Disease Markers

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Cardiac Biomarkers

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Research Article | Open Access

Volume 2015 |Article ID 157812 | https://doi.org/10.1155/2015/157812

Maame Yaa Yiadom, Petr Jarolim, Cathy Jenkins, Stacy E. F. Melanson, Michael Conrad, Joshua M. Kosowsky, "Diagnostic Implications of an Elevated Troponin in the Emergency Department", Disease Markers, vol. 2015, Article ID 157812, 6 pages, 2015. https://doi.org/10.1155/2015/157812

Diagnostic Implications of an Elevated Troponin in the Emergency Department

Academic Editor: Bertil Lindahl
Received25 Aug 2014
Revised12 Dec 2014
Accepted30 Jan 2015
Published16 Apr 2015

Abstract

Objective. To determine the proportion of initial troponin (cTn) elevations associated with Type I MI versus other cardiovascular and noncardiovascular diagnoses in an emergency department (ED) and whether or not a relationship exists between the cTn level and the likelihood of Type I MI. Background. In the ED, cTn is used as a screening test for myocardial injury. However, the differential diagnosis for an initial positive cTn result is not clear. Methods. Hospital medical records were retrospectively reviewed for visits associated with an initial positive troponin I-ultra (cTnI), ≥0.05 μg/L. Elevated cTnI levels were stratified into low (0.05–0.09), medium (0.1–0.99), or high (≥1.0). Discharge diagnoses were classified into 3 diagnostic groups (Type I MI, other cardiovascular, or noncardiovascular). Results. Of 23,731 ED visits, 4,928 (21%) had cTnI testing. Of those tested, 16.3% had initial cTnI ≥0.05. Among those with elevated cTn, 11% were classified as Type I MI, 34% had other cardiovascular diagnoses, and 55% had a noncardiovascular diagnosis. Type I MI was more common with high cTnI levels (41% incidence) than among subjects with medium (9%) or low (6%). Conclusion. A positive cTn is most likely a noncardiovascular diagnosis, but Type I MI is far more common with cTnI levels ≥1.0.

1. Introduction

Myocardial infarction (MI) in emergency department (ED) patients is a frequently suspected but infrequently made diagnosis. In the ED patient population a troponin serum assay (cTn) is used as a generic screen for myocardial injury [1, 2]. Serum cTn testing is the biomarker of choice to test for myocardial infarction, one of the more critical conditions causing myocardial injury. An elevated troponin has been associated with increased morbidity and mortality. So this generally prompts a continued evaluation in hospital [3]. The biochemical specificity of contemporary cardiac troponin assays, a troponin I (cTnI) upon initial serum testing in the ED, is greater than 90% for myocardial injury [4, 5]. This permits the early identification of patients with likely myocardial injury. A 2008 study by Keller et al. suggests that the diagnosis of acute myocardial infarction can be made early for many patients with an initial early elevated cTn level in the right clinical context. However, the likelihood that an initial elevated cTnI specifically represents Type I MI is less clear. Troponin based diagnostic decision-making primarily pertains to patients with potential non-ST-elevation MI (NSTEMI), since the diagnosis of STEMI is made by EKG. However, troponin testing still has a role in differentiating cases of MI from those where ST elevations on EKG may be attributed to other causes.

Even among causes of MI, there are several other mechanisms of injury to be noted. In these cases, acute management focuses on treating the underlying causes, rather than medication or procedural coronary intervention. This diversity was recognized within the universal definition of myocardial infarction as classified by the international consortium of cardiology associations. (see Table 1) [6]. Type I MI was independently distinguished from other mechanisms of acute myocardial infarction (AMI), as myocardial cell loss from ischemia caused by acute atherosclerotic plaque rupture with thrombus formation within a coronary artery lumen, fissuring, or dissection (i.e., acute coronary syndrome).


TypeDefinition

IInfarction due to ischemia from a primary coronary event such as atherosclerotic plaque rupture and thrombus formation, arterial wall erosion, fissuring, or dissection

IIInfarction secondary to ischemia from either increased oxygen demand or decreased supply (coronary artery spasm, hypotension, hypertension, anemia, and dysrhythmia)

IIISudden cardiac death/arrest with symptoms suggestive of STEMI or thrombus in a coronary artery found on angiography or autopsy

IVaInfarction resulting from percutaneous coronary intervention (PCI)

IVbInfarction from stent thrombosis

VInfarction due to ischemia related to coronary artery bypass grafting

The loss of myocardium occurs on the order of minutes; thus a diagnosis of Type I MI prompts an acute shift in focus toward early antiplatelet and anticoagulant therapy with the possibility of urgent percutaneous coronary intervention (PCI). Little epidemiological data exists to guide practitioners in gauging the suspicion for Type I MI, amongst other causes, when the cTn is elevated in the context of a broad differential diagnosis. This situation is typical in the ED. The first objective of this study is to assess the frequency and implications of the diagnosis of Type I MI in an undifferentiated ED patient population. In addition, it is commonly assumed that the higher the cTn elevation, the greater the likelihood of Type I MI. A 2001 substudy by Lindahl et al. [7] suggested that this was the case with a cTnT assay. We challenge this hypothesis using a cTnI assay.

2. Materials and Methods

2.1. Study Population

This study was performed at a tertiary care academic medical and trauma center with 56,000 adult ED patient visits a year using a sensitive contemporary troponin biomarker for the evaluation of MI. Prior to the initiation of this retrospective chart review, it was approved by the hospital human research committee. The study period was March 1–July 31, 2007. The study population included all patients ≥18 years of age with a positive (≥0.05 g/L) initial ultrasensitive cTnI (TnI-Ultra, Siemens Healthcare Diagnostics, Tarrytown, New York) [8, 9] during their ED evaluation. Patients presenting in cardiac arrest were excluded. Typical practice in the ED at this time was to test appropriate patients for a cTn elevation upon initial evaluation and then 6 hours after presentation. Patients with a cTn elevation at first measurement were included. Results were obtained from the laboratory information system and merged, with the associated patient data from the electronic medical record system, in Microsoft Excel.

2.2. Adjudication of the Final Diagnosis

The final hospital discharge diagnosis was confirmed through a review of each patient’s ED and in-hospital record by a senior emergency medicine attending physician. Patients were categorized into diagnostic groups as either Type I MI (on the basis of care consistent with MI management including urgent revascularization, sustained antithrombotic therapy, or percutaneous coronary intervention during the hospital course), other cardiovascular diagnoses (including dysrhythmias, pulmonary embolism, and congestive heart failure), or a noncardiovascular diagnosis. In addition, deaths and the incidence of urgent revascularization were noted.

2.3. Analysis of Troponin Results

TnI results were stratified as low (0.05–0.09 g/L), medium (0.1–0.99 g/L), and high (≥1.0 g/L). Frequencies of primary diagnoses were determined by troponin strata, major diagnostic grouping, and the total population outcomes. The association of diagnostic grouping and categorized cTn level was assessed using Pearson’s chi-square test. All statistical analyses were performed using the programming language R, Version 3.1.2 (http://cran.r-project.org/).

3. Results

During the 5-month study period, 23,731 patients were seen in the ED of which 4,928 (21%) had a cTnI testing as part of their ED evaluation (see Figure 1). Among the tested subjects, 804 had an elevated initial cTnI. This represents 3.4% of all patients seen and 16.3% of those that had a cTnI ordered. The leading causes of an elevated cTnI across all diagnostic groups were from congestive heart failure (17%), infection (16%), dysrhythmia (6%), and blood loss (4%). In the low troponin level strata (0.05–0.9 ng/mL) were 383 patients (48%), 339 (42%) fell into the medium strata (0.1–0.99 ng/mL), and 82 (10%) fell into the high strata (≥1.0) (See Table 2). The type of primary diagnosis was significantly associated with categorized cTnI (). Eleven percent had a final diagnosis of Type I MI. This was only 1.8% of those who had a troponin level checked and 0.03% of all patients evaluated. Fifteen (17%) had ST-elevation MI and 74 (83%) had non-ST-elevation MI. Eight percent had urgent revascularization.


LowMediumHighCombined value
= 383 = 339 = 82 = 804

Age 804 59 72 82 58 70 81 57 67 80 58 71 81 0.221
Sex 804 0.952
 Female 46% (177) 47% (160) 48% (39) 47% (376)
 Male 54% (206) 53% (179) 52% (43) 53% (428)
First cTnI 804 0.05 0.06 0.08 0.12 0.20 0.35 1.73 3.00 6.29 0.06 0.10 0.27 <0.0011
Type of diagnosis 804 <0.0012
 Type 1 MI 6% (23) 9% (32) 41% (34) 11% (89)
 Other cardiovascular diagnoses39% (148) 33% (111) 22% (18) 34% (277)
 Noncardiovascular 55% (212) 58% (196) 37% (30) 54% (438)
eGFR 758 30 53 75 26 49 72 38 64 85 29 52 75 0.0151
CKMB 759 1.2 2.4 4.0 1.6 3.0 5.3 5.1 9.2 21.3 1.6 2.9 5.5 <0.0011
Creatinine 758 0.90 1.21 2.00 0.94 1.30 2.30 0.87 1.08 1.60 0.90 1.24 2.04 0.0261
MI 804 <0.0012
 No 94% (360) 91% (307) 59% (48) 89% (715)
 Yes 6% (23) 9% (32) 41% (34) 11% (89)
Urgent revascularization 804 <0.0012
 No 95% (364) 94% (320) 66% (54) 92% (738)
 Yes 5% (19) 6% (19) 34% (28) 8% (66)
Status 804 0.0012
 Alive 93% (355) 88% (299) 79% (65) 89% (719)
 Died 7% (28) 12% (40) 21% (17) 11% (85)

     represent the lower quartile , the median , and the upper quartile for continuous variables.
is the number of nonmissing values.
Numbers after percents are frequencies.
Tests used: 1Kruskal-Wallis test; 2Pearson’s test.

Among those with Type I MI, 26% had low troponin levels, 36% had medium, and 38% had high. Sixty-six patients (74%) underwent urgent revascularization, and 6% died. These deaths accounted for a minority (7%) of all deaths. Other cardiovascular diagnoses occurred in 277 (35%) of patients with an elevated cTnI. The most frequent diagnoses in this group were congestive heart failure (53%), dysrhythmia (18%), and hypertension (9%). Ten (4%) of these patients died accounting for 12% of all deaths. Noncardiovascular diagnoses were identified for 438 (55%) patients. The top diagnoses in this group were infection (29%), blood loss (7%), and intracranial hemorrhage or stroke (7%). Seventy (16%) of these patients died and accounted for 82% of all deaths.

In examining the troponin level (see Table 3) we found that within the low strata 6% had a final diagnosis of Type I MI, 5% underwent urgent revascularization, 39% had other cardiovascular diagnoses, 55% of patients had a noncardiovascular diagnosis (see Figure 2), and 7% died. These deaths were 33% of all deaths. Within the medium strata, 9% had an end diagnosis of Type I MI, 6% of the group experienced urgent revascularization, 33% had other cardiovascular diagnoses, 58% had a noncardiovascular diagnosis, and 12% died. These deaths accounted for 47% of all deaths. The leading diagnoses within this group were dysrhythmia with atrial fibrillation accounting for all cases. In the high strata the leading diagnoses were Type I MI, AICD firing, and blood loss. Within this group 41% of patients had Type I MI, 34% had urgent revascularization, 22% had other cardiovascular diagnoses, 37% had a noncardiovascular diagnosis, and 21% of all patients with a high troponin died. This was 20% of all deaths.


Type I MIOther cardiovascular diagnosesNoncardiovascularCombined value
= 89 = 277 = 438 = 804

Age 804 57 64 77 57 69 80 60 74 83 58 71 81 <0.0011
Sex 804 0.382
 Female 40% (36) 46% (128) 48% (212) 47% (376)
 Male 60% (53) 54% (149) 52% (226) 53% (428)
First cTnI 804 0.09 0.34 2.49 0.06 0.09 0.21 0.06 0.10 0.24 0.06 0.10 0.27 <0.0011
First cTnI (categorized) 804 <0.0012
 Low 26% (23) 53% (148) 48% (212) 48% (383)
 Medium 36% (32) 40% (111) 45% (196) 42% (339)
 High 38% (34) 6% (18) 7% (30) 10% (82)
eGFR 758 52 73 90 30 51 72 25 50 72 29 52 7 <0.0011
CKMB 759 1.9 3.6 9.5 1.6 2.7 4.2 1.5 2.9 5.6 1.6 2.9 5.5 0.0031
Creatinine 758 0.80 1.00 1.26 0.90 1.30 2.00 0.98 1.30 2.35 0.90 1.24 2.04 <0.0011
MI 804 <0.0012
 No 0% (0) 100% (277) 100% (438) 89% (715)
 Yes 100% (89) 0% (0) 0% (0) 11% (89)
Urgent revascularization 804 <0.0012
 No 26% (23) 100% (277) 100% (438) 92% (738)
 Yes 74% (66) 0% (0) 0% (0) 8% (66)
Status 804 <0.0012
 Alive 94% (84) 96% (267) 84% (368) 89% (719)
 Died 6% (5) 4% (10) 16% (70) 11% (85)

     represent the lower quartile , the median , and the upper quartile for continuous variables.
is the number of nonmissing values.
Numbers after percents are frequencies.
Tests used: 1Kruskal-Wallis test; 2Pearson’s test.

4. Discussion

This study demonstrates that myocardial infarction is the cause of troponin elevation in a minority of cases. The striking finding from the study is the diversity (see Figure 1) within the differential diagnosis for an elevated cTnI in an undifferentiated patient population. The majority of deaths among those with a positive troponin (82%) were attributed to noncardiovascular diagnoses. Our results support prior work that has identified the incidence of MI in this population to be between 9 and 13% and the troponin elevations to be mostly attributed to noncardiac diagnoses [10, 11]. However, we also found that patients with high initial troponin levels had a much higher incidence of Type I MI (see Figure 2). The result of the first troponin test in the ED helps gauge the likelihood of admission versus discharge and the likely focus of early in-hospital care. Unlike other MI types, treatment is focused on early antithrombotic coronary artery therapi