ABSTRACT
BACKGROUND: Guidelines recommend the use of risk scores to select patients for further investigation after myocardial infarction has been ruled out but their utility to identify those with coronary artery disease is uncertain. METHODS: In a prospective cohort study, patients with intermediate high-sensitivity cardiac troponin I concentrations (5 ng/L to sex-specific 99th percentile) in whom myocardial infarction was ruled out were enrolled and underwent coronary CT angiography (CCTA) after hospital discharge. History, ECG, Age, Risk factors, Troponin (HEART), Emergency Department Assessment of Chest Pain Score (EDACS), Global Registry of Acute Coronary Event (GRACE), Thrombolysis In Myocardial Infarction (TIMI), Systematic COronary Risk Evaluation 2 and Pooled Cohort Equation risk scores were calculated and the odds ratio (OR) and diagnostic performance for obstructive coronary artery disease were determined using established thresholds. RESULTS: Of 167 patients enrolled (64±12 years, 28% female), 29.9% (50/167) had obstructive coronary artery disease. The odds of having obstructive disease were increased for all scores with the lowest and highest increase observed for an EDACS score ≥16 (OR 2.2 (1.1-4.6)) and a TIMI risk score ≥1 (OR 12.9 (3.0-56.0)), respectively. The positive predictive value (PPV) was low for all scores but was highest for a GRACE score >88 identifying 39% as high risk with a PPV of 41.9% (30.4-54.2%). The negative predictive value (NPV) varied from 77.3% to 95.2% but was highest for a TIMI score of 0 identifying 26% as low risk with an NPV of 95.2% (87.2-100%). CONCLUSIONS: In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been excluded, clinical risk scores can help identify patients with and without coronary artery disease, although the performance of established risk thresholds is suboptimal for utilisation in clinical practice. TRIAL REGISTRATION NUMBER: NCT04549805.
Subject(s)
Acute Coronary Syndrome , Biomarkers , Coronary Angiography , Coronary Artery Disease , Troponin I , Humans , Female , Male , Middle Aged , Prospective Studies , Risk Assessment/methods , Biomarkers/blood , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/epidemiology , Aged , Troponin I/blood , Risk Factors , Computed Tomography Angiography , Predictive Value of Tests , PrognosisABSTRACT
BACKGROUND: The HEART score, the T-MACS model and the GRACE score support early decision-making for acute chest pain, which could be complemented by CT coronary angiography (CTCA). However, their performance has not been directly compared. METHODS: In this secondary analysis of a multicentre randomised controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, C-statistics and performance metrics (using the predefined cut-offs) of clinical decision aids and CTCA, alone and then in combination, for the index hospital diagnosis of acute coronary syndrome and for 30-day coronary revascularisation were assessed in those who underwent CTCA and had complete data. RESULTS: Among 699 patients, 358 (51%) had an index hospital diagnosis of acute coronary syndrome, for which the C-statistic was higher for CTCA (0.80), followed by the T-MACS model (0.78), the HEART score (0.74) and the GRACE score (0.60). The negative predictive value was higher for the absence of coronary artery disease on CTCA (0.90) or a T-MACS estimate of <0.05 (0.83) than a HEART score of <4 (0.81) and a GRACE score of <109 (0.55). For 30-day coronary revascularisation, CTCA had the greatest C-statistic (0.80) with a negative predictive value of 0.96 and 0.92 in the absence of coronary artery disease and obstructive coronary artery disease, respectively. The combination of the T-MACS estimates and the CTCA findings was most discriminative for the index hospital diagnosis of acute coronary syndrome (C-statistic, 0.88) and predictive of 30-day coronary revascularisation (C-statistic, 0.85). No patients with a T-MACS estimate of <0.05 and normal coronary arteries had acute coronary syndrome during index hospitalisation or underwent coronary revascularisation within 30 days. CONCLUSIONS: In intermediate-risk patients with suspected acute coronary syndrome, the T-MACS model combined with CTCA improved discrimination of the index hospital diagnosis of acute coronary syndrome and prediction of 30-day coronary revascularisation. TRIAL REGISTRATION NUMBER: NCT02284191.
Subject(s)
Acute Coronary Syndrome , Computed Tomography Angiography , Coronary Angiography , Decision Support Techniques , Humans , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/diagnosis , Male , Female , Middle Aged , Coronary Angiography/methods , Coronary Angiography/statistics & numerical data , Computed Tomography Angiography/methods , Aged , Predictive Value of Tests , Risk Assessment/methods , Tomography, X-Ray Computed/methodsSubject(s)
Early Diagnosis , Sepsis , Humans , Sepsis/diagnosis , Sepsis/therapy , Practice Guidelines as TopicABSTRACT
OBJECTIVES: International guidelines recommend IV crystalloid as the primary fluid for sepsis resuscitation, with 5% human albumin solution (HAS) as the second line. However, it is unclear which fluid has superior clinical effectiveness. We conducted a trial to assess the feasibility of delivering a randomized controlled trial comparing balanced crystalloid against 5% HAS as sole early resuscitation fluid in patients with sepsis presenting to hospital. DESIGN: Multicenter, open, parallel-group randomized feasibility trial. SETTING: Emergency departments (EDs) in 15 U.K. National Health Service (NHS) hospitals. PATIENTS: Adult patients with sepsis and a National Early Warning Score 2 greater than or equal to five requiring IV fluids withing one hour of randomization. INTERVENTIONS: IV fluid resuscitation with balanced crystalloid or 5% HAS for the first 6 hours following randomization. MEASUREMENTS AND MAIN RESULTS: Primary feasibility outcomes were recruitment rate and 30-day mortality. We successfully recruited 301 participants over 12 months. Mean (sd) age was 69 years (± 16 yr), and 151 (50%) were male. From 1303 participants screened; 502 participants were potentially eligible and 300 randomized to receive trial intervention with greater than 95% of participants receiving the intervention. The median number of participants per site was 19 (range, 1-63). Thirty-day mortality was 17.9% (n = 53). Thirty-one participants died (21.1%) within 30 days in the 5% HAS arm, compared with 22 participants (14.8%) in the crystalloid arm (adjusted odds ratio, 1.50; 95% CIs, 0.84-2.83). CONCLUSIONS: Our results suggest it is feasible to recruit critically ill patients to a fluid resuscitation trial in U.K. EDs using 5% HAS as a primary resuscitation fluid. There was lower mortality in the balanced crystalloid arm. Given these findings, a definitive trial is likely to be deliverable, but the point estimates suggest such a trial would be unlikely to demonstrate a significant benefit from using 5% HAS as a primary resuscitation fluid in sepsis.
ABSTRACT
BACKGROUND: Supporting people to quit smoking is one of the most powerful interventions to improve health. The Emergency Department (ED) represents a potentially valuable opportunity to deliver a smoking cessation intervention if it is sufficiently resourced. The objective of this trial was to determine whether an opportunistic ED-based smoking cessation intervention can help people to quit smoking. METHODS: In this multicentre, parallel-group, randomised controlled superiority trial conducted between January and August 2022, adults who smoked daily and attended one of six UK EDs were randomised to intervention (brief advice, e-cigarette starter kit and referral to stop smoking services) or control (written information on stop smoking services). The primary outcome was biochemically validated abstinence at 6 months. RESULTS: An intention-to-treat analysis included 972 of 1443 people screened for inclusion (484 in the intervention group, 488 in the control group). Of 975 participants randomised, 3 were subsequently excluded, 17 withdrew and 287 were lost to follow-up. The 6-month biochemically-verified abstinence rate was 7.2% in the intervention group and 4.1% in the control group (relative risk 1.76; 95% CI 1.03 to 3.01; p=0.038). Self-reported 7-day abstinence at 6 months was 23.3% in the intervention group and 12.9% in the control group (relative risk 1.80; 95% CI 1.36 to 2.38; p<0.001). No serious adverse events related to taking part in the trial were reported. CONCLUSIONS: An opportunistic smoking cessation intervention comprising brief advice, an e-cigarette starter kit and referral to stop smoking services is effective for sustained smoking abstinence with few reported adverse events. TRIAL REGISTRATION NUMBER: NCT04854616.
ABSTRACT
BACKGROUND: Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) is a validated clinical decision support tool that uses machine learning with or without serial cardiac troponin measurements at a flexible time point to calculate the probability of myocardial infarction (MI). How CoDE-ACS performs at different time points for serial measurement and compares with guideline-recommended diagnostic pathways that rely on fixed thresholds and time points is uncertain. METHODS: Patients with possible MI without ST-segment-elevation were enrolled at 12 sites in 5 countries and underwent serial high-sensitivity cardiac troponin I concentration measurement at 0, 1, and 2 hours. Diagnostic performance of the CoDE-ACS model at each time point was determined for index type 1 MI and the effectiveness of previously validated low- and high-probability scores compared with guideline-recommended European Society of Cardiology (ESC) 0/1-hour, ESC 0/2-hour, and High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome) pathways. RESULTS: In total, 4105 patients (mean age, 61 years [interquartile range, 50-74]; 32% women) were included, among whom 575 (14%) had type 1 MI. At presentation, CoDE-ACS identified 56% of patients as low probability, with a negative predictive value and sensitivity of 99.7% (95% CI, 99.5%-99.9%) and 99.0% (98.6%-99.2%), ruling out more patients than the ESC 0-hour and High-STEACS (25% and 35%) pathways. Incorporating a second cardiac troponin measurement, CoDE-ACS identified 65% or 68% of patients as low probability at 1 or 2 hours, for an identical negative predictive value of 99.7% (99.5%-99.9%); 19% or 18% as high probability, with a positive predictive value of 64.9% (63.5%-66.4%) and 68.8% (67.3%-70.1%); and 16% or 14% as intermediate probability. In comparison, after serial measurements, the ESC 0/1-hour, ESC 0/2-hour, and High-STEACS pathways identified 49%, 53%, and 71% of patients as low risk, with a negative predictive value of 100% (99.9%-100%), 100% (99.9%-100%), and 99.7% (99.5%-99.8%); and 20%, 19%, or 29% as high risk, with a positive predictive value of 61.5% (60.0%-63.0%), 65.8% (64.3%-67.2%), and 48.3% (46.8%-49.8%), resulting in 31%, 28%, or 0%, who require further observation in the emergency department, respectively. CONCLUSIONS: CoDE-ACS performs consistently irrespective of the timing of serial cardiac troponin measurement, identifying more patients as low probability with comparable performance to guideline-recommended pathways for MI. Whether care guided by probabilities can improve the early diagnosis of MI requires prospective evaluation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00470587.
Subject(s)
Acute Coronary Syndrome , Myocardial Infarction , Humans , Female , Middle Aged , Male , Acute Coronary Syndrome/diagnosis , Biomarkers , Myocardial Infarction/diagnosis , Troponin , Machine Learning , Troponin TABSTRACT
C-reactive protein (CRP) is an established acute-phase marker for infection, inflammation and tissue injury, used to guide clinical decision-making in primary and secondary care. This study compared the analytical performance of the quantitative microfluidic point-of-care LumiraDx CRP Test to a laboratory-based reference method (Siemens RCRP Flex assay on the Dimension® Xpand®) and evaluated equivalence of sample matrices (blood versus plasma) in point-of-care settings using samples from patients presenting with symptoms of infection or inflammation. The LumiraDx CRP Test demonstrated close agreement with the lab reference test (range, 5.1 to 245.2 mg/L, r = 0.992, slope = 0.998, intercept = -0.476; n = 205) and notable agreement between fingerstick and venous blood and plasma (r = 0.974-0.983; n = 44). Paired replicate precision had mean coefficients of variation of 6.4 % (plasma), 6.6 % (capillary direct) and 8.1 % (venous blood); overall error rates were 2.9 %. The quantitative LumiraDx CRP Test showed robust analytical performance across sample matrices and close agreement compared to the laboratory reference method when used at the point of care.
ABSTRACT
BACKGROUND: Computed tomography coronary angiography (CTCA) offers detailed assessment of the presence of coronary atherosclerosis and helps guide patient management. We investigated influences of early CTCA on the subsequent use of preventative treatment in patients with suspected acute coronary syndrome. METHODS: In this secondary analysis of a multicenter randomized controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, prescription of aspirin, P2Y12 receptor antagonist, statin, renin-angiotensin system blocker, and beta-blocker therapies from randomization to discharge were compared within then between those randomized to early CTCA or to standard of care only. Effects of CTCA findings on adjustment of these therapies were further examined. RESULTS: In 1,743 patients (874 randomized to early CTCA and 869 to standard of care only), prescription of P2Y12 receptor antagonist, dual antiplatelet, and statin therapies increased more in the early CTCA group (between-group difference: 4.6% [95% confidence interval, 0.3-8.9], 4.5% [95% confidence interval, 0.2-8.7], and 4.3% [95% confidence interval, 0.2-8.5], respectively), whereas prescription of other preventative therapies increased by similar extent in both study groups. Among patients randomized to early CTCA, there were additional increments of preventative treatment in those with obstructive coronary artery disease and higher rates of reductions in antiplatelet and beta-blocker therapies in those with normal coronary arteries. CONCLUSIONS: Prescription patterns of preventative treatment varied during index hospitalization in patients with suspected acute coronary syndrome. Early CTCA facilitated targeted individualization of these therapies based on the extent of coronary artery disease.
Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/prevention & control , Coronary Artery Disease/complications , Coronary Angiography/methods , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/drug therapy , Acute Coronary Syndrome/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Tomography, X-Ray Computed/methods , Computed Tomography AngiographyABSTRACT
BACKGROUND: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death. METHODS: TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. After myocardial infarction and clear alternative diagnoses have been ruled out, participants with intermediate cardiac troponin concentrations (5 ng/L to 99th centile upper reference limit) will be randomised 1:1 to outpatient CTCA plus standard of care or standard of care alone. The primary endpoint is myocardial infarction or cardiac death. Secondary endpoints include clinical, patient-centred, process and cost-effectiveness. Recruitment of 2270 patients will give 90% power with a two-sided P value of 0.05 to detect a 40% relative risk reduction in the primary endpoint. Follow-up will continue until 97 primary outcome events have been accrued in the standard care arm with an estimated median follow-up of 36 months. DISCUSSION: This randomised controlled trial will determine whether high-sensitivity cardiac troponin-guided CTCA can improve outcomes and reduce subsequent major adverse cardiac events in patients presenting to the emergency department who do not have myocardial infarction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03952351. Registered on May 16, 2019.
Subject(s)
Myocardial Infarction , Troponin , Humans , Coronary Angiography , Prospective Studies , Computed Tomography Angiography , Chest Pain , Myocardial Infarction/diagnostic imagingABSTRACT
The COVID-19 pandemic has highlighted the need for FAIR (Findable, Accessible, Interoperable, and Reusable) data more than any other scientific challenge to date. We developed a flexible, multi-level, domain-agnostic FAIRification framework, providing practical guidance to improve the FAIRness for both existing and future clinical and molecular datasets. We validated the framework in collaboration with several major public-private partnership projects, demonstrating and delivering improvements across all aspects of FAIR and across a variety of datasets and their contexts. We therefore managed to establish the reproducibility and far-reaching applicability of our approach to FAIRification tasks.
Subject(s)
COVID-19 , Datasets as Topic , Humans , Pandemics , Public-Private Sector Partnerships , Reproducibility of ResultsABSTRACT
The notion that data should be Findable, Accessible, Interoperable and Reusable, according to the FAIR Principles, has become a global norm for good data stewardship and a prerequisite for reproducibility. Nowadays, FAIR guides data policy actions and professional practices in the public and private sectors. Despite such global endorsements, however, the FAIR Principles are aspirational, remaining elusive at best, and intimidating at worst. To address the lack of practical guidance, and help with capability gaps, we developed the FAIR Cookbook, an open, online resource of hands-on recipes for "FAIR doers" in the Life Sciences. Created by researchers and data managers professionals in academia, (bio)pharmaceutical companies and information service industries, the FAIR Cookbook covers the key steps in a FAIRification journey, the levels and indicators of FAIRness, the maturity model, the technologies, the tools and the standards available, as well as the skills required, and the challenges to achieve and improve data FAIRness. Part of the ELIXIR ecosystem, and recommended by funders, the FAIR Cookbook is open to contributions of new recipes.
ABSTRACT
Although guidelines recommend fixed cardiac troponin thresholds for the diagnosis of myocardial infarction, troponin concentrations are influenced by age, sex, comorbidities and time from symptom onset. To improve diagnosis, we developed machine learning models that integrate cardiac troponin concentrations at presentation or on serial testing with clinical features and compute the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) score (0-100) that corresponds to an individual's probability of myocardial infarction. The models were trained on data from 10,038 patients (48% women), and their performance was externally validated using data from 10,286 patients (35% women) from seven cohorts. CoDE-ACS had excellent discrimination for myocardial infarction (area under curve, 0.953; 95% confidence interval, 0.947-0.958), performed well across subgroups and identified more patients at presentation as low probability of having myocardial infarction than fixed cardiac troponin thresholds (61 versus 27%) with a similar negative predictive value and fewer as high probability of having myocardial infarction (10 versus 16%) with a greater positive predictive value. Patients identified as having a low probability of myocardial infarction had a lower rate of cardiac death than those with intermediate or high probability 30 days (0.1 versus 0.5 and 1.8%) and 1 year (0.3 versus 2.8 and 4.2%; P < 0.001 for both) from patient presentation. CoDE-ACS used as a clinical decision support system has the potential to reduce hospital admissions and have major benefits for patients and health care providers.
Subject(s)
Acute Coronary Syndrome , Myocardial Infarction , Humans , Female , Male , Biomarkers , Troponin I , Myocardial Infarction/diagnosis , Acute Coronary Syndrome/diagnosis , Machine LearningABSTRACT
Background: Patients presenting with suspected sepsis to secondary care often require fluid resuscitation to correct hypovolaemia and/or septic shock. Existing evidence signals, but does not demonstrate, a benefit for regimes including albumin over balanced crystalloid alone. However, interventions may be started too late, missing a critical resuscitation window. Methods: ABC Sepsis is a currently recruiting randomised controlled feasibility trial comparing 5% human albumin solution (HAS) with balanced crystalloid for fluid resuscitation in patients with suspected sepsis. This multicentre trial is recruiting adult patients within 12 hours of presentation to secondary care with suspected community acquired sepsis, with a National Early Warning Score ≥5, who require intravenous fluid resuscitation. Participants are randomised to 5% HAS or balanced crystalloid as the sole resuscitation fluid for the first 6 hours. Objectives: Primary objectives are feasibility of recruitment to the study and 30-day mortality between groups. Secondary objectives include in-hospital and 90-day mortality, adherence to trial protocol, quality of life measurement and secondary care costs. Discussion: This trial aims to determine the feasibility of conducting a trial to address the current uncertainty around optimal fluid resuscitation of patients with suspected sepsis. Understanding the feasibility of delivering a definitive study will be dependent on how the study team are able to negotiate clinician choice, Emergency Department pressures and participant acceptability, as well as whether any clinical signal of benefit is detected.
ABSTRACT
INTRODUCTION: Attendees of emergency departments (EDs) have a higher than expected prevalence of smoking. ED attendance may be a good opportunity to prompt positive behaviour change, even for smokers not currently motivated to quit. This study aims to determine whether an opportunist smoking cessation intervention delivered in the ED can help daily smokers attending the ED quit smoking and is cost-effective. METHODS AND ANALYSIS: A two-arm pragmatic, multicentred, parallel-group, individually randomised, controlled superiority trial with an internal pilot, economic evaluation and mixed methods process evaluation. The trial will compare ED-based brief smoking cessation advice, including provision of an e-cigarette and referral to local stop smoking services (intervention) with the provision of contact details for local stop smoking services (control). Target sample size is 972, recruiting across 6 National Health Service EDs in England and Scotland. Outcomes will be collected at 1, 3 and 6 months. The primary outcome at 6 months is carbon monoxide verified continuous smoking abstinence. ETHICS AND DISSEMINATION: The trial was approved by the South Central-Oxford B Research Committee (21/SC/0288). Dissemination will include the publication of outcomes, and the process and economic evaluations in peer-reviewed journals. The findings will also be appropriately disseminated to relevant practice, policy and patient representative groups. TRIAL REGISTRATION NUMBER: NCT04854616; protocol V.4.2.
Subject(s)
Electronic Nicotine Delivery Systems , Smoking Cessation , Humans , Smoking Cessation/methods , State Medicine , Smoking/epidemiology , Smoking/therapy , England , Randomized Controlled Trials as Topic , Multicenter Studies as TopicABSTRACT
OBJECTIVES: To estimate the cost-effectiveness of early CT coronary angiography (CTCA) for intermediate risk patients with suspected acute coronary syndrome (ACS), compared with standard care METHODS: We performed within-trial economic analysis using data from the RAPID-CTCA randomised trial, and long-term modelling of cost-effectiveness using secondary data sources to estimate the cost-effectiveness of early CTCA compared with standard care for patients with suspected ACS attending acute hospitals in the UK. Cost-effectiveness was estimated as the incremental cost per quality-adjusted life year (QALY) gained, and the probability of each strategy being cost-effective at varying willingness-to-pay per QALY gained. RESULTS: The within-trial analysis showed that there were no demonstrable differences in costs or QALYs between early CTCA and standard care, with point estimates suggesting higher costs (£7414 vs £6845: mean difference £569, 95% CI -£208 to £1335; p=0.1521) and lower QALYs (0.749 vs 0.758, mean difference -0.009, 95% CI -0.026 to 0.010; p=0.377) in the CTCA arm. The long-term economic analysis suggested that, on average, CTCA was slightly less effective than standard care alone with 0.025 quality-adjusted life years lost per patient treated and was more expensive with additional costs of £481 per patient treated. At a threshold of £20 000 per QALY, CTCA has 24% probability of being cost-effective. CONCLUSIONS: There are no demonstrable differences in within-trial costs and QALYs, and long-term cost-effectiveness modelling suggested higher long-term costs with CTCA and uncertain effect on long-term QALYs, making routine use of CTCA for suspected ACS unlikely to be a cost-effective use of NHS resources.
Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Humans , Coronary Angiography , Cost-Benefit Analysis , Coronary Artery Disease/therapy , Computed Tomography Angiography , Quality-Adjusted Life YearsABSTRACT
Purpose: To determine whether quantitative plaque characterization by using CT coronary angiography (CTCA) can discriminate between type 1 and type 2 myocardial infarction. Materials and Methods: This was a secondary analysis of two prospective studies (ClinicalTrials.gov registration nos. NCT03338504 [2014-2019] and NCT02284191 [2018-2020]) that performed blinded quantitative plaque analysis on findings from CTCA in participants with type 1 myocardial infarction, type 2 myocardial infarction, and chest pain without myocardial infarction. Logistic regression analyses were performed to identify predictors of type 1 myocardial infarction. Results: Overall, 155 participants (mean age, 64 years ± 12 [SD]; 114 men) and 36 participants (mean age, 67 years ± 12; 19 men) had type 1 and type 2 myocardial infarction, respectively, and 136 participants (62 years ± 12; 78 men) had chest pain without myocardial infarction. Participants with type 1 myocardial infarction had greater total (median, 44% [IQR: 35%-50%] vs 35% [IQR: 29%-46%]), noncalcified (39% [IQR: 31%-46%] vs 34% [IQR: 29%-40%]), and low-attenuation (4.15% [IQR: 1.88%-5.79%] vs 1.64% [IQR: 0.89%-2.28%]) plaque burdens (P < .05 for all) than those with type 2. Participants with type 2 myocardial infarction had similar low-attenuation plaque burden to those with chest pain without myocardial infarction (P = .4). Low-attenuation plaque was an independent predictor of type 1 myocardial infarction (adjusted odds ratio, 3.44 [95% CI: 1.84, 6.96]; P < .001), with better discrimination than noncalcified plaque burden and maximal area of coronary stenosis (C statistic, 0.75 [95% CI: 0.67, 0.83] vs 0.62 [95% CI: 0.53, 0.71] and 0.61 [95% CI: 0.51, 0.70] respectively; P ≤ .001 for both). Conclusion: Higher low-attenuation coronary plaque burden in patients with type 1 myocardial infarction may help distinguish these patients from those with type 2 myocardial infarction.Keywords: Ischemia/Infarction, CT Angiography, Quantitative CTClinical trial registration nos. NCT03338504 and NCT02284191 Supplemental material is available for this article. © RSNA, 2022.
ABSTRACT
BACKGROUND: In patients with stable chest pain, computed tomography (CT) plaque burden is an independent predictor of future coronary events. OBJECTIVES: The purpose of this study was to determine whether plaque burden and characteristics can predict subsequent death or myocardial infarction in patients with acute chest pain. METHODS: In a post hoc analysis of a multicenter trial of early coronary CT angiography, the authors performed quantitative plaque analysis to assess the association between primary endpoint of 1-year all-cause death or nonfatal myocardial infarction and the GRACE (Global Registry of Acute Coronary Events) score, presence of obstructive coronary artery disease, and plaque burden in 404 patients with suspected acute coronary syndrome. RESULTS: Following the index event, 25 patients had a primary event that was associated with a higher GRACE score (134 ± 44 vs 113 ± 35; P = 0.012), larger burdens of total (46% [IQR: 43%-50%] vs 36% [IQR: 21%-46%]; P < 0.001), noncalcified (41% [IQR: 37%-%47] vs 33% [IQR: 20%-41%]; P < 0.001), and low-attenuation plaque (4.22% [IQR: 3.3%-5.68%] vs 2.14% [IQR: 0.5%-4.88%]; P < 0.001), but not obstructive coronary artery disease (P = 0.065). Total, noncalcified, and low-attenuation plaque burden were the strongest predictors of future events independent of GRACE score and obstructive coronary artery disease (P ≤ 0.002 for all). Patients with a low-attenuation burden above the median had nearly an 8-fold increased risk of the primary endpoint (HR: 7.80 [95% CI: 2.33-26.0]; P < 0.001), outperforming either a GRACE score of >140 (HR: 3.80 [95% CI :1.45-6.98]; P = 0.004) or obstructive coronary artery disease (HR: 2.07 [95% CI: 0.94-4.53]; P = 0.07). CONCLUSIONS: In patients with suspected acute coronary syndrome, low-attenuation plaque burden is a major predictor of 1-year death or recurrent myocardial infarction. (Rapid Assessment of Potential Ischaemic Heart Disease With CTCA [RAPID-CTCA]; NCT02284191).
Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Myocardial Infarction , Plaque, Atherosclerotic , Humans , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Coronary Artery Disease/complications , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/therapy , Coronary Angiography/methods , Predictive Value of Tests , Chest Pain/etiology , Computed Tomography Angiography/adverse effects , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/therapy , Myocardial Infarction/complications , Risk FactorsABSTRACT
BACKGROUND: Acute coronary syndrome is a common medical emergency. The optimal strategy to investigate patients who are at intermediate risk of acute coronary syndrome has not been fully determined. OBJECTIVE: To investigate the role of early computed tomography coronary angiography in the investigation and treatment of adults presenting with suspected acute coronary syndrome. DESIGN: A prospective, multicentre, open, parallel-group randomised controlled trial with blinded end-point adjudication. SETTING: Thirty-seven hospitals in the UK. PARTICIPANTS: Adults (aged ≥ 18 years) presenting to the emergency department, acute medicine services or cardiology department with suspected or provisionally diagnosed acute coronary syndrome and at least one of the following: (1) a prior history of coronary artery disease, (2) a cardiac troponin level > 99th centile and (3) an abnormal 12-lead electrocardiogram. INTERVENTIONS: Early computed tomography coronary angiography in addition to standard care was compared with standard care alone. Participants were followed up for 1 year. MAIN OUTCOME MEASURE: One-year all-cause death or subsequent type 1 (spontaneous) or type 4b (stent thrombosis) myocardial infarction, measured as the time to such event adjudicated by two cardiologists blinded to the computerised tomography coronary angiography ( CTCA ) arm. Cost-effectiveness was estimated as the lifetime incremental cost per quality-adjusted life-year gained. RESULTS: Between 23 March 2015 and 27 June 2019, 1748 participants [mean age 62 years (standard deviation 13 years), 64% male, mean Global Registry Of Acute Coronary Events score 115 (standard deviation 35)] were randomised to receive early computed tomography coronary angiography (n = 877) or standard care alone (n = 871). The primary end point occurred in 51 (5.8%) participants randomised to receive computed tomography coronary angiography and 53 (6.1%) participants randomised to receive standard care (adjusted hazard ratio 0.91, 95% confidence interval 0.62 to 1.35; p = 0.65). Computed tomography coronary angiography was associated with a reduced use of invasive coronary angiography (adjusted hazard ratio 0.81, 95% confidence interval 0.72 to 0.92; p = 0.001) but no change in coronary revascularisation (adjusted hazard ratio 1.03, 95% confidence interval 0.87 to 1.21; p = 0.76), acute coronary syndrome therapies (adjusted odds ratio 1.06, 95% confidence interval 0.85 to 1.32; p = 0.63) or preventative therapies on discharge (adjusted odds ratio 1.07, 95% confidence interval 0.87 to 1.32; p = 0.52). Early computed tomography coronary angiography was associated with longer hospitalisations (median increase 0.21 days, 95% confidence interval 0.05 to 0.40 days) and higher mean total health-care costs over 1 year (£561 more per patient) than standard care. LIMITATIONS: The principal limitation of the trial was the slower than anticipated recruitment, leading to a revised sample size, and the requirement to compromise and accept a larger relative effect size estimate for the trial intervention. FUTURE WORK: The potential role of computed tomography coronary angiography in selected patients with a low probability of obstructive coronary artery disease (intermediate or mildly elevated level of troponin) or who have limited access to invasive cardiac catheterisation facilities needs further prospective evaluation. CONCLUSIONS: In patients with suspected or provisionally diagnosed acute coronary syndrome, computed tomography coronary angiography did not alter overall coronary therapeutic interventions or 1-year clinical outcomes, but it did increase the length of hospital stay and health-care costs. These findings do not support the routine use of early computed tomography coronary angiography in intermediate-risk patients with acute chest pain. TRIAL REGISTRATION: This trial is registered as ISRCTN19102565 and Clinical Trials NCT02284191. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 37. See the NIHR Journals Library website for further project information.
WHY DID WE DO THE RESEARCH?: Chest pain is a common medical emergency. It is important to decide if the cause is a heart attack. The two tests that are often used are a heart recording (electrocardiogram) and a blood test (troponin levels). If both are normal, the cause of chest pain is unlikely to be a heart attack and the patient is often discharged home. If either test is positive or if the patient has had previous heart problems, then the patient may require further investigation. We wanted to test whether or not adding a heart scan called a computerised tomography coronary angiogram improved patients' care. HOW DID WE DO THE RESEARCH?: We carried out a randomised trial in which half of the patients attending hospital with chest pain had a computerised tomography coronary angiography scan as part of their assessment and half of the patients did not. In total, 1749 patients were recruited and followed up for 1 year. BRINGING IT ALL TOGETHER: The use of an additional early computerised tomography coronary angiography scan for chest pain patients of medium risk produced only small improvements in patient care.
Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Acute Coronary Syndrome/diagnostic imaging , Adult , Coronary Angiography , Coronary Artery Disease/therapy , Cost-Benefit Analysis , Female , Humans , Male , Middle Aged , Quality of Life , Tomography , TroponinABSTRACT
BACKGROUND: The utility of magnetic resonance imaging (MRI) brain in patients with transient or minor neurological symptoms is uncertain. We sought to determine the proportion of participants with transient or minor neurological symptoms who had MRI evidence of acute ischemia at different clinical probabilities of transient ischemic attack (TIA) or minor stroke. METHODS: Cohort of participants with transient or minor neurological symptoms from emergency and outpatient settings. Clinicians at different levels of training gave each participant a diagnostic probability (probable when TIA/stroke was the most likely differential diagnosis; possible when TIA/stroke was not the most likely differential diagnosis; or uncertain when diagnostic probability could not be given) before 1.5 or 3T brain MRI ≤5 days from onset. Post hoc, each clinical syndrome was defined blind to MRI findings as National Institute of Neurological Disorders and Stroke criteria TIA/stroke; International Headache Society criteria migraine aura; non-TIA focal symptoms; or nonfocal symptoms. MRI evidence of acute ischemia was defined by 2 reads of MRI. Stroke was ascertained for at least 90 days and up to 18 months after recruitment. RESULTS: Two hundred seventy-two participated (47% female, mean age 60, SD 14), 58% with MRI ≤2 days of onset. Most (92%) reported focal symptoms. MR evidence of acute ischemia was found, for stroke/TIA clinical probabilities of probable 23 out of 75 (31% [95% CI, 21%-42%]); possible 26 out of 151 (17% [12%-24%]); and uncertain 9 out of 43, (20% [10%-36%]). MRI evidence of acute ischemia was found in National Institute of Neurological Disorders and Stroke criteria TIA/stroke 40 out of 95 (42% [32%-53%]); migraine aura 4 out of 38 (11% [3%-25%]); non-TIA focal symptoms 16 out of 99 (16% [10%-25%]); and no focal features 1 out of 29 (3% [0%-18%]). After MRI, a further 14 (5% [95% CI, 3-8]) would be treated with an antiplatelet drug compared with treatment plan before MRI. By 18 months, a new ischemic stroke occurred in 9 out of 61 (18%) patients with MRI evidence of acute ischemia and 2 out of 211 (1%) without (age-adjusted hazard ratio, 13 [95% CI, 3-62]; P<0.0001). CONCLUSIONS: MRI evidence of acute brain ischemia was found in about 1 in 6 transient or minor neurological symptoms patients with a nonstroke/TIA initial diagnosis or uncertain diagnosis. Methods to determine the clinical and cost-effectiveness of MRI are needed in this population.
Subject(s)
Epilepsy , Ischemic Attack, Transient , Migraine with Aura , Stroke , Humans , Female , Middle Aged , Male , Ischemic Attack, Transient/diagnosis , Prospective Studies , Platelet Aggregation Inhibitors , Stroke/epidemiology , Magnetic Resonance Imaging , Cohort StudiesABSTRACT
AIMS: To evaluate the potential associations between presentation cardiac troponin and the clinical impact of early computed tomography coronary angiography (CTCA) in intermediate-risk patients with suspected acute coronary syndrome. METHODS AND RESULTS: In a large multicentre randomized controlled trial of patients with intermediate-risk chest pain due to suspected acute coronary syndrome, early CTCA had no effect on the primary outcome-death or subsequent Type 1 or 4b myocardial infarction-but reduced the rate of invasive coronary angiography. In this pre-specified secondary analysis, cardiovascular testing and clinical outcomes were compared between those with or without cardiac troponin elevation at presentation. Of 1748 patients, 1004 (57%) had an elevated cardiac troponin concentration and 744 (43%) had a normal concentration. Patients with cardiac troponin elevation had a higher Global Registry of Acute Coronary Events score (132 vs. 91; P < 0.001) and were more likely to have obstructive coronary artery disease (59 vs. 33%; P < 0.001), non-invasive (72 vs. 52%; P < 0.001) and invasive (72 vs. 38%; P < 0.001) testing, coronary revascularization (47 vs. 15%; P < 0.001), and the primary outcome (8 vs. 3%; P = 0.007) at 1 year. However, there was no evidence that presentation cardiac troponin was associated with the relative effects of early CTCA on rates of non-invasive (Pinteraction = 0.33) and invasive (Pinteraction = 0.99) testing, coronary revascularization (Pinteraction = 0.57), or the primary outcome (Pinteraction = 0.41). CONCLUSION: Presentation cardiac troponin had no demonstrable associations between the effects of early CTCA on reductions in non-invasive and invasive testing, or the lack of effect on coronary revascularization or the primary outcome in intermediate-risk patients with suspected acute coronary syndrome.