Article, Emergency Medicine

Should creatine kinase-MB index be eliminated in patients with indeterminate troponins in the ED?

Unlabelled imageAmerican Journal of Emergency Medicine (2012) 30, 1574-1576

Brief Report

Should creatine kinase-MB index be eliminated in patients with indeterminate troponins in the ED??

Kathryn A. Volz MD a,?, Gary L. Horowitz MD b, Daniel C. McGillicuddy MD a,

Shamai A. Grossman MD a, Leon D. Sanchez MD, MPH a

aDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA

bDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA

Received 13 July 2011; revised 25 August 2011; accepted 25 August 2011

Abstract

Objectives: The objective of this study is to determine whether creatine kinase-MB (CK-MB) index (CK-MBi) is useful in the evaluation of acute myocardial infarction (AMI) in patients with indeterminate troponin (Tn) in the emergency department (ED).

Methods: A retrospective cohort study was conducted of patients at an Urban academic ED with over 55 000 annual visits who underwent Tn T (Roche, Indianapolis, IN) and CK-MB testing. One year of ED patients who had Tn testing were identified, and their corresponding CK-MBi was examined to find patients with indeterminate Tn (0.01-0.09) and positive CK-MBi (N6.0). Subsequent cardiac enzymes and hospital course were reviewed to identify patients diagnosed with AMI. A 95% confidence interval around point estimates were used in data analysis.

Results: Over 1 year, 11 718 initial Tn were identified. Indeterminate Tn was seen in 2512 cases. Of these, 28 had positive CK-MBi. Of the 28, 5 were judged by treating physicians to be having AMI and underwent cardiac catheterization. Of the 5 patients, 4 had subsequent positive Tns on serial enzyme testing. One of the patients thought to be having AMI had no coronary artery disease on catheterization. The rate of true positive CK-MBi with indeterminate Tn was 0.16% (95% confidence interval, 0.04%-0.41%).

Conclusion: Initial results identify rare cases of AMI where CK-MBi is positive in the setting of indeterminate Tn. However, most patients with indeterminate Tn and positive CK-MBi were not judged to be having AMI. In most cases, CK-MBi is not positive with indeterminate Tn and when positive more commonly confuses the picture. This suggests CK-MBi could be eliminated in patients with indeterminate Tns.

(C) 2012

Introduction

Historically, creatine kinase-MB (CK-MB) has been used as an early identifier of non-ST-elevation acute myocardial

? Poster presentation at Society for Academic Emergency Medicine 2011 Annual Meeting.

* Corresponding author. Tel.: +1 617 754 2350.

E-mail address: [email protected] (K.A. Volz).

infarction (AMI). However, multiple studies have suggested that troponin (Tn) is statistically more sensitive and specific in identifying patients with AMI and has become the preferred biomarker for Myocardial necrosis among consen- sus recommendations [1-4]. Our prior data suggested that CK-MB may safely be eliminated in patients with negative (b0.01) Tns [5]. The significance of indeterminate (0.01- 0.09) Tns has not been well established. Many patients have indeterminate Tn caused by renal failure or other comorbid- ities [6,7]. Multiple studies have suggested that small

0735-6757/$ – see front matter (C) 2012 doi:10.1016/j.ajem.2011.08.017

Should CK-MBi be eliminated? 1575

increases in Tn below the Upper limit of normal are associated with increased odds of acute coronary syndrome (ACS) [8-12]. However, other studies suggest that physi- cians often do not consider patients with indeterminate Tns as different from those with negative Tns [12,13]. At least 1 study has suggested that discordant cardiac biomarkers may identify patients at increased risk for ACS [14]. Our study attempted to determine whether CK-MB can be helpful in the early identification of patients with AMI who have indeterminate Tns in the ED.

Methods

A retrospective cohort study was conducted at an urban academic level 1 trauma center with more than 55 000 annual visits. The project was approved by our hospital institutional review board.

Patient encounters were retrospectively examined using a previously studied data set based on Tn results in the laboratory database [5]. All patients with Tn testing in the ED were identified over a period of 12 months. Correspond- ing CK-MB and total Creatine kinase (CK) were performed with Roche Diagnostics equipment and reagents, and CK- MB indices (CK-MBi) were calculated. As opposed to our previous study, which looked at patients with negative Tns (b0.01), this study identified patients with indeterminate Tn (0.01-0.09) and positive CK-MBi (N6.0). Patients with negative Tn (b0.01) and positive Tn (N0.09) were excluded from further analysis. In patients with indeterminate Tn and positive CK-MBi, serial 6-hour cardiac enzymes and hospital course were evaluated. Data were entered into a Microsoft Excel 2003 (Redmond, WA) database. Data were analyzed using SPSS14 (SPSS, Chicago, IL).

Descriptive statistics including confidence intervals (CIs) and ?2 are reported when appropriate. A 95% CI around point estimate was used in data analysis.

Results

There were 11 092 separate patients with Tns ordered from the ED during the study period. Of the patients, 54.5% were female with a mean age of 68 years for females and 64 years for males.

There were 11 718 Tns sent from the ED over 12 months, with 97.9% associated CK-MBs sent. There were 2512 Tns (21.4%) that resulted as indeterminate in the ED.

Of these 2512 indeterminate Tns, 28 had positive CK- MBis. Among patients with negative Tn and positive CK- MBis, 4 ruled in for AMI by rising Tn and were in turn judged by treating physicians to be having acute AMI and sent for urgent cardiac catheterization after the second positive Tn had resulted. Of these 4, 1 had no coronary artery disease (CAD) identified on catheterization. One additional patient with

significant history of CAD and Hyperacute T waves on electrocardiogram (ECG) was judged to be having AMI based on history and ECG findings and was sent emergently to cardiac catheterization after the first set of cardiac enzymes returned. This patient was noted to have CAD on catheter- ization, although no interventions were made. This patient never developed a Tn elevation. Of 28 patients, 21 did not develop further significant elevation of Tn on serial testing and were judged by treating physicians not to have AMI despite the initial elevated CK-MBi. The remaining 2 patients were excluded, as they had only 1 Tn sent. One of these patients was found to have a large intracranial hemorrhage and was made comfort measures only; therefore, no further sets of cardiac enzymes were sent. The second patient was admitted for hyperkalemia and lower Extremity weakness, and no further cardiac workup was pursued by the admitting team. This patient was alive at 30 days.

The rate of true positive CK-MBi was 0.16% (95% CI, 0.04%-0.41%). Most patients with CK-MBi that were judged to be true positives would have been identified with subsequent serial Tn. In 1 patient, CK-MBi in the setting of an indeterminate Tn was helpful in identifying and changing management of a patient who was ultimately diagnosed as having a non-ST-elevation myocardial infarc- tion. This decision was made in the setting of Abnormal ECG findings in the setting of a patient with personal history of CAD. No other patient with a positive CK-MBi in the setting of an indeterminate Tn went to the cardiac catheterization laboratory before the second Tn resulted as positive.

Discussion

Previously, we have shown that, in patients with negative Tn, CK-MB adds no benefit in the evaluation of AMI. After this previous study, our institution eliminated CK-MB from the initial screening in patients being evaluated for AMI [5]. Since that time, we have continued to “add-on” CK-MB to patients with indeterminate Tn. A retrospective review of the data before instituting this change in our laboratory ordering process over 1 year with 11 718 Tns showed 28 of the 2512 patients with intermittent to have a positive CK-MBi. There were only 4 cases (0.16%) of 2512 where an indeterminate Tn was associated with a clinically relevant positive CK-MBi. When evaluating all Tns sent from the emergency department (ED), only 4 cases of 11 718 (0.034%) were noted to have the result of an indeterminate Tn and with a true positive CK-MBi.

In 3 of 4 of these cases where the initial CK-MBi was positive and represented AMI based on subsequent labora- tory values or findings on cardiac catheterization, treating physicians did not make a decision to perform cardiac catheterization based on the positive CK-MBi in the setting of an indeterminate Tn. These patients only went to cardiac catheterization when the subsequent Tn became positive,

1576 K.A. Volz et al.

suggesting that the CK-MBi is not routinely used by the treating admitting physicians in decision making. This may be related to the extremely small numbers of patients who have this presentation. Furthermore, 21 of 26 patients had positive CK-MBis and were ultimately judged by treating physicians not to be having AMI, as further Tns never rose significantly. Thus, these positive CK-MBs may be identi- fied as false positive and serve to only confuse the picture in most cases. Adding CK-MBi appeared to add little to the evaluation of AMI except cost and confusion when the value was falsely positive.

Converting the concurrent ordering of CK-MB to a reflex test eliminated close to 70% of all CK-MBs currently ordered at our institution. Based on these data, we feel the remaining CK-MBis that are currently being added on may also be eliminated, completely removing CK-MB from the labora- tory screening of AMI in our ED.

Limitations

Limitations of our retrospective study include enrollment bias and incomplete records. Furthermore, as a single-center study, our study was subject to local practice patterns and evaluated only a Tn T assay. These results may not be transferable to hospitals using a different Tn assay; further research would be needed to determine if these results are transferable to other assays. We did not follow up patients with negative CK-MB and indeterminate Tn assays or identify the odds of ACS with indeterminate Tns, as this was beyond the scope of this project. We also did not attempt to determine the reason for patients’ indeterminate Tns.

Conclusions

Initial results suggest that there are rare cases of AMI where CK-MBi is positive in the setting of indeterminate Tn. However, most patients with indeterminate Tn and positive CK-MBi do not subsequently rule in for AMI by rising Tn and were not judged to have AMI. In most cases, CK-MBi is

not positive with indeterminate Tn and, when positive, more commonly confuses the picture. Thus, CK-MBi likely should not be routinely added to the evaluation of patients with indeterminate Tns in the ED.

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