Pathophysiology of Myocardial Infarction With Nonobstructive Coronary Artery Disease: A Contemporary Systematic Review.

Background: Myocardial infarction with nonobstructive coronary artery disease (MINOCA) is defined as acute myocardial infarction (AMI) with angiographically nonobstructive coronary artery disease. MINOCA represents 6% of all AMI cases and is associated with increased mortality and morbidity. However, the wide array of pathophysiological factors and causes associated with MINOCA presents a diagnostic conundrum. Therefore, we conducted a contemporary systematic review of the pathophysiology of MINOCA. Methods: A comprehensive systematic review of MINOCA was carried out through the utilization of the PubMed database. All systematic reviews, meta-analyses, randomized controlled trials, and cohort studies available in English or French that reported on the pathophysiology of MINOCA published after January 1, 2013 were retained. Results: Of the 600 identified records, 80 records were retained. Central to the concept of MINOCA is the definition of AMI, characterized by the presence of myocardial damage reflected by elevated cardiac biomarkers in the setting of acute myocardial ischemia. As a result, a structured approach should be adopted to thoroughly assess and address clinically overlooked obstructive coronary artery disease, and cardiac and extracardiac mechanisms of myocyte injury. Once these options have been ruled out, a diagnosis of MINOCA can be established, and the appropriate multimodal assessment can be conducted to determine its specific underlying cause (plaque disruption, epicardial coronary vasospasm, coronary microvascular dysfunction, and coronary embolism and/or spontaneous coronary dissection or supply-demand mismatch). Conclusions: Integrating a suitable definition of AMI and understanding the pathophysiological mechanisms of MINOCA are crucial to ensure an effective multimodal diagnostic evaluation and the provision of adequate tailored therapies.

Contexte: L'infarctus du myocarde sans obstruction des artères coronaires (MINOCA) est défini comme un infarctus aigu du myocarde (IAM) en présence d'une coronaropathie non obstructive confirmée par angiographie. Le MINOCA représente 6 % de tous les cas d'IAM et est associé à une hausse des taux de mortalité et de morbidité. Cependant, le large éventail de facteurs physiopathologiques et de causes associés au MINOCA représente une énigme diagnostique. C'est pourquoi nous avons réalisé une analyse systématique des publications contemporaines sur la physiopathologie du MINOCA. Méthodologie: Une analyse exhaustive des publications sur le MINOCA a été menée au moyen de la base de données PubMed. L'ensemble des analyses systématiques, des méta-analyses, des essais contrôlés randomisés et des études de cohorte publiés en anglais ou en français après le 1er janvier 2013 qui faisaient état de la physiopathologie du MINOCA ont été retenus. Résultats: Parmi les 600 dossiers relevés, 80 ont été retenus. La définition de l'IAM était centrale au concept de MINOCA et était caractérisée par la présence d'une lésion myocardique attestée par des taux élevés de biomarqueurs cardiaques en contexte d'ischémie myocardique aiguë. Par conséquent, une approche structurée devrait être adoptée pour évaluer pleinement et traiter les coronaropathies obstructives qui passent inaperçues en clinique ainsi que les mécanismes cardiaques et extracardiaques des lésions aux myocytes. Une fois ces options exclues, un diagnostic de MINOCA peut être établi et l'évaluation multimodale appropriée peut être menée pour déterminer la cause sous-jacente précise (rupture de plaque, vasospasme d'une artère coronaire épicardique, dysfonction microvasculaire coronarienne et embolie coronarienne et/ou dissection spontanée d'une artère coronaire ou déséquilibre entre apports et besoins). Conclusions: Il est crucial d'intégrer une définition convenable de l'IAM et de comprendre les mécanismes physiopathologiques du MINOCA pour assurer une évaluation diagnostique multimodale efficace et une prestation de traitements adaptés et adéquats.

The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 9: Summary of Current Status, Challenges, Opportunities, and Recommendations.

This final chapter of the Canadian Women's Heart Health Alliance "ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women" presents ATLAS highlights from the perspective of current status, challenges, and opportunities in cardiovascular care for women. We conclude with 12 specific recommendations for actionable next steps to further the existing progress that has been made in addressing these knowledge gaps by tackling the remaining outstanding disparities in women's cardiovascular care, with the goal to improve outcomes for women in Canada.

Dans ce chapitre final de l'ATLAS sur l'épidémiologie, le diagnostic et la prise en charge de la maladie cardiovasculaire chez les femmes de l'Alliance canadienne de santé cardiaque pour les femmes, nous présentons les points saillants de l'ATLAS au sujet de l'état actuel des soins cardiovasculaires offerts aux femmes, ainsi que des défis et des occasions dans ce domaine. Nous concluons par 12 recommandations concrètes sur les prochaines étapes à entreprendre pour donner suite aux progrès déjà réalisés afin de combler les lacunes dans les connaissances, en s'attaquant aux disparités qui subsistent dans les soins cardiovasculaires prodigués aux femmes, dans le but d'améliorer les résultats de santé des femmes au Canada.

Antithrombotic Management and Outcomes of Anterior ST-Elevation Myocardial Infarction With New-Onset Wall Motion Abnormalities in Men and Women.

Background: In patients with anterior ST-elevation myocardial infarction (STEMI) and new-onset antero-apical wall motion abnormalities (WMAs), whether the rate of prophylaxis against left ventricular thrombus and outcomes differ between men and women is unknown. Methods: A multicentre retrospective cohort study of patients with STEMI and new-onset antero-apical WMAs treated with primary percutaneous coronary intervention was conducted. Patients with an established indication of oral anticoagulation (OAC) were excluded. The rates of triple therapy (double antiplatelet therapy + OAC) at discharge were compared for women vs men. The rates of net adverse clinical events, a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 6 months were compared across sex using a multivariate logistic regression model. Results: A total of 1664 patients were included in the primary analysis, of whom 402 (24.2%) were women and 1262 (75.8%) were men. A total of 138 women (34.3%) and 489 men (38.7%) received a triple therapy prescription at discharge (P = 0.11). At 6 months, 33 women (8.2%) and 96 men (7.6%) experienced a net adverse clinical event (adjusted odds ratio 0.82; 95% confidence interval 0.49-1.37). No difference occurred in the risk of bleeding events and ischemic events between men and women, when these were analyzed separately. Conclusions: The rates of OAC prescription for left ventricular thrombus prophylaxis and clinical outcomes at 6 months were similar in women and men following anterior STEMI with new-onset antero-apical WMAs.

Contexte: On ignore si le taux de prophylaxie contre le thrombus ventriculaire gauche et les résultats thérapeutiques diffèrent entre les hommes et les femmes qui ont subi un infarctus du myocarde avec élévation du segment ST (STEMI) antérieur et ont des anomalies du mouvement pariétal (AMP) antéroapical d'apparition récente. Méthodes: Nous avons mené une étude de cohorte rétrospective multicentrique auprès de patients qui ont subi un STEMI et ont des AMP d'apparition récente traitées par une intervention coronarienne percutanée primaire. Nous avons exclu les patients chez lesquels il existait une indication établie à l'anticoagulation orale (ACO). Nous avons comparé les taux de trithérapie (bithérapie antiplaquettaire + ACO) à la sortie de l'hôpital entre les femmes et les hommes. Nous avons comparé les taux d'événements indésirables cliniques nets, le critère composite de mortalité, d'infarctus du myocarde, d'accident vasculaire cérébral ou d'accident ischémique transitoire, la thromboembolie systémique ou l'hémorragie de type 3 ou 5 selon le Bleeding Academic Research Consortium (BARC) après 6 mois entre les sexes au moyen du modèle de régression logistique multivariée. Résultats: Au sein des 1 664 patients de l'analyse principale, 402 (24,2 %) étaient des femmes et 1262 (75,8 %) étaient des hommes. Un total de 138 femmes (34,3 %) et de 489 hommes (38,7 %) ont reçu une ordonnance de trithérapie à la sortie de l'hôpital (P = 0,11). Après 6 mois, 33 femmes (8,2 %) et 96 hommes (7,6 %) ont subi un événement indésirable net (rapport de cotes ajusté 0,82 ; intervalle de confiance à 95 % 0,49-1,37). Aucune différence n'a été notée dans le risque d'événements hémorragiques et d'événements ischémiques entre les hommes et les femmes lorsque ces événements étaient analysés séparément. Conclusions: Les taux d'ordonnances d'ACO en prophylaxie du thrombus ventriculaire gauche et les résultats cliniques après 6 mois étaient similaires entre les femmes et les hommes à la suite du STEMI antérieur et des AMP antéroapicale d'apparition récente.

Hyperventilation testing in the diagnosis of vasospastic angina: A clinical review and meta-analysis.

BACKGROUND: Given the limited access to invasive vasospastic reactivity testing in Western Countries, there is a need to further develop alternative non-invasive diagnostic methods for vasospastic angina (VSA). Hyperventilation testing (HVT) is defined as a class IIa recommendation to diagnose VSA by the Japanese Society of Cardiology. METHODS: In this systematic review and meta-analysis reported according to the PRISMA statement, we review the mechanisms, methods, modalities and diagnostic accuracy of non-invasive HVT for the diagnostic of VSA. RESULTS: A total of 106 articles published between 1980 and 2022 about VSA and HVT were included in the systematic review, among which 16 were included in the meta-analysis for diagnostic accuracy. Twelve electrocardiogram-HVT studies including 804 patients showed a pooled sensitivity of 54% (95% confidence intervals [CI]; 30%-76%) and a pooled specificity of 99% (95% CI; 88%-100%). Four transthoracic echocardiography-HVT studies including 197 patients revealed a pooled sensitivity of 90% (95% CI; 82%-94%) and a pooled specificity of 98% (95% CI; 86%-100%). Six myocardial perfusion imaging-HVT studies including 112 patients yielded a pooled sensitivity of 95% (95% CI; 63%-100%) and a pooled specificity of 78% (95% CI; 19%-98%). Non-invasive HVT resulted in a low rate of adverse events, ventricular arrhythmias being the most frequently reported, and were resolved with the administration of nitroglycerin. CONCLUSIONS: Non-invasive HVT offers a safe alternative with high diagnostic accuracy to diagnose VSA in patients with otherwise undiagnosed causes of chest pain.

Antipsychotics and Risks of Cardiovascular and Cerebrovascular Diseases and Mortality in Dwelling Community Older Adults.

This study aims to investigate the effect of antipsychotic agents on cardiovascular and cerebrovascular diseases (CVD/CEV) and mortality risks in the older population living in a community. A cohort of 42,650 new users of antipsychotic agents was built using Quebec healthcare databases (1998-2011). The outcomes were CVD/CEV and mortality incidence in 5 years of follow-up in the total cohort, sub-cohort of patients with no schizophrenia/dementia, sub-cohort with schizophrenia, and sub-cohort with dementia. Comparisons were made between the new users who continued the treatment (adherent level ≥ 60%) vs. those ceasing treatment (adherence level < 60%) using inverse probability of treatment weighting and Cox models. Comparing high adherence vs. low levels, CVD/CEV risk was increased by 36% in the sub-cohort with schizophrenia for atypical antipsychotic users and by 25% in the sub-cohort with dementia for typical antipsychotic users. An increasing mortality risk of 2- to 3-fold was linked with the typical antipsychotic use in all cohorts except the sub-cohort with schizophrenia; in addition, mortality risk is linked with the use of high vs. low doses. Antipsychotics were not linked with CVD/CEV risk, except for atypical antipsychotics in patients with schizophrenia and typical antipsychotics in patients with dementia. The mortality risk was linked with the use of typical antipsychotics and the dose used.

Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology 2023 Focused Update of the Guidelines for the Use of Antiplatelet Therapy.

Antiplatelet therapy (APT) is the foundation of treatment and prevention of atherothrombotic events in patients with atherosclerotic cardiovascular disease. Selecting the optimal APT strategies to reduce major adverse cardiovascular events, while balancing bleeding risk, requires ongoing review of clinical trials. Appended, the focused update of the Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology guidelines for the use of APT provides recommendations on the following topics: (1) use of acetylsalicylic acid in primary prevention of atherosclerotic cardiovascular disease; (2) dual APT (DAPT) duration after percutaneous coronary intervention (PCI) in patients at high bleeding risk; (3) potent DAPT (P2Y12 inhibitor) choice in patients who present with an acute coronary syndrome (ACS) and possible DAPT de-escalation strategies after PCI; (4) choice and duration of DAPT in ACS patients who are medically treated without revascularization; (5) pretreatment with DAPT (P2Y12 inhibitor) before elective or nonelective coronary angiography; (6) perioperative and longer-term APT management in patients who require coronary artery bypass grafting surgery; and (7) use of APT in patients with atrial fibrillation who require oral anticoagulation after PCI or medically managed ACS. These recommendations are all on the basis of systematic reviews and meta-analyses conducted as part of the development of these guidelines, provided in the Supplementary Material.

Association between cardiovascular diseases and dementia among various age groups: a population-based cohort study in older adults.

The link between cardiovascular (CV) risk factors or diseases and dementia is documented. There is conflicting evidence whether age moderates the association. We need to study this gap so that research and clinical initiatives target appropriate age groups. A cohort of 320,630 adult patients without dementia was built using Quebec healthcare databases (1998-2010). The CV risk factors were hypertension, diabetes and dyslipidemia, while diseases included stroke, myocardial infarction (MI), chronic heart failure (HF), and atrial fibrillation (AF). Dementia risk and CV risk factors or diseases were assessed using incidence rate ratios and Cox regression across age groups. The cohort presented by mainly female sex (67.7%) and mean age of 74.1 years. Incident rate of dementia increased with age, ranging from 4.1 to 93.5 per 1000 person-years. Diabetes, stroke, HF and AF were significantly associated with dementia risk, hazard ratios ranged from 1.08 to 3.54. The strength of association decreased in advanced age for diabetes, stroke and HF. The results suggest that prevention of diabetes, stroke, HF and AF are crucial to mitigate dementia risk. The pathophysiology of dementia in younger and older populations seems to differ, with less impact of CV risk factors in advanced age.

Canadian Cardiovascular Society-Canadian Heart Failure Society Focused Clinical Practice Update of Patients With Differing Heart Failure Phenotypes.

A number of societies produce heart failure (HF) management guidelines, comprising official recommendations on the basis of recent research discoveries, but their applicability to specific situations encountered in daily practice might be difficult. In this clinical practice update we aim to provide responses to fundamental questions that face health care providers, like appropriate timing for the introduction and optimization of different classes of medication according to specific patient phenotypes, when second-line therapies and valvular interventions should be considered, and management of difficult clinical scenarios such as cardiorenal syndrome and frailty. A consensus-based methodology was used. Approaches to 5 different phenotypes are presented: (1) The wet HF phenotype is the easiest to manage, decongestion being performed alongside introduction of guideline-directed medical therapy (GDMT); (2) The de novo HF phenotype requires the introduction of the 4 pillars of GDMT, personalizing the order on the basis of the individuals' biological and physiological characteristics; (3) The worsening HF phenotype is a marker of poor prognosis, and therefore should motivate optimization of GDMT, start second-line therapies, and/or reevaluate goals of care/advanced HF therapies; (4) The cardiorenal phenotypes require correct volume assessment, because renal function usually improves with decongestion; and (5) The frail HF phenotype require special attention, careful drug titration, and consideration of cardiac rehabilitation programs. In conclusion, specific common HF phenotypes call for a personalized approach to improve adoption of the HF guidelines into clinical practice.

Evolution of and Evidence-Practice Gaps in Antithrombotic Management of Atrial Fibrillation Patients After Percutaneous Coronary Intervention.

Background: The management of atrial fibrillation and flutter (AF) patients undergoing percutaneous coronary intervention (PCI) has evolved rapidly in the past decade. We determine whether the publication of the 2016 Canadian Cardiovascular Society AF guidelines were associated with a shift in practice patterns. Methods: Using Quebec provincial administrative database information for the period from 2010-2017, a retrospective cohort of patients with inpatient or outpatient coding for AF, who subsequently underwent PCI with placement of a coronary stent, was created and analyzed for the antithrombotic regimen received in the following year. Prescribing behavior was compared among 3 time periods (2010-2011, 2012-2015, 2016-2017), and use of antithrombotics was compared to guideline-predicted therapy using the χ2 test. Predictors of oral anticoagulation (OAC) prescription were identified using adjusted logistic regression. Results: A total of 3740 AF patients undergoing PCI were included. The proportion of OAC prescription increased over time (2010-2011 = 51.4%; 2012-2015 = 54.3%; 2016-2017 = 56.6%; P = 0.13), with a significant increase in direct OAC prescription (P < 0.01). A substantial treatment gap in OAC prescription persisted after publication of the 2016 guidelines (56.6% observed vs 89.7% predicted; P < 0.01). Previous stroke, CHADS2 score, Charlson Comorbidity Index ≥ 4, and prior use of direct OAC or warfarin were predictors of being exposed to OAC claims; previous major bleeding, and low-dose acetylsalicylic acid or P2Y12 inhibitor use were predictors of not being exposed to OACs. Conclusion: Expert guidance contributed to an increase in OAC prescription following PCI, but up to 2017, substantial further changes in practice patterns would have been required to achieve the recommended rates of OAC prescription.

Contexte: La prise en charge des patients qui sont atteints de fibrillation auriculaire (FA) ou de flutter auriculaire et qui subissent une intervention coronarienne percutanée (ICP) a évolué rapidement au cours de la dernière décennie. Nous avons voulu déterminer si la publication des lignes directrices sur la fibrillation auriculaire de la Société canadienne de cardiologie en 2016 s'était traduite par un changement de pratiques. Méthodologie: À partir de renseignements recueillis dans la base de données administratives du Québec en ciblant la période allant de 2010 à 2017, nous avons créé une cohorte rétrospective de patients qui, selon le code diagnostique, avaient été hospitalisés ou reçus en consultation externe pour cause de FA ou de flutter auriculaire et qui avaient par la suite subi une ICP avec mise en place d'une endoprothèse coronaire. La cohorte a été l'objet d'une analyse visant à caractériser le traitement antithrombotique administré au cours de l'année suivant l'opération, et le comportement des prescripteurs a été comparé sur trois périodes (2010-2011, 2012-2015, 2016-2017). En outre, le recours aux antithrombotiques a été comparé au traitement prévu suivant les lignes directrices au moyen du test χ2. Les facteurs prédictifs de prescription d'anticoagulants oraux (ACO) ont été cernés par régression logistique corrigée. Résultats: Au total, 3 740 patients atteints de FA ou de flutter auriculaire et ayant subi une ICP ont été inclus dans la cohorte. La proportion d'ordonnances d'ACO a augmenté au fil du temps (2010-2011 = 51,4 %, 2012-2015 = 54,3 %, 2016-2017 = 56,6 %; P = 0,13), et la prescription d'ACO directs a connu une augmentation significative (P < 0,01). Un écart important sur le plan thérapeutique en matière de prescription d'ACO a persisté après la publication des lignes directrices en 2016 (proportion observée de 56,6 % vs proportion prévue de 89,7 %; P < 0,01). Les antécédents d'AVC, le score CHADS2, un indice de comorbidité de Charlson ≥ 4 et les antécédents de traitement par des ACO directs ou la warfarine étaient des facteurs prédictifs d'exposition aux ACO; les antécédents de saignement majeur et la prise à faible dose d'acide acétylsalicylique ou d'un inhibiteur de P2Y12 étaient des facteurs prédictifs de non-exposition aux ACO. Conclusion: Les avis des spécialistes ont contribué à une augmentation de la prescription d'ACO après une ICP. Toutefois, jusqu'en 2017, d'autres changements de pratique substantiels auraient été nécessaires pour atteindre les taux recommandés d'utilisation des ACO.

Contemporary incidence and predictors of left ventricular thrombus in patients with anterior acute myocardial infarction.

BACKGROUND: The incidence of left ventricular thrombus (LVT) after anterior acute myocardial infarction (AMI) has not been well established in the era of primary percutaneous coronary intervention (pPCI) and potent dual antiplatelet therapy. The objective of this study is to establish the contemporary incidence of LVT in this population, to identify their risk factors, and to examine their association with clinical outcomes. METHODS: A multicenter retrospective cohort study including AMI patients with new-onset antero-apical wall motion abnormalities treated with pPCI between 2009 and 2017 was conducted. The primary outcome was LVT during the index hospitalization. Predictors of LVT were identified using multivariate logistic regression. Net adverse clinical events (NACE), a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or BARC type 3 or 5 bleeding at 6 months were compared between the LVT and no LVT groups. RESULTS: Among the 2136 patients included, 83 (3.9%) patients developed a LVT during index hospitalization. A lower left ventricular ejection fraction (LVEF) [adjusted odds ratio (aOR) 0.97; 95% confidence intervals (CI) 0.94-0.99] and the degree of worse anterior WMA (aOR 4.34; 95% CI 2.24-8.40) were independent predictors of LVT. A NACE occurred in 5 (5.72 per 100 patient-year) patients in the LVT group and in 127 (6.71 per 100 patient-year) patients in the no LVT group at 6 months [adjusted hazard ratio (aHR): 0.87; 95% CI 0.35-2.14]. CONCLUSIONS: The risk of LVT after anterior AMI with new-onset wall motion abnormalities is low, but this complication remains present in the contemporary era of timely pPCI and potent dual antiplatelet therapy .

Femoral Vascular Closure Devices and Bleeding, Hemostasis, and Ambulation Following Percutaneous Coronary Intervention.

Background The effectiveness of vascular closure devices (VCDs) to reduce bleeding after transfemoral percutaneous coronary intervention remains unsettled. Methods and Results Participants in the REGULATE-PCI (Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention) trial who underwent transfemoral percutaneous coronary intervention with VCD implantation were compared with those who underwent manual compression. The primary effectiveness end point was type 2, 3, or 5 Bleeding Academic Research Consortium access site bleeding at day 3. Univariate and multivariate analyses were adjusted by the inverse probability weighting method using propensity score. Time to hemostasis and time to ambulation were compared between groups. Of the 1580 patients who underwent transfemoral percutaneous coronary intervention, 1004 (63.5%) underwent VCD implantation and 576 (36.5%) had manual compression. The primary effectiveness end point occurred in 64 (6.4%) participants in the VCD group and in 38 (6.6%) participants in the manual compression group (inverse probability weighting-adjusted odds ratio, 1.02 [95% CI, 0.77-1.36]; P=0.89). There were statistically significant 2-way interactions between VCD use and female sex, chronic kidney disease, and use of high-potency P2Y12 inhibition (ticagrelor or prasugrel) (P<0.05 for all) with less bleeding with VCD use in these high-risk subgroups. Median time to hemostasis and time to ambulation were shorter in the VCD versus the manual compression group (P<0.01 for both). Conclusions Following transfemoral percutaneous coronary intervention, VCD use is associated with a shorter time to hemostasis and time to ambulation but not less bleeding. Further study of patients with high-bleeding risk is required, including women, patients with chronic kidney disease, and those using high-potency P2Y12 inhibitors. Registration URL: https://clinicaltrials.gov/ct2/show/NCT01848106; Unique identifier: NCT01848106.

Effectiveness and safety of apixaban and rivaroxaban vs warfarin in patients with atrial fibrillation and chronic kidney disease.

BACKGROUND: Randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) included a low proportion of atrial fibrillation (AF) patients with chronic kidney disease (CKD), and suggested that DOACs are safe and effective in patients with mild-to-moderate CKD. In a metanalysis of RCTs and observational studies, DOACs were associated with better efficacy (vs warfarin) in early CKD and had similar efficacy and safety profiles in patients with stages IV-V CKD. But few studies have provided data on the safety and effectiveness of each DOAC vs warfarin in patients with stage III CKD. The effectiveness and safety of DOACs in those patients are still subject to debate. AIM: To assess and compare the effectiveness and safety of apixaban and rivaroxaban vs warfarin in this patient population. METHODS: A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed apixaban and rivaroxaban was created using the administrative databases from the Quebec province of Canada between 2013 and 2017. The primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, and death, whereas the primary safety outcome was a composite of major bleeding within a year of DOAC vs warfarin initiation. Treatment groups were compared in an under-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards. RESULTS: A total of 8899 included patients filled out a new oral anticoagulation therapy claim; 3335 for warfarin and 5564 for DOACs. Compared with warfarin, 15 mg and 20 mg rivaroxaban presented a similar effectiveness and safety composite risk. Apixaban 5.0 mg was associated with a lower effectiveness composite risk [Hazard ratio (HR) 0.76; 95% confidence interval (CI): 0.65-0.88] and a similar safety risk (HR 0.94; 95%CI: 0.66-1.35). Apixaban 2.5 mg was associated with a similar effectiveness composite (HR 1.00; 95%CI: 0.79-1.26) and a lower safety risk (HR 0.65; 95%CI: 0.43-0.99. Although, apixaban 5.0 mg was associated with a better effectiveness (HR 0.76; 95%CI: 0.65-0.88), but a similar safety risk profile (HR 0.94; 95%CI: 0.66-1.35). The observed improvement in the effectiveness composite for apixaban 5.0 mg was driven by a reduction in mortality (HR 0.61; 95%CI: 0.43-0.88). CONCLUSION: In comparison with warfarin, rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.

Oral Anticoagulation for the Prevention of Thromboembolic Events in Patients With Anterior ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: The objective is to assess the comparative effectiveness and safety of dual-antiplatelet therapy (DAPT) vs triple therapy (TT) with DAPT + oral anticoagulant (OAC) in patients with anterior ST-segment elevation myocardial infarction (STEMI) and with new-onset anterior/apical wall-motion abnormalities (WMAs) treated with primary percutaneous coronary intervention (PCI). BACKGROUND: Patients with STEMI and new-onset anterior/apical WMA may benefit from the addition of OAC to prevent left ventricular thrombus and cardioembolic events. METHODS: A multicenter, retrospective cohort study was conducted. Patients with a concomitant indication for OAC were excluded. Patients discharged on TT were compared with patients discharged on DAPT using adjusted Cox proportional hazards analysis and inverse probability of treatment weighting. The primary endpoint was the net adverse clinical event (NACE) rate at 6 months (composite of all-cause mortality, non-fatal MI, stroke, or transient ischemic attack, systemic thromboembolism or type 3 or 5 Bleeding Academic Research Consortium [BARC] bleeding). RESULTS: A total of 1666 patients were included, among which 627 were treated with TT and 1039 were treated with DAPT. A NACE occurred in 55 patients (6.03 per 100 patient-years) in the TT group and in 74 patients (7.18 per 100 patient-years) in the DAPT group (adjusted hazard ratio, 0.86; 95% confidence interval, 0.55-1.32). Adjusted risk of the individual components of the primary endpoint, ischemic events, and bleeding events were similar between both groups (P>.05 for all). CONCLUSIONS: The addition of OAC to DAPT in anterior STEMI patients with new-onset WMA treated with PCI was not associated with a significant reduction in NACE.

Polypharmacy and risk of mortality among patients with heart failure following hospitalization: a nested case-control study.

Heart failure (HF) is associated with morbidity, rehospitalization and polypharmacy. The incidence rate of mortality in HF patients with polypharmacy is poorly studied. We examine the association of polypharmacy with mortality risk in incident hospitalized HF patients with a primary diagnosis after discharge from the hospital using Quebec administrative databases, Canada from 1999 to 2015. Polypharmacy, cardiovascular (CV) polypharmacy and non-CV polypharmacy were respectively defined as exposure to ≥ 10 drugs, ≥ 5 CV drugs and ≥ 5 non-CV drugs within three months prior to the case or the control selection date. We conducted a nested case-control study to estimate rate ratios (RR) of all-cause mortality using a multivariate conditional logistic regression during one-year of follow-up. We identified 12,242 HF patients with a mean age of 81.6 years. Neither CV polypharmacy (RR 0.97, 95%CI 0.82-1.15) nor non-CV polypharmacy (RR 0.93, 95%CI 0.77-1.12) were associated with lower mortality risk. However, all polypharmacy (RR 1.31, 95%CI 1.07-1.61) showed an association with mortality risk. Myocardial infarction, valvular disease, peripheral artery disease, diabetes, major bleeding, chronic kidney disease, high comorbidity score, high Frailty score, hydralazine and spironolactone users were associated with increasing mortality risk, ranging from 15 to 61%, while use of angiotensin II inhibitors, beta-blockers, statins, anticoagulant, and antiplatelets were associated with lower risk, ranging from 23 to 32%.

Trends of use and factors that determine the choice of oral anticoagulants in women and men with atrial fibrillation.

The aim was to identify sex-specific factors linked with oral anticoagulant initiation in a cohort of patients with atrial fibrillation using administrative data from Quebec (Canada) between 2014 and 2017. Cohort entry defined as new users, that is, no claims in last 12 months, a cohort of 32 050 patients was stratified in two groups, that is, women and men. Multivariable regression models were used to identify factors of initiations for low- and standard-dose direct oral anticoagulants (DOACs) versus warfarin, and low- versus standard-dose DOACs. In both sexes, warfarin initiation decreased and DOAC initiation increased, with year of initiation as major factors of DOACs use. In 2017, the increase was of 2- to 4-fold and 3- to 8-fold for low- and standard-dose DOACs (vs. warfarin), respectively. The proportion of patients starting on a low-dose DOAC was higher in women than men. Older age for both sexes and CHADS2 score ≥2 (only women) were major factors of low-dose dabigatran and rivaroxaban versus warfarin use. The only significant factor of standard-dose DOAC versus warfarin use was age of 65-79 for women or men treated with apixaban by 1.8- and 1.4-fold, respectively. Factors that made women and men less likely to receive a standard-dose DOAC versus warfarin were higher CHADS2 (for dabigatran and rivaroxaban), HAS-BLED and frailty scores, prior coronary disease, major bleeding, and chronic kidney disease (CKD) status. The choice of a low- versus standard-dose DOAC was mainly driven by age and CKD, and higher CHADS2 score (for dabigatran and apixaban) for both sexes.

Prehospital STEMI Referral Systems and Sex-Related Bias in Canada: A National Survey.

Background: Prehospital electrocardiographic ST-elevation myocardial infarction (STEMI) diagnosis and prehospital cardiac catheterization laboratory activation have been shown to significantly reduce average treatment delay, and further standardization of such systems may help reduce sex-related treatment and outcome gaps. However, what types of prehospital STEMI activation systems are in place across Canada, and to what extent sex-based STEMI treatment disparities are tracked, is unknown. Methods: We conducted a national survey of catheterization laboratory directors between October 11 and December 25, 2021. Seventeen catheterization laboratory directors representing 6 community and 11 academic centres completed the survey (40% response rate). Results: : All responding centres use a prehospital STEMI diagnosis and cardiac catheterization laboratory activation system, and the majority (59%) rely on real-time physician oversight. Slightly less than half (47%) of percutaneous coronary intervention centres reported prospectively tracking sex-related differences in STEMI care, and only one respondent believed that a significant systemic sex-related bias was present in their prehospital STEMI referral system. Patient factors (symptom description or time to presentation; 23.5%) and limitations of electrocardiogram diagnosis of STEMI in women (23.5%) were cited most frequently as contributing to sex-related bias in STEMI referral systems. In contrast, implicit bias in the referral algorithm, prehospital provider bias, and physician bias were not considered important contributing factors. Conclusions: Although all responding centres employ prehospital activation systems, less than half tracked sex-related differences, and most respondents believed that no sex-related bias existed in their prehospital STEMI system.

Contexte: Il a été démontré que le diagnostic préhospitalier par électrocardiogramme de l'infarctus du myocarde avec élévation du segment ST (STEMI) et l'activation du laboratoire de cathétérisme cardiaque préhospitalier permettent de réduire significativement le délai moyen de traitement, et un usage plus standardisé de ces systèmes pourrait contribuer à la réduction des écarts liés au sexe dans les traitements et les résultats de santé. Toutefois, on ignore quels types de systèmes d'activation préhospitaliers pour la prise en charge du STEMI sont en place à travers le Canada, ni dans quelle mesure les disparités de traitement liées au sexe font l'objet d'un suivi. Méthodologie: Nous avons mené un sondage national auprès des directeurs de laboratoires de cathétérisme entre le 11 octobre et le 25 décembre 2021. Notre questionnaire a été rempli par les directeurs de 17 laboratoires de cathétérisme, dont six centres communautaires et 11 centres universitaires (taux de réponse de 40 %). Résultats: Pour tous les centres répondants, un système de diagnostic préhospitalier du STEMI et d'activation de laboratoire de cathétérisme cardiaque était en place, dont la surveillance était assurée majoritairement par un médecin en temps réel (59 %). Un peu moins de la moitié des centres d'intervention coronarienne percutanée (47 %) ont rapporté faire un suivi prospectif des différences liées au sexe dans la prise en charge du STEMI, et un seul répondant a dit croire qu'un biais systématique lié au sexe était présent dans le système d'orientation préhospitalier pour les STEMI. Les facteurs liés aux patients (la description des symptômes ou le temps écoulé depuis leur apparition; 23,5 %) et les limites inhérentes au diagnostic du STEMI par électrocardiogramme chez les femmes (23,5 %) étaient les facteurs les plus fréquemment mentionnés comme sources de biais liés au sexe dans les systèmes d'orientation pour les STEMI. Par ailleurs, les biais implicites dans l'algorithme d'orientation et les biais des prestataires de soins préhospitaliers et des médecins n'étaient pas des facteurs contributifs jugés importants. Conclusions: Bien que des systèmes d'activation préhospitaliers soient en place dans tous les centres répondants, moins de la moitié d'entre eux ont rapporté faire le suivi des différences liées au sexe, et la plupart des répondants étaient d'avis que leur système préhospitalier de prise en charge des STEMI ne comportait pas de biais liés au sexe.

Percutaneous Mechanical Circulatory Support in Post-Myocardial Infarction Cardiogenic Shock: A Systematic Review and Meta-analysis.

BACKGROUND: Cardiogenic shock (CS) complicates 5%-10% of acute myocardial infarction (AMI) and is the leading cause of early mortality. It remains unclear whether percutaneous mechanical support (pMCS) devices improve post-AMI CS outcome. METHODS: A systematic review of original studies comparing the effect of pMCS on AMI-CS mortality was conducted with the use of Medline, Embase, Google Scholar, and the Cochrane Library databases. RESULTS: Of 8672 records, 50 were retained for quantitative analysis. Four additional references were added from other sources. Four references reported a significant mortality reduction with intra-aortic balloon pump (IABP) in patients with failed primary percutaneous coronary intervention (pPCI) or managed with thrombolysis. Meta-analyses showed no advantage of Impella over conventional therapy (pooled OR 0.55, 95% CI 0.20-1.46; I2 = 0.85) and increased mortality compared with IABP (pooled OR 1.32; 95% CI 1.08-1.62; I2 = 0.85). No study reported a mortality advantage for extracorporeal membrane oxygenation (ECMO) over conventional therapy, IABP, or Impella support. Early mortality might be improved with the addition of IABP or Impella to ECMO. Bleeding Academic Research Consortium ≥ 3 bleeding was increased with every pMCS strategy. CONCLUSIONS: The current evidence is of poor to moderate quality, with only 1 in 5 included articles reporting randomised data and several reporting unadjusted outcomes. Yet, there is some evidence to favour IABP use in the setting of thrombolysis or with failed pPCI, and adding IABP or Impella should be considered for patients requiring ECMO.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants vs Warfarin Among Obese Patients With Atrial Fibrillation.

Background: Obese patients are underrepresented in clinical trials assessing the comparative effectiveness and safety of use of direct oral anticoagulants vs use in atrial fibrillation (AF) patients. Methods: Using data from Quebec provincial administrative databases, for the years2010-2017, we created a retrospective cohort of patients with inpatient or outpatient coding for AF and obesity who were newly prescribed an oral anticoagulant. The primary safety outcome was a composite of intracranial, gastrointestinal, and major bleeding from other sites, and the primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, acute myocardial infarction, and death in the first year after oral anticoagulant initiation. Treatment groups were compared using inverse-probability-of-treatment-weighting Cox proportional-hazards models. Results: A total of 2263 patients were included, of whom 1253, 403, and 539 filled a warfarin, standard-dose rivaroxaban, and standard-dose apixaban prescription, respectively. Standard-dose rivaroxaban was associated with a similar composite safety (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.44-1.91) and composite effectiveness risk (HR 1.42; 95% CI 0.99-2.04) compared to warfarin, whereas standard-dose apixaban was associated with a lower composite safety (HR 0.40; 95% CI 0.16-0.98) and similar composite effectiveness risk (HR 0.96; 95% CI 0.67-1.39). Conclusion: Use of direct oral anticoagulants in obese AF patients was associated with a similar effectiveness and safety profile to that of warfarin use.

Introduction: Les patients obèses sont sous-représentés dans les essais cliniques qui portent sur l'évaluation de l'efficacité comparative et l'innocuité de l'utilisation d'anticoagulants oraux directs vs leur utilisation chez les patients atteints de fibrillation auriculaire (FA). Méthodes: À l'aide des données de la base de données administratives provinciales du Québec, des années 2010-2017, nous avons créé une cohorte rétrospective de patients dont le codage des séjours hospitaliers et en ambulatoire étaient la FA et l'obésité qui avaient récemment reçu une ordonnance d'anticoagulants oraux. Le principal critère d'évaluation de l'innocuité était un critère composite qui associait les hémorragies intracrâniennes, gastro-intestinales et majeures d'autres sites, et le principal critère d'évaluation de l'efficacité était un critère composite d'accident vasculaire cérébral, d'embolie systémique, d'infarctus aigu du myocarde et de décès dans la première année après l'amorce des anticoagulants oraux. Nous avons comparé les groupes de traitement à l'aide des modèles à risques proportionnels de Cox basés sur la probabilité inverse de pondération de traitement. Résultats: Nous avons retenu un total de 2 263 patients, dont 1 253, 403 et 539 ont pris de façon respective les médicaments prescrits suivants : la warfarine, le rivaroxaban à la posologie standard et l'apixaban à la posologie standard. Le rivaroxaban à la posologie standard était associé à un risque de survenue d'un événement compris dans le critère composite de l'innocuité (ratio d'incidence approché [RIA] 0,91; intervalle de confiance [IC] à 95 % 0,44-1,91) et un risque de survenue d'un événement compris dans le critère composite de l'efficacité (RIA 1,42; IC à 95 % 0,99-2,04) similaires par rapport à la warfarine, tandis que l'apixaban à la posologie standard était associé à un risque de survenue d'un événement compris dans le critère composite de l'innocuité plus faible (RIA 0,40; IC à 95 % 0,16-0,98) et un risque de survenue d'un événement compris dans le critère composite de l'efficacité similaire (RIA 0,96; IC à 95 % 0,67-1,39). Conclusion: L'utilisation d'anticoagulants oraux directs chez les patients obèses atteints de FA était associée à un profil d'efficacité et d'innocuité similaire à celui de l'utilisation de la warfarine.

Evolution of Antithrombotic Management of Atrial Fibrillation After Percutaneous Coronary Intervention Over 10 Years and Guidelines Uptake.

BACKGROUND: The management of atrial fibrillation and/or flutter (AF) patients requiring percutaneous coronary intervention (PCI) has evolved significantly. The Canadian Cardiovascular Society AF guidelines, last updated in 2020, seek to aid physicians in balancing both bleeding and thrombotic risks. METHODS: A tertiary academic centre registry of patients with AF who had PCI was examined for the antithrombotic therapy at discharge in 4 time periods (cohort 2010-2011; cohort 2014-2015; cohort 2017; cohort 2019). Discharge prescription patterns were compared among the cohorts, using the χ2 test. In addition, antithrombotic management in cohorts 2017 and 2019 were compared to guideline-expected therapy, using the χ2 test. RESULTS: A total of 576 AF patients undergoing PCI were included. Clinical and procedural characteristics were similar among cohorts, except for an increase in drug-eluting stent use in the most recent cohort (94% vs 99%; P = 0.04). The rate of oral anticoagulation increased over time (75% vs 89%; P < 0.01), driven primarily by an increase in direct oral anticoagulants prescription (63% vs 84%; P < 0.01). In contrast to previous cohorts, there was no significant difference between the observed and the guideline-expected anticoagulation rate in cohort 2019 (89% vs 94%; P = 0.23). CONCLUSIONS: A combination of expert guidance and educational initiatives in the past decade contributed to dramatic changes in the management of patients with AF undergoing PCI.

INTRODUCTION: La prise en charge des patients atteints de fibrillation auriculaire et/ou de flutter (FA) qui ont besoin d'une intervention coronarienne percutanée (ICP) a considérablement évolué. La dernière révision, en 2020, des lignes directrices sur la FA de la Société canadienne de cardiologie vise à aider les médecins à établir l'équilibre entre les risques d'hémorragie et de thrombose. MÉTHODES: Nous avons fouillé le registre d'un centre universitaire en soins tertiaires portant sur des patients atteints de FA qui avaient subi une ICP pour nous pencher sur le traitement antithrombotique offert à la sortie de l'hôpital de quatre périodes (cohorte 2010­2011; cohorte 2014­2015; cohorte 2017; cohorte 2019). Nous avons comparé les pratiques en matière d'ordonnances à la sortie de l'hôpital entre les cohortes à l'aide du test du χ2 . De plus, nous avons comparé la prise en charge des cohortes de 2017 et de 2019 qui avaient reçu le traitement antithrombotique à celles qui avaient reçu le traitement prévu dans les lignes directrices à l'aide du test du χ2 . RÉSULTATS: Nous avons sélectionné un total de 576 patients atteints de FA qui avaient subi une ICP. Les caractéristiques cliniques et interventionnelles étaient similaires entre les cohortes, à l'exception d'une augmentation de l'utilisation d'une endoprothèse médicamentée dans la plus récente cohorte (94 % vs 99 %; P = 0,04). Le taux d'anticoagulation par voie orale qui avait augmenté au fil du temps (75 % vs 89 %; P < 0,01) était principalement attribuable à l'augmentation des ordonnances d'anticoagulants d'action directe par voie orale (63 % vs 84 %; P < 0,01). Contrairement aux cohortes précédentes, il n'y avait aucune différence significative entre le taux d'anticoagulation observé et le taux d'anticoagulation prévu dans les lignes directrices dans la cohorte de 2019 (89 % vs 94 %; P = 0,23). CONCLUSIONS: La combinaison des conseils d'experts et des initiatives éducationnelles de la dernière décennie a contribué à des changements radicaux dans la prise en charge des patients atteints de FA qui subissaient une ICP.

Impact of STEMI Diagnosis and Catheterization Laboratory Activation Systems on Sex- and Age-Based Differences in Treatment Delay.

BACKGROUND: Women and the elderly with ST-elevation myocardial infarction (STEMI) experience longer treatment delays despite prehospital STEMI diagnosis and catheterization laboratory activation systems. It is not known what role specific STEMI referral systems might play in mediating this gap in care. We therefore examined sex- and age-based differences in STEMI treatment delay (TD) in different STEMI activation systems. METHODS: This observational comparative effectiveness study comprised 3 retrospective STEMI cohorts: a traditional hospital-based activation cohort (Cohort 1), an automated "physician-blind" prehospital activation cohort (Cohort 2), and a prehospital activation with real-time physician oversight cohort (Cohort 3). Outcomes of interest included sex and age group (< or ≥ 75 years) differences in suboptimal (> 90 minutes) first medical contact-to-device time (FMC-to-device) within each cohort, as well as independent predictors of suboptimal FMC-to-device and in-hospital mortality across cohorts. RESULTS: Five hundred-sixty STEMI activations were analyzed. In Cohort 1 (n = 179), women and those ≥ 75 were more likely to experience suboptimal FMC-to-device times (78.7% vs 36.4%, P = 0.02 and 85.0% vs 58.3%, < 0.01, respectively). Similar findings were observed in Cohort 3 (n = 109) (53.5% vs 32.9%, 56.5% vs 33.3%, respectively; P = 0.05, for both). In Cohort 2 (n = 272), however, there was no significant age-based difference (30.4% vs 21.7%, P = 0.18), and the gap was numerically lower but still significant for women (32.1% vs 20.1%, P = 0.04). When examining prehospital activation cohorts only, female sex (P = 0.03), off-hours presentation (P < 0.01), and physician oversight (P < 0.01) were independent predictors of longer FMC-to-device times. Age ≥ 75 (P < 0.01), Killip class (P < 0.01), and female sex (P = 0.04) were independently associated with in-hospital mortality. CONCLUSIONS: Automated "physician-blind" STEMI activation was associated with a reduced TD gap in women and the elderly, suggesting possible systemic bias. Appropriately powered confirmatory studies are required, but incorporating automated diagnosis and catheterization laboratory activation may be a solution to treatment gaps in STEMI care.

INTRODUCTION: Les femmes et les personnes présentant ont un infarctus du myocarde avec élévation du segment ST (STEMI) subissent de plus longs retards de traitement en dépit du diagnostic préhospitalier de STEMI et des systèmes d'activation de laboratoires de cathétérisme. On ignore le rôle que pourraient jouer les systèmes d'aiguillage des personnes atteintes de STEMI pour combler cette lacune en matière de soins. Nous avons donc examiné les différences selon le sexe et l'âge dans le retard de traitement du STEMI des différents systèmes d'activation de laboratoire en présence de STEMI. MÉTHODES: La présente étude comparative sur l'efficacité regroupait trois cohortes rétrospectives de STEMI : une cohorte traditionnelle d'activation à l'hôpital (cohorte 1), une cohorte d'activation du laboratoire lors de diagnostic préhospitalier automatisé « à l'insu du médecin ¼ (cohorte 2) et une cohorte d'activation du laboratoire de diagnostic préhospitalier dont la surveillance est assurée par un médecin en temps réel (cohorte 3). Les critères d'intérêt étaient les différences selon le sexe et le groupe d'âge (< ou ≥ 75 ans) dans le taux d'intervalle sous-optimal entre la première prise de contact avec les services médicaux et la pose d'un dispositif (> 90 minutes) au sein de chaque cohorte, ainsi que les prédicteurs indépendants de l'intervalle sous-optimal entre la première prise de contact avec les services médicaux et la pose d'un dispositif et la mortalité à l'hôpital de toutes les cohortes. RÉSULTATS: Cinq cents soixante (560) activations de diagnostic de STEMI ont fait l'objet d'une analyse. Dans la cohorte 1 (n = 179), les femmes et les personnes ≥ 75 ans étaient plus susceptibles de subir des intervalles sous-optimaux entre la première prise de contact avec les services médicaux et la pose d'un dispositif (78,7 % vs 36,4 %, P = 0,02 et 85,0 % vs 58,3 %, < 0,01, respectivement). Nous avons observé des résultats similaires dans la cohorte 3 (n = 109) (53,5 % vs 32,9 %, 56,5 % vs 33,3 %, respectivement ; P = 0,05, pour les deux). Toutefois, dans la cohorte 2 (n = 272), il n'y avait aucune différence significative selon l'âge (30,4 % vs 21,7 %, P = 0,18) et l'écart était numériquement plus faible, mais encore significatif chez les femmes (32,1 % vs 20,1 %, P = 0,04). Lorsque nous examinions seulement les cohortes d'activation du laboratoire lors de diagnostic préhospitalier, le sexe féminin (P = 0,03), la survenue dans les heures creuses (P < 0,01) et la surveillance du médecin (P < 0,01) étaient des prédicteurs indépendants d'intervalles plus longs entre la première prise de contact avec les services médicaux et la pose d'un dispositif. L'âge ≥ 75 ans (P < 0,01), la classification de Killip (P < 0,01) et le sexe féminin (P < 0,04) étaient indépendamment associés à la mortalité à l'hôpital. CONCLUSIONS: L'activation du laboratoire lors de diagnostic automatisé du STEMI « à l'insu du médecin ¼ a été associée à une réduction de l'écart dans le retard de traitement chez les femmes et les personnes âgées. Ceci indique un possible biais systémique. Des études confirmatives d'une puissance suffisante sont nécessaires, mais l'incorporation du diagnostic et de l'activation du laboratoire de cathétérisme atuomatisés peut être une solution aux écarts de traitement dans les soins de STEMI.