1. What is cardiac troponin (cTn)?
Cardiac troponin is the preferred biomarker for diagnosis of acute myocardial infarction (AMI) on the basis of sensitivity and myocardial specificity.1,2
2. How is AMI diagnosed?
Patients presenting to the emergency department with chest pain are evaluated clinically and by electrocardiogram (ECG).1,2 Patients with ST elevation upon ECG are immediately treated; those without ST elevation may be experiencing non-ST-elevation myocardial infarction (NSTEMI), unstable angina, another cardiac or noncardiac cause, or are normal. Repeat testing for a cardiac marker such as cTn will differentiate NSTEMI patients from those with other causes of chest pain. Depending on the clinical assessment, NSTEMI patients are among those who will demonstrate a significant serial change in cTn.1,2
3. What is the definition of a high-sensitivity cardiac troponin (hs-cTn) assay?
The International Federation of Clinical Chemistry (IFCC) task force on cardiac biomarkers defines hs-cTn assays as those that reliably detect cTn below the 99th percentile and above the limit of detection (LoD) in at least 50% of healthy subjects.3 Total imprecision (coefficient of variation [CV]) should be ≤10% at the 99th percentile of healthy subjects.1-3
4. What is an accelerated serial-collection protocol?
Contemporary sensitive cTn assays were subject to serial-collection protocols, with up to 6 hours between serial collections. With higher sensitivity and the ability to reliably detect cTn below the 99th percentile and above the limit of quantitation (LoQ), it is possible to decrease the time between serial collections to as little as 1 hour using a high-sensitivity cardiac troponin assay.1,2
5. Why is precision at the low end of the hs-cTn assay range important?
Precision at the low end is important to minimize analytic variation that could confound assessment of a clinically significant change. While this is important for both traditional and accelerated serial-collection protocols, it is especially important for protocols that test in intervals less than 3 hours, since serial-change values could be lower than the specified analytic variation.1
6. What are the most recent American College of Cardiology guidelines?
The Fourth Universal Definition of Myocardial Infarction was published in Circulation in August 2018.1 The document states that cTnI and cTnT are the preferred biomarkers to both rule in and rule out myocardial injury and to define MI and each subtype of MI (types 1–5).
Detection of an elevated cTn value above the 99th percentile upper reference limit (URL) is defined as “myocardial injury.” The injury is considered acute if there is a rise and/or fall of cTn values when serial testing is performed. The diagnosis of myocardial infarction is made if there is myocardial injury and clinical evidence of ischemia. The benefits of using hs-cTn assays is emphasized.
When using hs-cTn assays, an accelerated protocol of 1–2 hours can be used. A “significant” rise and/or fall to diagnose acute myocardial injury is defined as:
- If hs-cTn value is <99th percentile: 50–60%
- If hs-cTn value is >99th percentile: 20%1
7. Is there a value for hs-cTn outside of an acute setting?
A growing body of evidence suggests that low levels of cTn are prognostic.4-9 This may have utility in aiding assessment and management of patients at risk of an adverse cardiac event.4-9 Cardiac troponin detected with hs-cTn assays may find utility in other nonacute coronary syndrome scenarios.10-12
8. Are there clinical conditions other than AMI that may result in elevated levels of cTn?
There are conditions other than AMI that are known to cause myocardial injury and elevated TnI values.1,2,13
Siemens Healthineers conducted a high-sensitive troponin clinical trial that enrolled 1755 patients presenting with symptoms suggestive of acute myocardial infarction (AMI). Blood samples drawn at presentation,1 hour, and 2 hours were analyzed for troponin concentrations with the ADVIA Centaur TNIH assay.14 Some of these patients had an acute or chronic condition other than AMI.
In the clinical trial, 11% of patients without an AMI diagnosis had at least one ADVIA Centaur TNIH test result above the 99th percentile (>47.34 pg/mL [ng/L]) on one or more serial draws. 89% of these patients were found to have one or more of the following cardiac or noncardiac conditions.14
- Atrial fibrillation
- Coronary artery disease
- Heart failure
- Hypertensive urgency
- Recent cardiac intervention
- Severe valvular heart disease
- Chronic lung disease
- Cardiac contusion related to a traumatic injury
- Renal failure
- Pulmonary embolism
- Systemic sclerosis
9. How does the increased sensitivity impact the clinical utility of the cTn assay?
The increased sensitivity of the troponin assay allows detection of smaller areas of cardiac necrosis, earlier detection of myocardial damage, and implementation of shorter serial testing protocols. These advantages can lead to improvements in the timely triage of chest-pain patients.1,2,19
To determine if a patient is experiencing AMI with an hs-cTn assay, it is important to use the assay in conjunction with patient presentation, clinical suspicion, and a serial-collection protocol. For patients who show an increased result above the specified 99th percentile value, it may be possible to make the determination in as little as 1 hour; however, not all patients can be diagnosed that quickly. Patients with initial hs-cTn levels above the 99th percentile may require repeat testing to detect a significant serial change, generally 3 hours or longer after presentation. Some patients for whom suspicion remains high for AMI are observed beyond three to six hours.1,2
NSTEMI patients presenting early (within less than 2 hours of chest-pain onset) or late after chest-pain onset may not demonstrate a significant serial change within the specified time limits used for an accelerated serial-collection protocol. Those presenting early require further testing. Imaging, serial ECGs, and additional hs-cTn testing can aid in triage of these patients, along with signs and symptoms.1,2
- Thygesen K, et al. Fourth universal definition of myocardial infarction (2018). Circulation. [published online 2018 Aug 25]. doi: 10.1161/ CIR.0000000000000617.
- Roffi M, et al./Task Force. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2015; 37:267-315.
- Apple FS, et al. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. Clin Biochem. 2015; 48:201-3.
- de Lemos JA, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010; 304:2503-12.
- Hijazi Z, et al. Application of Biomarkers for Risk Stratification in Patients with Atrial Fibrillation. Clin Chem. 2015; 61: 368-78.
- McKie PM, et al. High-Sensitivity Troponin I and Amino-Terminal Pro–B-Type Natriuretic Peptide Predict Heart Failure and Mortality in the General Population. Clin Chem. 2014;60:1225-33.
- Zeller T, et al. High population prevalence of cardiac troponin I measured by a high-sensitivity assay and cardiovascular risk estimation: the MORGAM Biomarker Project Scottish Cohort. Eur Heart J. 2014; 35:271-81.
- Devereaux PJ, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012: 307:2295-304.
- Parsonage WA, et al. Detectable High-Sensitivity Cardiac Troponin within the Population Reference Interval Conveys High 5-Year Cardiovascular Risk: An Observational Study. Clin Chem. 2017; 63:45-9.
- Dhesy-Thind S, et al. Cardiac and Inflammation Biomarker Profile after Initiation of Adjuvant Trastuzumab Therapy. Clin Chem. 2013; 59:327-9.
- Katsurada K, et al. High-sensitivity troponin T as a marker to predict cardiotoxicity in breast cancer patients with adjuvant trastuzumab therapy. Springerplus. 2014; 3:620.
- Noordzij PG, et al. High-sensitive cardiac troponin T measurements in prediction of non-cardiac complications after major abdominal surgery. Br J Anaesth. 2015; 114:909-18.
- Siemens ADVIA Centaur XP/XPT High-Sensitivity Troponin I Instructions for Use. Rev. C, 2018-07.
- Boeddinghaus J, Twerenbold R, Nestelberger T, Badertscher P, et al. Validation of a Novel High-Sensitivity Troponin I Assay. Clinical Chemistry 64:9 (2018)
- Jaffe AS, et al. Diseased skeletal muscle: a noncardiac source of increased circulating concentrations of cardiac troponin T. J Am Coll Cardiol. 2011; 58:1819-24.
- Pim Pijnappel WW, et al. Commentary Clin Chem. 2017;63:48
- Parsonage WA et al. A 61-Year-Old Woman with Muscle Fatigue and Increased Cardiac Troponin. 2017 Clinical Chemistry 63(1): 45-49.
- Ritto D et al. Elevation of cardiac troponin T, but not cardiac troponin I, in patients with neuromuscular diseases: implications for the diagnosis of myocardial infarction. J Am Coll Cardiol. 2014 Jun 10;63(22):2411-20. doi: 10.1016
- Sandoval Y, Smith S, et al. Rapid Rule-Out of Acute Myocardial Injury Using a Single High-Sensitivity Cardiac Troponin I Measurement. Clin Chem. 2017; 63:369-76.