Direct Comparison of Cardiac Myosin-Binding Protein C with Cardiac Troponins for the Early Diagnosis of Acute Myocardial Infarction
Background—Cardiac myosin-binding protein C (cMyC) is a cardiac-restricted protein that is more abundant than cardiac troponins (cTn) and is released more rapidly following acute myocardial infarction (AMI). We evaluated cMyC as an adjunct or alternative to cTn in the early diagnosis of AMI.
Methods—In 1954 unselected patients presenting to the emergency department with symptoms suggestive of AMI, concentrations of cMyC and high (hs) and standard (s) sensitivity cTn were measured at 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.
Results—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 was comparable for cMyC (AUC; 0.924), hs-cTnT (0.927) and hs-cTnI (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 <3h), 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.
Conclusions—cMyC at presentation provides discriminatory power comparable to hs-cTnT and hs-cTnI in the diagnosis of acute myocardial infarction, and may perform favorably in patients presenting early after symptom onset.
Clinical Trial Registration—URL: www.clinicaltrials.gov Unique Identifier: NCT00470587
- Received February 25, 2017.
- Revision received July 13, 2017.
- Accepted August 10, 2017.
Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.