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Quantifying the Release of Biomarkers of Myocardial Necrosis from Cardiac Myocytes and Intact Myocardium
Jack Marjot1, Thomas E Kaier1, Eva D Martin1
1King's College London BHF Centre, The Rayne Institute, St Thomas' Hospital, London, UK.
Insights
Diagnosing myocardial infarction requires cardiac necrosis biomarkers to exceed the 99th centile. This study found that even minimal myocardial damage, approximately 40 mg, can elevate these levels, potentially confounding early rule-out strategies.
Area of Science:
- Cardiology
- Biomarkers
- Clinical Diagnostics
Background:
- Myocardial infarction diagnosis relies on cardiac necrosis biomarkers exceeding the 99th percentile.
- Guidelines suggest lower thresholds for early rule-out protocols.
- The study investigates the myocardial mass represented by these biomarker concentrations.
Purpose of the Study:
- To quantify the amount of myocardium corresponding to 99th percentile biomarker levels.
- To assess if dietary troponin can interfere with myocardial infarction rule-out algorithms.
- To determine the sensitivity of high-sensitivity assays for cardiac biomarkers.
Main Methods:
- Cardiac myocytes and myocardium (rat, ovine, human) were added to human serum.
- Blood samples were collected after ovine myocardium ingestion.
- High-sensitivity assays measured cardiac troponin T (cTnT), cardiac troponin I (cTnI), and cardiac myosin-binding protein C (cMyC).
Main Results:
- Each rat cardiac myocyte increased cTnT and cTnI by approximately 19 ng/L.
- Human myocardium increased cTnT, cTnI, and cMyC by 3.9, 4.3, and 41.0 ng/L per microg, respectively.
- Ingesting ovine myocardium did not alter cTnI or cTnT levels significantly.
Conclusions:
- Necrosis of approximately 40 mg of myocardium may exceed 99th percentile biomarker concentrations.
- This small myocardial mass is undetectable by current noninvasive imaging techniques.
- Dietary troponin did not confound the rule-out algorithm in this study.
Background:
Myocardial infarction is diagnosed when biomarkers of cardiac necrosis exceed the 99th centile, although guidelines advocate even lower concentrations for early rule-out. We examined how many myocytes and how much myocardium these concentrations represent. We also examined if dietary troponin can confound the rule-out algorithm.
Methods:
Individual rat cardiac myocytes, rat myocardium, ovine myocardium, or human myocardium were spiked into 400-microL aliquots of human serum. Blood was drawn from a volunteer after ingestion of ovine myocardium. High-sensitivity assays were used to measure cardiac troponin T (cTnT; Roche, Elecsys), cTnI (Abbott, Architect), and cardiac myosin-binding protein C (cMyC; EMD Millipore, Erenna®).
Results:
The cMyC assay could only detect the human protein. For each rat cardiac myocyte added to 400 microL of human serum, cTnT and cTnI increased by 19.0 ng/L (95% CI, 16.8-21.2) and 18.9 ng/L (95% CI, 14.7-23.1), respectively. Under identical conditions cTnT, cTnI, and cMyC increased by 3.9 ng/L (95% CI, 3.6-4.3), 4.3 ng/L (95% CI, 3.8-4.7), and 41.0 ng/L (95% CI, 38.0-44.0) per microg of human myocardium. There was no detectable change in cTnI or cTnT concentration after ingestion of sufficient ovine myocardium to increase cTnT and cTnI to approximately 1 × 108 times their lower limits of quantification.
Conclusions:
Based on pragmatic assumptions regarding cTn and cMyC release efficiency, circulating species, and volume of distribution, 99th centile concentrations may be exceeded by necrosis of 40 mg of myocardium. This volume is much too small to detect by noninvasive imaging.