Can a high sensitivity Troponin T rule out Acute Coronary Syndrome taken at 0-hour and 1-hour after presentation?
Date First Published:
January 29, 2018
Last Updated:
January 30, 2018
Report by:
Nil Kamal Samanta, Adrian Marsh, Samik Kumar Bandyopadhyay, Consultant ED, Consultant ED, Doctor Upper GI Surg (Shrewsbury and Telford Hospitals NHS Trust)
Search checked by:
Nil Kamal Samanta, Shrewsbury and Telford Hospitals NHS Trust
Three-Part Question:
In [an adult over 18 years of age presenting with low risk cardiac pain] is a [high sensitivity Troponin T (hs-cTnT) taken at 0-hour and 1-hour after presentation] sensitive enough to [rule out Acute Coronary Syndrome (ACS).]
Clinical Scenario:
A 45-year-old man attended the Emergency Department (ED) with one-hour history of chest pain that could be of cardiac origin. His ECG did not reveal acute ischemic changes. It is important to substantiate or rule-out ACS in this situation. This analysis is aimed at finding whether a hs-cTnT measurement taken at 0-hour and 1-hour after presentation is sensitive enough for this purpose.
Search Strategy:
MEDLINE, PubMed, EMBASE, CINAHL, Cochrane, Google Scholar, NICE, ESC guidelines and bibliographies.
(Low risk chest pain and Emergency Department and high sensitivity troponin T and (1 or one hour). LIMIT to Human and English
(Low risk chest pain and Emergency Department and high sensitivity troponin T and (1 or one hour). LIMIT to Human and English
Search Details:
558 papers were found of which 549 were considered irrelevant, duplicates or of insufficient quality. The remaining 9 papers were included in the analysis.
Outcome:
Analysis of the 9 papers are shown in the table.
MACE: Major adverse cardiac events, CAG: Coronary angiography, AMI: Acute myocardial infarction, NPV: Negative predictive value, CI: Confidence Interval, PPV: Positive predictive value, TIMI: Thrombolysis in Myocardial Infarction, LR: Likelihood ratio, hs-cTnI: High sensitivity cardiac troponin I
MACE: Major adverse cardiac events, CAG: Coronary angiography, AMI: Acute myocardial infarction, NPV: Negative predictive value, CI: Confidence Interval, PPV: Positive predictive value, TIMI: Thrombolysis in Myocardial Infarction, LR: Likelihood ratio, hs-cTnI: High sensitivity cardiac troponin I
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Utility of the 0-hour/1-hour high-sensitivity cardiac troponin T algorithm in Asian patients with suspected non-ST elevation myocardial infarction. 1.tShiozaki M et al. 7 september 2017 (accepted Japan and Taiwan | 413 Emergency Department (ED) patients with chest pain in three hospitals | Prospective cohort, international, multicentre, diagnostic | Primary endpoint: MACE, ACS, death and urgent admission for CAG in 30 days follow up from initial attendance | Ruled out AMI with NPV 100% (CI 95%, 96.8% - 100%) and sensitivity 100% (CI 95%, 88.0% - 100%) PPV for AMI 33.1%(95%CI, 25.1% - 41.9%) and specificity 66.3% (95%CI, 60.2% - 72.0%) | Small numbers recruited - possible selection bias Unclear if convenience sample or consecutive patients Treating physicians not blinded Sample included patients with Takotsubo cardiomyopathy and patients receiving haemodialysis |
| Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T Mueller C et al. Jul-16 USA, Europe and Australia | 1282 ED patients with chest pain in twelve institutes across three continents | Prospective observational diagnostic study to validate hs-cTnT 0-hour/1-hour algorithm for rapid rule-out and rule-in AMI | Primary: The NPV and sensitivity for AMI of the hs-cTnT 0-hr/1-hr rule-out rule Secondary: PPV and specificity of the hs-cTnT 0-hr/1-hr rule-in rule | NPV for AMI 99.1% (95%CI 98.2 - 99.7%) and sensitivity 96.7% (95% CI 93.4 - 98.7%) PPV for AMI 77.2% (95%CI 70.4 - 83.0%) and specificity 96.1% (95% CI 94.7 - 97.2%) | Observational diagnostic study – does not evaluate use of hs-cTnT in clinical decision making Convenience sample Large exclusion criteria - extrapolation to wider population difficult |
| Identifying Patients Suitable for Discharge After a Single-Presentation High-Sensitivity Troponin Result: A Comparison of Five Established Risk Scores and Two High-Sensitivity Assays E Carlton et al Dec-15 UK | 963 ED patients with chest pain | Prospective diagnostic cohort study | Primary outcome: Fatal or nonfatal AMI within 30 days of hospital attendance (including the index visit) | A TIMI and modified Goldman score 1 or less with hs-cTnT had the potential to achieve a NPV greater than or equal to 99.5% while identifying >30% patients as suitable for immediate discharge | Risk of incorporation bias - outcome measures based on the hs-cTnT results under evaluation Primary endpoints were fatal and non-fatal AMI - patients with unstable angina possibly missed Excluded patients over the age of 80 years Conflict of interests |
| A 1-h Combination Algorithm Allows Fast Rule-Out and Rule-In of Major Adverse Cardiac Events Mokhtari A et al January, 2016 Sweden | 1038 ED patients with chest pain | Prospective observational study | Primary outcome: MACE within 30 days including the index visit | The combination algorithm ruled out MACE 60% of all patients and had a higher sensitivity than the troponin only algorithm (97.5% vs. 87.6%; p<0.0001) The NPV was 99.5% and the LR was 0.04 with the combination algorithm versus 97.8% and 0.17 respectively, with the troponin only algorithm. The combination algorithm ruled-in with higher sensitivity (75.2% vs. 56.2%; p<0.001) but a slightly lower specificity (94.0% vs. 96.4%; p<0.001) than the troponin algorithm | Single centre study Convenience sample Not all patients had two hs-cTnT samples taken |
| A 0-Hour/1-Hour Protocol for Safe, Early Discharge of Chest Pain Patients A Mokhtari et al. February 27, 2017(accepted) Sweden | 1020 ED patients with chest pain | Secondary analysis of prospective observational study | Primary outcome: MACE within 30 days including the index visit | The combination of an adapted TIMI score 1 or less, a non-ischemic ECG, and either a 0-hour hs-cTnT<5ng/L or a 0-hour hs-cTnT <12ng/L combined with a 1-hour increase <3ng/L identified 42.4% patients as very low risk with a NPV of 99.5% (95%CI = 98.3% - 99.9%) and a negative LR of 0.04 (95%CI = 0.01 – 0.14) for 30-day MACE | Single centre study Convenience sample Excluded patients with missing data Unstable angina not included in final diagnosis, which altered results Few patients had hs-cTnT taken within 2 hours of onset – patient safety in this cohort is unclear |
| One-hour rule-out and rule-in of Acute Myocardial Infarction using high-sensitivity cardiac Troponin T. Reichlin et al. 2012 Switzerland | 872 ED patients with chest pain | Prospective multicentre study | Primary prognostic end point: 30 days’ all-cause of mortality | Sensitivity and NPV of 100% for rule-out, a specificity and PPV of 97% and 84%, respectively for rule-in of AMI | Proportion of patients with end diagnosis of AMI was higher than other studies - possible lack of external generalizability Death was the primary endpoint Observational data - not validated for clinical use Same assay used for derivation and validation of hs-cTnT |
| Assessment of European society of Cardiology 0-hour/1-hour algorithm to rule-out and rule-in Acute Myocardial Infarction J Pickering et al. November, 2016 Australia, New Zealand and Canada | 2222 ED patients with chest pain. Combined data from 5 studies in 3 countries | Secondary analysis of ADAPT-ADP RCT, EDACS-ADP RCT, Canada RING study |
Primary outcome: The sensitivity of rule-out strategy as a measure of safety and the proportion categorized as rule-out (low-risk) as a measure of efficacy. Secondary outcome: PPV and proportion categorized as rule-in (high-risk) as measure of efficacy | hs-cTnT algorithm ruled out 1425 (64.1%) with a sensitivity 97.1% (95%CI, 94.0% - 98.8%) and ruled-in 292 (13.1%) with a PPV of 63.4% (95%CI, 57.5%-68.9%) | Samples used collected at 90 minutes and 2 hours. Adjudication of final diagnosis not standardised - In 3 countries hs-cTnI was used, not hs-cTnT Conflicts of interests |
| Safety of a 1-hour rule-out high sensitive Troponin T protocol in patients with chest pain at the Emergency Department E Rottger, et al. Dec-17 2017, Netherlands | 374 ED patients with chest pain | Prospective study | Primary endpoint: 6-week occurrence of MACE following index visit to ED | No patients had AMI or died during 6 weeks follow up 16 patients (4.3%) suffered MACE and 3 diagnosed non-cardiac chest-pain patients (0.8%) returned with unstable angina | Possible incorporation bias as hs-cTnT was part of diagnosis standard One quarter of patients excluded due to missing values at one hour |
| Prospective validation of a 1-hour algorithm to rule-out and rule-in Acute Myocardial Infarction using a high-sensitivity cardiac troponin T assay T Reichlin et al. May, 2015 Switzerland, Spain and Italy | 1320 ED patients with chest pain in three countries | Prospective cohort study | Primary endpoint: AMI | Ruled-out AMI in 59.5% of patients with a sensitivity of 99.6% (95%CI 97.6 to 99.9%) and NPV 99.9% (95%CI 99.3-100%) Ruled-in AMI 16.4% of patients with specificity 95.7% (95%CI 94.3-98.6%), although PPV was 78.2% (95%CI 72.1-83.6%) | Possible incorporation bias as hs-cTnT was part of diagnosis standard One quarter of patients excluded due to missing values at one hour |
Author Commentary:
The primary end-point of most studies were MACE within 30 days including the index visit. The NPV and the sensitivity for AMI of the hs-cTnT 0-hr/1-hr rule-out rule was the primary outcome measure. The secondary outcome measures included mortality at 30 days and 1 year. This included the PPV and specificity of the hs-cTnT 0-hr/1-hr rule-in rule. All studies tested hs-cTnT and most of them produced NPV of 99.1% or above (100%), lowest being 99.1% in one study11 for rule out AMI. However, PPV for rule-in AMI varied between 63.4% to 84% except one study showing PPV 33.1%1.
Bottom Line:
Based on the findings of the studies reviewed, it would seem very appropriate to consider the 0-hour/1-hour hs-cTnT algorithm in combination with a current established risk scoring to rule-out ACS in adult patients with low risk chest pain.
References:
- 1.tShiozaki M et al. . Utility of the 0-hour/1-hour high-sensitivity cardiac troponin T algorithm in Asian patients with suspected non-ST elevation myocardial infarction.
- Mueller C et al. . Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T
- E Carlton et al. Identifying Patients Suitable for Discharge After a Single-Presentation High-Sensitivity Troponin Result: A Comparison of Five Established Risk Scores and Two High-Sensitivity Assays
- Mokhtari A et al. A 1-h Combination Algorithm Allows Fast Rule-Out and Rule-In of Major Adverse Cardiac Events
- A Mokhtari et al.. A 0-Hour/1-Hour Protocol for Safe, Early Discharge of Chest Pain Patients
- Reichlin et al.. One-hour rule-out and rule-in of Acute Myocardial Infarction using high-sensitivity cardiac Troponin T.
- J Pickering et al.. Assessment of European society of Cardiology 0-hour/1-hour algorithm to rule-out and rule-in Acute Myocardial Infarction
- E Rottger, et al.. Safety of a 1-hour rule-out high sensitive Troponin T protocol in patients with chest pain at the Emergency Department
- T Reichlin et al.. Prospective validation of a 1-hour algorithm to rule-out and rule-in Acute Myocardial Infarction using a high-sensitivity cardiac troponin T assay