High-sensitivity methods for cardiac troponins: The mission is not over yet
Aldo Clerico1, Martina Zaninotto2, Claudio Passino1
1Fondazione CNR-Regione Toscana, G. Monasterio, Pisa, Italy; Scuola Superiore Sant'Anna, Pisa, Italy.
Insights
High-sensitivity cardiac troponin (hs-cTn) assays are crucial for diagnosing Acute Coronary Syndromes. New methods are needed to distinguish reversible from irreversible myocardial injury based on specific circulating troponin forms.
Area of Science:
- Cardiology
- Biomarker Analysis
- Clinical Chemistry
Background:
- Cardiac troponin (cTn) measurement is the gold standard for diagnosing Acute Coronary Syndromes (ACS).
- High-sensitivity cardiac troponin (hs-cTn) assays are widely used but present challenges in differentiating myocardial injury mechanisms.
- Distinguishing between reversible and irreversible cardiomyocyte injury based on biomarker release remains a key clinical concern.
Purpose of the Study:
- To review critical analytical and clinical issues of current hs-cTn methods.
- To discuss the potential of novel hs-cTn assays for differentiating myocardial injury.
- To highlight the need for next-generation hs-cTn assays.
Main Methods:
- Review of experimental and clinical studies on hs-cTn assays.
- Analysis of circulating troponin isoforms (cTnI and cTnT) in myocardial injury.
- Discussion of immunometric immunoassays and chromatographic techniques for novel hs-cTn detection.
Main Results:
- Current hs-cTn methods struggle to differentiate pathophysiological mechanisms of biomarker release.
- Distinct circulating forms of cTnI and cTnT are associated with reversible versus irreversible myocardial injury.
- New assay generations could offer specificity for these different troponin forms.
Conclusions:
- Next-generation hs-cTn methods, potentially using immunometric immunoassays or chromatography, are needed.
- These assays should be specific for circulating troponin peptide forms indicative of reversible or irreversible myocardial injury.
- Such advancements will further refine the diagnosis, prognosis, and management of cardiac diseases.
Abstract:
The measurement of cardiac troponin (cTn) is recommended by all guidelines as the gold standard for the differential diagnosis of Acute Coronary Syndromes. The aim of this review is to discuss in details some key issues regarding both analytical and clinical characteristics of the high-sensitivity methods for cTn (hs-cTn), which are still considered controversial or unresolved. In particular, the major clinical concern regarding hs-cTn methods is the difficulty to differentiate the pathophysiological mechanism responsible for biomarker release from cardiomyocytes after reversible or irreversible injury, respectively. Indeed, recent experimental and clinical studies have demonstrated that different circulating forms of cTnI and cTnT can be respectively measured in plasma samples of patients with reversible or irreversible myocardial injury. Accordingly, a new generation of hs-Tn methods should be set up, based on immunometric immunoassays or chromatographic techniques, specific for circulating peptide forms more characteristics for reversible or irreversible myocardial injury. It is conceivable that this new generation of hs-cTn methods will complete the mission regarding the laboratory tests for specific cardiac biomarkers, started more than 20 years ago, which has already revolutionized the diagnosis, prognosis and management of patients with cardiac diseases.
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