Adoption of high-sensitivity cardiac troponin for risk stratification of patients with suspected myocardial infarction: a multicentre cohort study.

Background: Guidelines recommend high-sensitivity cardiac troponin to risk stratify patients with possible myocardial infarction and identify those eligible for discharge. Our aim was to evaluate adoption of this approach in practice and to determine whether effectiveness and safety varies by age, sex, ethnicity, or socioeconomic deprivation status. Methods: A multi-centre cohort study was conducted in 13 hospitals across the United Kingdom from November 1st, 2021, to October 31st, 2022. Routinely collected data including high-sensitivity cardiac troponin I or T measurements were linked to outcomes. The primary effectiveness and safety outcomes were the proportion discharged from the Emergency Department, and the proportion dead or with a subsequent myocardial infarction at 30 days, respectively. Patients were stratified using peak troponin concentration as low (<5 ng/L), intermediate (5 ng/L to sex-specific 99th percentile), or high-risk (>sex-specific 99th percentile). Findings: In total 137,881 patients (49% [67,709/137,881] female) were included of whom 60,707 (44%), 42,727 (31%), and 34,447 (25%) were stratified as low-, intermediate- and high-risk, respectively. Overall, 65.8% (39,918/60,707) of low-risk patients were discharged from the Emergency Department, but this varied from 26.8% [2200/8216] to 93.5% [918/982] by site. The safety outcome occurred in 0.5% (277/60,707) and 11.4% (3917/34,447) of patients classified as low- or high-risk, of whom 0.03% (18/60,707) and 1% (304/34,447) had a subsequent myocardial infarction at 30 days, respectively. A similar proportion of male and female patients were discharged (52% [36,838/70,759] versus 54% [36,113/67,109]), but discharge was more likely if patients were <70 years old (61% [58,533/95,227] versus 34% [14,428/42,654]), from areas of low socioeconomic deprivation (48% [6697/14,087] versus 43% [12,090/28,116]) or were black or asian compared to caucasian (62% [5458/8877] and 55% [10,026/18,231] versus 46% [35,138/75,820]). Interpretation: Despite high-sensitivity cardiac troponin correctly identifying half of all patients with possible myocardial infarction as being at low risk, only two-thirds of these patients were discharged. Substantial variation in the discharge of patients by age, ethnicity, socioeconomic deprivation, and site was observed identifying important opportunities to improve care. Funding: UK Research and Innovation.

Rapid Acute Coronary Syndrome Evaluation Over One Hour With High-Sensitivity Cardiac Troponin I: A United States-Based Stepped-Wedge, Randomized Trial.

STUDY OBJECTIVE: The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI) compared to routine care in the United States is uncertain. The objective was to compare a 0/1-hour accelerated protocol for evaluation of MI to a 0/3-hour standard care protocol. METHODS: The RACE-IT trial was a stepped-wedge, randomized trial across 9 emergency departments (EDs) that enrolled 32,609 patients evaluated for possible MI from July 2020 through April 2021. Patients undergoing high-sensitivity cardiac troponin I testing with concentrations less than or equal to 99th percentile were included. Patients who had MI excluded by the 0/1-hour protocol could be discharged from the ED. Patients in the standard care protocol had 0- and 3-hour troponin testing and application of a modified HEART score to be eligible for discharge. The primary endpoint was the proportion of patients discharged from the ED without 30-day death or MI. RESULTS: There were 13,505 and 19,104 patients evaluated in the standard care and accelerated protocol groups, respectively, of whom 19,152 (58.7%) were discharged directly from the ED. There was no significant difference in safe discharges between standard care and the accelerated protocol (59.5% vs 57.8%; adjusted odds ratio (aOR)=1.05, 95% confidence interval [CI] 0.95 to 1.16). At 30 days, there were 90 deaths or MIs with 38 (0.4%) in the standard care group and 52 (0.4%) in the accelerated protocol group (aOR=0.84, 95% CI 0.43 to 1.68). CONCLUSION: A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care.

Protocol for Improving Care by FAster risk-STratification through use of high sensitivity point-of-care troponin in patients presenting with possible acute coronary syndrome in the EmeRgency department (ICare-FASTER): a stepped-wedge cluster randomised quality improvement initiative.

INTRODUCTION: Clinical assessment in emergency departments (EDs) for possible acute myocardial infarction (AMI) requires at least one cardiac troponin (cTn) blood test. The turn-around time from blood draw to posting results in the clinical portal for central laboratory analysers is ~1-2 hours. New generation, high-sensitivity, point-of-care cardiac troponin I (POC-cTnI) assays use whole blood on a bedside (or near bedside) analyser that provides a rapid (8 min) result. This may expedite clinical decision-making and reduce length of stay. Our purpose is to determine if utilisation of a POC-cTnI testing reduces ED length of stay. We also aim to establish an optimised implementation process for the amended clinical pathway. METHODS AND ANALYSIS: This quality improvement initiative has a pragmatic multihospital stepped-wedge cross-sectional cluster randomised design. Consecutive patients presenting to the ED with symptoms suggestive of possible AMI and having a cTn test will be included. Clusters (comprising one or two hospitals each) will change from their usual-care pathway to an amended pathway using POC-cTnI-the 'intervention'. The dates of change will be randomised. Changes occur at 1 month intervals, with a minimum 2 month 'run-in' period. The intervention pathway will use a POC-cTnI measurement as an alternate to the laboratory-based cTn measurement. Clinical decision-making steps and logic will otherwise remain unchanged. The POC-cTnI is the Siemens (Erlangen Germany) Atellica VTLi high-sensitivity cTnI assay. The primary outcome is ED length of stay. The safety outcome is cardiac death or AMI within 30 days for patients discharged directly from the ED. ETHICS AND DISSEMINATION: Ethics approval has been granted by the New Zealand Southern Health and Disability Ethics Committee, reference 21/STH/9. Results will be published in a peer-reviewed journal. Lay and academic presentations will be made. Maori-specific results will be disseminated to Maori stakeholders. TRIAL REGISTRATION NUMBER: ACTRN12619001189112.

Cardiovascular and Noncardiovascular Prescribing and Mortality After Takotsubo Comparison With Myocardial Infarction and General Population.

Background: Takotsubo syndrome is an increasingly common cardiac emergency with no known evidence-based treatment. Objectives: The purpose of this study was to investigate cardiovascular mortality and medication use after takotsubo syndrome. Methods: In a case-control study, all patients with takotsubo syndrome in Scotland between 2010 and 2017 (n = 620) were age, sex, and geographically matched to individuals in the general population (1:4, n = 2,480) and contemporaneous patients with acute myocardial infarction (1:1, n = 620). Electronic health record data linkage of mortality outcomes and drug prescribing were analyzed using Cox proportional hazard regression models. Results: Of the 3,720 study participants (mean age, 66 years; 91% women), 153 (25%) patients with takotsubo syndrome died over the median of 5.5 years follow-up. This exceeded mortality rates in the general population (N = 374 [15%]; HR: 1.78 [95% CI: 1.48-2.15], P < 0.0001), especially for cardiovascular (HR: 2.47 [95% CI: 1.81-3.39], P < 0.001) but also noncardiovascular (HR: 1.48 [95% CI: 1.16-1.87], P = 0.002) deaths. Mortality rates were lower for patients with takotsubo syndrome than those with myocardial infarction (31%, 195/620; HR: 0.76 [95% CI: 0.62-0.94], P = 0.012), which was attributable to lower rates of cardiovascular (HR: 0.61 [95% CI: 0.44-0.84], P = 0.002) but not non-cardiovascular (HR: 0.92 [95% CI: 0.69-1.23], P = 0.59) deaths. Despite comparable medications use, cardiovascular therapies were consistently associated with better survival in patients with myocardial infarction but not in those with takotsubo syndrome. Diuretic (P = 0.01), anti-inflammatory (P = 0.002), and psychotropic (P < 0.001) therapies were all associated with worse outcomes in patients with takotsubo syndrome. Conclusions: In patients with takotsubo syndrome, cardiovascular mortality is the leading cause of death, and this is not associated with cardiovascular therapy use.

Safety outcomes following COVID-19 vaccination and infection in 5.1 million children in England.

The risk-benefit profile of COVID-19 vaccination in children remains uncertain. A self-controlled case-series study was conducted using linked data of 5.1 million children in England to compare risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. In 5-11-year-olds, we found no increased risks of adverse events 1-42 days following vaccination with BNT162b2, mRNA-1273 or ChAdOX1. In 12-17-year-olds, we estimated 3 (95%CI 0-5) and 5 (95%CI 3-6) additional cases of myocarditis per million following a first and second dose with BNT162b2, respectively. An additional 12 (95%CI 0-23) hospitalisations with epilepsy and 4 (95%CI 0-6) with demyelinating disease (in females only, mainly optic neuritis) were estimated per million following a second dose with BNT162b2. SARS-CoV-2 infection was associated with increased risks of hospitalisation from seven outcomes including multisystem inflammatory syndrome and myocarditis, but these risks were largely absent in those vaccinated prior to infection. We report a favourable safety profile of COVID-19 vaccination in under-18s.

Coronary Atherosclerotic Plaque Activity and Risk of Myocardial Infarction.

BACKGROUND: Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes. OBJECTIVES: We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction. METHODS: In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction. RESULTS: Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; Pinteraction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions. CONCLUSIONS: In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction.

EPidemiology Of Cardiogenic sHock in Scotland (EPOCHS): A multicentre, prospective observational study of the prevalence, management and outcomes of cardiogenic shock in Scotland.

Background: Despite high rates of cardiovascular disease in Scotland, the prevalence and outcomes of patients with cardiogenic shock are unknown. Methods: We undertook a prospective observational cohort study of consecutive patients with cardiogenic shock admitted to the intensive care unit (ICU) or coronary care unit at 13 hospitals in Scotland for a 6-month period. Denominator data from the Scottish Intensive Care Society Audit Group were used to estimate ICU prevalence; data for coronary care units were unavailable. We undertook multivariable logistic regression to identify factors associated with in-hospital mortality. Results: In total, 247 patients with cardiogenic shock were included. After exclusion of coronary care unit admissions, this comprised 3.0% of all ICU admissions during the study period (95% confidence interval [CI] 2.6%-3.5%). Aetiology was acute myocardial infarction (AMI) in 48%. The commonest vasoactive treatment was noradrenaline (56%) followed by adrenaline (46%) and dobutamine (40%). Mechanical circulatory support was used in 30%. Overall in-hospital mortality was 55%. After multivariable logistic regression, age (odds ratio [OR] 1.04, 95% CI 1.02-1.06), admission lactate (OR 1.10, 95% CI 1.05-1.19), Society for Cardiovascular Angiographic Intervention stage D or E at presentation (OR 2.16, 95% CI 1.10-4.29) and use of adrenaline (OR 2.73, 95% CI 1.40-5.40) were associated with mortality. Conclusions: In Scotland the prevalence of cardiogenic shock was 3% of all ICU admissions; more than half died prior to discharge. There was significant variation in treatment approaches, particularly with respect to vasoactive support strategy.

Long COVID and cardiovascular disease: a prospective cohort study.

BACKGROUND: Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known. OBJECTIVES: To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors. METHODS: In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health. RESULTS: From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86). CONCLUSION: Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need. TRAIL REGISTRATION NUMBER: ISRCTN10980107.

Development of a long noncoding RNA-based machine learning model to predict COVID-19 in-hospital mortality.

Tools for predicting COVID-19 outcomes enable personalized healthcare, potentially easing the disease burden. This collaborative study by 15 institutions across Europe aimed to develop a machine learning model for predicting the risk of in-hospital mortality post-SARS-CoV-2 infection. Blood samples and clinical data from 1286 COVID-19 patients collected from 2020 to 2023 across four cohorts in Europe and Canada were analyzed, with 2906 long non-coding RNAs profiled using targeted sequencing. From a discovery cohort combining three European cohorts and 804 patients, age and the long non-coding RNA LEF1-AS1 were identified as predictive features, yielding an AUC of 0.83 (95% CI 0.82-0.84) and a balanced accuracy of 0.78 (95% CI 0.77-0.79) with a feedforward neural network classifier. Validation in an independent Canadian cohort of 482 patients showed consistent performance. Cox regression analysis indicated that higher levels of LEF1-AS1 correlated with reduced mortality risk (age-adjusted hazard ratio 0.54, 95% CI 0.40-0.74). Quantitative PCR validated LEF1-AS1's adaptability to be measured in hospital settings. Here, we demonstrate a promising predictive model for enhancing COVID-19 patient management.

Application of the Universal Definition of Myocardial Infarction in Clinical Practice in Scotland and Sweden.

Importance: Whether the diagnostic classifications proposed by the universal definition of myocardial infarction (MI) to identify type 1 MI due to atherothrombosis and type 2 MI due to myocardial oxygen supply-demand imbalance have been applied consistently in clinical practice is unknown. Objective: To evaluate the application of the universal definition of MI in consecutive patients with possible MI across 2 health care systems. Design, Setting, and Participants: This cohort study used data from 2 prospective cohorts enrolling consecutive patients with possible MI in Scotland (2013-2016) and Sweden (2011-2014) to assess accuracy of clinical diagnosis of MI recorded in hospital records for patients with an adjudicated diagnosis of type 1 or type 2 MI. Data were analyzed from August 2022 to February 2023. Main Outcomes and Measures: The main outcome was the proportion of patients with a clinical diagnosis of MI recorded in the hospital records who had type 1 or type 2 MI, adjudicated by an independent panel according to the universal definition. Characteristics and risk of subsequent MI or cardiovascular death at 1 year were compared. Results: A total of 50 356 patients were assessed. The cohort from Scotland included 28 783 (15 562 men [54%]; mean [SD] age, 60 [17] years), and the cohort from Sweden included 21 573 (11 110 men [51%]; mean [SD] age, 56 [17] years) patients. In Scotland, a clinical diagnosis of MI was recorded in 2506 of 3187 patients with an adjudicated diagnosis of type 1 MI (79%) and 122 of 716 patients with an adjudicated diagnosis of type 2 MI (17%). Similar findings were observed in Sweden, with 970 of 1111 patients with adjudicated diagnosis of type 1 MI (87%) and 57 of 251 patients with adjudicated diagnosis of type 2 MI (23%) receiving a clinical diagnosis of MI. Patients with an adjudicated diagnosis of type 1 MI without a clinical diagnosis were more likely to be women (eg, 336 women [49%] vs 909 women [36%] in Scotland; P < .001) and older (mean [SD] age, 71 [14] v 67 [14] years in Scotland, P < .001) and, when adjusting for competing risk from noncardiovascular death, were at similar or increased risk of subsequent MI or cardiovascular death compared with patients with a clinical diagnosis of MI (eg, 29% vs 18% in Scotland; P < .001). Conclusions and Relevance: In this cohort study, the universal definition of MI was not consistently applied in clinical practice, with a minority of patients with type 2 MI identified, and type 1 MI underrecognized in women and older persons, suggesting uncertainty remains regarding the diagnostic criteria or value of the classification.

Is rapid acute coronary syndrome evaluation with high-sensitivity cardiac troponin less costly? An economic evaluation.

Objective: Protocols to evaluate for myocardial infarction (MI) using high-sensitivity cardiac troponin (hs-cTn) have the potential to drive costs upward due to the added sensitivity. We performed an economic evaluation of an accelerated protocol (AP) to evaluate for MI using hs-cTn to identify changes in costs of treatment and length of stay compared with conventional testing. Methods: We performed a planned secondary economic analysis of a large, cluster randomized trial across nine emergency departments (EDs) from July 2020 to April 2021. Patients were included if they were 18 years or older with clinical suspicion for MI. In the AP, patients could be discharged without further testing at 0 h if they had a hs-cTnI < 4 ng/L and at 1 h if the initial value were 4 ng/L and the 1-h value ≤7 ng/L. Patients in the standard of care (SC) protocol used conventional cTn testing at 0 and 3 h. The primary outcome was the total cost of treatment, and the secondary outcome was ED length of stay. Results: Among 32,450 included patients, an AP had no significant differences in cost (+$89, CI: -$714, $893 hospital cost, +$362, CI: -$414, $1138 health system cost) or ED length of stay (+46, CI: -28, 120 min) compared with the SC protocol. In lower acuity, free-standing EDs, patients under the AP experienced shorter length of stay (-37 min, CI: -62, 12 min) and reduced health system cost (-$112, CI: -$250, $25). Conclusion: Overall, the implementation of AP using hs-cTn does not result in higher costs.

Implementation of high sensitivity troponin into routine clinical practice - results of the extended CARdiac MArkers guideline uptake in Europe group (CARMAGUE) survey.

BACKGROUND: Measurement of cardiac troponin (cTn) by a high sensitivity method is now the recommended strategy for the detection of myocardial injury. An international survey was undertaken to assess how this has been implemented. METHODS: A questionnaire based around 14 domains on cardiac biomarkers was distributed electronically with the aid of professional societies accessed by a web link within the invitation. Results were returned electronically then extracted into a relational database for analysis. RESULTS: Responses were obtained from 663 laboratories across 76 countries ranging from 1 to 69 largest country. The majority of responses (79.6%) came from the European area. Responses were grouped into broad geographic areas for analysis. Most responses came from hospitals providing a local and regional service of which the majority provided angioplasty. cTn measurement was the dominant biomarker. The majority of laboratories include creatine kinase (CK) in their cardiac profile and approximately 50% also offer the MB isoenzyme of CK. The majority of laboratories (91.9%) measure cTn by a high sensitivity method. Sex specific reference ranges were typically implemented for cardiac troponin I but not for cardiac troponin T. The preferred unit of measurement was nanograms/L. A structured decision-making pathway utilising high sensitivity cTn measurement was used by 83.3% of laboratories who responded. Single sample rule out is common but the majority used serial sampling strategy based on measurement on admission and three hours. CONCLUSIONS: Measurement of cTn by a high sensitivity method is now well established internationally, the use of rapid diagnostic protocols lags behind.

Could paramedics use the HEART Pathway to identify patients at low-risk of myocardial infarction in the prehospital setting?

In the Emergency Department, patients with suspected myocardial infarction can be risk stratified using the HEART pathway, which has recently been amended for prehospital use and modified for the incorporation of a high-sensitivity cardiac troponin test. In a prospective analysis, the performance of both HEART pathways in the prehospital setting, with a high-sensitivity cardiac troponin test using 3 different thresholds, was evaluated for major adverse cardiac events at 30 days. We found that both low-risk HEART pathways, when using the most conservative cardiac troponin thresholds, approached but did not reach accepted rule-out performance in the Emergency Department.

Type 2 Myocardial Infarction-Poorly Understood, Underevaluated, and Too Often Ignored.

This Viewpoint discusses diagnosis of type 2 myocardial infarction.

An exploratory analysis of the structure of tetranychid and phytoseiid assemblages in walnut orchards in California.

Spider mites were considered secondary pests of walnut production in California, under the control of phytoseiid predators. Due to increased importance as walnut pests in recent decades there is renewed interest in the structure and function of the associated phytoseiid assemblage. In this study we report the results from a 3 year survey of the tetranychid and phytoseiid assemblages in walnut orchards in the Central Valley of California. The survey was conducted to determine the range and dominance of web-spinning Tetranychus species present, to investigate the species richness and dominance of the phytoseiid species present, and to explore whether patterns of variation in the relative abundance of phytoseiid species could be explained by one or more explanatory variables. Tetranychus urticae was the dominant spider mite in all growing regions and years with T. pacificus and T. turkestani also present in orchards in the southern San Joaquin Valley. Phytoseiid species richness declined with latitude among the three walnut growing regions and of the 13 species found Amblyseius similoides, Euseius stipulatus, Galendromus occidentalis and Typhlodromus caudiglans were the most abundant and widespread species present. Mean proportional abundance significantly increased from early (mid May-July) to late (August-mid October) season and from southern to northern growing regions for Type II and IV predators, but significantly decreased from early to late season and from southern to northern growing regions for Type III predators. The mean proportional abundance of Type II predators, particularly G. occidentalis, significantly increased and that of Type III predators significantly decreased with mean Tetranychus density in individual orchards. The current survey provides a more in-depth analysis of mite assemblages in walnut orchards in California and can be used to better inform adaptive management strategies for integrated mite management in the future.