Troponin and nothing more

troponin and nothin more

It’s almost impossible to have an ER shift without encountering a chest pain patient!

The first thing that always comes to mind is to rule out STEMI; well, unless the patient is having chest pain, and you see a knife stabbed in his chest!

It’s a no brainer situation; investigations wise, you will start with an EKG, and a set of labs, including cardiac markers.

Acute coronary syndrome (ACS) with its subcategories, ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina, is responsible for one third of total mortality in individuals more than 35 years of age.(1)

The role of cardiac markers in diagnosis and management of ACS and cardiovascular problems is vital. In the United States cardiac biomarkers testing occurs in nearly 30 million emergency department visits nationwide each year.(2)

What is a biomarker?

The National Institutes of Health defined a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” (3)

Biomarkers utilization in cardiovascular medicine is a wide domain; it’s used in screening, diagnosis, prognosis and monitoring. (4)

What’s available?

Numerous cardiac markers are available today and can be classified as:

  1. Biomarkers of myocardial injury, which is further divided into:
    1. Biomarkers of myocardial necrosis: CK-MB fraction, myoglobin, cardiac troponins
    2. Biomarkers of myocardial ischemia: Ischemia-modified albumin (IMA), heart-type fatty acid-binding protein (H-FABP)
  2. Biomarkers of hemodynamic stress: Natriuretic peptides (NPs): atrial natriuretic peptide (ANP), N-terminal proBNP (NT-proBNP), B-type natriuretic peptide (BNP)
  3. Inflammatory and prognostic markers: hs C-reactive protein (CRP), sCD40L, homocysteine. (4)

What’s best?

Cardiac Troponin and the B type cardiac natriuretic peptides are the two markers recommended by ACEP and AHA in diagnosis of ACS and heart failure respectively.(5)

The ACS biomarker of choice

ACS is subcategorized based on ECG and cardiac troponin. The fourth universal consensus definition of Myocardial Infarction (MI); by the European Society of Cardiology (ESC) and American College of Cardiology (ACC), takes Troponin as a detrimental parameter in case definition, because of its high sensitivity and specificity.(6)

ACEP and AHA guidelines recommend the use of Troponin as level A class 1 in diagnosis of ACS. (7) It was practiced before to consider multiple markers dealing with ACS, more precisely in NSTEMI ruling out recommendation. However, this practice is now outdated with the use of hs cT solely.(7-9)

What’s troponin and why do we like it?

It’s a protein that regulates the interaction between actin and myosin filaments, found in skeletal and cardiac myocytes. Cardiac troponin (cTn) has three subunits troponin T, troponin C and troponin I. Troponin T and I are highly specific and sensitive.(10) The half-life of troponin T and troponin I in the blood is about 2 hours and last in serum for 4 to 10 days10

For ACS, the sensitivity of troponin is about 95%, and the specificity is about 80%, higher than any other marker available.(12)

However, many causes can elevate serum troponin which includes pericarditis, myocarditis, heart failure and chest trauma; non-cardiac conditions are sepsis, renal disease, pulmonary embolism, COPD, strenuous exercise and hypertension.(14)

High-sensitivity cardiac troponin (hs-cTn T and I) can detect troponin at concentrations much lower than the old cTn tests, and has replaced it.7 For ACS, hs cT substituted and limited the roles of other markers; it’s proven to be safe, cost effective, and a valuable prognostic factor. (7-9, 14)

For all of the above and the heart score… In ACS, use Troponin and nothing more!

References and Further Reading

  1. Anumeha Singh; Abdulrahman S. Museedi; Shamai A. Grossman. Acute Coronary Syndrome. StatPearls[Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan.
  2. Alvin MD, Jaffe AS, Ziegelstein RC, Trost JC. Eliminating Creatine Kinase–Myocardial Band Testing in Suspected Acute Coronary Syndrome: A Value-Based Quality Improvement. JAMA Intern Med. 2017;177(10):1508-1512. doi:10.1001/jamainternmed.2017.3597.
  3. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Biomarkers Definitions Working Group. Clin Pharmacol Ther. 2001 Mar; 69(3):89-95. doi.org/10.1067/mcp.2001.113989.
  4. Jacob R, Khan M. Cardiac Biomarkers: What Is and What Can Be. Indian J Cardiovasc Dis Women WINCARS. 2018 Dec; 3(4): 240–244. doi: 10.1055/s-0039-1679104.
  5. Richards AM. Future biomarkers in cardiology: My favourites. European Heart Journal Supplements, Volume 20, Issue suppl_ G, 1 August 2018, Pages G37-G44. doi.org/10.1093/eurheartj/suy023.
  6. Thygesen K, Alpert JS, Jaffe AS, et al., on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018. Volume 72 DOI: 10.1016/j.jacc.2018.08.1038. 
  7. Ezra A. Amsterdam, Nanette K Wenger, Ralph G. Brindis, Donald E. CaseyJr, Theodore G. Ganiats, David. HolmesJr, Allan S. Jaffe, Hani Jneid, Rosemary F. Kelly, Michael C. Kontos, Glenn N. Levine, Philip R. Liebson,Debabrata Mukherjee, Eric D. Peterson, Marc S. Sabatine, Richard W. Smalling, Susan J. Zieman. 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 130:e344–e426. 2014. doi.org/10.1161/CIR.0000000000000134.
  8. Edward W Carlton, Louise Cullen, Martin Than, James Gamble, Ahmed Khattab, Kim Greaves. A novel diagnostic protocol to identify patients suitable for discharge after a single high-sensitivity troponin. Heart. 2015 Jul 1; 101(13): 1041–1046. doi: 10.1136/heartjnl-2014-307288.
  9. Ron M. Walls, Robert S. Hockberger, Marianne Gausche-Hill, Katherine Bakes, Jill Marjorie Baren, Timothy B. Erickson, Andy S. Jagoda, Amy H. Kaji, Michael VanRooyen, Richard D. Zane. Rosen’s Emergency Medicine: Concepts and clinical practice. 9th edition. Elseivier; 2018.
  10. Ooi DS1, Isotalo PA, Veinot JP. Correlation of antemortem serum creatine kinase, creatine kinase-MB, troponin I, and troponin T with cardiac pathology. Clin Chem. 2000 Mar; 46(3):338-44.
  11. Harvey D. White, DSC. Pathobiology of Troponin Elevations: Do Elevations Occur With Myocardial Ischemia as Well as Necrosis?. Journal of the American College of Cardiology. Vol. 57, No. 24, ISSN 0735-1097/$36.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2011.01.029.
  12. John E. Brush, Jr., Harlan M. Krumholz. A Brief Review of Troponin Testing for Clinicians. American College of Cardiology. 2017 Aug 7th. acc.org/latest-in-cardiology/articles/2017/08/07/07/46/a-brief-review-of-troponin-testing-for-clinicians.
  13. Asli Tanindi, Mustafa Cemri. Troponin elevation in conditions other than acute coronary syndromes. Vasc Health Risk Manag. 2011; 7: 597–603. PMID: 22102783. doi: 10.2147/VHRM.S24509.
  14. Donald Schreiber, Barry E Brenner. Cardiac Markers. emedicine.medscape.com/article/811905-overview [Accessed 2020 March 23rd].
Cite this article as: Israa M Salih, UAE, "Troponin and nothing more," in International Emergency Medicine Education Project, August 19, 2020, https://iem-student.org/2020/08/19/troponin/, date accessed: September 30, 2022

Is Troponin Enough?

You are the emergency doc working in a rural ED. It is the Saturday night at 23:25 and you have three patients with chest pain. All have unchanged ECGs and normal troponins. All feel well now and want to go home if you think their results are okay. What is your plan for each of them?

Patient 1. Isabel D. is a 45-year old female with a history of hypertension. She presented to the emergency department with left-sided sharp chest pain. Her pain started after his evening run, and she vomited once. Her pain continued for one hour, but then it lessened spontaneously. Now she is feeling well, and she wants to go home. Her ECG is completely normal. Her 0- and 3-hour troponins are negative.

Paint 2. Daniel B. Is a 65-year old male with a history of smoking, hypotension and left bundle branch block (LBBB). He is obese. He presented to the emergency department with left-sided heavy chest pain, radiating to his left arm, chin, and back. He went to bed early today, and his chest pain woke him up. For half an hour, he has felt sweaty and nauseated but now he is feeling well, and he wants to go home. His ECG shows LBBB, unchanged compared to his previous ECGs and without Sgarbossa Criteria. His 0- and 3- hour troponins are negative.

Patient 3. Hank P. is a 54-year old male with a history of hypertension, diabetes mellitus and prior stroke with no sequel. For twenty minutes, he experienced a sharp pain in the middle of his chest. His pain had started while he was watching TV and he felt sweaty all in a sudden. he had His ECG shows findings related to left ventricular hypertrophy.  His 0- and 3- hour troponins are negative.

HEART Score

HEART Score was developed to predict the 6-week risk of a major adverse cardiac event of patients with chest pain, precisely in the emergency department setting (1). It outperformed the others, especially in exclusion of low-risk patients (2) Patients with a combination of HEART score of 0-3 and two negative troponins can be safely discharged from ED with no major adverse cardiac events (3). Patients with HEART Score of 4-6 requires admission and are candidates for further noninvasive investigations (1). Patients with HEART Score of ≥7 requires admission and are candidates for early invasive strategies (1).

HEART Score

CategoryScoreExplanationRisk Features
HistoryHigh-risk features
• Middle- or left-sided chest pain
• Heavy chest pain
• Diaphoresis
• Radiation
• Nausea and vomiting
• Exertional
• Relief of symptoms by sublingual nitrates

Low-risk features
• Well localized
• Sharp pain
• Non-exertional
• No diaphoresis
• No nausea and vomiting
Slightly Suspicious 0Mostly low-risk features
Moderately Suspicious+1Mixture of high-risk and low-risk features
Highly Suspicious+2Mostly high-risk features
ECG
Normal0Completely Normal
Non-specific Repolarization Disturbance+1Non-specific repolarization disturbance• Repolarization abnormalities
• Non-specific T wave changes
• Non-specific ST wave depression or elevation
• Bundle branch blocks
• Pacemaker rhythms
• Left ventricular hypertrophy
• Early repolarization
• Digoxin effect
Significant ST Depression+2Significant ST depression• Ischemic ST-segment depression
• New ischemic T wave inversions
Age
<450
45-64+1
≥ 65+2
Risk Factors• Obesity (Body-Mass Index ≥ 30)
• Current or recent (≤ 90 days)smoker
• Currently treated diabetes mellitus
• Family history of coroner artery disease (1st degree relative < 55 year old)
• Hypercholesterolemia

OR

Any history of atherosclerotic disease earn 2 points:
• Know Coroner artery Disease: Prior myocardial infarctions, percutan coronary intervention (PCI) or coronary artery bypass graft
• Prior stroke or transient ischemic attack
• Peripheral arterial disease
No known risk factors0
1-2 risk factors+1
≥ 3 risk factors or history of atherosclerotic disease+2
Initial Troponin
≤ normal limit0
1-3 x normal limit+1
> 3x normal limit+2
Please read articles 1,2,4 for more information.

Now, let’s look back on our patients.

Isabel’s pain has both high-risk (exertional, left-sided pain with vomiting) and (sharp pain, no diaphoresis) features; therefore, her pain is moderately suspicious. (H: +1) Her ECG is completely normal. (E: 0) She is 45 years old. (A: +1). She has one risk factor, hypertension. (R: +1) Her troponins are normal. (T: 0) Her HEART score is 3, and she can safely go home from the emergency department. The expected MACE rate in 30 days is 0%.

Daniel’s pain has mostly high-features (left-sided, radiating heavy chest pain with nausea and vomiting); therefore his pain is highly suspicious. (H: +2) His ECG is not completely normal but free of new ischemic changes. (E: +1) He is 65 years old. (A: +2). He has three risk factors, smoking, obesity, and hypertension. (R: +2) His troponins are normal. (T: 0) His HEART score is 7, and he is a candidate for early invasive intervention. You should admit him and call the cardiologist.

Hank’s pain has both high-risk (middle-sided chest pain with diaphoresis) and low-risk (non-exertional, sharp pain) features; therefore, his pain is moderately suspicious. (H: +1) His ECG is not completely normal but free of new ischemic changes. (E: +1) He is 54 years old. (A: +1). He has three risk factors, hypertension, diabetes mellitus and prior stroke. (Note that prior stroke alone earns two points) (R: +2) His troponins are normal. (T: 0) His HEART score is 5, and he is a candidate for noninvasive investigation. You should admit him.

PEARLS and PITFALLS

  1. ECG: If the ECG shows STEMI, do not wait for troponin or consider the HEART score. Call the cardiologist and consider activating angiography unit for the primary PCI.
  2. Troponins: If you first troponin is highly abnormal, do not wait for the second troponin or consider the HEART score. Call the cardiologist and consider activating angiography unit for the primary PCI. Additionally, the magnitude of change between the first and the second troponin is important in diagnosing acute myocardial infarction (5).
  3. Clinical Gestalt: You will gain a clinical gestalt over the years. If your clinical gestalt and any scoring disagree, always stay on the safe side for the patient’s benefit (4).
  4. Patient Safety: In the original study, the HEART score was combined with only one troponin. The adverse event rate was 2.5% for the HEART score 0-3 patients, 20.3% for the HEART score 4-6 patients and 72.7% for the HEART score ≥7 patients. Therefore, the author believes, the HEART score combined with two troponins is safer in the discharge of low-risk patients. Low-risk patients (i.e., HEART Score 0-3) with negative two troponins had no MACE within 30 days (3).

Suggested Chapters

Chest Pain by Asaad S Shujaa

Acute Coronary Syndrome (ACS)

by Khalid Mohammed Ali, Shirley Ooi

REFERENCES

  1. Six, A. J., Backus, B. E., & Kelder, J. C. (2008). Chest pain in the emergency room: value of the HEART score. Netherlands Heart Journal, 16(6), 191-196. – link
  2. Radecki, R. (2013). Time to Move to the HEART Score. Available at: http://www.emlitofnote.com/?p=440 (Accessed: 17/07/2018) – link
  3. Mahler, S. A., Riley, R. F., Hiestand, B. C., Russell, G. B., Hoekstra, J. W., Lefebvre, C. W., … & Herrington, D. M. (2015). The Heart Pathway Randomized Trial: Identifying Emergency Department Patients With Acute Chest Pain for Early Discharge. Circulation: Cardiovascular Quality and Outcomes, 8(2), 195-203. – link
  4. Hyunjoo, L., & Rodriguez, C. (n.d.). HEART Score for Major Cardiac Events. Available at: https://www.mdcalc.com/heart-score-major-cardiac-events#evidence (Accessed: 17/07/2018) – link
  5. Roffi, M., Patrono, C., Collet, J. P., Mueller, C., Valgimigli, M., Andreotti, F., … & Gencer, B. (2016). 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). European heart journal, 37(3), 267-315. – link

FURTHER READING