Cardiac troponin is the preferred biomarker for the diagnosis of acute myocardial infarction (AMI), and the high-sensitive cardiac troponin T (hs-cTnT) assay permits detection of very low levels of cTnT.
Early diagnosis of myocardial infarction is the most important indication of hs-cTn assays.
Hs-cTn assays allow for the precise quantification of cardiomyocyte injury around the 99th percentile and thereby substantially increased the accuracy of MI detection from blood obtained at presentation to the emergency department (ED).
Using the hs-cTnT assay improves the overall diagnostic accuracy in patients with suspected AMI.
A negative hs-cTnT result also has a high negative predictive value.
The gain in sensitivity is particularly important in patients with a short duration from symptom onset to hospital admission.
Provides strong prognostic information in patients with acute syndromes, stable coronary artery disease, heart failure and even in the general population.
Persistently elevated high-sensitivity troponin levels indicate ongoing chronic myocardial injury and strongly associated with the risk of death and cardiovascular events.
Its increased sensitivity comes at a cost of decreased specificity.
It is difficult to differentiate a patient with acute myocardial infarction from patients who have other causes of myocardial injury.
Serial testing, clinical context and co-existing diseases, are increasingly important for the interpretation of hs-cTnT assay results.
The troponin complex regulates the contraction of striated muscles and consists of three subunits troponin C, troponin T, and troponin I
Troponin C is a 18 ku protein that binds to calcium ions.
Troponin T is a 37 ku protein that binds to tropomyosin, thereby attaching the troponin complex to the thin filament.
Troponin I is a 24 ku protein that binds to actin and decreases troponin C affinity for calcium, thus inhibiting actin-myosin interactions.
Troponin T and troponin I are present in cardiac and skeletal muscles.
Assays that are based on high-affinity antibodies and are specific for cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are available.
The majority of cardiac troponin (cTn) is bound to myofilaments, and the remainder is free in the cytosol which accounts for 3%-8% of the total amount.
After disruption of the sarcolemmal membrane of the cardiomyocyte, troponin from the cytoplasmic pool is initially released, followed by a more protracted release from quantities bound to deteriorating myofilaments.
In peripheral blood, cTnT begins to rise within three to four hours after the onset of myocardial injury and remains increased for 10-14 days.
High-sensitive cTnT (hs-cTnT) assay is a modification of the fourth-generation cTnT assay.
The early identification of individuals with myocardial ischemia is crucial because of the benefit of early and aggressive treatment.
Myocardial necrosis is associated with the release of structural proteins and other intracellular macromolecules into the cardiac interstitium, such as cTn, creatine kinase, and myoglobin.
The preferred biomarker for myocardial necrosis is cTn.
cTn has nearly absolute myocardial tissue specificity as well as high clinical sensitivity, and reflects even microscopic zones of myocardial necrosis.
The diagnosis of MI is based mainly on evidence of myocardial ischemia, together with an elevated cTn level exceeding the 99th percentile and demonstrating an increase or decrease over time.
In emergency department (ED) patients with symptoms suggestive of an AMI, the hs-cTnT assay significantly improved the early diagnosis of AMI compared with the standard troponin T assay.
With the diagnostic criterion for an AMI, a hs-cTnT level > the 99th percentile (0.014 ng/mL), has a sensitivity, specificity, negative predictive value, and positive predictive value of 95% (90%-98%), 80% (77%-83%), 99% (97%-100%), and 50% (43%-56%), respectively.
With a standard troponin T assay > 10% CV (0.035 ng/mL), the sensitivity, specificity, negative predictive value, and positive predictive value (95% CI) for diagnosis of AMI is 72% (64%-80%), 97% (96%-98%), 94% (92%-96%), and 85% (76%-91%), respectively.
The superiority of the hs-cTnT assay is most pronounced among patients with a recent onset of chest pain.
The hs-cTnT assay results are similar in patients with non-ST segment elevation MI (NSTEMI) and ST segment elevation MI.
The hs-cTnI assay improved the diagnostic ability in patients with AMIs.
More rapid diagnosis of AMI may facilitate an earlier revascularization, earlier transfer to the coronary care unit, and earlier initiation of treatment.
With the standard cTn assay in most patients, blood should be obtained for testing upon presentation and at 6-9 h after presentation to provide adequate clinical sensitivity for detecting a MI in a patient with chest pain.
With hs-cTnT diagnostic results are excellent, even in patients within two hours after the onset of chest pain.
By including a second sample within three hours of presentation, the sensitivity approaches 100%.
The hs-cTnT assay, has a negative predictive value for MI with a single test on admission of 95%.
An initial undetectable ED hs-cTnT has a sensitivity of 99.8% and a negative predictive value of 99.4% for ruling out an AMI, and this strategy may reduce the need for serial testing and empirical treatment, enabling earlier reassurance for patients with chest pain and fewer unnecessary evaluations and hospital admissions.
In patients with a suspected AMI, compared with the standard cTnT assay, the prognostic accuracy of hs-cTnT for death is significantly higher than cTnT
Among patients with chronic heart failure the cTnT was detectable in 92.0% of the patients using the hs-cTnT assay compared to 10.4% using the standard cTnT assay.
The risk of death and hospitalization for HF increased significantly with an increase in the hs-cTnT level.
A hs-cTnT cut-off value of 0.014 ng/mL has excellent prognostic sensitivity and negative predictive value
for patients with pulmonary embolism.
In pulmonary arterial hypertension the levels of cTnT were detectable in 90.9% of the participants using the hs-cTnT assay compared to 30.9% using the standard assay.
For the standard cTnT assay, the prevalence of detectable cTnT (0.01 ng/mL) is rare (0.7%) in the general population.
For the hs-cTnT assay, in the general population 54-74 years of age free from CAD, stroke and HF at baseline, a hs-cTnT concentrations > 0.014 ng/mL id detected in 7.4% of individuals.
In adults ? 65 years of age without prior HF, a hs-cTnT concentrations ? 12.94 ng/L was detected in 16.6% of individuals.
A correlation existS between the hs-TnT level and the total non-calcified plaque burden in patients with CAD.
Clinically silent rupture of non-calcified plaque with subsequent microembolisation may be a potential source of hs-cTnT elevation.
The prevalence of detectable troponin is high in heart failure.
Cardiomyocyte damage could contribute to the cTn release in patients with coronary artery disease, HF, inflammatory cytokines, oxidative stress, hibernating myocardium, and apoptosis.
With end-stage renal disease, the prevalence of elevated hs-cTnT concentrations is 100%, and the elevated hs-cTnT concentrations are highly prognostic of adverse events.
In addition to small areas of clinically silent myocardial necrosis, decreased clearance is another important factor for the elevated cTnT level in patients with CKD.
With essential hypertension, hs-cTnT is detectable in 78% of participants.
hs-cTnT levels were correlated with age, renal function, and electrocardiographic evidence of left ventricular hypertrophy.
In diabetes, the alterations in glucose metabolism which shift to fatty acid metabolism may lead to increased oxidative stress, and may be an important mechanism underlying myocardial cell injury and cTnT release.
Apoptosis of cardiomyocytes may play an important role
In compensatory hypertrophy due to hypertension, apoptosis of myocardiocytes may play o role in elevating hs-cTnT levels.
cTn elevation is common in many diseases, such as stroke, pulmonary embolism, sepsis, acute aortic dissection, acute perimyocarditis, hypovolemia, myocardial contusion, Tako-tsubo, and tachycardia.
Cardiomyocytes can be renewable, but approximately one gram of myocardial mass, corresponding to 64 million cells, is lost per year in the human heart.
Very low, but detectable hs-cTnT levels, may reflect a normal biological process of myocyte turnover.
In patients without acute myocardial infarction detectable hs-TnT may reflect accelerated cell turnover caused by increased catecholamine release, increase ventricular load, increased oxygen demand or decreased supply, inflammatory processes, hypoxia, and subendocardial ischemia.
There is a gradual decrease in cardiomyocyte regeneration, from 1% turning over annually at 20 years of age to 0.3% at 75 years of age.
Less than 50% of cardiomyocytes are exchanged during a normal lifespan.
Higher hs-cTnT levels predicted a worse prognosis regardless of conditions in cardiac or non-cardiac diseases.
In the case of reversible injury to the myocyte without necrosis, the cTn within the cytosol can be released as an intact protein via increased membrane permeability.
Because of the high prevalence of elevated cTnT concentrations in patients with ESRD, a change in cTn concentration > 20% at 6-9 h after presentation has been recommended for the diagnosis of MI.
Serial testing is required to separate AMI from other acute and chronic disorders also associated with low-level myocardial injury.
With minor elevation of cTn, observation of kinetic changes in cTn play an important role in distinguishing CAD from non-coronary diseases, especially with use of the hs-cTnT assay.
A negative hs-cTnT test has a high negative predictive value, and may thus serve as an exclusionary test early in the diagnosis of AMI.
In addition to risk stratification for ACS, the levels of hs-TnT can serve as a risk stratification in patients with stable CAD, HF, and non-cardiac disease conditions.
Patients with detectable high sensitivity cardiac troponin T levels, especially those with chronic myocardial injury, have an increased risk of stroke.
undetectable hi sensitive troponin T value admission allows a safe discharge without
occurrence of death myocardial infarction within 90 days (Vafaie M et al).