Derivation and validation of predictive indices for 30-day mortality after coronary and valvular surgery in Ontario, Canada.

BACKGROUND: Coronary artery bypass grafting (CABG) and surgical aortic valve replacement (AVR) are the 2 most common cardiac surgery procedures in North America. We derived and externally validated clinical models to estimate the likelihood of death within 30 days of CABG, AVR or combined CABG + AVR. METHODS: We obtained data from the CorHealth Ontario Cardiac Registry and several linked population health administrative databases from Ontario, Canada. We derived multiple logistic regression models from all adult patients who underwent CABG, AVR or combined CABG + AVR from April 2017 to March 2019, and validated them in 2 temporally distinct cohorts (April 2015 to March 2017 and April 2019 to March 2020). RESULTS: The derivation cohorts included 13 435 patients who underwent CABG (30-d mortality 1.73%), 1970 patients who underwent AVR (30-d mortality 1.68%) and 1510 patients who underwent combined CABG + AVR (30-d mortality 3.05%). The final models for predicting 30-day mortality included 15 variables for patients undergoing CABG, 5 variables for patients undergoing AVR and 5 variables for patients undergoing combined CABG + AVR. Model discrimination was excellent for the CABG (c-statistic 0.888, optimism-corrected 0.866) AVR (c-statistic 0.850, optimism-corrected 0.762) and CABG + AVR (c-statistic 0.844, optimism-corrected 0.776) models, with similar results in the validation cohorts. INTERPRETATION: Our models, leveraging readily available, multidimensional data sources, computed accurate risk-adjusted 30-day mortality rates for CABG, AVR and combined CABG + AVR, with discrimination comparable to more complex American and European models. The ability to accurately predict perioperative mortality rates for these procedures will be valuable for quality improvement initiatives across institutions.

Early Observations During the COVID-19 Pandemic in Cardiac Catheterization Procedures for ST-Elevation Myocardial Infarction Across Ontario.

BACKGROUND: In response to the COVID-19 pandemic, Ontario issued a declaration of emergency, implementing public health interventions on March 16, 2020. METHODS: We compared cardiac catheterization procedures for ST-elevation myocardial infarction (STEMI) between January 1 and May 10, 2020 to the same time frame in 2019. RESULTS: From March 16 to May 10, 2020, after implementation of provincial directives, STEMI cases significantly decreased by up to 25%. The proportion of patients who achieved guideline targets for first medical contact balloon for primary percutaneous coronary intervention (PCI) decreased substantially to 28% (median, 101 minutes) for patients who presented directly to a PCI site and to 37% (median, 149 minutes) for patients transferred from a non-PCI site, compared with 2019. CONCLUSIONS: STEMI cases across Ontario have been substantially affected during the COVID-19 pandemic.

INTRODUCTION: En réponse à la pandémie de COVID-19, l'Ontario a déclaré l'état d'urgence et mis en place des interventions de santé publique le 16 mars 2020. MÉTHODES: Nous avons comparé les procédures de cathétérisme cardiaque lors d'infarctus du myocarde avec sus-décalage du segment ST (STEMI) du 1er janvier au 10 mai 2020 à la même période en 2019. RÉSULTATS: Du 16 mars au 10 mai 2020, après la mise en place des directives provinciales, les cas de STEMI ont connu une diminution significative pouvant atteindre jusqu'à 25 %. La proportion de patients qui ont atteint les objectifs prévus aux lignes directrices entre le premier contact médical et le ballonnet de l'intervention coronarienne percutanée (IPC) a connu une diminution considérable de 28 % (médiane, 101 minutes) pour ceux qui se présentaient directement dans un site d'IPC et de 37 % (médiane, 149 minutes) pour ceux qui étaient dirigés vers un site non-ICP, et ce, en comparaison à 2019. CONCLUSIONS: La pandémie de COVID-19 a considérablement nui aux cas de STEMI de l'Ontario.

Inequity in Access to Transcatheter Aortic Valve Replacement: A Pan-Canadian Evaluation of Wait-Times.

BACKGROUND: There has been an exponential increase in the demand for transcatheter aortic valve replacement (TAVR). Our goal was to examine trends in TAVR capacity and wait-times across Canada. METHODS: All TAVR cases were identified from April 1, 2014, to March 31, 2017. Wait-time was defined as the duration in days from the initial referral to the TAVR procedure. TAVR capacity was defined as the number of TAVR procedures per million population/province/fiscal year. We performed multivariable multilevel Cox proportional hazards modelling of the time to TAVR as the dependant variable and the effect of provinces as random effects. We quantified the variation in wait-times among provinces using the median hazard ratio. RESULTS: We identified a total of 4906 TAVR procedures across 9 provinces. Despite a year over year increase in overall capacity, there was a greater than 3-fold difference in capacity between provinces. Crude median wait-times increased over time in all provinces, with marked variation from 71.5 days in Newfoundland to 190.5 and 203 days in Manitoba and Alberta, respectively. This suggests increasing demand outpaced the growth in capacity. We found a median hazard ratio of 1.62, indicating that in half of the possible pairwise comparisons, the time to TAVR for identical patients was at least 62% longer between different provinces. CONCLUSION: We found substantial geographic inequity in TAVR access. This calls for policy makers, clinicians, and administrators across Canada to address this inequity through revaluation of provincial funding mechanisms, as well as implementation of efficient care pathways.

The Use of Decision Modelling to Inform Timely Policy Decisions on Cardiac Resource Capacity During the COVID-19 Pandemic.

In Ontario on March 16, 2020, a directive was issued to all acute care hospitals to halt nonessential procedures in anticipation of a potential surge in COVID-19 patients. This included scheduled outpatient cardiac surgical and interventional procedures that required the use of intensive care units, ventilators, and skilled critical care personnel, given that these procedures would draw from the same pool of resources required for critically ill COVID-19 patients. We adapted the COVID-19 Resource Estimator (CORE) decision analytic model by adding a cardiac component to determine the impact of various policy decisions on the incremental waitlist growth and estimated waitlist mortality for 3 key groups of cardiovascular disease patients: coronary artery disease, valvular heart disease, and arrhythmias. We provided predictions based on COVID-19 epidemiology available in real-time, in 3 phases. First, in the initial crisis phase, in a worst case scenario, we showed that the potential number of waitlist related cardiac deaths would be orders of magnitude less than those who would die of COVID-19 if critical cardiac care resources were diverted to the care of COVID-19 patients. Second, with better local epidemiology data, we predicted that across 5 regions of Ontario, there may be insufficient resources to resume all elective outpatient cardiac procedures. Finally in the recovery phase, we showed that the estimated incremental growth in waitlist for all cardiac procedures is likely substantial. These outputs informed timely data-driven decisions during the COVID-19 pandemic regarding the provision of cardiovascular care.

An Update on the Development and Feasibility Assessment of Canadian Quality Indicators for Atrial Fibrillation and Atrial Flutter.

BACKGROUND: In 2010, the Canadian Cardiovascular Society Atrial Fibrillation/Atrial Flutter (AF/AFL) quality indicator (QI) working group was established to develop QIs and assess feasibility of measurement. After extensive review, 3 priority QIs were selected. However, none were measurable at a national level. METHODS: The working group reconvened in 2017 to review the relevance of previously proposed QIs, identify opportunities to develop new QIs, and propose an initial strategy for measuring and reporting. RESULTS: Two additional priority QIs were added to the previous 3: proportion of patients with nonvalvular (NV) AF/AFL sorted by stroke risk stratum and annual rate of hospitalization for a new heart failure diagnosis. An environmental scan was undertaken to determine the potential of existing databases to provide national and provincial estimates. On the basis of validated administrative codes, the Canadian Institute for Health Information discharge abstract database can be used for inpatients. In collaboration with the Canadian Primary Care Sentinel Surveillance Network, 2 of the 5 QIs can be assessed in outpatients (patients with NVAF/AFL sorted by stroke risk stratum and high risk for stroke NVAF/AFL receiving oral anticoagulation). Stroke prevention therapy can be further measured in selected provinces with linked databases including prescriptions. CONCLUSIONS: This first step could provide a better initial understanding of the quality of AF/AFL care in Canada, but important gaps in the meaningful measurement of QIs remain. The AF/AFL QI working group has limited capacity to make progress without national level leadership and the resources to support data aggregation, data analysis, and pan-Canadian reporting.

CONTEXTE: En 2010, le groupe de travail des indicateurs de qualité (IQ) de la Société canadienne de cardiologie sur la fibrillation auriculaire (FA) et le flutter auriculaire (FLA) a été mis sur pied pour élaborer des IQ et évaluer la faisabilité d'utiliser ces IQ comme outils de mesure. Après un examen approfondi, trois IQ prioritaires ont été sélectionnés, mais aucun n'a pu être mesuré à l'échelle nationale. MÉTHODOLOGIE: Le groupe de travail s'est réuni à nouveau en 2017 afin d'examiner la pertinence des IQ proposés au départ, de recenser des occasions d'élaborer de nouveau IQ et de proposer une stratégie initiale de mesure et de production de rapports à cet égard. RÉSULTATS: Deux IQ prioritaires supplémentaires ont été ajoutés aux trois premiers : la proportion de patients atteints de FA non valvulaire (FANV) ou de FLA ayant fait l'objet d'un tri selon la strate de risque d'AVC et le taux annuel d'hospitalisations attribuables à un nouveau diagnostic d'insuffisance cardiaque. Une analyse de l'environnement a été réalisée afin de déterminer si les bases de données existantes pouvaient fournir des estimations nationales et provinciales. Dans le cas de patients hospitalisés, on peut utiliser la Base de données sur les congés des patients de l'Institut canadien d'information sur la santé en se servant de codes administratifs validés. Dans le cas de patients non hospitalisés (patients atteints de FANV/FLA, triés par strate de risque, exposés à un risque élevé d'AVC en raison d'une FANV ou d'un FLA et recevant une anticoagulation orale), on peut mesurer deux des cinq IQ, en collaboration avec le Réseau canadien de surveillance sentinelle en soins primaires. Le traitement préventif de l'AVC peut continuer à faire l'objet de mesures dans certaines provinces grâce aux bases de données interreliées, comme les bases de données sur les ordonnances. CONCLUSIONS: Cette première étape a permis d'obtenir une meilleure compréhension initiale de la qualité de la prise en charge de la FA et du FLA au Canada, mais d'importantes lacunes restent à combler pour rendre pertinente la mesure des IQ. Le groupe de travail des IQ sur de la FA et le FLA n'a pas toutes les capacités requises pour réaliser des progrès en l'absence de leadership national et de ressources permettant de soutenir le regroupement et l'analyse des données, ainsi que la production de rapports à l'échelle pancanadienne.

The Transcatheter Aortic Valve Implantation (TAVI) Quality Report: A Call to Arms for Improving Quality in Canada.

Transcatheter aortic valve implantation (TAVI) is a disruptive technology that has dramatically changed the way clinicians care for patients with aortic stenosis. In 15 short years, this technology has progressed from first-in-human to the standard of care for high-risk and inoperable patients with aortic stenosis. In 2016 the Canadian Cardiovascular Society published the first ever report of quality of care for TAVI in Canada. This report provided multiple insights into evaluating such care delivered to Canadians and the challenges that lie ahead. In this article, we summarize these challenges and encourage cardiologists to join the call to arms for improving quality of TAVI care in Canada.

Interventions Supporting Long-term Adherence aNd Decreasing cardiovascular events (ISLAND): Pragmatic randomized trial protocol.

BACKGROUND: Guidelines recommend cardiac rehabilitation and long-term use of cardiac medications for most patients who have had a myocardial infarction (MI), but adherence to these secondary prevention treatments is suboptimal. METHODS: This is a multicenter, pragmatic, 3-arm randomized trial. Eligible patients (n = 2,742) with obstructive coronary artery disease are randomized post-MI to usual care or 1 of 2 intervention arms. Patients in the first intervention arm receive mail-outs sent on behalf of their cardiologist at 4, 8, 20, 32, and 44 weeks post-MI; content is designed to address determinants of adherence and facilitate discussion between the patient and their health care team. Patients in the second intervention arm receive mail-outs plus automated interactive voice response system telephone calls 2 weeks after each letter, as well as a telephone call by trained lay health workers if the interactive voice response system identifies challenges with adherence. Outcomes are assessed 12 months post-MI via patient self-report and administrative data sources. Co-primary outcomes are adherence to cardiac medications and completion of cardiac rehabilitation. Secondary outcomes include cardiovascular events and mortality. An embedded, theory-informed process evaluation will explore the mechanism of action; an economic evaluation is also planned. CONCLUSIONS: We describe a complete program evaluation of a highly pragmatic, health-system intervention to support adherence to recommended treatments. Research ethics boards approved waiver of consent for patients enrolled in the trial with provision of multiple opportunities to opt out and a debrief at the time of outcome assessment. The methods used here may provide a model for similar interventions.

Quality of Care for Percutaneous Coronary Intervention: Development of Canadian Cardiovascular Society Quality Indicators.

Currently there are more than 40 centres in Canada that perform more than 65,000 percutaneous coronary interventions (PCIs) in a year. Considering the high volume of procedures and number of operators, the potential for variation in processes of care is high, and might lead to variation in the quality of care. As part of its quality initiative, the Canadian Cardiovascular Society convened a working group to develop a set of PCI Quality Indicators (QIs) that would be relevant, scientifically acceptable, and feasible to measure and report. The working group was comprised of clinical experts from across Canada and members of provincial and federal organizations involved in promoting the quality of health care. Using the Canadian Cardiovascular Society "Best Practices for Developing Cardiovascular Quality Indicators" methodology, a total of 23 QIs were proposed. Subsequent ranking and discussion led to the selection of 8 QIs. The selection and ranking of QIs were on the basis of clinical importance and relevance, scientific acceptability, and feasibility of their operationalization at a national level. The data definitions and technical notes of the QIs were refined after feasibility testing and Web consultation. Feasibility testing indicated that standardization and enhancements of knowledge infrastructure are essential to provide the comprehensive patient data necessary to evaluate the quality of PCI across Canada.

The Development and Feasibility Assessment of Canadian Quality Indicators for Atrial Fibrillation.

In 2010, the Canadian Cardiovascular Society embarked on an initiative to develop pan-Canadian quality indicators (QIs) and standardized data definitions with the ultimate goal of monitoring, comparing, and contrasting national cardiovascular care and its outcomes. One of the first working groups to be established was tasked with identifying and then defining a set of QIs for atrial fibrillation/flutter (AF/AFL). The Canadian Cardiovascular Society "Best Practices for Developing Cardiovascular Quality Indicators" methodology was used to develop an initial catalogue of 25 QIs intended to measure critical issues around access, process, and outcomes relating to AF/AFL management. This list was subsequently pared down to 5 QIs felt to have the greatest relative importance for quality assurance and measurability so as to facilitate early adoption. Three of these QIs were finally selected to assess the feasibility of their measurement using existing administrative datasets. These were the number of patients with a diagnosis of nonvalvular AF/AFL at high risk of stroke (75 years or older, or CHADS2 ≥ 2) receiving an oral anticoagulant, and the rates of stroke and major haemorrhage in patients with nonvalvular AF/AFL according to CHA2DS2-VASc score and anticoagulant use. Despite their clear importance in assessing AF/AFL care, none of these 3 QIs were found to be readily measurable across Canada using existing national datasets. Investment in new medical data infrastructure is required to facilitate regular monitoring of QIs to improve cardiovascular care.

Quality of Care for Transcatheter Aortic Valve Implantation: Development of Canadian Cardiovascular Society Quality Indicators.

Transcatheter aortic valve implantation (TAVI) is a relatively new procedure to treat aortic stenosis in patients at high surgical risk, and it is becoming increasingly available in Canada. Variation exists in the clinical care, program coordination, evaluation, and funding across provinces and centres. As a part of the Canadian Cardiovascular Society (CCS) quality initiative, the TAVI Quality Indicator (QI) Working Group was established in 2014 to develop a set of indicators to measure quality of care for Canadians undergoing TAVI for aortic stenosis. The TAVI QI Working Group is composed of expert clinical and government agency representatives. The group developed consensus agreements for the selection of the first iteration of measurable structure, process, and outcome indicators reflective of the quality of care for patients undergoing TAVI. The objectives of the project are to develop quality indicators with the eventual goal of standardizing TAVI quality reports across Canada and to support local and national quality assurance, as well as engage multiple stakeholders to build a national strategy for the evaluation of quality of care.

Pan-Canadian development of cardiac rehabilitation and secondary prevention quality indicators.

The Canadian Cardiovascular Society (CCS) is implementing the Canadian Heart Health Strategy and Action Plan recommendation to build knowledge infrastructure, through its Data Definitions and Quality Indicator (QI) project. The CCS selected cardiac rehabilitation (CR) and secondary prevention as a content area for QI development. In accordance with the CCS QI Best Practice Methodology, rapid reviews of the literature were conducted. A long list of 37 QIs, in the areas of structure, process, and outcome were developed. Through an online survey, 26 (42%) of all contacted external experts rated each QI on importance, scientific acceptability, and feasibility, using a 7-point scale. The overall mean rating was 5.4 ± 1.4. Through a consensus process, the working group excluded 8 QIs based on this feedback, and several others were revised. A 30-day Web consultation was then undertaken, to solicit input from the broader CCS and CR community. A "top 5" list of QIs was requested by the CCS, which were: (1) inpatients referred to CR; (2) wait times from referral to CR enrollment; (3) patient self-management education; (4) increase in exercise capacity; and (5) emergency response strategy. Knowledge translation activities are now under way to promote utilization of the QIs and ultimately improve CR care.

Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway.

Elevated concentrations of unconjugated bilirubin (UCB) are responsible for neonatal jaundice and can eventually lead to kernicterus or death. The molecular mechanism of UCB toxicity is incompletely elucidated. The purpose of this study was to analyze changes in gene regulation mediated by UCB to determine novel pathways that contribute to UCB-mediated toxicity. We employed microarray analysis to determine changes in gene regulation mediated by UCB at both pro- (50 microM) and antioxidant (70 nM) concentrations in Hepa 1c1c7 cells at 1 and 6 h. The changes observed in select genes were validated with qPCR. Using immunoblot analysis, we validated these changes at the protein level for select genes and documented the activation of two proteins involved in the endoplasmic reticulum (ER) stress pathway, eIF2 alpha and PERK. Following treatment with 50 microM UCB, microarray analysis revealed the upregulation of many genes involved in ER stress (ATF3, BiP, CHOP, Dnajb1, and Herp). We demonstrate that upregulation of the proapoptotic transcription factor CHOP results in increased intracellular protein content. It was determined that activation of proteins involved in ER stress was an early event in UCB toxicity as eIF2 alpha and PERK were both phosphorylated and activated by 1 h posttreatment. We also demonstrate that procaspase-12 content, a proposed initiator caspase in ER stress-mediated apoptosis, is decreased by 4 h posttreatment. In conclusion, this study demonstrates that elevated concentrations of UCB (50 microM) are able to activate select components of the ER stress pathway in Hepa 1c1c7 cells, which may contribute to UCB-mediated apoptosis.

Early steps in bilirubin-mediated apoptosis in murine hepatoma (Hepa 1c1c7) cells are characterized by aryl hydrocarbon receptor-independent oxidative stress and activation of the mitochondrial pathway.

Unconjugated bilirubin (UCB), the end product of heme catabolism, causes apoptosis in cells of the central nervous system, endothelial cells, and hepatotoma cells. However, the molecular mechanisms that contribute to UCB cytotoxicity remain unclear. The purpose of this study was to characterize the sequence of early events leading to UCB-mediated cytotoxicity in murine hepatoma Hepa 1c1c7 cells. In the present study, UCB (5-50 microM) was found to markedly increase the intracellular generation of reactive oxygen species (ROS) in a concentration-dependent manner, which is significantly elevated by 30 min post-treatment. This generation of ROS by UCB is not dependent on aryl hydrocarbon receptor (Ahr) signaling, as cells deficient in the Ahr (C12 cells) or the Ahr nuclear translocator protein (Arnt; C4 cells) were as efficient at generating ROS as wild type (WT) Hepa 1c1c7 cells. Mitochondrial membrane depolarization, evaluated with the lipophilic cationic dye, JC-1, occurred at least by 2 h after treatment with 50 muM UCB. Analysis of the caspase cascade demonstrated that activation of caspase-9 preceded activation of caspase-3. No conversion of procaspase-2 to active caspase-2 was detected in this study. These results demonstrate that UCB-mediated apoptosis in Hepa 1c1c7 cells is associated with increased oxidative stress and that caspase-9, and definitely not caspase-2, is the initiator caspase for apoptosis in UCB-treated Hepa 1c1c7 cells.