluant une étude sur l'équité en utilisant le logiciel Qualtrics. Résultats: L'analyse de l'environnement a révélé que les femmes restent sous-représentées dans les programmes de formation du domaine CV que ce soit en tant que stagiaires (12 à 30 %), directrices de programme (33 %), dans les rôles de direction au niveau divisionnaire (21 %) et dans d'autres activités professionnelles ou associées à la carrière (< 30 %). Notre analyse a également montré une amélioration de l'engagement professionnel des femmes à ces niveaux au fil du temps. L'analyse thématique des réponses à l'enquête sur l'équité (n = 71 répondants; 83 % de femmes ; 9,7 % de taux de réponse parmi les membres féminins de la Société canadienne de cardiologie) a permis de dégager les thèmes suivants au sein du système socioécologique : désir de signaler les inégalités par rapport à la volonté de maintenir cap précis (au niveau individuel); désir de soutien social et de mentorat et défis liés à la double responsabilité (au niveau interpersonnel); préoccupations concernant les cliques exclusives et désir de respect et d’opportunité (au niveau organisationnel); et sensibilisation et actions accrues pour surmonter les obstacles institutionnels et les niveaux de responsabilité (au niveau sociétal). Conclusions: Bien que les femmes soient confrontées à des défis et restent sous-représentées dans les domaines de la médecine, de la chirurgie et des sciences CV, cette étude met en évidence les possibilités d'améliorer l'accès des stagiaires féminines et des professionnelles de la médecine, de la chirurgie et de la recherche à la formation spécialisée en cardiologie, à l'avancement de carrière, au rôle de direction et à la recherche.

BACKGROUND: In studies showing associations between ambient air pollution and myocardial infarction (MI), data have been lacking on the inherent spatial variability of air pollution. The aim of this study was to determine whether the long-term spatial distribution of air pollution influences short-term temporal associations between air pollution and admission to hospital for MI. METHODS: We identified adults living in Calgary who were admitted to hospital for an MI between 2004 and 2012. We evaluated associations between short-term exposure to air pollution (ozone [O(3)], nitrogen dioxide [NO(2)], sulfur dioxide [SO(2)], carbon monoxide [CO], particulate matter < 10 μm in diameter [PM(10)] and particulate matter < 2.5 μm in diameter [PM(2.5)]), and hospital admissions for MI using a time-stratified, case-crossover study design. Air Quality Health Index (AQHI) scores were calculated from a composition of O(3), NO(2) and PM(2.5). Conditional logistic regression models were stratified by low, medium and high levels of neighbourhood NO(2) concentrations derived from land use regression models; results of these analyses are presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: From 2004 to 2012, 6142 MIs were recorded in Calgary. Individuals living in neighbourhoods with higher long-term air pollution concentrations were more likely to be admitted to hospital for MI after short-term elevations in air pollution (e.g., 5-day average NO(2): OR 1.20, 95% CI 1.03–1.40, per interquartile range [IQR]) as compared with regions with lower air pollution (e.g., 5-day average NO(2): OR 0.90, 95% CI 0.78–1.04, per IQR). In high NO(2) tertiles, the AQHI score was associated with MI (e.g., 5-day average OR 1.13, 95% CI 1.02–1.24, per IQR; 3-day average OR 1.13, 95% CI 1.04–1.23, per IQR). INTERPRETATION: Our results show that the effect of air pollution on hospital admissions for MI was stronger in areas with higher NO(2) concentrations than that in areas with lower NO(2) concentrations. Individuals living in neighbourhoods with higher traffic-related pollution should be advised of the health risks and be attentive to special air quality warnings.

To assess randomized controlled trials evaluating the impact of nurse practitioner-led cardiovascular care.Systematic review of nurse practitioner-led care in patients with cardiovascular disease has not been completed.Systematic review and meta-analysis.The Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL, Web of Science, Scopus and ProQuest were systematically searched for studies published between January 2007 - June 2017.Cochrane methodology was used for risk of bias, data extraction and meta-analysis. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation approach.Out of 605 articles, five articles met the inclusion criteria. There was no statistical difference between nurse practitioner-led care and usual care for 30-day readmissions, health-related quality of life and length of stay. A 12% reduction in Framingham risk score was identified.There are a few randomized control trials assessing nurse practitioner-led cardiovascular care.Low to moderate quality evidence was identified with no statistically significant associated outcomes of care. Nurse practitioner roles need to be supported to conduct and publish high-quality research.目的: 在于评估随机对照试验,从而评估执业护士主导型护理心血管护理的影响。 背景: 尚未完成对心血管疾病患者进行执业护士主导型护理的系统综述。 设计: 系统综述和荟萃分析。 资料来源: 在 Cochrane Central Register of Controlled Trials (CENTRAL)、Medline、Embase、CINAHL、Web of Science、Scopus和ProQuest上系统地搜索了2007年1月至2017年6月间发表的研究。 综述方法: Cochrane方法学用于偏倚风险、数据提取和荟萃分析。证据质量的评估采用了GRADE(Grading of Recommendations Assessment, Development and Evaluation)法。 结果: 在605篇文章中,有5篇符合纳入标准。执业护士主导型护理和30天再度入院的常规护理、健康相关生活质量和住院天数之间没有统计学差异。确定Framingham 风险评分降低了12%。 结论: 有一些随机对照试验评估了执业护士主导型心血管护理。 影响: 确定了低等至中等质量的证据,没有统计学意义的相关护理结果。需要支持执业护士的角色,从而开展和发布高质量研究。.

In this Viewpoint concerns raised by Canadian emergency physicians regarding recommendations 2 and 6 from the recent Canadian Cardiovascular Society 2018 update for atrial fibrillation are discussed. These recommendations narrow the window for safe cardioversion and suggest 4 weeks of anticoagulation for all patients who undergo urgent cardioversion regardless of their CHADS-65 status. We discuss the implications of Grading of Recommendations, Assessment, Development, and Evaluation weak recommendations on the basis of low-quality evidence.

Peripheral arterial disease (PAD) is common in people referred for cardiac rehabilitation (CR). However, the associations between PAD diagnosis and CR attendance and mortality remain to be defined.All patients referred to a 12-week exercise-based CR program were included. Associations between PAD diagnosis and starting CR as well as between PAD diagnosis and completing CR were measured using multivariable logistic regression. Associations between CR completion and mortality were measured using adjusted Cox proportional hazards models, and a propensity-based matching sensitivity analysis was performed.23,215 patients (mean age 61.3 years; 21.6% female) were referred to CR; 1366 (5.9%) had PAD. Those with PAD were less likely to start CR (57.0% vs 68.2%, adjusted OR 0.81, 95%CI 0.72, 0.91) and complete CR if they started (70.6% vs 76.7%, adjusted OR 0.80, 95%CI 0.68, 0.94). Patients with PAD completing CR had lower exercise capacity at baseline (6.6 vs. 7.6 METs, p 0.0001) and completion (7.5 vs 8.6 METs, p 0.0001). There were 3510 deaths over follow-up; 10-year survival was lower in those with PAD (66.9 vs 84.5%; p 0.0001). CR completion was associated with lower mortality for all (adjusted HR 0.62 (95%CI 0.57, 0.67)), and the magnitude of the association was independent of PAD status.Patients with PAD referred to CR had a higher mortality than those without, and were less likely to start and complete CR. Completion of CR was associated with improved fitness and survival for PAD patients. These data support broader use of CR by those with PAD.

The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, since 2010 a large number of developments had accumulated in a wide range of areas, motivating the committee to complete a thorough guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to evaluate recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in atrial fibrillation (AF) management. This 2018 Focused Update addresses: (1) anticoagulation in the context of cardioversion of AF; (2) the management of antithrombotic therapy for patients with AF in the context of coronary artery disease; (3) investigation and management of subclinical AF; (4) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (5) acute pharmacological cardioversion of AF; (6) catheter ablation for AF, including patients with concomitant AF and heart failure; and (7) an integrated approach to the patient with AF and modifiable cardiovascular risk factors. The recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards. Individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included as Supplementary Material and are available on the CCS Web site. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF guidelines recommendations, from 2010 to the present 2018 Focused Update, which is provided in the Supplementary Material.

Aortic pressure ( ${P_a}$ ) is important for diagnosis of cardiovascular diseases, but it cannot be directly measured by noninvasive means. We present a method for its estimation by modeling arterial system as multichannel Weiner system with linear finite impulse response filter accounting for larger arteries transmission channel and nonlinear memoryless function block accounting for all nonlinearities due to narrowing of arteries, branching and visco-elastic forces. With this structure when pressure waveforms are measured from two distinct peripheral locations, multichannel blind system identification (MBSI) technique can be used to estimate common input pressure signal or ${P_a}$ . Nonlinear MBSI method was employed on previously acquired human hemodynamic measurements (seven datasets); results show ${P_a}$ can be accurately derived. This method by nature is self-calibrating to account for any interpersonal, along with intrapersonal, vascular dynamics inconstancy. Besides Pa estimation, the proposed MBSI method also allows extraction of system dynamics for vascular channels.

Background There is a paucity of data available on hospitalization and length of stay (LOS) for different anticoagulant therapies. We sought to compare and summarize admission rates and LOS, and describe the frequency of reporting these two outcomes in randomized control trials (RCTs) comparing different anticoagulant therapies for venous thromboembolism (VTE). Methods A literature search was conducted from inception to August 15, 2016 on RCTs of anticoagulant therapy for patients with VTE. Study selection, data extraction and risk of bias analysis were done by two reviewers independently. Meta-analyses were conducted for admission rates and LOS. Results A total of 4064 articles were identified. There were 74 articles of 70 studies included in the analysis. Hospitalization rates and LOS were reported in 13 (18.6%) and 12 (17.1%) of the 70 included studies, respectively. Low-molecular-weight heparin (LMWH)-treated patients were 33.0% less likely to be admitted to hospitals compared to unfractionated heparin (UFH) (RR = 0.67, 95% CI [0.58, 0.78]). The mean difference in LOS between LMWH and UFH was 2.54 days in favor of LMWH (95% CI [−4.94, −0.14]). Compared to parenteral therapy, using rivaroxaban was associated with a lower admission rate for a difference of 1.4–5.1% in VTE, 2.5% in DVT and 0.2% in PE. The LOS of patients receiving rivaroxaban was significant shorter than the LOS in parenteral therapy group for a difference of 1–5 days in VTE, 3 days in DVT and 1 day in PE. Conclusion Admission rates were lower and LOS was shorter using LMWH compared to UFH and oral therapy compared to parenteral therapy for acute VTE treatment in RCTs, based on limited eligible RCTs. These crucial clinically relevant outcomes are underreported in the existing VTE clinical trials.

Pulmonary embolism (PE) is a major cause of mortality and morbidity. It is known that the risk of death varies by provoking factors; however, it is unknown if the risk of death persists beyond the initial diagnosis among patients with cancer-associated and non-cancer provoked patients. In this study, we aimed to investigate the effect of cancer on overall, short- and long-term mortality in a cohort of consecutive incident PE patients. Using administrative databases, we identified all incident cases of PE between 2004 and 2012 in Alberta, Canada. Cases were stratified by provoking factors (i.e. unprovoked, provoked, and cancer-associated). A multivariate Cox survival model was used to estimate the hazard ratios of short- and long-term death. We identified 8641 patients with PE, among which 42.2% were unprovoked, 37.9% were provoked and 19.9% were cancer-associated. The 1-year and 5-year survival probabilities were 60% (95% CI: 57–64%) and 39% (95% CI: 36–43%) in patients with cancer-associated PE, 93% (95% CI: 92–94%) and 80% (95% CI: 78–81%) in provoked PE, and 94% (95% CI: 93–95%) and 85% (95% CI: 83–87%) in unprovoked PE, respectively. Compared to patients with unprovoked events, both short-term and long-term survival in patients with cancer-associated PE have a higher observed risk of all-cause mortality in all age groups ( p

Background Acute venous thromboembolism leads to significant morbidity and mortality. Advances in pharmacotherapy facilitate outpatient care in low-risk acute venous thromboembolism. The proportion of hospitalized acute venous thromboembolism cases and the average length of stay are not known. We sought to identify predictors of hospitalization, changes in hospitalization rates and length of stay of acute venous thromboembolism over a decade in Alberta, Canada. Methods Using linked administrative health databases, we identified adult patients diagnosed primarily with acute venous thromboembolism between April 2002 and March 2012. We measured trends using Poisson regression, adjusted length of stay using analysis of covariance. We identified predictors of hospitalization using multivariate logistic regression. Results 8198 out of 31,656 acute venous thromboembolism cases were hospitalized. The overall venous thromboembolism admission rates ranged between 23.7% and 27.8% with no evident temporal trend (P = 0.10). The average admission rate was 51.9% for pulmonary embolism and 16.1% for deep vein thrombosis. The mean length of stay for deep vein thrombosis and pulmonary embolism remained unchanged with an adjusted mean for venous thromboembolism of 6.9 ± 1.0 days. Higher Charlson index, older age, male gender, pulmonary embolism at presentation and multiple comorbidities were associated with hospitalization. Hospitalization was associated with 30-day mortality (odds ratio:2.8, 95% CI: 2.2–3.5) whereas the length of stay was not (odds ratio:1.0, 95% CI: 0.99–1.0). Conclusion Hospitalization rates and mean length of stay for acute venous thromboembolism did not change significantly between 2002 and 2012. Advances in pharmacotherapy have not yet reduced hospitalization rates or length of stay for venous thromboembolism.

Venous thromboembolism (VTE) is a major health problem for both men and women. Whether sex disparities exist for outcomes after acute VTE is unknown. We sought to measure sex-specific rates of hospitalization for and mortality from acute VTE. We used a population-based administrative dataset from Alberta, Canada, covering the years 2002 to 2012. We used Poisson regression to measure the incidence rate ratio for hospitalization and Cox regression to test for sex disparities in short-term all-cause mortality after adjusting for potential confounders. Of those diagnosed with VTE, 55.9% were women. The proportion of hospitalized women for VTE was 24.4 versus 27.8% in men (p

Background Patients with chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory response to exercise, contributing to exertional dyspnea and exercise intolerance. We recently demonstrated enhanced activity and sensitivity of the carotid chemoreceptor (CC) in COPD which may alter ventilatory and cardiovascular regulation and negatively affect exercise tolerance. We sought to determine whether CC inhibition improves ventilatory and cardiovascular regulation, dyspnea and exercise tolerance in COPD. Methods Twelve mild-moderate COPD patients (FEV1 83 ± 15 %predicted) and twelve age- and sex-matched healthy controls completed two time-to-symptom limitation (TLIM) constant load exercise tests at 75% peak power output with either intravenous saline or low-dose dopamine (2 μg·kg−1·min−1, order randomized) to inhibit the CC. Ventilatory responses were evaluated using expired gas data and dyspnea was evaluated using a modified Borg scale. Inspiratory capacity maneuvers were performed to determine operating lung volumes. Cardiac output was estimated using impedance cardiography and vascular conductance was calculated as cardiac output/mean arterial pressure (MAP). Results At a standardized exercise time of 4-min and at TLIM; ventilation, operating volumes and dyspnea were unaffected by dopamine in COPD patients and controls. In COPD, dopamine decreased MAP and increased vascular conductance at all time points. In controls, dopamine increased vascular conductance at TLIM, while MAP was unaffected. Conclusion There was no change in time to exhaustion in either group with dopamine. These data suggest that the CC plays a role in cardiovascular regulation during exercise in COPD; however, ventilation, dyspnea and exercise tolerance were unaffected by CC inhibition in COPD patients.

In this paper, tapered vs. uniform tube-load models are comparatively investigated as mathematical representation for blood pressure (BP) wave propagation in human aorta. The relationship between the aortic inlet and outlet BP waves was formulated based on the exponentially tapered and uniform tube-load models. Then, the validity of the two tube-load models was comparatively investigated by fitting them to the experimental aortic and femoral BP waveform signals collected from 13 coronary artery bypass graft surgery patients. The two tube-load models showed comparable goodness of fit: (i) the root-mean-squared error (RMSE) was 3.3+/−1.1 mmHg in the tapered tube-load model and 3.4+/−1.1 mmHg in the uniform tube-load model; and (ii) the correlation was r = 0.98+/−0.02 in the tapered tube-load model and r = 0.98+/−0.01 mmHg in the uniform tube-load model. They also exhibited frequency responses comparable to the non-parametric frequency response derived from the aortic and femoral BP waveforms in most patients. Hence, the uniform tube-load model was superior to its tapered counterpart in terms of the Akaike Information Criterion (AIC). In general, the tapered tube-load model yielded the degree of tapering smaller than what is physiologically relevant: the aortic inlet-outlet radius ratio was estimated as 1.5 on the average, which was smaller than the anatomically plausible typical radius ratio of 3.5 between the ascending aorta and femoral artery. When the tapering ratio was restricted to the vicinity of the anatomically plausible typical value, the exponentially tapered tube-load model tended to underperform the uniform tube-load model (RMSE: 3.9+/−1.1 mmHg; r = 0.97+/−0.02). It was concluded that the uniform tube-load model may be more robust and thus preferred as the representation for BP wave propagation in human aorta; compared to the uniform tube-load model, the exponentially tapered tube-load model may not provide valid physiological insight on the aortic tapering, and its efficacy on the goodness of fit may be only marginal.

Humans have fewer cardiovascular events and improved outcomes after cardiovascular events when living at low and moderate altitudes (, Normoxic low‐altitude simulation (714 mmHg), when applied acutely, has the capacity to improve limb blood perfusion after femoral artery ligation in mice. This is a novel finding that illustrates the capacity of normoxic low‐altitude simulation to be use as a non‐invasive therapy in human patients of peripheral arterial disease.

Background Clinical practice guideline ( CPG ) developers have yet to endorse a consistent and systematic approach for considering sex‐specific cardiovascular information in CPG s. This article describes an initiative led by the Canadian Cardiovascular Society to determine the feasibility and outcomes of a structured process for considering sex in a CPG for the management of ST‐segment–elevation myocardial infarction. Methods and Results A sex and gender champion was appointed to the guideline development committee. The feasibility of tailoring the CPG to sex was ascertained by recording (1) the male–female distribution of the study population, (2) the adequacy of sex‐specific representation in each study using the participation/prevalence ratio, and (3) whether data were disaggregated by sex. The outcome was to determine whether recommendations for CPG s based on an assessment of the evidence should differ by sex. In total, 175 studies were included. The mean percentage of female participants reported in the studies was 24.5% ( SD : 6.6%; minimum: 0%; maximum: 51%). The mean participation/prevalence ratio was 0.62 ( SD : 0.16; minimum: 0.00; maximum: 1.19). Eighteen (10.2%) studies disaggregated the data by sex. Based on the participation/prevalence ratio and the sex‐specific analyses presented, only 1 study provided adequate evidence to confidently inform the applicability of the CPG recommendations to male and female patients. Conclusions Implementing a systematic process for critically appraising sex‐specific evidence for CPG s was straightforward and feasible. Inadequate enrollment and reporting by sex hindered comprehensive sex‐specific assessment of the quality of evidence and strength of recommendations for a CPG on the management of ST‐segment–elevation myocardial infarction.

Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) are leading causes of morbidity and mortality. There are conflicting results regarding the association between COPD and CAD. We sought to measure the association between COPD and angiographically diagnosed CAD in a population-based cohort. We performed a retrospective analysis using data from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), a prospectively collected registry capturing all patients undergoing coronary angiography in Alberta, Canada, since 1995. We included adult patients who had undergone coronary angiogram between April 1, 2007 and March 31, 2014. CAD was present if at least one coronary artery had a significant stenosis ≥50%. COPD was present if the patient had a documented COPD history and was prescribed bronchodilators or inhaled steroids. We evaluated the association between COPD and CAD using univariable and multivariable logistic regression. There were 26,137 patients included with a mean age of 63.3 ± 12.2 years, and 19,542 (74.8%) were male. The crude odds ratio (OR) of having CAD was 0.83 (95% CI 0.74-0.92) for patients with COPD compared to those without COPD. The adjusted OR was 0.75 (95% CI 0.67-0.84) after controlling for age, sex, smoking history, body mass index, hypertension, diabetes, hyperlipidemia, peripheral artery disease and cardiac family history. In patients undergoing coronary angiography, COPD was negatively associated with CAD with and without the adjustment for classic risk factors. COPD patients should be properly examined for heart disease to reduce premature mortality.

By virtue of its direct association with the cardiovascular (CV) functions and compatibility to unobtrusive measurement during daily activities, the limb ballistocardiogram (BCG) is receiving an increasing interest as a viable means for ultra-convenient CV health and disease monitoring. However, limited insights on its physical implications have hampered disciplined interpretation of the BCG and systematic development of the BCG-based approaches for CV health monitoring. In this study, a mathematical model that can predict the limb BCG in responses to the arterial blood pressure (BP) waves in the aorta was developed and experimentally validated. The validated mathematical model suggests that (i) the limb BCG waveform reveals the timings and amplitudes associated with the aortic BP waves; (ii) mechanical filtering exerted by the musculoskeletal properties of the body can obscure the manifestation of the arterial BP waves in the limb BCG; and (iii) the limb BCG exhibits meaningful morphological changes in response to the alterations in the CV risk predictors. The physical insights garnered by the analysis of the mathematical model may open up new opportunities toward next generation of the BCG-based CV healthcare techniques embedded with transparency, interpretability, and robustness against the external variability.

Background Few studies have explored the influence of short-term exposure to atmospheric pressure changes on the abrupt onset of ST-elevation myocardial infarction (STEMI). We sought to evaluate the association between acute atmospheric pressure changes and the occurrence of STEMI. Methods We studied STEMI patients from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) from March 1, 2002 to December 31, 2016 in a case-crossover study design. Each case was matched with control intervals according to the same day of week, month, and year. All STEMI patients were linked with the nearest weather station within a 40-km radius according to residential postal code. The effect of exposure to air pressure changes, rate of air pressure changes, acute air pressure increase, and acute air pressure decrease 1 day to 7 days earlier on the onset of STEMI were analyzed with conditional logistic regression. All models were adjusted with daily average temperature, relative humidity, and average levels of 5 air pollutants. Results In 11,379 STEMI patients, positive associations with the onset of STEMI were only found at 7 days after exposure to acute air pressure decrease (odds ratio, 1.12; 95% confidence interval, 1.03-1.21), which was consistent in sensitivity and subgroup analyses. All the other models showed no evidence of statistically significant associations. Conclusions Acute air pressure decrease is associated with higher odds of a STEMI event 7 days after exposure. Weather advisories might be issued when atmospheric pressure decrease occurs.

New knowledge about male-female differences in pathophysiology, diagnosis, and treatment is shifting the practice of medicine from a one-size-fits all approach to a more individualized process that considers sex-specific interventions at the point of care. In this article, we review how clinical practice guideline committees can incorporate a structured framework to determine whether sex-specific assessments of the quality of the evidence or the particular recommendations should be made. The process can be operationalized by societies who author clinical practice guidelines by developing formal policies to approach biological sex in a systematic way, and by ensuring that writing committees include an individual who will champion the formal appraisal of the literature for associations between sex and the outcomes of interest. Ongoing challenges are discussed, and solutions are provided for how to disaggregate the evidence, how to assess bias, how to improve search strategies, and what to do when the data are insufficient to make sex-specific recommendations. Application of sex-specific recommendations will involve routinely asking whether the presentation, diagnostic workup, or management might change for each patient if they were the opposite sex.

Antiplatelet therapy (APT) has become an important tool in the treatment and prevention of atherosclerotic events, particularly those associated with coronary artery disease. A large evidence base has evolved regarding the relationship between APT prescription in various clinical contexts and risk/benefit relationships. The Guidelines Committee of the Canadian Cardiovascular Society and Canadian Association of Interventional Cardiology publishes regular updates of its recommendations, taking into consideration the most recent clinical evidence. The present update to the 2011 and 2013 Canadian Cardiovascular Society APT guidelines incorporates new evidence on how to optimize APT use, particularly in situations in which few to no data were previously available. The recommendations update focuses on the following primary topics: (1) the duration of dual APT (DAPT) in patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome and non-acute coronary syndrome indications; (2) management of DAPT in patients who undergo noncardiac surgery; (3) management of DAPT in patients who undergo elective and semiurgent coronary artery bypass graft surgery; (4) when and how to switch between different oral antiplatelet therapies; and (5) management of antiplatelet and anticoagulant therapy in patients who undergo PCI. For PCI patients, we specifically analyze the particular considerations in patients with atrial fibrillation, mechanical or bioprosthetic valves (including transcatheter aortic valve replacement), venous thromboembolic disease, and established left ventricular thrombus or possible left ventricular thrombus with reduced ejection fraction after ST-segment elevation myocardial infarction. In addition to specific recommendations, we provide values and preferences and practical tips to aid the practicing clinician in the day to day use of these important agents.

Canadian practice guidelines for nonvalvular atrial fibrillation (NVAF) recommend that most patients receive a novel oral anticoagulant (NOAC) in preference to warfarin to prevent stroke, but not all patients have insurance that covers NOACs. The gap between optimal therapy and drug coverage is unknown. We retrospectively assessed eligibility for NOACs in patients with NVAF at our single-centre anticoagulation clinic and ascertained whether provincial drug coverage would be in place. Most patients (89%-95%) were eligible, but only 39%-41% qualified for drug coverage. Our findings suggest most Albertans with NVAF might not have drug coverage for optimal medical therapy for stroke prevention.

This paper presents a novel minimally invasive method for quantifying blood pressure (BP) wave reflection in the arterial tree. In this method, two peripheral BP waveforms are analyzed to obtain an estimate of central aortic BP waveform, which is used together with a peripheral BP waveform to compute forward and backward pressure waves. These forward and backward waves are then used to quantify the strength of wave reflection in the arterial tree. Two unique strengths of the proposed method are that 1) it replaces highly invasive central aortic BP and flow waveforms required in many existing methods by less invasive peripheral BP waveforms, and 2) it does not require estimation of characteristic impedance. The feasibility of the proposed method was examined in an experimental swine subject under a wide range of physiologic states and in 13 cardiac surgery patients. In the swine subject, the method was comparable to the reference method based on central aortic BP and flow. In cardiac surgery patients, the method was able to estimate forward and backward pressure waves in the absence of any central aortic waveforms: on the average, the root-mean-squared error between actual versus computed forward and backward pressure waves was less than 5 mmHg, and the error between actual versus computed reflection index was less than 0.03.

Background Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity, mortality, and healthcare resource use. The prevalence of AF is increasing with a growing and aging population, and timely access to care for these patients is a concern. Nontraditional models of care delivery, such as nurse practitioner (NP)-led clinics, may improve access to care and quality of care, but they require formal assessment. The objective of this study is to assess the effect of NP-led care on the health-related quality of life (HRQoL) of adult patients with AF. Methods/design We plan a randomized controlled trial comparing NP-led care vs. standard care. Inclusion criteria are ≥18 years of age, documented nonvalvular AF, willingness to give informed consent, and capacity to complete questionnaires. Patients referred for electrophysiological intervention who are clinically unstable or unable to attend follow-up visits will not be eligible to participate. Patients will be asked for verbal consent during the initial triage phone call from the nurse. Randomization will occur via a secure website. The intervention includes an NP consult, including medical history, physical examination, patient teaching, treatment plan, and follow-up at 3 and 6 months. The control arm involves usual cardiologist consultation with follow-up determined by the cardiologist’s practice pattern. The primary outcome will be the difference in change in Atrial Fibrillation Effect on Quality of Life Survey scores at 6 months between groups. Secondary outcomes will include difference in change of EQ-5D scores at 6 months between groups, difference in composite outcomes of death resulting from cardiovascular cause, hospitalizations and emergency department visits between groups, and satisfaction with NP-led care measured by the Consultant Satisfaction Questionnaire. A sample size of 70 per group will ensure adequate power despite a potential 10% loss to follow-up. Discussion Our study will determine the effect of NP-led AF care on HRQoL in patients with AF, as well as measure its impact on relevant outcomes such as death, hospitalization, and emergency department visits. Our findings may have implications for delivery of care to patients with AF. Trial registration ClincalTrials.gov, NCT02745236. Registered on 16 April 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2111-4) contains supplementary material, which is available to authorized users.

To determine whether the timing of notification of critical international normalized ratio (INR) results (during or after clinic hours) altered the clinician's ability to affect same-day patient care.Retrospective chart review.The Anticoagulation Management Service at the University of Alberta Hospital in Edmonton.A total of 276 patients with critical INR results (5.0) separated by at least 30 days were identified to have 200 critical INR results reported during clinic hours and 200 reported after hours.Differences in the proportion of patients with critical INR results having same-day care altered (by changing warfarin dose, administering vitamin K, or referring for assessment) between those with results reported during clinic hours compared with those with results reported after clinic hours. Differences by highly critical INR results (9.0 vs ≤ 9.0) and whether patients experienced thromboembolism or bleeding within 30 days were also assessed.Same-day patient care was affected for 174 out of 200 (87.0%) critical INR results reported during clinic hours compared with 101 out of 200 (50.5%) reported after clinic hours (Same-day care was less likely to be affected by critical INR results communicated after hours, most commonly because the patient had already taken their daily warfarin dose. However, after-hours care was still affected for 1 out of 2 patients, which is meaningful and supports current practice.

This paper demonstrates preliminary in-human validity of a novel subject-specific approach to estimation of central aortic blood pressure (CABP) from peripheral circulatory waveforms. In this "Individualized Transfer Function" (ITF) approach, CABP is estimated in two steps. First, the circulatory dynamics of the cardiovascular system are determined via model-based system identification, in which an arterial tree model is characterized based on the circulatory waveform signals measured at the body's extremity locations. Second, CABP waveform is estimated by de-convolving peripheral circulatory waveforms from the arterial tree model. The validity of the ITF approach was demonstrated using experimental data collected from 13 cardiac surgery patients. Compared with the invasive peripheral blood pressure (BP) measurements, the ITF approach yielded significant reduction in errors associated with the estimation of CABP, including 1.9-2.6 mmHg (34-42 %) reduction in BP waveform errors (p < 0.05) as well as 5.8-9.1 mmHg (67-76 %) and 6.0-9.7 mmHg (78-85 %) reductions in systolic and pulse pressure (SP and PP) errors (p < 0.05). It also showed modest but significant improvement over the generalized transfer function approach, including 0.1 mmHg (2.6 %) reduction in BP waveform errors as well as 0.7 (20 %) and 5.0 mmHg (75 %) reductions in SP and PP errors (p < 0.05).

Introduction The frequency and case fatality of venous thromboembolism (VTE) and major bleeding during the initial 3 months of therapy in those treated for symptomatic VTE with either direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA) are important clinically relevant outcomes. We sought to measure it during the initial months of anticoagulation for symptomatic VTE. Material and Methods We searched MEDLINE, EMBASE, and CENTRAL to identify studies that enrolled patients with acute symptomatic VTE treated with DOACs or VKA and reported data on bleeding, VTE recurrence and death. Studies were evaluated according to a priori inclusion criteria and critically appraised using established internal validity criteria. Single-proportion random-effects models were used to pool estimates. Results Of the 2453 citations retrieved, 5 RCTs that enrolled 24,507 patients were included. The rate of major bleeding was 1.8 (95% CI: 1.3-2.5) and 3.1 (95% CI: 2.4-3.9) per 100 patient-years in DOAC and VKA arms, respectively. The rate of VTE recurrence was 3.7 (95% CI: 2.7-4.7) and 4.1 (95% CI: 3.0-5.4) per 100 patient-years of DOAC and VKA, respectively. The case fatality rate of bleeding was significantly higher in the VKA arms 10.4% (95% CI: 6.6-15.4) compared to DOACs 6.1% (95% CI: 2.7-11.7; p value for difference = 0.029) with no statistical difference between the case fatalities for recurrent VTE. The rate of death from either definite major bleeding or definite recurrent VTE was 0.27 (95% CI: 0.16-0.40) and 0.46 (95% CI: 0.32-0.63) per 100 patient-years for DOACs and VKAs respectively, resulting in a number needed to treat of 875 for DOACs to prevent one death. Conclusion DOACs are attractive alternatives to VKAs for initial treatment of symptomatic VTE, with lower frequency and case fatality for major bleeding. However, the incremental safety benefit of DOACs over VKAs is small, with large numbers needed to treat.

An aortic aneurysm is characterized by widening of the aortic lumen diameter with adverse remodelling of the vascular extracellular matrix. A thoracic aortic aneurysm (TAA) is highly prevalent in patients with a bicuspid aortic valve (BAV). We investigated the structural remodelling in the aneurysmal ascending aorta in correlation to molecular alterations in male versus female BAV-TAA patients. Aneurysmal aortic samples (diameter >4.4 cm) from male and female patients were compared to non-aneurysmal non-BAV samples. The diameter of the aneurysmal aorta was smaller in females but comparable to that of male patients when normalized to body mass index. Disorganized elastin fibres and reduced elastin protein were found in samples from males and females with BAV-TAA. However, disarrayed collagen fibres and reduced protein were detected only in aortas from males with BAV-TAA. Elastin and collagen I messenger RNA (mRNA)levelswerecomparableintheBAV-TAAandcontrol groups of both genders, suggesting post-translation degradation. Total elastase activity was elevated similarly in both genders. The activity of MT1-MMP, a potent collagenase, was increased more in aortic samples from males thanfemales with BAV-TAA samples. MMP8 and MMP13 were lower whereas MMP2 was higher in female compared to samples from male BAV-TAA group. TIMP3 and TIMP4 decreased similarly in both genders, while TIMP2 increased in the female BAV-TAA group. Lower smooth muscle cell density in the medial layer of aortas from males with BAV-TAA samples corresponded to the increased caspase-3 cleavage compared to that of females. Conclusion :W e report a gender-dependent MMP/TIMP axis, collagen remodelling and smooth muscle cell (SMC) survival in the BAV-TAA aorta. The elevated TIMP2 could protect against the collagenolytic activity of MT1-MMP, leading to reduced collagen disarray and degradation in female BAV. Key message & More collagen degradation/disarray and smooth muscle cell loss in male BAV-TAA patients. & Similar elastin degradation/disarray in the aneurysmal aorta of both genders. & Reduced collagen and elastin in BAV-TAA due to enhanced degradation, not reduced synthesis. & Elevated TIMP2 in female BAV-TAA aortas protects against collagen degradation by MT1-MMP.

Background: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study’s four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. Methods: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated “abnormal” laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. Results: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors’ diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96–5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6–41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. Conclusion: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

Pioglitazone was associated with increased hazard for surgical or percutaneous lower extremity revascularization in patients with diabetes in a large clinical trial, but this clinical finding has not been adequately explored in animal models. We hypothesized that pioglitazone would decrease hypoxia-inducible factor 1α (HIF-1α)-dependent angiogenesis in rat ischemic hindlimb models by altering mitochondrial-derived signals supporting HIF-1α activation. We tested oral pioglitazone (10 mg/kg/day) versus placebo in two cohorts of rats with hindlimb ischemia (normal Sprague–Dawley rats and insulin-resistant JCR:La-cp rats), and evaluated direct and paracrine effects of pioglitazone on angiogenesis in vitro using human skeletal muscle and endothelial cells. Pioglitazone treatment was associated with reductions in limb perfusion at 2 weeks measured by contrast-enhanced ultrasound and Tc99m-Sestamibi SPECT-CT. Ischemic muscle capillary density was also reduced by pioglitazone. HIF-1α and vascular endothelial growth factor (VEGF) expression in ischemic muscle were also reduced by pioglitazone. In vitro, pioglitazone's effects on both skeletal muscle cells and microvascular endothelial cells were associated with a decrease in autocrine and paracrine angiogenesis measured by matrigel assay, decreased HIF-1α expression and activation, as well as increases in both mitochondrial reactive oxygen species and α-ketoglutarate, both mitochondria-derived signals which promote HIF-1α degradation. We conclude that pioglitazone is associated with decreased ischemic limb perfusion and capillary density in relevant rat models of hindlimb ischemia, and these effects are mediated by mitochondria-dependent reductions in HIF-1α-dependent angiogenesis. Key messages Pioglitazone inhibits angiogenesis in rats with and without insulin resistance. Pioglitazone inhibits HIF-1α by inhibiting mitochondrial stabilization of HIF-1. Pioglitazone inhibits both autocrine and paracrine angiogenesis. Inhibition of angiogenesis may explain unexpected results of a pioglitazone human clinical trial. Electronic supplementary material The online version of this article (doi:10.1007/s00109-013-1115-0) contains supplementary material, which is available to authorized users.

Humans have a lower risk of death from myocardial infarction (MI) living at low elevations (5000 m, and intermittent hypobaric hypoxia post-MI can reduce MI size in rodents, and it is believed that hypoxia is the key stimulus. To explore mechanisms beyond hypoxia we studied whether altitude simulation

Chronic kidney disease (CKD) is prevalent in elderly patients with atrial fibrillation and is an independent risk factor for stroke. Warfarin anticoagulation is efficacious for stroke prevention in atrial fibrillation patients with moderate CKD (stage III, estimated glomerular filtration rate 30-59 mL/min), but recent observational studies have challenged its value for patients with end-stage renal disease requiring dialysis. The novel oral anticoagulants (i.e., dabigatran, apixaban, rivaroxaban) all undergo renal metabolism to varying degrees, and hence dosing, efficacy, and safety require special consideration in CKD patients. In randomized trials to date involving 11,169 patients with moderate CKD, the novel oral anticoagulants performed well, with similar efficacy and safety profiles as for non-CKD patients. For atrial fibrillation patients with stage III CKD, the available data are strongest for dabigatran 150 mg twice daily as superior to warfarin for stroke prevention and for apixaban as superior to warfarin regarding reduced major hemorrhage. Renal function should be monitored at least annually in patients receiving a novel oral anticoagulant, and more often in elderly patients and those with underlying CKD or comorbidities who are at special risk for dehydration and deterioration of renal function. Much remains to be learned about the optimal use of the novel oral anticoagulants in CKD patients; additional studies about optimal dosing of the novel oral anticoagulants and frequency of monitoring renal function in CKD patients with atrial fibrillation are needed. Anticoagulation options for hemodialysis patients require testing in randomized trials.