NIHR Signal Blood test and ECG may safely rule out heart attack

Published on 12 September 2017

A high sensitivity troponin test accurately ruled out a heart attack amongst a third of patients presenting to the emergency department with chest pain. A patient with no detectable troponin and normal electrocardiogram was almost certain not to have had a heart attack.

Many people come to hospital with chest pain, but more than 75% of them have not had a heart attack. The two tests accurately ruled out heart attack in 30% of all chest pain presentations, but more than a third of people who didn’t have a heart attack also tested positive. Only around a quarter of people with raised troponin have had a heart attack. The tests were less reliable in people who had chest pain for less than three hours.

The findings support existing NICE guidelines to use high sensitivity troponin testing in people with a suspected heart attack but without the classic features on an electrocardiogram. The test should not be used indiscriminately for all chest pain presentations.

Caution is needed due to the variability in individual study results, patient populations and testing protocols.

Blood test and ECG may safely rule out heart attack

Why was this study needed?

Each year about 150,000 men and women in the UK suffer a heart attack, but over 700,000 attend hospital emergency departments with chest pain.

Patients with a heart attack usually have a blockage in one of the arteries supplying blood to the heart. They need urgent treatment to restore the blood supply to reduce permanent damage to the heart. Doctors need to quickly determine whether or not heart attack may be the cause of chest pain. Early rule-out may avoid unnecessary hospital admission, investigations and treatment.

Troponin protein is released from damaged heart muscle into the bloodstream. New high-sensitivity blood tests allow detection of a very low level of troponin soon after the onset of symptoms. The electrocardiogram (ECG) measures the heart’s electrical activity and can show abnormalities in a heart attack. This review aimed to see whether a negative high sensitivity troponin T assay and normal ECG can accurately rule out heart attack in the emergency department.

What did this study do?

This review identified 11 cohorts including 9,241 adults presenting to the emergency department with chest pain. All received an ECG and high sensitivity troponin T test.

Researchers looked at whether a troponin level of less than 0.005 µg/L (the lowest detectable level) when combined with normal ECG, was accurate in ruling out a heart attack. Heart attack was confirmed, independently in most studies, according to the Universal Global Task Force definition. Other outcomes were death or major adverse cardiac event (such as revascularisation) within 30 days.

Nine of the 11 studies had a high or unclear risk of bias. Individual studies varied in patient characteristics, timing and number of troponin tests, and their results. These factors may make meta-analysis inappropriate. All studies were from developed countries, but only one was from the UK.

What did it find?

  • 30.6% of patients with chest pain were defined as low risk and tested negative, with a normal ECG and high sensitivity troponin below threshold (95% confidence interval [CI] 3.8% to 73.5%).
  • These patients, testing negative, were almost certain not to have had a heart attack. The pooled negative predictive value was 99.3% (95% CI 97.3% to 99.8%).
  • Only 14 patients (0.5%) had a ‘false negative’ result and were later confirmed to have had a heart attack. Seven of these were tested within three hours of the start of the pain. The pooled sensitivity was 98.7% (95% CI 96.6% to 99.5%) and was good across studies, ranging from 87.5% to 100%.
  • The test wasn’t good for diagnosing a heart attack and gave a high number of incorrect ‘positive’ results in people without a heart attack. Pooled specificity was 64% (95% CI 49% to 77%). Specificity was low across studies but highly variable, ranging from 5% to 79%. Overall less than a quarter of people testing positive had a heart attack (positive predictive value 22%, 95% CI 19% to 27%).
  • The test accurately identified almost all patients who died or had a major cardiac adverse event within 30 days (sensitivity 98.0%, 95% CI 94.7% to 99.3%). A total of 126 patients died (1.3% of the cohort), none of whom was in the low risk/test negative category.

Troponin test results for people with heart attack

Troponin test results for people without heart attack

What does current guidance say on this issue?

Current NICE guidance on chest pain (updated 2016) recommends that patients with a suspected heart attack should receive an ECG and high sensitivity troponin test on hospital arrival. If patients do not have the typical ECG features of a heart attack (ST elevation), a repeat high sensitivity troponin three hours later can confirm or rule out non-ST elevation heart attack.

Troponin measurement is not recommended for people presenting with chest pain who are not clinically suspected of having a heart attack.

What are the implications?

This meta-analysis generally supports NICE recommendations around the use of the high sensitivity troponin test in people with a suspected heart attack but without the classic ECG signs of ischaemia.

Although it is not reliable less than three hours after the onset of pain, where the ECG is normal the new high sensitivity assay may reduce waiting times and avoid unnecessary hospital admissions and associated costs.

Citation and Funding

Pickering JW, Than MP, Cullen L, et al. Rapid rule-out of acute myocardial infarction with a single high-sensitivity cardiac troponin T measurement below the limit of detection: a collaborative meta-analysis. Ann Intern Med. 2017;166(10):715-24.

This study was funded by the Emergency Care Foundation.

Bibliography

Goodacre S, Thokala P, Carroll C et al. Systematic review, meta-analysis and economic modelling of diagnostic strategies for suspected acute coronary syndrome. Health Technol Assess. 2013;17(1).

NHS Choices. Heart attack: diagnosis. London: Department of Health; 2016.

NHS Choices. Chest pain. London: Department of Health; 2015.

NICE. Myocardial infarction (acute): early rule out using high-sensitivity troponin tests (Elecsys Troponin T high-sensitive, ARCHITECT STAT High Sensitive Troponin I and AccuTnl+3 assays. DG15. London: National Institute for Health and Care Excellence; 2014.

NICE. Chest pain of recent onset: assessment and diagnosis. CG95. London: National Institute for Health and Care Excellence; 2010.

Why was this study needed?

Each year about 150,000 men and women in the UK suffer a heart attack, but over 700,000 attend hospital emergency departments with chest pain.

Patients with a heart attack usually have a blockage in one of the arteries supplying blood to the heart. They need urgent treatment to restore the blood supply to reduce permanent damage to the heart. Doctors need to quickly determine whether or not heart attack may be the cause of chest pain. Early rule-out may avoid unnecessary hospital admission, investigations and treatment.

Troponin protein is released from damaged heart muscle into the bloodstream. New high-sensitivity blood tests allow detection of a very low level of troponin soon after the onset of symptoms. The electrocardiogram (ECG) measures the heart’s electrical activity and can show abnormalities in a heart attack. This review aimed to see whether a negative high sensitivity troponin T assay and normal ECG can accurately rule out heart attack in the emergency department.

What did this study do?

This review identified 11 cohorts including 9,241 adults presenting to the emergency department with chest pain. All received an ECG and high sensitivity troponin T test.

Researchers looked at whether a troponin level of less than 0.005 µg/L (the lowest detectable level) when combined with normal ECG, was accurate in ruling out a heart attack. Heart attack was confirmed, independently in most studies, according to the Universal Global Task Force definition. Other outcomes were death or major adverse cardiac event (such as revascularisation) within 30 days.

Nine of the 11 studies had a high or unclear risk of bias. Individual studies varied in patient characteristics, timing and number of troponin tests, and their results. These factors may make meta-analysis inappropriate. All studies were from developed countries, but only one was from the UK.

What did it find?

  • 30.6% of patients with chest pain were defined as low risk and tested negative, with a normal ECG and high sensitivity troponin below threshold (95% confidence interval [CI] 3.8% to 73.5%).
  • These patients, testing negative, were almost certain not to have had a heart attack. The pooled negative predictive value was 99.3% (95% CI 97.3% to 99.8%).
  • Only 14 patients (0.5%) had a ‘false negative’ result and were later confirmed to have had a heart attack. Seven of these were tested within three hours of the start of the pain. The pooled sensitivity was 98.7% (95% CI 96.6% to 99.5%) and was good across studies, ranging from 87.5% to 100%.
  • The test wasn’t good for diagnosing a heart attack and gave a high number of incorrect ‘positive’ results in people without a heart attack. Pooled specificity was 64% (95% CI 49% to 77%). Specificity was low across studies but highly variable, ranging from 5% to 79%. Overall less than a quarter of people testing positive had a heart attack (positive predictive value 22%, 95% CI 19% to 27%).
  • The test accurately identified almost all patients who died or had a major cardiac adverse event within 30 days (sensitivity 98.0%, 95% CI 94.7% to 99.3%). A total of 126 patients died (1.3% of the cohort), none of whom was in the low risk/test negative category.

Troponin test results for people with heart attack

Troponin test results for people without heart attack

What does current guidance say on this issue?

Current NICE guidance on chest pain (updated 2016) recommends that patients with a suspected heart attack should receive an ECG and high sensitivity troponin test on hospital arrival. If patients do not have the typical ECG features of a heart attack (ST elevation), a repeat high sensitivity troponin three hours later can confirm or rule out non-ST elevation heart attack.

Troponin measurement is not recommended for people presenting with chest pain who are not clinically suspected of having a heart attack.

What are the implications?

This meta-analysis generally supports NICE recommendations around the use of the high sensitivity troponin test in people with a suspected heart attack but without the classic ECG signs of ischaemia.

Although it is not reliable less than three hours after the onset of pain, where the ECG is normal the new high sensitivity assay may reduce waiting times and avoid unnecessary hospital admissions and associated costs.

Citation and Funding

Pickering JW, Than MP, Cullen L, et al. Rapid rule-out of acute myocardial infarction with a single high-sensitivity cardiac troponin T measurement below the limit of detection: a collaborative meta-analysis. Ann Intern Med. 2017;166(10):715-24.

This study was funded by the Emergency Care Foundation.

Bibliography

Goodacre S, Thokala P, Carroll C et al. Systematic review, meta-analysis and economic modelling of diagnostic strategies for suspected acute coronary syndrome. Health Technol Assess. 2013;17(1).

NHS Choices. Heart attack: diagnosis. London: Department of Health; 2016.

NHS Choices. Chest pain. London: Department of Health; 2015.

NICE. Myocardial infarction (acute): early rule out using high-sensitivity troponin tests (Elecsys Troponin T high-sensitive, ARCHITECT STAT High Sensitive Troponin I and AccuTnl+3 assays. DG15. London: National Institute for Health and Care Excellence; 2014.

NICE. Chest pain of recent onset: assessment and diagnosis. CG95. London: National Institute for Health and Care Excellence; 2010.

Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis

Published on 19 April 2017

Pickering, J. W.,Than, M. P.,Cullen, L.,Aldous, S.,Ter Avest, E.,Body, R.,Carlton, E. W.,Collinson, P.,Dupuy, A. M.,Ekelund, U.,Eggers, K. M.,Florkowski, C. M.,Freund, Y.,George, P.,Goodacre, S.,Greenslade, J. H.,Jaffe, A. S.,Lord, S. J.,Mokhtari, A.,Mueller, C.,Munro, A.,Mustapha, S.,Parsonage, W.,Peacock, W. F.,Pemberton, C.,Richards, A. M.,Sanchis, J.,Staub, L. P.,Troughton, R.,Twerenbold, R.,Wildi, K.,Young, J.

Ann Intern Med , 2017

Background: High-sensitivity assays for cardiac troponin T (hs-cTnT) are sometimes used to rapidly rule out acute myocardial infarction (AMI). Purpose: To estimate the ability of a single hs-cTnT concentration below the limit of detection (<0.005 microg/L) and a nonischemic electrocardiogram (ECG) to rule out AMI in adults presenting to the emergency department (ED) with chest pain. Data Sources: EMBASE and MEDLINE without language restrictions (1 January 2008 to 14 December 2016). Study Selection: Cohort studies involving adults presenting to the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT measurements were obtained and AMI outcomes adjudicated during initial hospitalization. Data Extraction: Investigators of studies provided data on the number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements <0.005 microg/L) and the number who had AMI during hospitalization (primary outcome) or a major adverse cardiac event (MACE) or death within 30 days (secondary outcomes), by risk classification (low or not low risk). Two independent epidemiologists rated risk of bias of studies. Data Synthesis: Of 9241 patients in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%) low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7% (95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%; pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died. Limitation: Few studies, variation in timing and methods of reference standard troponin tests, and heterogeneity of risk and prevalence of AMI across studies. Conclusion: A single hs-cTnT concentration below the limit of detection in combination with a nonischemic ECG may successfully rule out AMI in patients presenting to EDs with possible emergency acute coronary syndrome. Primary Funding Source: Emergency Care Foundation.

The Global Task Force definition of acute heart attack is the detection of a rise and/or fall in cardiac biomarkers (preferably troponin with at least one value >99th percentile), along with symptoms of ischaemia, compatible ECG changes, new signs of heart muscle damage on imaging, or a clot in the blood vessels on angiography.

Sensitivity is the proportion of people with a disease who are correctly identified as having that disease by the test.

Specificity is the proportion of people without a disease who are correctly identified as not having that disease by the test.

The negative predictive value is the probability that someone with a negative test result does not have the condition.

The positive predictive value is the probability that someone with a positive result has the condition.

Expert commentary

This emerging approach to emergency department (ED) chest pain patients identifies a group that has a very low risk of cardiac events and death within the next 30 days. It has the potential to reduce unnecessary hospital admissions and improve ED patient flow.

However, given the scale of the problem the evidence base remains limited by methodological complications and a relatively small number of patients in the included studies. Issues of timing are also not fully resolved; this strategy wouldn't necessarily be right for a patient who develops chest pain while walking past their local ED.

Jonathan Benger, National Clinical Director for Urgent Care, NHS England; Professor of Emergency Care, University of the West of England, Bristol; Consultant in Emergency Medicine, University Hospitals Bristol NHS Foundation Trust

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  •   Cardiovascular system disorders, Diagnostics, Emergency and urgent care, Acute and general medicine