Validation of the 0/1-hour cardiac myosin-binding protein C algorithm and establishment of sex-specific reference
Yuta Hotchi1, Risa Tanaka1, Yuhei Kojima2
1Department of Emergency and Critical Care Medicine, Juntendo University Nerima Hospital, Tokyo, Japan; Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Insights
This study established sex-specific cardiac myosin-binding protein C (cMyC) reference values in Japan and validated a 0/1-h cMyC algorithm for acute coronary syndrome (ACS). The cMyC algorithm showed comparable triage to high-sensitivity cardiac troponin T (hs-cTnT), but hs-cTnT offered higher safety in rule-out.
Area of Science:
- Cardiology
- Biomarker Discovery
- Clinical Diagnostics
Background:
- Cardiac myosin-binding protein C (cMyC) is a cardiac-specific protein.
- A 0/1-hour diagnostic algorithm using cMyC has shown promise in European populations for acute coronary syndrome (ACS).
Purpose of the Study:
- Establish sex-specific 99th percentile reference limits for cMyC in a healthy Japanese population.
- Evaluate the diagnostic performance of a cMyC immunoassay using a 0/1-hour algorithm in patients with suspected ACS.
- Compare cMyC algorithm performance with the established high-sensitivity cardiac troponin T (hs-cTnT) algorithm.
Main Methods:
- Prospective observational study.
- Determined sex-specific cMyC reference limits in 602 healthy Japanese individuals.
- Evaluated a cMyC immunoassay in 260 patients with suspected ACS within 12 hours of symptom onset.
- Compared results with the European Society of Cardiology (ESC)-recommended 0/1-hour hs-cTnT algorithm.
Main Results:
- Established 99th percentile cMyC values: 11.4 ng/L for males and 8.1 ng/L for females.
- In the ACS cohort (20% with myocardial infarction), the cMyC 0/1-h algorithm achieved 95.2% negative predictive value (NPV) and 83.3% sensitivity for rule-out, and 70.0% positive predictive value (PPV) and 90.3% specificity for rule-in.
- The hs-cTnT algorithm showed comparable triage but higher safety with 100% NPV and sensitivity for rule-out.
Conclusions:
- First sex-specific cMyC reference values established for an East Asian population.
- Validated a 0/1-hour cMyC algorithm in a real-world ACS cohort, demonstrating similar triage proportions to hs-cTnT.
- The hs-cTnT strategy exhibited superior safety in the rule-out arm compared to the cMyC algorithm.
Background:
Cardiac myosin-binding protein C (cMyC) is an abundant, cardiac-specific protein. A 0/1-h diagnostic algorithm based on cMyC has shown promising performance in European cohorts.
Methods:
In this prospective observational study, we established sex-specific 99th percentile reference limits for cMyC in a healthy Japanese population and evaluated the diagnostic performance of a cMyC immunoassay (Sysmex HISCL platform) in 260 consecutive patients who presented with suspected acute coronary syndrome (ACS) within 12 h of symptom onset. The results were compared with those of the ESC-recommended 0/1-h algorithm based on high-sensitivity cardiac troponin T (hs-cTnT).
Results:
After outlier removal, 324 male and 278 female were included, yielding 99th percentile cMyC concentrations of 11.4 ng/L and 8.1 ng/L, respectively. In the diagnostic cohort, 51 patients (20 %) were diagnosed with acute myocardial infarction. The cMyC 0/1-h algorithm classified 43.8 % of patients as ruled-out at presentation and 56.5 % after 1 h, with a negative predictive value (NPV) of 95.2 % and sensitivity of 83.3 %. For rule-in, 10.0 % were identified at 0 h and 19.2 % after 1 h, with a positive predictive value (PPV) of 70.0 % and specificity of 90.3 %. Application of the hs-cTnT algorithm yielded comparable results (rule-out: 48.8 %, NPV 100 %, sensitivity 100 %; rule-in: 25.4 %, PPV 62.1 %, specificity 83.6 %).
Conclusions:
We established the first sex-specific cMyC reference values in an East Asian population and validated a 0/1-h cMyC algorithm in a real-world ACS cohort. The algorithm yielded triage proportions similar to those of the hs-cTnT strategy, although the hs-cTnT rule-out arm demonstrated higher safety.
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