How do we best use high-sensitivity cardiac troponin (hs-cTn) to risk stratify patients with symptoms concerning for an acute myocardial infarction (AMI)? The 2022 American College of Cardiology (ACC) pathway provides timely guidance [1]. We help you translate this to your clinical practice, by illustrating with a case. Time to know your hs-cTn better.

Take-to-work points

  • When interpreting the hs-cTn, you can use either of the following pathways to optimize both accuracy and patient throughput:
    • European Society of Cardiology (ESC) 2020 0/1 hour or 0/2 hour pathway
    • High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome (High-STEACS)
  • These clinical decision pathways utilizing hs-cTn are complicated to calculate on your own.
    • Encourage your ED to set up an algorithm that you can follow based on your laboratory’s assay.
    • Otherwise, apply a simplified approach. When patients present with <6 hours of symptoms, they are low risk if the 0- and 3-hour troponin levels are less than the 99th percentile upper reference limit (URL).
  • Low-risk patients do not routinely require stress testing in the ED.
  • Intermediate-risk patients may be further stratified based on recent stress testing or coronary angiogram findings plus a modified HEART or Emergency Department Assessment of Chest Pain (EDACS) score.

Applying the 2022 ACC guideline

Before delving into the specifics of the hs-cTn pathways, start with the ECG. The ACC 2022 pathway has a section dedicated to ECGs in ischemia [1], and FOAMcast has a great visual summary.

The 2022 ACC pathway [1] endorses clinical decision pathways that:

  • Use hs-cTn AND
  • Enable rapid rule-out using very low hs-cTn values (far below the 99th percentile) on arrival, or a very small change (delta) between 2 hs-cTn values.

Examples of such pathways include [2]:

  • The ESC 0/1 hour pathway, where hs-cTn is obtained on arrival, and if needed, 1 hour later.
  • The ESC 0/2 hour pathway, where hs-cTn is obtained on arrival, and if needed, 2 hours later.
  • The High STEACS pathway, where hs-cTn is obtained on arrival, and if needed, 3 hours later.

These clinical decision pathways take advantage of the diagnostic power of the delta hs-cTn value, resulting in higher sensitivity for AMI (99%) [3], more patients being able to be ruled-out for AMI [4], and more patients being discharged home with a shorter ED length of stay [5]. This contrasts traditional risk-stratification approaches, which compare hs-cTn values solely to the 99th percentile upper reference limit.

  • Note: Using the pathways and using a single hs-cTn result are not mutually exclusive concepts. Clinical decision pathways DO allow us to rule out AMI with a single hs-cTn value in some instances. An example is if the patient has a very low value (e.g., below limit of detection) AND the chest pain onset is >3 hours ago AND the ECG is non-ischemic.

Let’s apply the ESC 2020 0/1 hour pathway [2], with some modifications based on the 2022 ACC guidelines [1]:

high sensitivity cardiac troponin hs-cTn risk stratification

Figure 1. Stratification of patients for AMI based on high sensitivity troponin testing and the ESC 0/1 hour pathway (second hs-cTn drawn 1 hour after the initial hs-cTn test)

Notice how numbers are replaced with values A, B, C, D and E. That’s because these values are assay specific. You (or someone in your department) needs to know which assay your ED has, and use the appropriate values for that assay. Examples of cutoffs:

Figure 2: Assay-based cutoffs for different high sensitivity cardiac troponin tests from the 2022 ACC guideline [1] (Limit of quantification, LoQ)

One concept that cuts across all assays is the limit of quantification (LoQ). That’s the lowest hs-cTn value that can be reliably reported as a number for that assay. In the risk stratification pathway (figure 1), value E is often the LoQ, or an optimized threshold slightly above the LoQ.

Case #1

A 52-year-old woman presents with vague heaviness over the left side of the chest that does not radiate elsewhere. She does not recall clearly how it started, and it has been persistent for 5 hours. Its intensity does not change with walking or changes in posture. There are no associated symptoms such as diaphoresis, breathlessness, vomiting, fever, cough, or leg swelling.

She has hypertension and hyperlipidemia treated with lifestyle modification. She does not smoke. There is no family history of heart disease. She has no other recent illnesses or travel history.

On examination, her vital signs are normal. Heart sounds are dual with no murmurs and breath sounds are equal bilaterally. Pulses are well felt in all four limbs. There is no lower limb swelling or tenderness.

A 12-lead electrocardiogram (ECG) and chest x-ray (CXR) are unremarkable. The hs-cTn level on arrival is below the limit of quantification (LoQ).

Because the patient’s chest pain started >3 hours ago and she has a non-ischemic ECG, the initial hs-cTn is below LoQ already stratifies her as a LOW-RISK patient for AMI by the pathway. She does not need a repeat hs-cTn test. Caveat: Patients with known coronary artery disease might still have considerable risk for AMI even with this constellation of findings, requiring clinical judgment beyond this pathway [6].

Also do not forget that you still need to address other important potential causes of chest pain:

  • Aortic dissection appears unlikely, given the lack of suggestive features on history or physical examination. The onset was gradual with no radiation to the back or abdomen, and no features of distal ischemia such as neurological or pulse deficits. The CXR did not show any abnormalities consistent with a dissection.
  • Pulmonary embolism (PE) appears unlikely. She would be low risk by gestalt or structured scoring systems (Wells or revised Geneva), and a negative D-dimer would essentially rule out pulmonary embolism here. Note that the PE rule-out criteria do not help in this case, because she is >50 years old.

Thankfully, most patients will be low risk after walking through the above. What’s the disposition and follow-up plan for them? In short, less is more. As long as your clinical judgment concurs with a low-risk stratification, you should send the patient home with chest pain advice, return precautions, and recommendations to follow-up with their primary care provider within 30 days for optimal management of cardiovascular risk factors. You do not have to routinely order stress testing from the ED! This is endorsed in the 2022 ACC pathway [1] and the 2021 AHA chest pain guidelines [7].

The high-risk category

High-risk category hs-cTn values in the ESC 2020 0/1 hour pathway or high STEACS pathway come in 2 types:

  • A high absolute value
  • A high delta between two hs-cTn samples, which is suggestive of the rise or fall seen in AMI

Those values are assay- and pathway-specific, so you’ll need to find out more about your local assay. These in the high-risk category are usually admitted to the hospital to assess for AMI as well as other causes of troponin elevation.

What if you have a patient with intermediate findings?

Case #2

A 66-year-old man with hypertension, hyperlipidemia, diabetes mellitus, and chronic renal failure presents with poorly localized central chest discomfort while trying to sleep. It started 2 hours ago. The discomfort has a burning character, though he has never been diagnosed with reflux before.

His vital signs and physical exam are unremarkable other than an arteriovenous fistula on his left arm for hemodialysis. His ECG shows left ventricular hypertrophy.

The first hs-cTn results in the intermediate range on your assay-specific cutoff for the ESC 2020 pathway or high-STEACS pathway.

The first step is to repeat hs-cTn testing in 3-6 hours. Those with a significant change in hs-cTn (e.g., ≥ value D in the ESC 2020 pathway) will be diagnosed with acute myocardial infarction or acute myocardial injury (e.g., as seen in heart failure, arrhythmias, or sepsis).

How about those with no significant change? The ACC now endorses that these intermediate-risk patients can be considered for discharge with rapid follow-up, if 1 of these 4 criteria are met:

  1. Invasive or CT coronary angiogram <2 years ago without coronary plaque
  2. Stress test <1 year ago without ischemia
  3. Modified HEART score (where troponin is excluded) ≤3 [MDCalc] or EDACS<16 [MDCalc]
  4. Chronic elevations in hs-cTn similar to previously measured levels

Patients who do not meet these criteria above should get some form of additional evaluation such as non-invasive testing, such as a CT coronary angiogram, myocardial perfusion imaging, or stress echocardiography. If not, consider cardiology consultation or admission, or at least a shared decision-making with the patient for an expedited outpatient workup with the understanding that this group has a 30-day rate of death or MI ranging from 5% to 22% [1, 8, 9].

You repeat a hs-cTn 3 hours later and it remains unchanged. The patient has no previous stress testing or coronary angiogram, and he is not low risk by HEART or EDACS scoring.

You thus consult the cardiologist, who recommends to admit the patient to the hospital for further observation and evaluation.

Conclusion

  • Use the European Society of Cardiology (ESC) 2020 0/1 hour or 0/2 hour protocol, or the high-STEACS pathway when interpreting hs-cTn. They optimize both accuracy and patient throughput.
  • These clinical decision pathways utilizing hs-cTn are complicated to calculate on your own. Encourage your ED to set up an algorithm that you can follow based on your laboratory’s assay.
  • Otherwise, apply a simplified approach. When patients present with <6 hours of symptoms, they are low risk if the 0- and 3-hour troponin levels are less than the 99th percentile upper reference limit.
  • Low-risk patients do not routinely require stress testing in the ED.
  • Intermediate-risk patients may be further stratified based on recent stress testing, coronary angiogram findings, modified HEART score, EDACS score, or similar previous chronic hs-cTn elevations.

References

  1. Writing Committee, Kontos MC, de Lemos JA, et al. 2022 ACC Expert Consensus Decision Pathway on the Evaluation and Disposition of Acute Chest Pain in the Emergency Department: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022;80(20):1925-1960. doi:10.1016/j.jacc.2022.08.750
  2. Collet JP, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation [published correction appears in Eur Heart J. 2021 May 14;42(19):1908] [published correction appears in Eur Heart J. 2021 May 14;42(19):1925] [published correction appears in Eur Heart J. 2021 May 13;:]. Eur Heart J. 2021;42(14):1289-1367. doi:10.1093/eurheartj/ehaa575
  3. Burgos LM, Trivi M, Costabel JP. Performance of the European Society of Cardiology 0/1-hour algorithm in the diagnosis of myocardial infarction with high-sensitivity cardiac troponin: Systematic review and meta-analysis [published online ahead of print, 2020 Jun 29]. Eur Heart J Acute Cardiovasc Care. 2020;2048872620935399. doi:10.1177/2048872620935399
  4. Badertscher P, Boeddinghaus J, Twerenbold R, et al. Direct Comparison of the 0/1h and 0/3h Algorithms for Early Rule-Out of Acute Myocardial Infarction. Circulation. 2018;137(23):2536-2538. doi:10.1161/CIRCULATIONAHA.118.034260
  5. Chew DP, Lambrakis K, Blyth A, et al. A Randomized Trial of a 1-Hour Troponin T Protocol in Suspected Acute Coronary Syndromes: The Rapid Assessment of Possible Acute Coronary Syndrome in the Emergency Department With High-Sensitivity Troponin T Study (RAPID-TnT) [published correction appears in Circulation. 2021 Jun 22;143(25):e1118]. Circulation. 2019;140(19):1543-1556. doi:10.1161/CIRCULATIONAHA.119.042891
  6. Ashburn NP, Snavely AC, O’Neill JC, et al. Performance of the European Society of Cardiology 0/1-Hour Algorithm With High-Sensitivity Cardiac Troponin T Among Patients With Known Coronary Artery Disease. JAMA Cardiol. 2023;8(4):347-356. doi:10.1001/jamacardio.2023.0031
  7. Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2021 Nov 30;144(22):e455]. Circulation. 2021;144(22):e368-e454. doi:10.1161/CIR.0000000000001029
  8. Mueller C, Giannitsis E, Christ M, et al. Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T. Ann Emerg Med. 2016;68(1):76-87.e4. doi:10.1016/j.annemergmed.2015.11.013
  9. Twerenbold R, Neumann JT, Sörensen NA, et al. Prospective Validation of the 0/1-h Algorithm for Early Diagnosis of Myocardial Infarction. J Am Coll Cardiol. 2018;72(6):620-632. doi:10.1016/j.jacc.2018.05.040

Featured image adapted from Adobe Firefly

Matthew J.W. Low, MBBS(Hons), FAMS

Matthew J.W. Low, MBBS(Hons), FAMS

Adjunct Assistant Professor
Yong Loo Lin School of Medicine
National University of Singapore
Matthew J.W. Low, MBBS(Hons), FAMS

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