Protection of prior SARS-CoV-2 infection, COVID-19 boosters, and hybrid immunity against Omicron severe illness: A population-based cohort study of five million residents in Canada.

BACKGROUND: Evidence on protection of different patterns of infection- and vaccine-acquired immunity against Omicron-associated severe illness is useful in planning booster vaccination strategies. We examined protection of prior SARS-CoV-2 infection, a third or a fourth COVID-19 vaccine dose, and hybrid immunity against Omicron-associated severe illness. METHODS AND FINDINGS: This population-based cohort study followed five million individuals with at least one SARS-CoV-2 RT-PCR test before November 21, 2021 until an Omicron-associatedhospitalization or death. We used Cox regression models to estimate risks of Omicron-associated hospitalization and a composite severe outcome (hospitalized and death), among individuals with infection- and/or vaccination-acquired immunity. Individuals who were unvaccinated and had no history of a prior infection severed as the reference group. Both adjusted hazard ratios (HR) and corresponding protection (one minus adjusted HR), with 95% confidence intervals (CIs), were reported. Three doses provided 94% (95%CI 93-95) and 93% (95%CI 91-94) protection against Omicron-associated hospitalization at 2-3 and ≥3 months post-vaccination respectively, similar to the protection conferred by three doses and a prior infection (2-3 months: 99%, 95%CI 97-100; ≥3 months: 97%, 95%CI 92-99) and four doses (1 month: 87%, 95%CI 79-92; 1-2 months: 96%, 95%CI 92-98). In individuals ≥65 years old, protection of four doses increased to 95% (95%CI 91-98) at 1-2 months, significantly higher than that of three doses over the follow-up period. Similar results were observed with the composite severe outcome. CONCLUSION: At least three antigenic exposures, achieved by vaccination or infection, confers significant protection against Omicron-associated hospitalization and death in all age groups. Our findings support a third dose for the overall population, regardless of prior infection status, and a fourth dose for the elderly to maintain high level of immunity and substantially reduce risk of severe illness at individual level.

Outcomes of COVID-19 Infection and Vaccination Among Individuals With Myasthenia Gravis.

Importance: There are limited data regarding COVID-19 outcomes and vaccine uptake and safety among people with myasthenia gravis (MG). Objective: To investigate COVID-19-related outcomes and vaccine uptake among a population-based sample of adults with MG. Design, Setting, and Participants: This population-based, matched cohort study in Ontario, Canada, used administrative health data from January 15, 2020, and August 31, 2021. Adults with MG were identified using a validated algorithm. Each patient was matched by age, sex, and geographic area of residence to 5 controls from the general population and from a cohort of individuals with rheumatoid arthritis (RA). Exposure: Patients with MG and matched controls. Main Outcomes and Measures: Main outcomes were COVID-19 infection and related hospitalizations, intensive care unit admissions, and 30-day mortality among patients with MG vs controls. Secondary outcomes were uptake of COVID-19 vaccination among patients with MG vs controls. Results: Among 11 365 233 eligible Ontario residents, 4411 patients with MG (mean [SD] age, 67.7 [15.6] years; 2274 women [51.6%]) were matched to 22 055 general population controls (mean [SD] age, 67.7 [15.6] years; 11 370 women [51.6%]) and 22 055 controls with RA (mean [SD] age, 67.7 [15.6] years; 11 370 women [51.6%]). In the matched cohort, 38 861 of 44 110 individuals (88.1%) were urban residents; in the MG cohort, 3901 (88.4%) were urban residents. Between January 15, 2020, and May 17, 2021, 164 patients with MG (3.7%), 669 general population controls (3.0%), and 668 controls with RA (3.0%) contracted COVID-19. Compared with general population controls and controls with RA, patients with MG had higher rates of COVID-19-associated emergency department visits (36.6% [60 of 164] vs 24.4% [163 of 669] vs 29.9% [200 of 668]), hospital admissions (30.5% [50 of 164] vs 15.1% [101 of 669] vs 20.7% [138 of 668]), and 30-day mortality (14.6% [24 of 164] vs 8.5% [57 of 669] vs 9.9% [66 of 668]). By August 2021, 3540 patients with MG (80.3%) vs 17 913 general population controls (81.2%) had received 2 COVID-19 vaccine doses, and 137 (3.1%) vs 628 (2.8%), respectively had received 1 dose. Of 3461 first vaccine doses for patients with MG, fewer than 6 individuals were hospitalized for MG worsening within 30 days of vaccination. Vaccinated patients with MG had a lower risk than unvaccinated patients with MG of contracting COVID-19 (hazard ratio, 0.43; 95% CI, 0.30-0.60). Conclusions and Relevance: This study suggests that adults with MG who contracted COVID-19 had a higher risk of hospitalization and death compared with matched controls. Vaccine uptake was high, with negligible risk of severe MG exacerbations after vaccination, as well as evidence of effectiveness. The findings support public health policies prioritizing people with MG for vaccination and new COVID-19 therapeutics.

Epidemiology of COVID-19 and Its Cardiac and Neurologic Complications Among Chinese and South Asians in Ontario: Waves 1, 2, and 3.

Background: Although we had previously reported the cardiac and neurologic outcomes of Chinese and South Asian Ontarians in wave 1 of COVID-19, data on subsequent waves of COVID-19 remain unexamined. This is an extension study of this cohort in waves 2 and 3. Methods: We identified adult Ontarians with a positive COVID-19 polymerase chain reaction test from January 1, 2020 to June 30, 2021, and they were classified as being Chinese or South Asian using a validated surname algorithm; we compared their outcomes of mortality, and cardiac and neurologic complications with those of the general population using multivariable logistic regression models. Results: Compared to the general population (n = 439,977), the Chinese population (n = 15,208) was older (mean age 44.2 vs 40.6 years, P < 0.001) and the South Asian population (n = 46,333) was younger (39.2 years, P < 0.001). The Chinese population had a higher 30-day mortality (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.61) and more hospitalization or emergency department visits (OR, 1.14; 95% CI, 1.09-1.28), with a trend toward a higher incidence of cardiac complications (OR, 1.03; 95% CI, 0.87-1.12) and neurologic complications (OR, 1.23; 95% CI, 0.96-1.58). South Asians had a lower 30-day mortality (OR, 0.88; 95% CI, 0.78-0.98) but a higher incidence of hospitalization or emergency department visits (OR, 1.17; 95% CI, 1.14-1.20) with a trend toward a lower incidence of cardiac complications (OR, 0.76; 95% CI, 0.67-0.87) and neurologic complications (OR, 0.89; 95% CI, 0.73-1.09). There was also a significant difference in these outcomes between wave 1, 2 and 3, with a greater mortality in all groups in waves 2 and 3. Conclusions: Ethnicity continues to be an important determinant of mortality, cardiac and neurologic outcomes, and healthcare use among patients with COVID-19, requiring further studies to understand factors driving these differences.

Contexte: Nous avons déjà présenté les issues cliniques cardiaques et neurologiques chez les Ontariens de descendance chinoise ou sud-asiatique pour la première vague de la pandémie de COVID-19, mais les données au sujet des vagues ultérieures n'avaient pas encore été analysées. Nous présentons ici une prolongation de cette étude de cohortes pour la seconde et la troisième vague de COVID-19. Méthodologie: Notre analyse porte sur des adultes ontariens ayant obtenu un résultat positif à un test de COVID-19 par réaction en chaîne de la polymérase entre le 1er janvier 2020 et le 30 juin 2021. Un algorithme validé pour l'analyse des noms de famille a été utilisé pour isoler les sujets de descendance chinoise ou sud-asiatique, et leur taux de mortalité de même que les complications cardiaques et neurologiques ont été comparés à ceux de la population générale à l'aide de modèles de régression logistique multivariée. Résultats: En comparaison de la population générale (n = 439 977), les personnes de descendance chinoise (n = 15 208) se sont révélées plus âgées (âge moyen de 44,2 ans contre 40,6 ans, P < 0,001), tandis que les personnes de descendance sud-asiatique (n = 46 333) étaient plus jeunes (39,2 ans, P < 0,001). Dans la population de descendance chinoise, le taux de mortalité après 30 jours était plus élevé (rapport de cotes [RC] de 1,44; intervalle de confiance [IC] à 95 % de 1,28 à 1,61), et davantage d'hospitalisations ou de consultations aux urgences sont survenues (RC de 1,14; IC à 95 % de 1,09 à 1,28). L'incidence de complications cardiaques (RC de 1,03; IC à 95 % de 0,87 à 1,12) et de complications neurologiques (RC de 1,23; IC à 95 % de 0,96 à 1,58) avait également tendance à être plus élevée. Chez les personnes de descendance sud-asiatique, le taux de mortalité après 30 jours était plus faible (RC de 0,88; IC à 95 % de 0,78 à 0,98), mais l'incidence d'hospitalisations ou de consultations aux urgences était plus élevée (RC de 1,17; IC à 95 % de 1,14 à 1,20). Elles présentaient également une tendance vers une plus faible incidence de complications cardiaques (RC de 0,76; IC à 95 % de 0,67 à 0,87) et de complications neurologiques (RC de 0,89; IC à 95 % de 0,73 à 1,09). Des différences significatives ont également été observées pour ces paramètres entre les vagues 1, 2 et 3 de la maladie, et le taux de mortalité était plus élevé pour tous les groupes des vagues 2 et 3. Conclusions: L'origine ethnique demeure un déterminant important de la mortalité, des issues cliniques cardiaques et neurologiques ainsi que de l'utilisation des ressources en santé chez les patients atteints de la COVID-19. D'autres études sont toutefois nécessaires pour mieux comprendre les facteurs qui expliquent ces différences.

Troponin testing after noncardiac surgery: a population-based historical cohort study on variation and factors associated with testing in Ontario.

BACKGROUND: International practice guidelines make different recommendations for postoperative troponin testing to detect perioperative myocardial infarction and myocardial injury after noncardiac surgery. To gain insights into current testing patterns, we evaluated predictors of routine troponin testing after three commonly performed major noncardiac surgeries. METHODS: We conducted a population-based historical cohort study of adults having major orthopedic, colorectal, or vascular surgery in Ontario, Canada from 1 January 2010 to 31 December 2017. We used hierarchical logistic regression modelling to assess the association of patient, surgery, and hospital factors with postoperative troponin testing, while accounting for clustering at the hospital level. We characterized hospital-level variation by the intraclass correlation coefficient (ICC), which was adjusted for various characteristics. RESULTS: The cohort included 176,454 eligible patients. Hospital-specific adjusted testing rates ranged from 0-20.1% for orthopedic surgery, 0-43.8% for colorectal surgery, and 19.6-88.0% for vascular surgery. Older age, urgent surgery status, and surgery duration were consistently associated with higher rates of testing for all three surgeries. Higher Revised Cardiac Risk Index scores were associated with higher odds of testing for orthopedic and colorectal surgery, but not for vascular surgery. Even after adjustment, the ICCs were 9.2%, 7.4%, and 24.1% for orthopedic, general, and vascular surgery, respectively. CONCLUSIONS: Troponin testing varied substantially across hospitals for selected major noncardiac surgery procedures even after accounting for differences in patient-level cardiac risk factors. Our observations lend support to a more standardized approach for troponin testing after noncardiac surgery.

RéSUMé: CONTEXTE: Les directives de pratique internationales émettent différentes recommandations en ce qui concerne les dosages postopératoires de troponines afin de détecter l'infarctus du myocarde et les lésions myocardiques périopératoires après une chirurgie non cardiaque. Pour mieux comprendre les habitudes de test actuelles, nous avons évalué les prédicteurs de dosage de troponines de routine après trois chirurgies non cardiaques majeures couramment réalisées. MéTHODE: Nous avons réalisé une étude de cohorte historique basée sur la population d'adultes bénéficiant d'une chirurgie orthopédique, colorectale ou vasculaire majeure en Ontario, au Canada, entre le 1er janvier 2010 et le 31 décembre 2017. Nous avons utilisé un modèle de régression logistique hiérarchique afin d'évaluer l'association des facteurs liés au patient, à la chirurgie et à l'hôpital avec les dosages de troponines postopératoires, tout en tenant compte des groupements au niveau hospitalier. Nous avons caractérisé la variation hospitalière par le coefficient de corrélation intraclasse (CCI), qui a été ajusté pour tenir compte de diverses caractéristiques. RéSULTATS: La cohorte comprenait 176 454 patients éligibles. Les taux de tests ajustés propres à l'hôpital variaient de 0 à 20,1 % pour les chirurgies orthopédiques, de 0 à 43,8 % pour les chirurgies colorectales et de 19,6 à 88,0 % pour les chirurgies vasculaires. Un âge plus avancé, un statut de chirurgie urgente et la durée de la chirurgie étaient systématiquement associés à des taux plus élevés de dosages pour les trois chirurgies. Des scores plus élevés sur l'Indice de risque cardiaque révisé étaient associés à des probabilités plus élevées de dosages pour les chirurgies orthopédiques et colorectales, mais pas pour les chirurgies vasculaires. Même après ajustement, les CCI étaient de 9,2 %, 7,4 % et 24,1 % pour les chirurgies orthopédiques, générales et vasculaires, respectivement. CONCLUSION: Les dosages de troponines varient considérablement d'un hôpital à l'autre pour certaines interventions chirurgicales non cardiaques majeures, même après avoir pris en compte les différences dans les facteurs de risque cardiaques liés au patient. Nos observations appuient une approche plus standardisée des dosages de troponines après une chirurgie non cardiaque.

COVID-19 and its Cardiac and Neurological Complications among Ontario Visible Minorities.

BACKGROUND: Due to lack of data on the epidemiology, cardiac, and neurological complications among Ontario visible minorities (Chinese and South Asians) affected by coronavirus disease (COVID-19), this population-based retrospective study was undertaken to study them systematically. METHODS: From January 1, 2020 to September 30, 2020 using the last name algorithm to identify Ontario Chinese and South Asians who were tested positive by PCR for COVID-19, their demographics, cardiac, and neurological complications including hospitalization and emergency visit rates were analyzed compared to the general population. RESULTS: Chinese (N = 1,186) with COVID-19 were found to be older (mean age 50.7 years) compared to the general population (N = 42,547) (mean age 47.6 years) (p < 0.001), while South Asians (N = 3,459) were younger (age of 42.1 years) (p < 0.001). The 30-day crude rate for cardiac complications among Chinese was 169/10,000 (p = 0.069), while for South Asians, it was 64/10,000 (p = 0.008) and, for the general population, it was 112/10,000. For neurological complications, the 30-day crude rate for Chinese was 160/10,000 (p < 0.001); South Asians was 40/10,000 (p = 0.526), and general population was 48/10,000. The 30-day all-cause mortality rate was significantly higher for Chinese at 8.1% vs 5.0% for the general population (p < 0.001), while it was lower in South Asians at 2.1% (p < 0.001). CONCLUSIONS: Chinese and South Asians in Ontario affected by COVID-19 during the first wave of the pandemic were found to have a significant difference in their demographics, cardiac, and neurological outcomes.

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

BACKGROUND: Given changes in the care and outcomes of acute myocardial infarction (AMI) patients over the past several decades, we sought to develop prediction models that could be used to generate accurate risk-adjusted mortality and readmission outcomes for hospitals in current practice across Canada. METHODS: A Canadian national expert panel was convened to define appropriate AMI patients for reporting and develop prediction models. Preliminary candidate variable evaluation was conducted using Ontario patients hospitalized with a most responsible diagnosis of AMI from April 1, 2015 to March 31, 2018. National data from the Canadian Institute for Health Information was used to develop AMI prediction models. The main outcomes were 30-day all-cause in-hospital mortality and 30-day urgent all-cause readmission. Discrimination of these models (measured by c-statistics) was compared with that of existing Canadian Institute for Health Information models in the same study cohort. RESULTS: The AMI mortality model was assessed in 54,240 Ontario AMI patients and 153,523 AMI patients across Canada. We observed a 30-day in-hospital mortality rate of 6.3%, and a 30-day all-cause urgent readmission rate of 10.7% in Canada. The final Canadian AMI mortality model included 12 variables and had a c-statistic of 0.834. For readmission, the model had 13 variables and a c-statistic of 0.679. Discrimination of the new AMI models had higher c-statistics compared with existing models (c-statistic 0.814 for mortality; 0.673 for readmission). CONCLUSIONS: In this national collaboration, we developed mortality and readmission models that are suitable for profiling performance of hospitals treating AMI patients in Canada.

CONTEXTE: Compte tenu des changements apportés au cours des dernières décennies aux soins des patients ayant subi un infarctus aigu du myocarde (IAM) et aux issues d'un tel événement, nous avons voulu élaborer des modèles prédictifs pouvant servir à calculer de façon précise les résultats relatifs à la mortalité et aux réadmissions, ajustés selon les risques, pour les hôpitaux dans la pratique actuelle au Canada. MÉTHODOLOGIE: Un groupe national d'experts canadiens a été mis sur pied et a reçu le mandat de définir les critères appropriés applicables aux patients ayant subi un IAM aux fins de déclaration des cas et d'élaborer des modèles prédictifs. L'évaluation préliminaire des variables proposées a été effectuée à partir de patients hospitalisés en Ontario entre le 1er avril 2015 et le 31 mars 2018 chez lesquels l'IAM était le diagnostic principal à l'origine de l'hospitalisation. Les données à l'échelle nationale de l'Institut canadien d'information sur la santé (ICIS) ont été utilisées pour élaborer des modèles prédictifs d'IAM. Les deux principales issues évaluées étaient la mortalité hospitalière toutes causes confondues à 30 jours et la réadmission urgente toutes causes confondues à 30 jours. Le pouvoir discriminant de ces modèles (mesuré par la statistique C) a été comparé à celui des modèles existants de l'ICIS dans la même cohorte de l'étude. RÉSULTATS: Le modèle de mortalité par IAM a été évalué auprès de patients ayant subi un IAM, dont 54 240 en Ontario et 153 523 dans l'ensemble du Canada. Nous avons observé un taux de mortalité hospitalière à 30 jours de 6,3 % et un taux de réadmission urgente à 30 jours toutes causes confondues de 10,7 % au Canada. Le modèle canadien final de prédiction de la mortalité par IAM était constitué de 12 variables et avait une statistique C de 0,834. Pour la réadmission, le modèle comportait 13 variables et présentait une statistique C de 0,679. Le pouvoir discriminant des nouveaux modèles d'IAM présentait une statistique C supérieure à celle des modèles existants (statistique C de 0,814 pour la mortalité et de 0,673 pour la réadmission). CONCLUSIONS: Dans le cadre de cette collaboration nationale, nous avons élaboré des modèles prédictifs de la mortalité et de la réadmission hospitalière qui permettent d'établir un profil des résultats obtenus par les hôpitaux traitant des patients ayant subi un IAM au Canada.

Renin-angiotensin-aldosterone system inhibitors and major cardiovascular events and acute kidney injury in patients with coronary artery disease.

BACKGROUND: Renin-angiotensin-aldosterone system inhibitors (RAASIs) are recommended for most patients with coronary artery disease (CAD). However, there is debate across guidelines as to which patients with CAD benefit the most from these agents. This study investigated the association between RAASIs and cardiovascular outcomes and acute kidney injury in a contemporary cohort of patients with CAD. METHODS: Patients ≥65 years of age with CAD alive on April 1, 2012 in Ontario, Canada were included. Outcomes included major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction (MI), unstable angina, stroke, or coronary revascularization), and acute kidney injury (AKI) hospitalizations at 4 years. Inverse probability of treatment-weighted Cox proportional hazards regression models was used to compare the rates of each outcome in patients treated with and without RAASIs (angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers). RESULTS: There were 165,058 patients with CAD identified (mean age 75 years, 65.5% male, 64.7% prescribed RAASIs). After inverse-probability weighting, treatment with RAASIs was associated with a lower rate of MACE compared with treatment without RAASIs (17.6% vs 18.2%, hazard ratio [HR]: 0.96, 95% CI: 0.93-0.99, respectively). However, treatment with RAASIs was associated with a higher rate of AKI compared with treatment without RAASIs (1.7% vs 1.5%, HR: 1.14, 95% CI: 1.02-1.29, respectively). The reduction in MACE was greater in patients with prior MI (HR: 0.87, 95% CI: 0.82-0.92) compared with patients without prior MI (HR: 1.00, 95% CI: 0.97-1.04, interaction p < 0.01). The increase in AKI was lower in patients with prior MI (HR: 0.82, 95% CI: 0.66-1.00) compared with patients without prior MI (HR: 1.37, 95% CI: 1.19-1.57, interaction p < 0.01). CONCLUSIONS: This study supports the continued use of RAASIs in patients with CAD, although the benefit appears smaller in magnitude than observed in prior trials. High-risk patients, particularly those with prior MI, appear to benefit the most from RAASIs.

Troponin Testing After Noncardiac Surgery in Ontario: An Observational Study.

BACKGROUND: In 2017, the Canadian Cardiovascular Society (CCS) published guidelines recommending postoperative troponin surveillance in higher-risk patients having major noncardiac surgery. The objective of this study was to evaluate the proportion of major noncardiac surgery patients that would meet recommendations for troponin testing and to assess the rates of troponin testing before guideline adoption. METHODS: We conducted a retrospective observational study of patients age 40 to 105 undergoing a subset of major noncardiac surgeries that included orthopedics, gynecology, general, urology, vascular, and thoracic surgeries in Ontario, Canada from January 1, 2010 to December 31, 2017. The primary outcomes were the proportion of patients recommended for testing based on the guidelines and rates of troponin testing within 2 days of surgery. RESULTS: We identified 257,704 patients who underwent noncardiac surgery. Mean age was 66.4 ± 11.9 years, and 12.4% underwent urgent surgery. Applying the CCS guidelines, 71.2% of elective surgery patients and 81.0% of urgent surgery patients would have met recommendations for postoperative troponin screening, whereas 10.8% and 27.1% received postoperative troponin testing, respectively. Most elective surgery patients met recommendations for testing based on the age criterion (54.9%), followed by diabetes (24.6%) and high-risk surgery (22.7%) criteria. Troponin testing varied substantially by types of surgery: highest for open abdominal aortic aneurisms and lowest for hysterectomies. CONCLUSIONS: Based on the CCS guidelines, most patients undergoing the subset of surgeries assessed would have met recommendations for routine troponin testing. In contrast, routine troponin testing before guideline adoption was done infrequently in Ontario, with substantial variations based on the surgery type.

INTRODUCTION: En 2017, la Société canadienne de cardiologie (SCC) a publié des lignes directrices dont les recommandations portaient sur la surveillance de la troponine en phase postopératoire chez les patients exposés à un risque accru de subir une intervention chirurgicale non cardiaque importante. L'objectif de la présente étude était d'évaluer le nombre de patients subissant une intervention chirurgicale non cardiaque importante qui répondraient aux recommandations sur le dosage de la troponine et de déterminer la fréquence des dosages de la troponine avant l'adoption des lignes directrices. MÉTHODES: Nous avons mené une étude observationnelle rétrospective auprès de patients âgés de 40 à 105 ans subissant des interventions chirurgicales non cardiaques importantes, à savoir des interventions de chirurgie orthopédique, de chirurgie gynécologique, de chirurgie générale, de chirurgie urologique, de chirurgie vasculaire et de chirurgie thoracique en Ontario, au Canada, du 1er janvier 2010 au 31 décembre 2017. Les principaux critères d'évaluation étaient le nombre de patients pour qui le dosage était recommandé selon les lignes directrices, et la fréquence des dosages de la troponine dans les deux jours après l'intervention chirurgicale. RÉSULTATS: Nous avons relevé 257 704 patients qui avaient subi une intervention chirurgicale non cardiaque. L'âge moyen était de 66,4 ± 11,9 ans, et 12,4 % avaient subi une intervention chirurgicale urgente. En appliquant les lignes directrices de la SCC, 71,2 % des patients avaient subi une intervention chirurgicale élective et 81,0 % des patients qui avaient subi une intervention chirurgicale urgente répondaient aux recommandations de dépistage de la troponine en phase postopératoire, alors que respectivement 10,8 % et 27,1 % avaient reçu le dosage de la troponine en phase postopératoire. La plupart des patients qui avaient subi une intervention chirurgicale élective répondaient aux recommandations sur le dosage selon le critère d'âge (54,9 %), puis selon le critère de diabète (24,6 %) et le critère d'intervention chirurgicale à risque élevé (22,7 %). Le dosage de la troponine variait de façon substantielle selon le type d'intervention chirurgicale : le dosage le plus élevé lors des traitements chirurgicaux ouverts des anévrismes de l'artère abdominale et le dosage le plus faible lors d'hystérectomies. CONCLUSIONS: Selon les lignes directrices de la SCC, la plupart des patients qui subissaient les interventions chirurgicales évaluées avaient répondu aux recommandations de dosage systématique de la troponine. En revanche, le dosage systématique de la troponine avant l'adoption des lignes directrices était rarement réalisé en Ontario, et des variations substantielles selon le type d'intervention chirurgicale étaient observées.

Prescribing of two potentially interacting cardiovascular medications in atrial fibrillation patients on direct oral anticoagulants.

BACKGROUND: Amiodarone and diltiazem are commonly recommended cardiovascular medications for use in atrial fibrillation (AF) patients. They are known to have drug-drug interactions (DDIs) with direct oral anticoagulants (DOACs). We aimed to evaluate frequency of use of amiodarone or diltiazem among continuous users of DOACs in AF patients and to determine factors associated with their co-use. METHODS: The study population included all AF patients with continuous DOAC use in Ontario, Canada, ≥66 years, from April 1, 2017 to March 31, 2018. Concurrent use of amiodarone or diltiazem was determined by identifying the presence of an overlapping prescription. Multivariable logistic regression models were used to identify predictors of amiodarone or diltiazem use. RESULTS: In total, 5,390 AF patients, ≥66 years, with continuous DOAC use were identified. Amiodarone was co-prescribed in 6.4% patients and diltiazem was co-prescribed in 11.2% patients. Prior percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) were associated with significantly increased odds of amiodarone co-use (OR 2.51 [95% CI 1.54, 4.09], p = 0.0002 and OR 5.28 [95% CI 3.52, 7.93], p= <0.001, respectively). Patients with a heart failure (HF) history also had increased co-use of amiodarone (OR 2.05 [95% CI 1.57, 2.67], p < 0.001). The presence of chronic obstructive pulmonary disease (COPD) was associated with significantly increased odds of diltiazem co-use (OR 1.58 [95% CI 1.31, 1.9], p=<0.001). CONCLUSIONS: Among AF patients with continuous DOAC use, amiodarone was co-prescribed in 1 in 16 patients and diltiazem was co-prescribed in 1 in 9 patients. Predictors such as history of HF, PCI, CABG or COPD help identify vulnerable populations at increased risk of DDIs.

Association Between Adherence to Fractional Flow Reserve Treatment Thresholds and Major Adverse Cardiac Events in Patients With Coronary Artery Disease.

Importance: Fractional flow reserve (FFR) is an invasive measurement used to assess the potential of a coronary stenosis to induce myocardial ischemia and guide decisions for percutaneous coronary intervention (PCI). It is not known whether established FFR thresholds for PCI are adhered to in routine interventional practice and whether adherence to these thresholds is associated with better clinical outcomes. Objective: To assess the adherence to evidence-based FFR thresholds for PCI and its association with clinical outcomes. Design, Setting, and Participants: A retrospective, multicenter, population-based cohort study of adults with coronary artery disease undergoing single-vessel FFR assessment (excluding ST-segment elevation myocardial infarction) from April 1, 2013, to March 31, 2018, in Ontario, Canada, and followed up until March 31, 2019, was conducted. Two separate cohorts were created based on FFR thresholds (≤0.80 as ischemic and >0.80 as nonischemic). Inverse probability of treatment weighting was used to account for treatment selection bias. Exposures: PCI vs no PCI. Main Outcomes and Measures: The primary outcome was major adverse cardiac events (MACE) defined by death, myocardial infarction, unstable angina, or urgent coronary revascularization. Results: There were 9106 patients (mean [SD] age, 65 [10.6] years; 35.3% female) who underwent single-vessel FFR measurement. Among 2693 patients with an ischemic FFR, 75.3% received PCI and 24.7% were treated only with medical therapy. In the ischemic FFR cohort, PCI was associated with a significantly lower rate and hazard of MACE at 5 years compared with no PCI (31.5% vs 39.1%; hazard ratio, 0.77 [95% CI, 0.63-0.94]). Among 6413 patients with a nonischemic FFR, 12.6% received PCI and 87.4% were treated with medical therapy only. PCI was associated with a significantly higher rate and hazard of MACE at 5 years compared with no PCI (33.3% vs 24.4%; HR, 1.37 [95% CI, 1.14-1.65]) in this cohort. Conclusions and Relevance: Among patients with coronary artery disease who underwent single-vessel FFR measurement in routine clinical practice, performing PCI, compared with not performing PCI, was significantly associated with a lower rate of MACE for ischemic lesions and a higher rate of MACE for nonischemic lesions. These findings support the performance of PCI procedures according to evidence-based FFR thresholds.

Use of Cardiac Noninvasive Testing After Emergency Department Discharge: Association of Hospital Network Testing Intensity and Outcomes in Ontario, Canada.

Background The relationship between noninvasive cardiac diagnostic testing intensity and downstream clinical outcomes is unclear. Our objective was to examine the relationship between hospital network noninvasive cardiac diagnostic testing intensity and downstream clinical outcomes in patients who were discharged from the emergency department after assessment for chest pain. Methods and Results We employed a retrospective cohort study design of 387 809 patients evaluated for chest pain in the emergency department between April 1, 2010 and March 31, 2016. Hospital networks were divided into tertiles based on usage of noninvasive cardiac diagnostic testing. The primary outcome was a composite of acute myocardial infarction or all-cause mortality. Adjusted Cox proportional hazards models were used to compare the hazard of the composite outcome of myocardical infarction and/or all-cause mortality between the tertiles. After adjustment for clinically relevant covariates, patients evaluated for chest pain in intermediate noninvasive cardiac diagnostic testing usage tertile hospital networks did not have significantly different hazards of the composite outcome when compared with those evaluated in low usage tertile hospital networks >90 days (hazard ratio [HR], 1.00; 95% CI, 0.83-1.21), 6 months (HR, 1.07; 95% CI, 0.92-1.24), and 1 year (HR, 1.03; 95% CI, 0.94-1.14). Patients evaluated in the high usage tertile also did not have significantly different hazards of the composite outcome compared with those evaluated in the low usage tertile at 90 days (HR, 0.98; 95% CI, 0.80-1.19), 6 months (HR, 1.01; 95% CI, 0.87-1.17); and 1 year (HR, 0.95; 95% CI, 0.86-1.05). Conclusions Our population-based study demonstrated that high noninvasive cardiac diagnostic testing use intensity was not associated with reductions in downstream myocardial infarction or all-cause mortality.

Low-Density Lipoprotein Cholesterol and Adverse Cardiovascular Events After Percutaneous Coronary Intervention.

BACKGROUND: After percutaneous coronary interventions (PCIs), patients remain at high risk of developing late cardiovascular events. Although controlling low-density lipoprotein cholesterol (LDL-C) may improve outcomes after PCI, practice guidelines do not have specific recommendations on LDL-C management for this subgroup. OBJECTIVES: The purpose of this study was to evaluate LDL-C testing and levels after PCIs, and to assess the association between LDL-C and longer-term cardiovascular events after PCIs. METHODS: All patients who received their first PCI from October 1, 2011, to September 30, 2014, in Ontario, Canada, were considered for inclusion. Patients who had LDL-C measurement within 6 months after PCI were categorized as: <70 mg/dl, 70 to <100 mg/dl, and ≥100 mg/dl. The primary composite outcome was cardiovascular death, myocardial infarction, coronary revascularization, and stroke through December 31, 2016. RESULTS: Among 47,884 included patients, 52% had LDL-C measured within 6 months of PCI and 57% had LDL-C <70 mg/dl. After a median 3.2 years, the rates of cardiovascular events were 55.2/1,000 person-years for the LDL-C <70 mg/dl group, 60.3/1,000 person-years for 70 to <100 mg/dl, and 94.0/1,000 person-years for ≥100 mg/dl. The adjusted subdistribution hazard ratios for cardiovascular events were 1.17 (95% confidence interval: 1.09 to 1.26) for LDL-C of 70 to <100 mg/dl, and 1.78 (95% confidence interval: 1.64 to 1.94) for LDL-C ≥100 mg/dl when compared with LDL-C <70 mg/dl. CONCLUSIONS: One in 2 patients had LDL-C measured within 6 months after PCI, and only 57% had LDL-C <70 mg/dl. Higher levels of LDL-C were associated with an increased incidence of late cardiovascular events. Improved cholesterol management after PCI should be considered to improve the outcomes of these patients.

Population Trends in All-Cause Mortality and Cause Specific-Death With Incident Atrial Fibrillation.

BACKGROUND Limited studies have evaluated population-level temporal trends in mortality and cause of death in patients with contemporary managed atrial fibrillation. This study reports the temporal trends in 1-year overall and cause-specific mortality in patients with incident atrial fibrillation. METHODS AND RESULTS Patients with incident atrial fibrillation presenting to an emergency department or hospitalized in Ontario, Canada, were identified in population-level linked administrative databases that included data on vital statistics and cause of death. Temporal trends in 1-year all-cause and cause-specific mortality was determined for individuals identified between April 1, 2007 (fiscal year [FY] 2007) and March 31, 2016 (FY 2015). The study cohort consisted of 110 302 individuals, 69±15 years of age with a median congestive heart failure, hypertension, age (≥75 years), diabetes mellitus, stroke (2 points), vascular disease, age (≥65 years), sex category (female) score of 2.8. There was no significant decline in the adjusted 1-year all-cause mortality between the first and last years of the study period (adjusted mortality: FY 2007, 8.0%; FY 2015, 7.8%; P for trend=0.68). Noncardiovascular death accounted for 61% of all deaths; the adjusted 1-year noncardiovascular mortality rate rose from 4.5% in FY 2007 to 5.2% in FY 2015 (P for trend=0.007). In contrast, the 1-year cardiovascular mortality rate decreased from 3.5% in FY 2007 to 2.6% in FY 2015 (P for trend=0.01). CONCLUSIONS Overall 1-year all-cause mortality in individuals with incident atrial fibrillation has not improved despite a significant reduction in the rate of cardiovascular death. These findings highlight the importance of recognizing and managing concomitant noncardiovascular conditions in patients with atrial fibrillation.

Calibration and discrimination of the Framingham Risk Score and the Pooled Cohort Equations.

BACKGROUND: Although accurate risk prediction is essential in guiding treatment decisions in primary prevention of atherosclerotic cardiovascular disease, the accuracy of the Framingham Risk Score (recommended by a Canadian guideline) and the Pooled Cohort Equations (recommended by US guidelines) has not been assessed in a large contemporary Canadian population. Our primary objective was to assess the calibration and discrimination of the Framingham Risk Score and Pooled Cohort Equations in Ontario, Canada. METHODS: We conducted an observational study involving Ontario residents aged 40 to 79 years, without a history of atherosclerotic cardiovascular disease, who underwent cholesterol testing and blood pressure measurement from Jan. 1, 2010, to Dec. 31, 2014. We compared predicted event rates generated by the Framingham Risk Score and the Pooled Cohort Equations with observed event rates at 5 years using linkages from validated administrative databases. RESULTS: Our study cohort included 84 617 individuals (mean age 56.3 yr, 56.9% female). Over a maximum follow-up period of 5 years, we observed 2162 (2.6%) events according to the outcome definition of the Framingham Risk Score, and 1224 (1.4%) events according to the outcome definition of the Pooled Cohort Equations. The predicted event rate of 5.78% by the Framingham Risk Score and 3.51% by the Pooled Cohort Equations at 5 years overestimated observed event rates by 101% and 115%, respectively. The degree of overestimation differed by age and ethnicity. The C statistics for the Framingham Risk Score (0.74) and Pooled Cohort Equations (0.73) were similar. INTERPRETATION: The Framingham Risk Score and Pooled Cohort Equations significantly overpredicted the actual risks of atherosclerotic cardiovascular disease events in a large population from Ontario. Our finding suggests the need for further refinement of cardiovascular disease risk prediction scores to suit the characteristics of a multiethnic Canadian population.

Healthcare costs and resource utilization associated with treatment of out-of-hospital cardiac arrest.

BACKGROUND: The management of out-of-hospital cardiac arrest (OHCA) patients requires the coordination of prehospital, in-hospital and post-discharge teams. Data reporting a comprehensive analysis of all costs associated with treating OHCA are scarce. We aimed to describe the total costs (and their components) related to the management of OHCA patients. PATIENT AND METHODS: We performed an analysis on a merged database of the Toronto Regional RescuNet Epistry database (prehospital data) and administrative population-based databases in Ontario. All non-traumatic OHCA patients over 18 years of age treated by the EMS between January 1, 2006, and March 31, 2014, were included in this study. The primary outcome was per patient longitudinal cumulative healthcare costs, from time of collapse to a maximum follow-up until death or 30 days after the event. We included all available cost sectors, from the perspective of the health system payer. We used multivariable generalized linear models with a logarithmic link and a gamma distribution to determine predictors of healthcare costs. RESULTS: 25,826/44,637 patients were treated by EMS services for an OHCA (mostly male 64.4%, mean age 70.1). 11,727 (45%) were pronounced dead on scene, 8359 (32%) died in the emergency department, 3640 (14%) were admitted to hospital but died before day-30, and 2100 (8.1%) were still alive at day-30. Total cost was $690 [interquartile range (IQR) $308, $1742] per patient; ranging from $290 [IQR $188, $390] for patients who were pronounced on scene to $39,216 [IQR 21,802, 62,093] for patients who were still alive at day-30. In-hospital costs accounted for 93% of total costs. After adjustment for age and gender, rate of patient survival was the main driver of total costs: the rate ratio was 3.88 (95% confidence interval 3.80, 3.95), 49.46 and 148.89 for patients who died in the ED, patients who died after the ED but within 30 days, and patients who were still alive at day-30 compared to patients who were pronounced dead on scene, respectively. Factors independently associated with costs were the number of prehospital teams (rate ratio (RR) 5.50 [5.32, 5.67] for being treated by 4 teams vs. 1), the need for hospital transfer (RR 2.38 [2.01, 2.82]), coronary angiography (RR 1.43 [1.27, 1.62]) and targeted temperature management (RR 1.25 [1.09, 1.44]). CONCLUSION: Survival is the main driver of total costs of treating OHCA patients in a large Canadian health system. Inpatient costs accounted for the majority of the total costs; potentially modifiable factors include the number of prehospital teams that arrive to the scene of the arrest and the need for between-hospital transfers after successful resuscitation.

Clinical Outcomes With Beta-Blocker Use in Patients With Recent History of Myocardial Infarction.

BACKGROUND: It is uncertain whether beta-blockers (BBs) are beneficial in contemporary stable patients with prior myocardial infarction (MI). Therefore, we sought to examine the effectiveness of BB use in this population. METHODS: We conducted a cohort study with the use of administrative databases of patients ≥ 65 years of age, alive on April 1, 2012 (index date) with a hospital discharge diagnosis of MI within the previous 3 years. The primary outcome was time to death or hospitalization for MI or angina 1 year after the index date, with inverse probability of treatment weighting. RESULTS: We included 33,811 patients with prior MI, of whom 21,440 (63.4%) were dispensed a BB. The median age was 78 years, and 56% were male. There was no difference in the 1-year hazard of death/hospitalization for MI or angina (14.8% vs 14.7%, hazard ratio 1.00, 95% confidence interval 0.94-1.07; P = 0.90) in those receiving vs not receiving BB. Similarly, there was no difference in the individual end points in composite nor in 3-year outcomes. Subgroup analysis by age, sex, MI timing, MI type, heart failure, and atrial fibrillation found no benefit. Patients with a history of revascularisation treated with BBs had a lower rate of the composite outcome compared with those without such history (P = 0.006 for interaction) at 1 year but not at 3 years. CONCLUSIONS: In this large contemporary population-based observational study of older stable patients with prior MI, BBs were not associated with a reduction in major cardiovascular events or mortality in those with MI within the previous 3 years. This study supports the need to conduct contemporary clinical trials evaluating the use of BBs after MI.

Field Implementation of Remote Ischemic Conditioning in ST-Segment-Elevation Myocardial Infarction: The FIRST Study.

BACKGROUND: Remote ischemic conditioning (RIC) is a noninvasive therapeutic strategy that uses brief cycles of blood pressure cuff inflation and deflation to protect the myocardium against ischemia-reperfusion injury. We sought to compare major adverse cardiovascular events (MACE) for patients who received RIC before PCI for ST-segment-elevation myocardial infarction (STEMI) compared with standard care. METHODS: We conducted a pre- and postimplementation study. In the preimplementation phase, STEMI patients were taken directly to the PCI lab. After implementation, STEMI patients received 4 cycles of RIC by paramedics or emergency department staff before PCI. The primary outcome was MACE at 90 days. Secondary outcomes included MACE at 30, 60, and 180 days. Inverse probability of treatment weighting using propensity scores estimated causal effects independent from baseline covariables. RESULTS: A total of 1667 (866 preimplementation, 801 postimplementation) patients were included. In the preimplementation phase, 13.4% had MACE at 90 days compared with 11.8% in the postimplementation phase (odds ratio [OR] 0.86, 95% CI 0.62-1.21). There were no significant differences in MACE at 30, 60, and 180 days. Patients presenting with cardiogenic shock or cardiac arrest before PCI were less likely to have MACE at 90 days (42.7% pre vs 27.8% post) if they received RIC before PCI (OR 0.52, 95% CI 0.27-0.98). CONCLUSIONS: A strategy of RIC before PCI for STEMI did not reduce 90-day MACE. Future research should explore the impact of RIC before PCI for longer-term clinical outcomes and for patients presenting with cardiogenic shock or cardiac arrest.

Evaluation of Machine Learning Algorithms for Predicting Readmission After Acute Myocardial Infarction Using Routinely Collected Clinical Data.

BACKGROUND: The ability to predict readmission accurately after hospitalization for acute myocardial infarction (AMI) is limited in current statistical models. Machine-learning (ML) methods have shown improved predictive ability in various clinical contexts, but their utility in predicting readmission after hospitalization for AMI is unknown. METHODS: Using detailed clinical information collected from patients hospitalized with AMI, we evaluated 6 ML algorithms (logistic regression, naïve Bayes, support vector machines, random forest, gradient boosting, and deep neural networks) to predict readmission within 30 days and 1 year of discharge. A nested cross-validation approach was used to develop and test models. We used C-statistics to compare discriminatory capacity, whereas the Brier score was used to indicate overall model performance. Model calibration was assessed using calibration plots. RESULTS: The 30-day readmission rate was 16.3%, whereas the 1-year readmission rate was 45.1%. For 30-day readmission, the discriminative ability for the ML models was modest (C-statistic 0.641; 95% confidence interval (CI), 0.621-0.662 for gradient boosting) and did not outperform previously reported methods. For 1-year readmission, different ML models showed moderate performance, with C-statistics around 0.72. Despite modest discriminatory capabilities, the observed readmission rates were markedly higher in the tenth decile of predicted risk compared with the first decile of predicted risk for both 30-day and 1-year readmission. CONCLUSIONS: Despite including detailed clinical information and evaluating various ML methods, these models did not have better discriminatory ability to predict readmission outcomes compared with previously reported methods.

Readmission and Mortality After Hospitalization for Myocardial Infarction and Heart Failure.

BACKGROUND: Readmission rates after acute myocardial infarction (AMI) and heart failure (HF) hospitalizations have decreased in the United States since the implementation of the Hospital Readmissions Reduction Program. OBJECTIVES: This study was designed to examine the temporal trends of readmission and mortality after AMI and HF in Ontario, Canada, where reducing hospital readmissions has not had a policy incentive. METHODS: The cohort was comprised of AMI or HF patients 65 years of age or older who had been hospitalized from 2006 to 2017. Primary outcomes were 30-day readmission and post-discharge mortality. Secondary outcomes included in-hospital mortality, 30-day mortality from admission, and in-hospital mortality or 30-day mortality post-discharge. Adjusted monthly trends for each outcome were examined over the study period. RESULTS: Our cohorts included 152,808 AMI and 223,283 HF patients. Age- and sex-standardized AMI hospitalization rates in Ontario declined 32% from 2006 to 2017 while HF hospitalization rates declined slightly (9.1%). For AMI, risk-adjusted 30-day readmission rates declined from 17.4% in 2006 to 14.7% in 2017. All AMI risk-adjusted mortality rates also declined from 2006 to 2017 with 30-day post-discharge mortality from 5.1% to 4.4%. For HF, overall risk-adjusted 30-day readmission was largely unchanged from 2006 to 2014 at 21.9%, followed by a decline to 20.8% in 2017. Risk-adjusted 30-day post-discharge mortality declined from 7.1% in 2006 to 6.6% in 2017. CONCLUSIONS: The patterns of outcomes in Ontario are consistent with the United States for AMI, but diverge for HF. For AMI and HF, admissions, readmissions, and mortality rates declined over this period. The reasons for the country-specific patterns for HF need further exploration.