Cardiac Myosin-Binding Protein C for Diagnosing AMI

Study Questions:

What is the predictive ability of the novel biomarker cardiac myosin-binding protein C (cMyC) as compared to high-sensitivity cardiac troponin I (hs-cTnI) for the early diagnosis of acute myocardial infarction (AMI)?


The investigators measured concentrations of cMyC and high (hs) and standard (s) sensitivity cTn in 1,954 unselected patients presenting to the emergency department with symptoms suggestive of AMI at time of presentation. The final diagnosis of AMI was independently adjudicated using all available clinical and biochemical information without knowledge of cMyC. The prognostic endpoint was long-term mortality. Predictive value of the biomarkers during follow-up was assessed two-fold—one using Harrell’s C statistic for each biomarker at presentation for endpoints AMI, death, or the composite of AMI and all-cause mortality during follow-up (excluding the index event), and secondly, using Kaplan-Meier survival curves.


Final diagnosis was AMI in 340 patients (17%). Concentrations of cMyC at presentation were significantly higher in those with vs. without AMI (median 237 ng/L vs. 13 ng/L, p < 0.001). Discriminatory power for AMI, as quantified by the area under the receiver operating characteristic curve (AUC), was comparable for cMyC (0.924), hs-cTnT (0.927), and hscTnI (0.922) and superior to cTnI measured by a contemporary sensitivity assay (0.909). Combination of cMyC with hs-cTnT or s-cTnI (but not hs-cTnI) led to an increase in AUC to 0.931 (p < 0.0001) and 0.926 (p = 0.003), respectively. Use of cMyC more accurately classified patients with a single blood test into rule-out or rule-in categories: net reclassification improvement (NRI) +0.149 vs. hs-cTnT, +0.235 vs. hs-cTnI (p < 0.001). In early presenters (chest pain <3 hours), the improvement in rule-in/rule-out classification with cMyC was larger compared with hs-cTnT (NRI +0.256) and hs-cTnI (NRI +0.308; both p < 0.001). Comparing the C statistics, cMyC was superior to hs-cTnI and s-cTnI (p < 0.05 both) and similar to hs-cTnT at predicting death at 3 years.


The authors concluded that cMyC at presentation provides discriminatory power comparable to hs-cTnT and hs-cTnI in the diagnosis of AMI.


This cohort study reports that discrimination for MI with cMyC was similar to that of hs-cTnT and hs-cTnI and superior to s-cTnI. Furthermore, in patients presenting within 3 hours of chest pain onset, cMyC was superior to hs-cTnT. Using cutoffs for cMyC calibrated against those recommended in guidelines, cMyC correctly and safely rules-out and rules-in AMI in a greater proportion of patients than either hs-cTnT or hs-cTnI. These findings suggest that cMyC may be better able to triage patients presenting to the ED with suspected AMI and facilitate early discharge of low-risk patients, reducing the number of observation patients. While cMyC appears to be a promising new biomarker of MI with overall discriminatory power comparable with the current troponin assays, these findings need external validation in an independent cohort.

Clinical Topics: Acute Coronary Syndromes, ACS and Cardiac Biomarkers

Keywords: Acute Coronary Syndrome, Biological Markers, Cardiac Myosins, Chest Pain, Emergency Service, Hospital, Hematologic Tests, Myocardial Infarction, Myocardial Ischemia, Protein C, Triage, Troponin I, Troponin T

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