BET Title: Can the Manchester Acute Coronary Syndromes (MACS) and Troponin-only MACS (TMACS) decision aids rule out acute coronary syndromes in the Emergency Department?

1st Author Dr Charles Reynard1,2, Academic Clinical Fellow

2nd AuthorDr Husam Ismail3, Locum Consultant in Emergency Medicine

3rd AuthorMr Nicholas Hadden2, Medical Student

InstitutionManchester University NHS Foundation Trust1, University of Manchester2

Wrightington, Wigan and Leigh NHS Foundation Trust 3 UK

Abstract

A short cut review was carried out to establish whether the Manchester Acute Coronary Syndromes (MACS) and Troponin-only MACS (T-MACS) decision aids can safely rule out acute coronary syndromes in patients presenting to the Emergency Department with suspected cardiac chest pain. Six studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that both rules have high sensitivity for acute coronary syndromes, including the detection of major adverse cardiac events at 30 days. The original MACS algorithm may have marginally greater sensitivity than T-MACS but has inferior specificity and requires the use of a biomarker assay (for heart-type fatty acid binding protein) that is not currently widely used in practice.

Clinical Scenario

A patient arrives at the emergency department complaining of chest pain and the attending clinician suspects a cardiac aetiology. After one serum blood test the patients risk of acute coronary syndrome is calculated using the Troponin-only Manchester Acute Coronary Syndrome decision rule (TMACS) and the Manchester Acute Coronary Syndrome decision rule (MACS). The patient is deemed to be low risk by both decision rules (30 day risk of ACS <2%). The attending clinician has read some reports that these tools can enable early discharge, and is curious as to the strength of the evidence for the safe discharge of such patients.

Variables Present in Diagnostic algorithm / MACS / TMACS
Heart-type fatty acid binding protein (h-FABP) / ✔ / ✖
High sensitivity cardiac troponin T (hs-cTNT) / ✔ / ✔
ECG ischaemia / ✔ / ✔
Sweating observed by treating clinician / ✔ / ✔
Vomiting associated with presenting symptoms / ✔ / ✔
Systolic BP <100 mmHg on arrival / ✔ / ✔
Symptoms of Crescendo Angina / ✔ / ✔
Pain radiating to the right arm / shoulder / ✔ / ✔

Three-part question

In [adults presenting to the ED with suspected cardiac chest pain] does [use of the Manchester Acute Coronary Syndromes decision rule] enable [accurate ‘rule out’ of acute coronary syndromes]?

Search Strategy

We searched Medline via the Ovid online web interface and Embase via the Ovid online web interface up to October 2017.

Medline

(chest pain.mp. or exp Chest Pain/ OR exp Acute Coronary Syndrome/ or ACS.mp. OR myocardial infarction.mp. or exp Myocardial Infarction/ OR exp Myocardial Infarction/ or AMI.mp. OR mi.mp. OR acute myocardial infarction.mp.) AND (troponin only manchester acute coronary syndromes.mp. OR TMACS.mp. OR MACS.mp. OR “manchester acute coronary syndromes”.mp. OR manchester.mp.)

Embase

(chest pain.mp. or exp thorax pain/ OR acute coronary syndrome.mp. OR exp coronary artery thrombosis/ OR exp acute coronary syndrome/ OR exp unstable angina pectoris/ OR exp heart infarction/ OR myocardial infarction.mp. OR exp heart infarction/) AND (troponin only manchester acute coronary syndromes.mp. OR TMACS.mp. OR manchester acute coronary syndromes.mp. OR MACS.mp.)

Outcome

The search yielded 530 peer reviewed articles, of which 6 were found to be relevant. See Table 1.

Comments

The literature review for MACS found 5 papers: one randomised control trial, one secondary analysis of a different randomised control trial and three prospective diagnostic cohort studies. The literature review of TMACS found two papers, one multicentre prospective diagnostic cohort study and one secondary analysis of a different randomised control trial. The sensitivity of MACS for 30-day MACE ranged from 97.9% to 100. However the study reporting the lowest sensitivity, stated that the two coronary stenoses (accounting for all the missed MACEs) in the very low risk group did not require any coronary intervention. TMACS demonstrated a sensitivity of 98.7% for 30-day MACE in the original study and 96.3% in the external validation in Australia and New Zealand. The decrease in accuracy could be related to methodological difficulties in secondary analyses, but it could also be attributable to the differing populations and rates of AMI. These statements are supported by the fact that both MACS and TMACS demonstrated a lower sensitivity in this secondary analysis. TMACS’s allocation of patients to the very low risk ‘ruled out’ group was compared to: a) the ‘limit of detection’ strategy (LoD - allocating any patient with a hs-cTnT <5ng/L and no ECG ischaemia to the very low risk group) and b) MACS. This demonstrated that TMACS ruled out ACS in 40.4% of patients, LoD ruled out in 32.1%, MACS ruled out 35.5%. TMACS rules out ACS in a greater proportion of patients, whilst maintaining a very high sensitivity despite omitting h-FABP and its associated inaccessibility.

Clinical Bottom Line

The research suggests that MACS has greater sensitivity for ruling out ACS, however the assay required (h-FABP) is not widely used, minimising the utility of such a tool. TMACS only requires hs-cTnT, which is already widely used in practice. It has a sensitivity of up to 98.7% for MACE at 30 days, and it can rule out ACS in more patients than LoD and MACS based strategies. In its current form, it is feasible that these tools could be used to enable risk-stratified admission policies, with patients at very low risk being admitted to ambulatory or observational medical units. It may be desirable to run a randomized controlled trial in order to generate further evidence supporting the ‘one test rule out’ function of TMACS.

References

1- Body R, Carley S, McDowell G et al. "The Manchester Acute Coronary Syndromes (MACS) decision rule for suspected cardiac chest pain: derivation and external validation." Heart 2014;100:1462–1468.

2 - Body R, Burrows G, Carley S et al."The Manchester Acute Coronary Syndromes (MACS) decision rule: validation with a new automated assay for heart-type fatty acid binding protein." Emerg Med J 2015;32:769–774.

3 - Carlton E, Body R, Greaves K. "External validation of the Manchester Acute Coronary Syndromes decision rule." Academic Emergency Medicine 2016;23:136–143.

4 - Body R, Carlton E, Sperrin M et al. "Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid: single biomarker re-derivation and external validation in three cohorts." Emerg Med J 2017;34:349–356.

5 - Body R, Boachie C, McConnachie A et al. "Feasibility of the Manchester Acute Coronary Syndromes (MACS) decision rule to safely reduce unnecessary hospital admissions: a pilot randomised controlled trial." Emerg Med J 2017;34:586–592.

6 - Greenslade JH, Nayer R, Parsonage W, et al. "Validating the Manchester Acute Coronary Syndromes (MACS) and Troponin-only Manchester Acute Coronary Syndromes (T-MACS) rules for the prediction of acute myocardial infarction in patients presenting to the emergency department with chest pain." Emerg Med J 2017;34:517–523.

Table 1.

Author, country, date / Patient group / Study type / Outcomes / Key results / Study weaknesses
Body et al, UK, 30/04/2014 1 / Derivation cohort n=698, Validation cohort n=463, adults presenting to the emergency department with suspected cardiac chest pain. / Prospective diagnostic cohort study at two centres / MACS Sensitivity for MACE 30 days / 98.0 (93.0-99.8) / The study re-uses a small amount of data from original derivation studies, as such may introduce confounding
Body et al, UK, 24/12/2014 2 / n=456, adults presenting to the emergency department with suspected cardiac chest pain. / Prospective diagnostic cohort study / MACS Sensitivity for MACE 30 days / 97.9 (92.8-99.8) / Two MACEs occurred in the very low risk group, both of which were coronary stenoses. However on angiography no coronary intervention was deemed necessary.
Carlton et al, UK, 01/02/2016 3 / n=782, adults presenting to the emergency department with suspected cardiac chest pain. / Secondary analysis of a prospective single centre cohort study / MACS Sensitivity for MACE (30 days) / 100 (95.4-100) / The study is a secondary analysis and as such may introduce bias.
Body R et al, UK,
30/12/2016 4 / Derivation cohort n=703, Validation cohort n=1459. Adults presenting to the emergency department suspected cardiac chest pain. Very low risk patient group reported here (<2% risk of AMI) / Multi-centre prospective diagnostic cohort study, with multivariate analysis logistic regression. / TMACS Sensitivity for MACE (30 days) / 98.7 (95% CI 95.3-99.8) / The study re-uses a small amount of data from original derivation studies, as such may introduce confounding. One study site excluded patients with ECG ischaemia, thereby potentially depleting the study of some high risk patients.
Body R et al, UK,
25/02/2017 5 / n=138. Adults presenting to the emergency department with suspected cardiac chest pain. / Pilot Randomised controlled trial, across two sites / MACS Sensitivity for MACE (180 days) / 100 (71.5 -100) / - A small sample size, as the study states, making it a feasibility trial for a larger RCT.
Greenslade JH et al, Australia and New Zealand,
28/03/2017 6 / n=1244. Adults presenting to the emergency department with suspected cardiac chest pain. Very low risk patient group reported here (<2% risk of AMI) / Secondary analysis of the pooled data from two prospective RCTs. / TMACS Sensitivity for MACE (30 days) / 96.3 (92.2-98.6) / - TMACS includes a dichotomous value for crescendo angina, which was not originally collected in this study and therefore a substitute was used.
- A further dichotomous value of attending clinician observing hidrosis was not originally collected and a surrogate of patient reported hidrosis was drawn from medical records.
- Of the 1715 patients enrolled, 471 (33%) were excluded as their blood had not been stored and therefore could not be analysed.
MACS Sensitivity for MACE (30 days) / 98.2 (94.7-99.6)