The Etiology and Prognostic Significance of Cardiac Troponin I Elevation in Unselected Emergency Department Patients

doi:10.1016/j.jemermed.2007.09.060

The Journal of Emergency Medicine

Volume 38, Issue 1, January 2010, Pages 1-5

https://doi.org/10.1016/j.jemermed.2007.09.060 Get rights and content

Abstract

Background: Cardiac troponin elevations are associated not only with acute coronary syndromes (ACS) but also with multiple other cardiac and non-cardiac conditions. Study Objectives: To investigate the etiology and clinical significance of cardiac troponin I elevations in an unselected Emergency Department (ED) patient cohort. Methods: The study population consisted of 991 consecutive troponin-positive patients admitted to the ED of a university hospital with ACS as the presumptive diagnosis. Cardiac troponin I was measured on admission and a follow-up sample was obtained at 6–12 h. Clinical diagnosis was ascertained retrospectively using all the available information including electrocardiogram, clinical data, laboratory tests, and available coronary angiograms. Results: At admission, 805 (81.2%) patients were already troponin positive; of these, the troponin elevation was related to myocardial infarction (MI) in 654 (81.2%) patients. Finally, 83.0% of the troponin elevations were due to MI, 7.9% were related to other cardiac causes, and 9.1% to non-cardiac diseases. The leading non-cardiac causes were pulmonary embolism, renal failure, pneumonia, and sepsis. Non-cardiac patients with elevated troponin I at admission showed significantly higher in-hospital mortality (26.7% vs. 13.4%, p = 0.002) compared to cardiac patients. Conclusion: Elevated troponin levels for reasons other than MI are common in the ED and are a marker of poor in-hospital prognosis.

Introduction

In 2000, the European Society of Cardiology (ESC) and American College of Cardiology (ACC) Joint committee redefined the diagnostic criteria of myocardial infarction (MI) (1).The primary goal was to define MI more accurately. The new definition was based on more sensitive and more specific markers of cardiac myocyte necrosis, especially cardiac troponins (cTn) I and T (2). As a consequence of the novel criteria, an increased proportion of acute coronary syndrome (ACS) patients are diagnosed with MI compared to the previous World Health Organization definition of MI (3). As the cTns are structural proteins of cardiac myocytes, cTn positivity indicates only myocardial injury. There are multiple cardiac and non-cardiac causes that are associated with non-specific troponin elevations (4, 5, 6).

Cardiac troponins are frequently measured in emergency settings. We could not find a study that had investigated the clinical spectrum and significance of non-ACS cTn positivity in the Emergency Department (ED). Therefore we evaluated this phenomenon in an unselected acute hospital patient cohort.

Section snippets

Study Population

The study population consisted of 991 prospective patients (568 male, 423 female) with a presumptive diagnosis of ACS at admission to the ED who developed cTnI elevation. The study was performed in one hospital (Tampere University Hospital, Tampere, Finland) and all consecutive patients with any reason for cTnI analysis were recruited for the study. The study period was 1 year (2002), as previously described (7). Only patients who were cTnI positive either on admission (n = 805) or at 6–12 h (n

Clinical Diagnosis

Based on ECG, clinical data, laboratory tests, and available coronary angiograms, 823/991 (83.0%) of the troponin-positive patients turned out to have MI, whereas 78 (7.9%) had non-MI cardiac conditions. In 90 (9.1%) patients, elevated cTnI was associated with a non-cardiac condition. The baseline characteristics of all cTnI positive patients are shown in Table 1, Table 2.

Figure 1A shows the causes of non-MI cardiac cTnI elevations. Supraventricular dysrhythmias, heart failure, myocarditis, and

Discussion

We found that in an unselected multidisciplinary ED patient cohort admitted with ACS as the presumptive diagnosis, 18.8% of cTnI positivity at admission was due to causes other than MI; 57% of these patients did not have any acute cardiac problems. The proportion of non-MI patients was somewhat lower in our ED patient cohort compared to that observed by Wong et al. (38%) and by Alcalai et al. (41%) (4, 5). These studies included all patients with elevated cTn measured during hospitalization as

Conclusions

Elevated cTnI levels for reasons other than MI are common in the ED. Troponin elevations related to non-cardiac conditions indicate a poor in-hospital prognosis.

Acknowledgments

Hanna Näppilä, rn and Johanna Muhos, rn are acknowledged for expert care of the study subjects.

References (8)

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There are more references available in the full text version of this article.

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An emergency medicine approach to troponin elevation due to causes other than occlusion myocardial infarction
2020, American Journal of Emergency Medicine
Troponin is an integral component of the evaluation for acute coronary syndrome (ACS) and occlusion myocardial infarction (OMI). However, troponin may be elevated in conditions other than OMI.
This narrative review provides emergency clinicians with a focused evaluation of troponin elevation in patients with myocardial injury due to conditions other than OMI.
ACS includes the diagnosis of myocardial infarction (MI), which incorporates assessment for elevated troponin. Troponin I and T are the most common biomarkers used in assessment of myocardial injury and may be released with myocyte injury and necrosis, myocyte apoptosis and cell turnover, and oxygen supply demand mismatch. Troponin elevation is a reflection of myocardial injury, and many conditions associated with critical illness may result in troponin elevation. These include cardiac and non-cardiac conditions. Cardiac conditions include heart failure, dysrhythmia, and dissection, while non-cardiac causes include pulmonary embolism, sepsis, stroke, and many others. Clinicians should consider the clinical context, patient symptoms, electrocardiogram, and ultrasound in their assessment of the patient with troponin elevation. In most cases, elevated troponin is a marker for poor outcomes including increased rates of mortality.
Troponin can be elevated in many critical settings. The causes of troponin elevation include cardiac and non-cardiac conditions. Clinicians must consider the clinical context and other factors, as an inappropriate diagnosis of OMI may result in patient harm and misdiagnosis of another condition.
Prognostic Impact of Myocardial Injury Related to Various Cardiac and Noncardiac Conditions
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Citation Excerpt :
Also, it appears that acute infection is the most frequent single noncardiac condition, comprising as much as 41% of group C patients. These observations support the retrospective data by Ilva et al,12 who identified infectious diseases – mainly pneumonia and sepsis – in about one-third of unselected patients with nonmyocardial infarction troponin elevations admitted to an emergency department. The large proportion of patients with cardiac troponin I elevations related to noncardiac conditions in our study probably has more explanations.
Elevated cardiac troponins in clinical conditions other than myocardial infarction are well known. For such occurrences, the term “myocardial injury” has been proposed. The long-term outcome in patients with myocardial injury related to various cardiac and noncardiac clinical disorders is unknown.
During January 2010 to January 2011, we prospectively studied hospitalized patients who had cardiac troponin I measured on clinical indication. Patients with cardiac troponin I values >30 ng/L and no evidence of myocardial ischemia were diagnosed as having myocardial injury. Patients were classified into 5 categories of plausible related conditions: cardiac ischemic, cardiac nonischemic, noncardiac, multifactorial, or indeterminate. Follow-up was a minimum of 3 years, with all-cause mortality as the single end-point.
A total of 3762 patients were considered, of whom 1089 (29%) had myocardial injury. The most common associated conditions were noncardiac (n = 346) or multifactorial (n = 359). Cardiac ischemic (n = 183) and cardiac nonischemic (n = 134) conditions occurred less frequently. After a median of 3.2 years, 645 patients (59%) had died. A multivariate Cox regression analysis showed no difference in mortality between patients with cardiac ischemic and cardiac nonischemic conditions (hazard ratio [HR] 0.75; 95% confidence interval [CI], 0.50-1.13; P = .2). Patients with noncardiac or multifactorial disorders, however, had significantly higher mortality than those with associated cardiac ischemic conditions (HR 1.39; 95% CI, 1.06-1.80; P = .02, and HR 1.94; 95% CI, 1.50-2.51; P <.001), respectively.
In patients with myocardial injury, the most common associated conditions were noncardiac or multifactorial. Of notice, these patients had significantly higher long-term mortality when compared with those with associated cardiac conditions.
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Citation Excerpt :
The study recommended that those with lower troponin levels should be interpreted with caution. In a study by Ilva et al [6], 991 consecutive ED patients believed to have ACS had troponins drawn. In this study, 83% had ACS as a cause with 17% determined to be non-ACS causes.
Troponin elevation can be caused by etiologies other than acute coronary syndromes (ACS). Our hypothesis was that elevated troponins occur more frequently in non-ACS cases but that ACS cases (type 1 ST-elevation myocardial infarction [STEMI] and type 1 non-STEMI [NSTEMI]) have significantly higher troponin elevations.
This was a cross-sectional cohort analysis of a random subset of all patients with elevated troponins (defined as ≥ 0.06 ng/mL) over a 1-year period from July 2013 to June 2014. The first positive troponin I and the peak were used in this study. All included patients had medical record reviews looking for whether our cardiologists or hospitalists attributed the elevated troponin to an ACS (NSTEMI or STEMI) or non-ACS cause. Non-ACS causes were categorized as infection, cancer, renal diseases, cardiovascular disease, pulmonary disease, trauma, cardiac arrest, neurologic disease, hypertension, or other. Data were extracted by 2 investigators on the cause of the elevated troponin. Three sessions to educate data extractors were arranged and methods of data extraction discussed, then a 5% sample was reevaluated by the other extractor to determine interrater agreement measures. Parametric data were evaluated with t test and analysis of variance. Dichotomous variables were compared using χ² test. Troponin data were evaluated using nonparametric Kruskal-Wallis or Mann-Whitney U. A logistic regression model was created with variables selected a priori to evaluate the predictive ability of these variables in differentiating ACS vs non-ACS causes of elevated troponin.
We evaluated 458 randomly selected patients from 1317 unique cases of all patients with initial elevated troponins at least 0.06 mg/mL during the study period. There was 84% interrater agreement in the 5% sampling. Seventy-nine percent had a non-ACS cause of elevated troponin, and the average initial positive troponin I level was significantly lower in the non-ACS cases (0.14; 95% confidence interval [CI], 0.08-0.37) than those with documented STEMI (10.2; 95% CI, 0.75-20.1) or NSTEMIs (0.4; 95% CI, 0.13-1.7). In the non-ACS group, the median initial troponin was 0.14 ng/mL (0.08-0.37 ng/mL). Peak troponin levels were highest in STEMI, next NSTEMI, and lowest in non ACS causes. The most frequent subgroups in the non-ACS group were non-ACS cardiovascular, infectious, renal, or hypertensive causes. In a linear regression model adjusting for age and sex, higher troponin levels had higher odds of being related to ACS causes (adjusted odds ratio, 1.4; 95% CI, 1.2-1.6) than non-ACS causes.
The etiology for most initial elevated troponin I levels in a randomly selected population is the result of non-ACS causes. As initial + troponin levels increased, they were more likely associated with ACS causes than with non-ACS causes. Average initial + and peak troponin values were highest in STEMIs, next highest in NSTEMIs, and lowest overall in non-ACS causes.
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Cardiac troponin levels help risk-stratify patients presenting with an acute coronary syndrome. Although cardiac troponin levels may be elevated in patients presenting with non-acute coronary syndrome conditions, specific diagnoses and long-term outcomes within that cohort are unclear.
By using the Veterans Affairs centralized databases, we identified all hospitalized patients in 2006 who had a troponin assay obtained during their initial reference hospitalization. On the basis of the diagnostic codes of the International Classification of Diseases, 9th Revision, primary diagnoses were categorized as acute coronary syndrome or non-acute coronary syndrome conditions.
Of a total of 21,668 patients with an elevated troponin level who were discharged from the hospital, 12,400 (57.2%) had a non-acute coronary syndrome condition. Among that cohort, the most common diagnostic category involved the cardiovascular system, and congestive heart failure (N = 1661) and chronic coronary artery disease (N = 1648) accounted for the major classifications. At 1 year after hospital discharge, mortality in patients with a non-acute coronary syndrome condition was 22.8% and was higher than in the acute coronary syndrome cohort (odds ratio 1.39; 95% confidence interval, 1.30-1.49). Despite the high prevalence of cardiovascular diseases in patients with a non-acute coronary syndrome diagnosis, use of cardiac imaging within 90 days of hospitalization was low compared with that in patients with acute coronary syndrome (odds ratio 0.25; 95% confidence interval, 0.23-0.27).
Hospitalized patients with an elevated troponin level more often have a primary diagnosis that is not an acute coronary syndrome. Their long-term survival is poor and justifies novel diagnostic or therapeutic strategy-based studies to target the highest risk subsets before hospital discharge.
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Paroxysmal supraventricular tachycardia (PSVT), a common dysrhythmia seen in the emergency department (ED), is usually managed without difficulty and with a favorable prognosis. Serum cardiac troponin I (cTnI) testing provides important risk stratification information in certain patients; its use in PSVT patients, however, has not been explored. A retrospective review of consecutive adult ED PSVT patients seen for 21 months was performed. Fifty-four PSVT patients were identified on the basis of International Classification of Disease, Ninth Edition codes and the ED patient log at a university hospital. Three patients were excluded for incorrect rhythm, leaving 51 who were included in data analysis. Thirty-eight patients had at least one serum cTnI value measured. Of those, 11 had a positive result, defined as serum cTnI of more than 0.02 ng/dL. Thirty-day outcomes for these patients were evaluated and showed one ED return, no PSVT recurrences, and no deaths at our regional hospital. In this sample, serum cTnI testing did not identify PSVT patients at risk for poor outcome. Further consideration of the use of this testing modality in the PSVT patient population is recommended.

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: This study was supported financially by Kanta-Hame Central Hospital Research Fund and Elli and Elvi Oksanen Fund of the Pirkanmaa Fund under the auspices of the Finnish Cultural Foundation, the Medical Research Fund of Tampere University Hospital, and the Finnish Foundation for Cardiovascular Research.

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Original contributionThe Etiology and Prognostic Significance of Cardiac Troponin I Elevation in Unselected Emergency Department Patients

Abstract

Introduction

Section snippets

Study Population

Clinical Diagnosis

Discussion

Conclusions

Acknowledgments

Am J Cardiol

Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction

Eur Heart J

Improved detection of minor ischemic myocardial injury with measurement of serum cardiac troponin I

Clin Chem

Epidemiological consequences of introducing new biochemical markers for detection of acute myocardial infarction

Scand Cardiovasc J

Original contribution
The Etiology and Prognostic Significance of Cardiac Troponin I Elevation in Unselected Emergency Department Patients