Troponin is in the HEART

September 2016 - Vol.5 No. 7 - Page #2

In December 2015, the journal Clinical Biochemistry published an article titled: Utilization of cardiac troponin assays in adult and pediatric populations: Guideline recommendations vs. reality.1 This article confirmed a concept many laboratorians and clinicians suspected—there is a broad disparity on how cardiac troponins (cTn) are utilized and reported. Moreover, there is evidence that not all laboratories are adhering to guidelines for cTn testing.2,3 As a laboratorian working in a non-academic hospital, I appreciate articles like this because they provide information on the practices of our peers and allow us to demonstrate to our clinicians through benchmarking how the laboratory compares to others. I hope this survey will be repeated in the future to see if we have made collective progress in cTn standardization, but this is just one aspect of a multifaceted issue.

Another significant aspect addresses the challenges our physicians face everyday regarding acute coronary syndrome (ACS) diagnosis. Chest pain is one of the most common primary complaints presented in the emergency department (ED) and this pain can result from a wide range of etiologies, among them: Heart attack, angina, aortic dissection, pericarditis, heartburn, swallowing disorders, gallbladder or pancreas problems, costochondritis, sore muscles, injured ribs, pulmonary embolism, pleurisy, collapsed lung, pulmonary hypertension, shingles, and panic attack. These conditions carry significantly discordant levels of distress; some require urgent attention, while others do not. Pointedly, the ED is compelled to rule-in ACS quickly and accurately, but also to identify those patients who can be safely discharged (ie, heartburn, sore muscles, and other minor injuries or events), or those patients who would benefit from an expended observation period (usually less than 24 hours).

To address this fairly universal issue, some hospitals have developed observation units (see SIDEBAR 1), also known as clinical decision support units, while other hospitals have developed chest pain clinics or centers. Thus, there are clinical variations in how and where patients presenting with chest pain in the ED are managed and diagnosed, as well as who performs patient evaluations (eg, ED physicians versus hospitalists).

These variables elicit further inquiry; can clinical setting variability explain some of the disparity between how cTn are utilized and reported (especially regarding serial cTn), as well as the adoption of the 99th percentile cutoff point for cTn or the use of other cardiac markers? It is worth noting, there are numerous troponin I reagents, as well as troponin T test reagents available, and most of these have differing 99th percentile values. Thus, a lack of standardization among facilities is common.

Initial Evaluation of ACS in the ED

Rapid evaluation of a patient presenting with ACS is imperative to identify true life-threatening conditions, thus, when patients present in the ED with chest pain, this scenario prompts two essential questions for the physician:

  • What is the probability the patient is experiencing ACS?
  • What are the odds of adverse clinical outcomes?3

Differential diagnosis of ACS generally includes medical history, physical examination, electrocardiogram (ECG), cTn measurements, and imaging studies. Beyond these measures, risk assessment scores were developed in order to help identify those patients with ACS who are at increased risk of adverse outcomes.3

Among the common risk stratification scoring methods are the PURSUIT, TIMI, GRACE, FRISC, and the HEART score.3,5 The first four of these methods focus on helping the physician identify patients with a higher likelihood of adverse outcomes, while the fifth method—HEART—not only identifies patients at increased risk, but also patients at low risk.5


The PURSUIT risk score was developed from the results of the Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy trial and published in 2000. The PURSUIT score calculates the risk of death at 30 days after patient admission. The caveat is that this study took place before the wide adoption of cTn assays, so the PURSUIT score does not include cTn and is largely dependent on the patient’s age.5

The TIMI Score

The TIMI risk score was developed from the Thrombolysis in Myocardial Infarction (TIMI)-11B trial, also published in 2000. The TIMI score calculates the mortality (of all causes), as well as myocardial infarction and severe recurrent ischemia that will benefit from urgent revascularization within 14 days of admission. The TIMI score is simple to calculate, rendering it useful, but its poor predictive value is a drawback.5

The GRACE Score

The GRACE risk score was developed from the Global Registry of Acute Coronary Events registry, which published its results in 2003. The GRACE score calculates the risk of hospital death and also post-discharge death at six months after ACS diagnosis and is based on eight independent risk factors. The GRACE score has a good predictive value; however, it is very complex to use and requires software to calculate the risk score at the patient’s bedside. Furthermore, the score does not stratify patients into different risk groups, which provides little assistance to the treating physician in interpreting the patient’s risk score.5

The FRISC Score

The FRISC risk score was developed from the Fast Revascularization in Instability in Coronary disease II trial and published in 2005. The FRISC score—based on seven independent risk factors—provides risk stratification and selection of patients to an early invasive treatment strategy for those presenting with unstable angina. The FRISC score focuses on the treatment effects of utilizing an early invasive strategy. The FRISC score is simple to use, like the TIMI, but it has intermediate predictive value.5

Despite the fact that clinicians rely heavily on a patient’s medical history, none of these first four scores (PURSUIT, TIMI, GRACE, and FRISC) incorporate patient history in their calculations.

The HEART Score

The HEART risk score accounts for a patient’s medical history, ECG result, age, risk factors for coronary artery disease (CAD), and the troponin level assessed at the time the patient presents in the ED.5,6 This risk score produces a number from zero to 10 that stratifies patients into three categories according to the likelihood of having MACE (major adverse cardiac events) within 6 weeks.6,7,8

  • A patient with a score of zero to 3 (a low HEART score) has a 0.9%8 to 1.7%7 risk of MACE within 6 weeks
  • For a patient with a score of 4 to 6, the risk for MACE is 11.6%8 to 16.6%7 within 6 weeks
  • When the HEART score is high (7 to 10), the risk for MACE is 50.1%7 to 65.2%8

A 2011 study demonstrated that the HEART score can be used to decrease stress testing and cardiac imaging in the ED setting for a patient population with low pre-test probability of ACS.9 Furthermore, the HEART score was validated against the TIMI and GRACE methods; the two most reputable risk scores for ACS among the four described above. Most important, the HEART score has a better predictive value to discriminate among all causes of patient-described chest pain presented in the ED, as well as the patient’s risk of MACE when compared to the TIMI and GRACE scores (developed only for ACS).7

The HEART risk score is now being implemented and used in EDs because it is easy to use, produces good predictive values, and was developed to be applied to all patients presenting with chest pain, not just those with ACS.

The HEART Score and the Lab

Perhaps, at first glance, there is little obvious relationship between a clinical risk stratification tool (such as GRACE or HEART) and laboratory testing, but remember troponin is in—and integral to—the HEART score. However, the HEART score was developed using the 99th percentile as the normal limit.6 Going back to the article from Doctors Saenger and Haymond,1 we know that only 59% of laboratories are using the 99th percentile as their troponin reference range cutoff, which means that 41% of laboratories are using other cut-off ranges that could result in the incorrect calculation of the HEART score, if utilized by ED or observation-unit physicians.

If a laboratory is not using the 99th percentile, yet its physicians are using the HEART risk score tool in the ED or observation unit, those physicians could be underestimating the HEART score by up to 2 points. This, in turn, could lead to the incorrect risk stratification of patients with chest pain and improper clinical decision making, as the physicians could conflate the lab’s reference value with the normal limit, not the 99th percentile.

Adapt to the HEART Score

Regardless of whether the lab is using the 99th percentile cut off, including the values for your specific troponin into the HEART tool is good laboratory practice and contributes to physician satisfaction. Likewise, if you are affiliated with or work within a multi-hospital system that uses different troponin reagents (T versus I, or different cTn-I tests with different 99th percentile values), it critical to know what the troponin decision points are per test to avoid confusion and error.

One method is to develop a HEART risk score tool in the EMR or paper medical record that includes the specific values (in ng/mL) corresponding to three troponin score points. For example, if your 99th percentile is 0.04 ng/mL, the HEART tool could list the following:

A. Greater than or equal to 3 times the normal limit [eg, greater than or equal to 0.120 ng/mL]

B. Greater than 1, but less than 3 times the normal limit [eg, between 0.040 and 0.120 ng/mL]

C. Less than, or equal to normal limit [eg, less than or equal to 0.040 ng/mL]

My humble advice is, find out if your hospital has implemented or will be implementing the HEART risk score tool and determine what normal limit will be used. After all, troponin is in the HEART score, and patient safety is at stake.


  1. Saenger AK, Haymond S. Utilization of cardiac troponin assays in adult and pediatric populations: Guideline recommendations vs. reality. Clin Biochem. 2015;48(18):1213-18.
  2. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60(16):1581-98.
  3. Amsterdam EA, Wenger NK, Brindis RG, et al. Guideline for the management of patients with non-ST-elevation acute coronary syndromes. J Am Coll Cardiol. 2014;64(24):e139-228.
  4. American College of Emergency Physicians. ACEP Policy Statements. Emergency Department Observation Services. October 2015. Accessed 6/2/2016
  5. Backus BE, Six AJ, Kelder JH, et al. Risk scores for patients with chest pain: Evaluation in the emergency department. Curr Cardiol Rev. 2011;7(1):2-8.
  6. Six AJ, Backus BE, Kelder JC. Chest pain in the emergency room: Value of the HEART score. Neth Heart J. 2008;16(6):191-96.
  7. Backus BE, Six AJ, Kelder JC, et al. A prospective validation of the HEART score for chest pain patients at the emergency department. Int J Cardiol. 2013;168(3):2153-58.
  8. Backus BE, Six AJ, Kelder JC, et al. Chest pain in the emergency room: a multicenter validation of the HEART score. Crit Pathw Cardiol. 2010;9(3):164-69.
  9. Mahler SA, Hiestand BC, Goff DC Jr, et al. Can the HEART score safely reduce stress testing and cardiac imaging in patients at low risk for major adverse cardiac events? Crit Pathw Cardiol. 2011;10(3):128-33.

Eugenio H. Zabaleta, PhD, is a clinical chemist at OhioHealth Mansfield Hospital in Mansfield, Ohio, and is a lecturer in Cleveland State University’s clinical chemistry graduate program. He graduated from the Catholic University of Cordoba (Argentina) with a degree in biochemistry and received his PhD in chemistry from the University of Akron.

Click here to see SIDEBAR 2.


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