MedicalResearch.com: What are the main findings of the study?
Dr. Body: This paper actually reports the findings of two consecutive, separate studies. We aimed to derive and then externally validate a clinical decision rule to risk stratify patients with suspected acute coronary syndromes in the Emergency Department (ED). This rule could then be used to reduce unnecessary hospital admissions while also making judicious use of specialist high dependency resources.
In the first study we derived a clinical decision rule that incorporates 8 variables: high sensitivity troponin T, heart-type fatty acid binding protein; ECG ischaemia; worsening angina; hypotension (systolic blood pressure <100mmHg on arrival); sweating observed in the ED; pain associated with vomiting; and pain radiating to the right arm or shoulder. When we validated the rule at a different centre, we found that its use could have avoided hospital admission for over a quarter of patients while effectively risk stratifying others. Of the 10% of patients who were identified as ‘high risk’, approximately 95% had a major adverse cardiac event within 30 days. The findings suggest that the Manchester Acute Coronary Syndromes (MACS) decision rule could be used to ‘rule in’ and ‘rule out’ acute coronary syndromes immediately, using information gathered at the time of initial presentation to the ED. Before clinical implementation, we recommend that effect of using the MACS rule in practice should first be evaluated in a trial setting. This will enable us to determine:
(a) whether physicians and patients are likely to comply with (and be satisfied with) the MACS rule;
(b) the safety of the MACS rule when used in practice; and
(c) whether use of the MACS rule leads to cost savings for the health service.
MedicalResearch.com: Were any of the findings unexpected?
Dr. Body: When we first started out we suspected that the most useful biomarkers may be markers of the earliest stages in the disease process such as plaque rupture, rather than markers of myocardial necrosis. However, the markers of plaque rupture that we evaluated had relatively disappointing performance. In contrast, we found that high sensitivity troponin T and heart-type fatty acid binding protein are excellent markers with independent predictive value. Both were found to be useful additions to the decision rule.
The other finding that was perhaps unexpected was the inclusion of pain radiating to the right arm or shoulder, which we would normally consider as an ‘atypical’ symptom of an acute coronary syndrome. However, we found that this feature helped to differentiate those with acute myocardial infarction (AMI) from those without, which is actually consistent with other reports in the literature.
This doesn’t mean that pain radiating to the right arm or shoulder should now be considered as more ‘typical’ than, for example, pain radiating to the left arm or shoulder. In our derivation study, approximately a third of patients with AMI had pain radiating to the left arm or shoulder. However, the same proportion of patients who did not have acute myocardial infarction also reported pain radiating to the left arm or shoulder, so this feature just didn’t help to differentiate between the two groups. Pain radiating to the right arm or shoulder was less common among patients with AMI. A little more than 1 in 5 patients with acute myocardial infarction had this symptom compared to less than 1 in 10 patients who did not have AMI. As such, this symptom helped to differentiate patients with acute myocardial infarction from those without. When we ran the multivariate analysis, this symptom was found to have independent predictive value, hence its inclusion in the rule.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Body: First and foremost, what we’ve described is a really promising strategy for use in patients presenting to the Emergency Department with suspected cardiac chest pain. Using the MACS rule, it may be possible to immediately ‘rule out’ an acute coronary syndrome (ACS) and safely discharge more than 1 in 4 patients, to ‘rule in’ ACS for 1 in 10 patients, and to effectively risk stratify the remaining patients who still need further tests. This does need further evaluation as part of a trial and we’re looking for potential sites, both in the UK and internationally, to participate.
Second, we’ve described a fairly novel approach to interpreting biomarker levels. We considered troponin and H-FABP as continuous variables, i.e. we didn’t artificially dichotomise the levels at an arbitrary level such as the 99th percentile in a healthy reference population. The higher the level of these biomarkers, the greater the risk. By using a computer model, we were able to retain the richness of diagnostic information and optimise the risk stratification. Potentially this method could be effectively applied in other situations.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Body: It’s imperative that we evaluate use of the MACS rule in practice to ensure that physicians and patients will comply and find the rule acceptable, to verify safety and to evaluate the economic impact for health services. We should also look at ways to refine and build upon the MACS rule. We know that serial troponin testing over 1 to 2 hours may enable exclusion of acute coronary syndromes. Potentially the MACS rule could be used to ‘rule out’ Acute Coronary Syndromes in a proportion of patients. Others may then undergo further testing after 1 to 2 hours, at which stage it may be possible to ‘rule out’ Acute Coronary Syndromes in even more patients. Thus, we would have a ‘staggered’ rule out strategy. This needs to be prospectively evaluated.
The Manchester Acute Coronary Syndromes (MACS) decision rule for suspected cardiac chest pain: derivation and external validation Richard Body, Simon Carley, Garry McDowell, Philip Pemberton, Gillian Burrows, Gary Cook, Philip S Lewis, Alexander Smith, Kevin Mackway-Jones