Abstract
Cardiac troponins (cTns) are released and cleared slowly after myocardial injury. Cardiac myosin–binding protein C (cMyC) is a similar cardiac-restricted protein that has more rapid release and clearance kinetics. Direct comparisons are hampered by the lack of an assay for cMyC that matches the sensitivity of the contemporary assays for cTnI and cTnT. Using a novel pair of monoclonal antibodies, we generated a sensitive assay for MyC on the Erenna platform (Singulex) and compared serum concentrations with those of cTnI (Abbott) and cTnT (Roche) in stable ambulatory cardiac patients without evidence of acute cardiac injury or significant coronary artery stenoses. The assay for cMyC had a lower limit of detection of 0.4 ng/L, a lower limit of quantification (LLoQ) of 1.2 ng/L (LLoQ at 20% coefficient of variation [CV]) and reasonable recovery (107.1 ± 3.7%; mean ± standard deviation), dilutional linearity (101.0 ± 7.7%), and intraseries precision (CV, 11 ± 3%) and interseries precision (CV, 13 ± 3%). In 360 stable patients, cMyC was quantifiable in 359 patients and compared with cTnT and cTnI measured using contemporary high-sensitivity assays. cMyC concentration (median, 12.2 ng/L; interquartile range [IQR], 7.9–21.2 ng/L) was linearly correlated with those for cTnT (median, <3.0 ng/L; IQR, <3.0–4.9 ng/L; R = 0.56, P < 0.01) and cTnI (median, 2.10 ng/L; IQR, 1.3–4.2 ng/L; R = 0.77, P < 0.01) and showed similar dependencies on age, renal function, and left ventricular function. We have developed a high-sensitivity assay for cMyC. Concentrations of cMyC in clinically stable patients are highly correlated with those of cTnT and cTnI. This high correlation may enable ratiometric comparisons between biomarkers to distinguish clinical instability.
Highlights
Acute myocardial infarction (AMI) carries a poor prognosis that can be improved by timely intervention
This article acts as the foundation for a study using the assay described here in patients presenting with suspected acute myocardial infarction to compare the diagnostic and prognostic performances of Cardiac myosin–binding protein C (cMyC) with cTnT and cTnI
Sera from 5 individuals were spiked with 200 ng/L of cMyC and subjected to repeated measurement
Summary
Acute myocardial infarction (AMI) carries a poor prognosis that can be improved by timely intervention It must be rapidly identified and differentiated from other causes of chest pain.[1] Cardiac necrosis biomarkers have become crucial in affirming or excluding AMI in suspected non–ST-elevation acute coronary syndromes (NSTE-ACSs) and are needed to confirm the diagnosis in an appropriate clinical context.[2] Cardiac troponins (cTns) have emerged as the gold standard and are incorporated in the universal definition of AMI.[2] the cTns have potential drawbacks and new necrosis biomarkers could prove invaluable.[3]. This article acts as the foundation for a study using the assay described here in patients presenting with suspected acute myocardial infarction to compare the diagnostic and prognostic performances of cMyC with cTnT and cTnI This article describes a high-sensitivity assay for cMyC, which demonstrates that it can be measured at baseline in almost all individuals, and in a stable population its concentration correlates with those for cTnI and cTnT.
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