scholarly journals High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in people with acute chest pain: a systematic review and cost-effectiveness analysis

2015 ◽  
Vol 19 (44) ◽  
pp. 1-234 ◽  
Author(s):  
Marie Westwood ◽  
Thea van Asselt ◽  
Bram Ramaekers ◽  
Penny Whiting ◽  
Praveen Thokala ◽  
...  

BackgroundEarly diagnosis of acute myocardial infarction (AMI) can ensure quick and effective treatment but only 20% of adults with emergency admissions for chest pain have an AMI. High-sensitivity cardiac troponin (hs-cTn) assays may allow rapid rule-out of AMI and avoidance of unnecessary hospital admissions and anxiety.ObjectiveTo assess the clinical effectiveness and cost-effectiveness of hs-cTn assays for the early (within 4 hours of presentation) rule-out of AMI in adults with acute chest pain.MethodsSixteen databases, including MEDLINE and EMBASE, research registers and conference proceedings, were searched to October 2013. Study quality was assessed using QUADAS-2. The bivariate model was used to estimate summary sensitivity and specificity for meta-analyses involving four or more studies, otherwise random-effects logistic regression was used. The health-economic analysis considered the long-term costs and quality-adjusted life-years (QALYs) associated with different troponin (Tn) testing methods. The de novo model consisted of a decision tree and Markov model. A lifetime time horizon (60 years) was used.ResultsEighteen studies were included in the clinical effectiveness review. The optimum strategy, based on the Roche assay, used a limit of blank (LoB) threshold in a presentation sample to rule out AMI [negative likelihood ratio (LR–) 0.10, 95% confidence interval (CI) 0.05 to 0.18]. Patients testing positive could then have a further test at 2 hours; a result above the 99th centile on either sample and a delta (Δ) of ≥ 20% has some potential for ruling in an AMI [positive likelihood ratio (LR+) 8.42, 95% CI 6.11 to 11.60], whereas a result below the 99th centile on both samples and a Δ of < 20% can be used to rule out an AMI (LR– 0.04, 95% CI 0.02 to 0.10). The optimum strategy, based on the Abbott assay, used a limit of detection (LoD) threshold in a presentation sample to rule out AMI (LR– 0.01, 95% CI 0.00 to 0.08). Patients testing positive could then have a further test at 3 hours; a result above the 99th centile on this sample has some potential for ruling in an AMI (LR+ 10.16, 95% CI 8.38 to 12.31), whereas a result below the 99th centile can be used to rule out an AMI (LR– 0.02, 95% CI 0.01 to 0.05). In the base-case analysis, standard Tn testing was both most effective and most costly. Strategies considered cost-effective depending upon incremental cost-effectiveness ratio thresholds were Abbott 99th centile (thresholds of < £6597), Beckman 99th centile (thresholds between £6597 and £30,042), Abbott optimal strategy (LoD threshold at presentation, followed by 99th centile threshold at 3 hours) (thresholds between £30,042 and £103,194) and the standard Tn test (thresholds over £103,194). The Roche 99th centile and the Roche optimal strategy [LoB threshold at presentation followed by 99th centile threshold and/or Δ20% (compared with presentation test) at 1–3 hours] were extendedly dominated in this analysis.ConclusionsThere is some evidence to suggest that hs-CTn testing may provide an effective and cost-effective approach to early rule-out of AMI. Further research is needed to clarify optimal diagnostic thresholds and testing strategies.Study registrationThis study is registered as PROSPERO CRD42013005939.FundingThe National Institute for Health Research Health Technology Assessment programme.

2021 ◽  
Vol 25 (33) ◽  
pp. 1-276
Author(s):  
Marie Westwood ◽  
Bram Ramaekers ◽  
Sabine Grimm ◽  
Gill Worthy ◽  
Debra Fayter ◽  
...  

Background Early diagnosis of acute myocardial infarction is important, but only 20% of emergency admissions for chest pain will actually have an acute myocardial infarction. High-sensitivity cardiac troponin assays may allow rapid rule out of myocardial infarction and avoid unnecessary hospital admissions. Objectives To assess the clinical effectiveness and cost-effectiveness of high-sensitivity cardiac troponin assays for the management of adults presenting with acute chest pain, in particular for the early rule-out of acute myocardial infarction. Methods Sixteen databases were searched up to September 2019. Review methods followed published guidelines. Studies were assessed for quality using appropriate risk-of-bias tools. The bivariate model was used to estimate summary sensitivity and specificity for meta-analyses involving four or more studies; otherwise, random-effects logistic regression was used. The health economic analysis considered the long-term costs and quality-adjusted life-years associated with different troponin testing methods. The de novo model consisted of a decision tree and a state–transition cohort model. A lifetime time horizon (of 60 years) was used. Results Thirty-seven studies (123 publications) were included in the review. The high-sensitivity cardiac troponin test strategies evaluated are defined by the combination of four factors (i.e. assay, number and timing of tests, and threshold concentration), resulting in a large number of possible combinations. Clinical opinion indicated a minimum clinically acceptable sensitivity of 97%. When considering single test strategies, only those using a threshold at or near to the limit of detection for the assay, in a sample taken at presentation, met the minimum clinically acceptable sensitivity criterion. The majority of the multiple test strategies that met this criterion comprised an initial rule-out step, based on high-sensitivity cardiac troponin levels in a sample taken on presentation and a minimum symptom duration, and a second stage for patients not meeting the initial rule-out criteria, based on presentation levels of high-sensitivity cardiac troponin and absolute change after 1, 2 or 3 hours. Two large cluster randomised controlled trials found that implementation of an early rule-out pathway for myocardial infarction reduced length of stay and rate of hospital admission without increasing cardiac events. In the base-case analysis, standard troponin testing was both the most effective and the most costly. Other testing strategies with a sensitivity of 100% (subject to uncertainty) were almost equally effective, resulting in the same life-year and quality-adjusted life-year gain at up to four decimal places. Comparisons based on the next best alternative showed that for willingness-to-pay values below £8455 per quality-adjusted life-year, the Access High Sensitivity Troponin I (Beckman Coulter, Brea, CA, USA) [(symptoms > 3 hours AND < 4 ng/l at 0 hours) OR (< 5 ng/l AND Δ < 5 ng/l at 0 to 2 hours)] would be cost-effective. For thresholds between £8455 and £20,190 per quality-adjusted life-year, the Elecsys® Troponin-T high sensitive (Roche, Basel, Switzerland) (< 12 ng/l at 0 hours AND Δ < 3 ng/l at 0 to 1 hours) would be cost-effective. For a threshold > £20,190 per quality-adjusted life-year, the Dimension Vista® High-Sensitivity Troponin I (Siemens Healthcare, Erlangen, Germany) (< 5 ng/l at 0 hours AND Δ < 2 ng/l at 0 to 1 hours) would be cost-effective. Conclusions High-sensitivity cardiac troponin testing may be cost-effective compared with standard troponin testing. Study registration This study is registered as PROSPERO CRD42019154716. Funding This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 33. See the NIHR Journals Library website for further project information.


CJEM ◽  
2018 ◽  
Vol 20 (S1) ◽  
pp. S28-S28
Author(s):  
A. D. McRae ◽  
S. Vatanpour ◽  
J. Ji ◽  
H. Yang ◽  
D. Southern ◽  
...  

Introduction: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular events, and have worse outcomes following acute myocardial infarction (AMI). Cardiac troponin is often elevated in CKD, making the diagnosis of AMI challenging in this population. We sought to quantify test characteristics for AMI of a high-sensitivity troponin T (hsTnT) assay performed at emergency department (ED) arrival in CKD patients with chest pain, and to derive rule-out cutoffs specific to patient subgroups stratified by estimated glomerular filtration rate (eGFR). We also quantified the sensitivity and classification performance of the assays limit of detection (5 ng/L) and the FDA-approved limit of quantitation (6 ng/L) for ruling out AMI at ED arrival. Methods: Consecutive patients in four urban EDs from the 2013 calendar year with suspected cardiac chest pain who had a Roche Elecsys hsTnT assay performed on arrival were included f. This analysis was restricted to patients with an eGFR< 60 ml/min/1.73m2. The primary outcome was 7-day AMI. Secondary outcomes included major adverse cardiac events (death, AMI and revascularization). Test characteristics were calculated and ROC curves were generated for eGFR subgroups. Results: 1416 patients were included. 7-day AMI incidence was 10.1%. 73% of patients had an initial hsTnT concentration greater than the assays 99th percentile (14 ng/L). TCurrently accepted cutoffs to rule out MI at ED arrival ( 5 ng/L and 6 ng/L) had 100% sensitivity for AMI, but no patients with an eGFR less than 30 ml/min/1.73M had hsTnT concentrations below these thresholds. We derived eGFR-adjusted cutoffs to rule out MI with sensitivity >98% at ED arrival, which were able to rule out 6-42% of patients, depending on eGFR category. The proportion of patients able to be accurately ruled-in with a single hsTnT assay was substantially lower among patients with an eGFR <30 ml/min/1.73m2 (6-20% vs 25-43%). We also derived eGFR-adjusted cutoffs to rule-in AMI with specificity >90%, which accurately ruled-in up to 18% of patients. Conclusion: Cutoffs achieving acceptable diagnostic performance for AMI using single hsTnT sampling on ED arrival may have limited clinical utility, particularly among patients with very low eGFR. The ideal diagnostic strategy for AMI in patients with CKD likely involves serial high-sensitivity troponin testing with diagnostic thresholds customized to different eGFR categories.


2011 ◽  
Vol 57 (9) ◽  
pp. 1318-1326 ◽  
Author(s):  
Willibald Hochholzer ◽  
Tobias Reichlin ◽  
Raphael Twerenbold ◽  
Claudia Stelzig ◽  
Kirsten Hochholzer ◽  
...  

BACKGROUND High-sensitivity cardiac troponin assays have better analytical precision and sensitivity than earlier-generation assays when measuring cardiac troponin at low concentrations. We evaluated whether use of a high-sensitivity assay could further improve risk stratification compared with a standard cardiac troponin assay. METHODS We enrolled consecutive patients presenting with acute chest pain, 30% of whom were diagnosed with acute coronary syndrome. Blood samples were drawn at the time of presentation. We measured cardiac troponin T with a standard fourth-generation assay (cTnT) and a high-sensitivity assay (hs-cTnT) (both Roche Diagnostics) and followed the patients for 24 months. RESULTS Of the 1159 patients, 76 died and 42 developed an acute myocardial infarction (AMI). Prognostic accuracy of hs-cTnT for death was significantly higher [area under ROC curve (AUC) 0.79, 95% CI 0.74–0.84] than that of cTnT (AUC 0.69, 95% CI 0.62–0.76; P &lt; 0.001). After adjustment for Thrombolysis in Myocardial Infarction (TIMI) risk score (that included the cTnT assay result), hs-cTnT above the 99th percentile (0.014 μg/L) was associated with a hazard ratio for death of 2.60 (95% CI 1.42–4.74). Addition of hs-cTnT to the risk score improved the reclassification of patients (net reclassification improvement 0.91; 95% CI 0.67–1.14; P &lt; 0.001). Subgroup analyses showed that this effect resulted from the better classification of patients without AMI at time of testing. hs-cTnT outperformed cTnT in the prediction of AMI during follow-up (P=0.02), but was not independently predictive for this endpoint. CONCLUSIONS Concentrations of hs-cTnT &gt;0.014 μg/L improve the prediction of death but not subsequent AMI in unselected patients presenting with acute chest pain.


Author(s):  
Christiaan Vrints ◽  
Janina Stepinska ◽  
Marc J Claeys

The diagnosis and assessment of acute chest pain remain challenging. Inappropriate discharge of patients with unrecognised life-threatening acute cardiovascular disease such as acute myocardial infarction or acute aortic syndromes from the hospital can result in potentially avoidable death. By contrast, routine hospital admission of patients with non-significant chest pain can lead to unnecessary investigations and interventions, with associated potential harm and increased healthcare costs. As only a small minority of the patients presenting with acute chest pain will ultimately be diagnosed with an acute coronary syndrome or another life-threatening acute cardiovascular syndrome it is essential to use rapid and straightforward diagnostic methods that allow accurate identification of high-risk chest pain patients and safe and early discharge of low risk patients in order to avoid congestion in the emergency department. Triage and diagnosis of patients presenting with acute chest pain should rely on careful history taking, judicious interpretation of the 12 lead ECG on presentation and the use of rapid rule-in/rule out diagnostic algorithms of acute myocardial infarction using high sensitivity cardiac troponin assays for the detection of myocardial cell necrosis. Chest pain units (CPU) are organizational short-stay units with specific management protocols designed to facilitate and optimize the diagnosis of patients presenting with chest pain. Implementation of CPU has results in increased adherence to guidelines and an improved clinical outcome.


CJEM ◽  
2018 ◽  
Vol 20 (S1) ◽  
pp. S92-S92
Author(s):  
A. D. McRae ◽  
M. Graham ◽  
T. Abedin ◽  
J. Ji ◽  
H. Yang ◽  
...  

Introduction: ex-specific diagnostic cutoffs may improve the test characteristics of high-sensitivity troponin assays for the diagnosis of myocardial infarction. Sex-specific cutoffs for ruling in MI improve the sensitivity of the assay for MI among women, and improve the specificity of diagnosis among men. We hypothesized that the use of sex-specific high-sensitivity Troponin T (hsTnT) cutoffs for ruling out MI at the time of ED arrival would improve the classification efficiency of the assay by enabling more patients to have MI ruled out at the time of ED arrival while maintaining diagnostic sensitivity. The objective of this study was to quantify the test characteristics of sex-specific cutoffs of an hsTnT assay for acute myocardial infarction (AMI) when performed at ED arrival in patients with chest pain. Methods: This retrospective study included consecutive ED patients with suspected cardiac chest pain evaluated in four urban EDs were, excluding those with ST-elevation AMI, cardiac arrest or abnormal kidney function. The primary outcomes was AMI at 7 days. Secondary outcomes included major adverse cardiac events (MACE: all-cause mortality, AMI and revascularization) and the individual MACE components. We quantified test characteristics (sensitivity, negative predictive value, likelihood ratios and proportion of patients ruled out) for multiple combinations of sex-specific rule-out cutoffs. We calculated net reclassification improvement compared to universal rule-out cutoffs of 5ng/L (the assays limit of detection) and 6ng/L (the FDA-approved limit of quantitation for US laboratories). Results: 7130 patients, including 3931 men and 3199 women, were included. The 7-day incidence of AMI was 7.38% among men and 3.78% among women. Universal cutoffs of 5 and 6 ng/L ruled out AMI with 99.7% sensitivity in 33.6 and 42.2% of patients. The best-performing combination of sex-specific cutoffs (8g/L for men and 6ng/L for men) ruled out AMI with 98.7% sensitivity in 51.9% of patients. Conclusion: Sex-specific hsTnT cutoffs for ruling out AMI at ED arrival may achieve substantial improvement in classification performance, enabling more patients to be ruled out at ED arrival, while maintaining acceptable diagnostic sensitivity for AMI. Universal and sex-specific rule-out cutoffs differ by only small changes in hsTnT concentration. Therefore, these findings should be confirmed in other datasets.


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