Definition
- Cardiac troponin T and troponin I, also known as TnI, TnT, cTnI, cTnT, and cTn, are cardiac regulatory proteins specific to the myocardium that control the calcium-mediated interaction between actin and myosin. Troponin I remains increased longer than Ck-MB and is more specific, and cTnI is more sensitive but less specific.
- Normal range:
- Troponin T: 0.0 " “0.1 ng/mL
- Troponin I: 0.0 " “0.04 ng/mL
Use
- Cardiac troponin is the preferred test for diagnosis of acute coronary syndrome (ACS). cTn establishes the diagnosis of irreversible myocardial necrosis (e.g., anoxia, contusion, inflammation), even when ECG changes or CK-MB are nondiagnostic (which occurs in ≤50% of patients with ACS). It is important to note that several distinct pathobiologic may cause elevated troponin, not all of which involve myocyte necrosis.
- The diagnosis of myocardial infarction is predicated upon the rise and fall of cardiac troponin along with other clinical factors (see Chapter 3). However, serial normal cTn rules out myocardial necrosis.
- In patients with a clinical syndrome consistent with ACS, a peak concentration exceeding the 99th percentile of values for a reference control group should be considered indicative of increased mortality, myocardial infarcts, and recurrent ischemic events.
- Patients with ACS patients and cTnI and cTnT results above the decision limit should be labeled as having myocardial injury and a high-risk profile.
- Troponin elevation above the 99th percentile due to pathobiologic mechanisms (below) other than myocardial necrosis also have an elevated risk profile for short- and long-term morbidity.
- Troponin testing on hospital presentation followed by serial sampling with timing of sampling based on the clinical circumstances. cTnI may remain increased for ≤9 days, and cTnT may remain increased for ≤14 days.
- The long duration of increased cTn provides a longer diagnostic window than CK-MB but may make it difficult to recognize reinfarction. Recurrent reinfarction is diagnosed if a 20% increase in troponin is observed with 3 " “6 hours after the initial assessment.
- cTn is as sensitive as CK-MB during the first 48 hours after an AMI (>85% concordance with CK-MB); sensitivity is 33% from 0 to 2 hours, 50% from 2 to 4 hours, 75% from 4 to 8 hours, and approaching 100% from 8 hours after onset of chest pain. It may take ≤12 hours for all patients to show an increase. Sensitivity remains high for 6 days. Specificity is close to 100%.
- Serial cTn values may be indicator of cardiac allograft rejection. In selecting heart donors, cTnT >1.6 ng/mL predicts early graft failure with S/S = 73%/94%; cTnT >0.1 ng/mL predicts early graft failure with S/S = 64%/>98%.
- Troponin measurements are also useful in the differential diagnosis of skeletal muscle injury. Normal cTn values exclude myocardial necrosis in patients with increased CK of skeletal muscle origin (e.g., arduous physical exercise).
- Useful for diagnosis of perioperative AMI when CK-MB may be increased by skeletal muscle injury.
- Troponin may also be increased in <50% of patients with acute pericarditis. A value <0.5 ng/mL indicates no myocardial damage. A value >2.0 ng/mL indicates some myocardial necrosis.
Interpretation
Increased In
- Myocardial infarction
- Cardiac trauma, including ablation, pacing, cardioversion, cardiac surgery
- CHF (acute and chronic)
- Aortic dissection, aortic valve disease, or hypertrophic cardiomyopathy
- Tachy- or bradyarrhythmias, or heart block
- Myocarditis
- Rhabdomyolysis with cardiac injury
- Hypotension
- Apical ballooning syndrome
- Renal failure
- Acute neurologic disease (stroke or subarachnoid hemorrhage)
- Infiltrative disease (amyloid, sarcoid)
- Drug toxicity (doxorubicin, 5-fluorouracil, trastuzumab, snake venom)
- Critically ill patients (especially ARDS and sepsis)
- Burns (particularly when >30% surface area)
- Technical lab error
- High concentrations of alkaline phosphate (interferes with some cTnI assays)
Limitations
- cTnT may be increased in some patients with skeletal muscle injury and myotonic dystrophy but not in third-generation assays. cTnI is not increased by skeletal muscle injury, making it more highly specific for myocardial injury.
- Heterophile antibodies are one of the most common reasons for false-positive results due to interference with the immunoassay. Human antimouse antibodies, autoantibodies, rheumatoid factor also may cause false-positive results in addition to hemolysis of sample or fibrin clots in the specimen.
- Unfortunately, most point-of-care assays are not as sensitive as those performed in central laboratories. If a single value is out of proportion to others, it is recommended to respin the point-of-care sample and reanalyze.
- As troponin is able to detect very early stages of disease and confer a worse prognosis if elevated, if confounding factors for laboratory analysis of troponin are suspected, the use of other cardiac biomarkers in addition to direct cardiac imaging (or biopsy for transplant recipients) is strongly recommended.
Suggested Readings
1Apple ‚ FS, Jesse ‚ RL, Newby ‚ LK National Academy of Clinical Biochemistry. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical issues for biochemical markers of acute coronary syndromes. Clin Chem. 2007;53(4):547 " “551. 2Jaffe ‚ AS. The clinical impact of the universal diagnosis of myocardial infarction. Clin Chem Lab Med. 2008;46(11):1485 " “1488. 3Morrow ‚ DA, Cannon ‚ CP, Jesse ‚ RL National Academy of Clinical Biochemistry. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Circulation. 2007;115(13):e356 " “e375. 4Roongsritong ‚ C, Warraich ‚ I, Bradley ‚ C. Common causes of troponin elevations in the absence of acute myocardial infarction incidence and clinical significance. Chest. 2004;125(5):1877 " “1884. 5Starrow ‚ AB, Apple ‚ FS, Wu ‚ AH National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: point of care testing, oversight, and administration of cardiac biomarkers for acute coronary syndromes. Point Care. 2007;6(4):215 " “222. 6Thygesen ‚ K, Alpert ‚ JS, White ‚ HD, Joint ESC/ACCF/AHA/WHF Task Redefinition myocardial infarction. Eur Heart J. 2007;28:2525 " “2538; Circulation. 2007;116:2634 " “2653; J Am Coll Cardiol. 2007;50:2173 " “2195. 7Vafaie ‚ M, Biener ‚ M, Mueller ‚ M Analytically false or true positive elevations of high sensitivity cardiac troponin: a systematic approach. Heart. Online April 25. Doi: 10.1136/heartjnl-2012-303202