The Utility of Cardiac Myosin-Binding Protein C in the Early Triage of Patients with Suspected Acute Coronary Syndromes (ULYCES Trial)

Date of Award

2022

Degree Name

Master of Philosophy (School of Medicine)

Schools and Centres

Medicine

First Supervisor

Associate Professor Christopher Judkins

Second Supervisor

Professor Graham Hills

Abstract

Background: Acute chest pain is a common reason for patients to present to an Emergency Department (ED). The majority (>75%) of these individuals are at low risk of serious complications, with only a small proportion diagnosed with an acute coronary syndrome (ACS) or other major pathology. The consequences of misdiagnosis are, however, potentially serious. Thus, considerable time and resources are expended to ensure the accurate triage of such patients. Currently, high sensitivity troponin (hsTn) assays are used to aid in the diagnosis of ACS. However, in patients presenting early (i.e. ≤ 2 hrs) after the onset of their symptoms, hsTn may not yet have been released in great enough quantities to be detected, as a result further testing is required and this may lead to a treatment delay for these patients. Recently a new biomarker, cardiac myosin-binding protein C (cMyC) has been identified that rises more rapidly than hsTnI in patients with acute myocardial infarction (AMI). The aim of our study is to compare the utility of cMyC with hsTnI in the early assessment of patients presenting to the ED with chest pain.

Methods: This study prospectively recruited adult patients presenting to Royal Perth Hospital Emergency Department with suspected acute coronary syndrome, who attended ≤ 2hrs from the onset of their symptoms. We compared the utility of an index hsTnI measurement taken on arrival, with a novel biomarker, cMyC, to triage these patients into three groups; ‘rule-out’, ‘rule-in’, and ‘observe’. All patients were managed according to usual practice using hsTnI, with a cMyC level being performed retrospectively on biobanked blood samples.

Results: Between March 2020 and July 2021 we recruited 108 patients. Twenty-one percent of patients were diagnosed with an AMI and 79% had a non-ACS diagnosis. There was a significant difference in the cMyC levels for patients with AMI and non-ACS diagnoses (median 23ng/L [IQR 214ng/L] vs 4ng/L [IQR 4ng/L]). cMyC had a similar power of discrimination compared with hsTnI (AUC = 0.887 (95% CI 0.81-0.94) vs. AUC = 0.851 (95% CI 0.77-0.91), p=0.30). cMyC ruled-out more patients than hsTnI (cMyC: 79% vs hsTnI: 66%), and with a similar, diagnostic accuracy (NPV 91% vs 92%). The NRI index demonstrated superiority of cMyC over hsTnI in patients with a non-ACS diagnosis (NRI = +0.14), but there was no overall benefit (NRI(dimensionless) = - 0.16).

Conclusion: In adult patients with suspected ACS presenting ≤ 2 hours after symptom onset, a single cMyC measurement ‘ruled-out’ more patients than a single hsTnI, however both tests had a low diagnostic accuracy and discrimination power was similar. In clinical practice, further evaluation would be required in both groups.

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