Brief Report

Estimating the clinical impact of bringing a multimarker cardiac panel to the bedside in the ED^?

Robert H. Birkhahn MD?, Elizabeth Haines DO, Wendy Wen MD, Lakshmi Reddy MD, William M. Briggs PhD, Paris A. Datillo RN

Department of Emergency Medicine, New York Methodist Hospital, Brooklyn, NY 11215, USA

Received 28 October 2009; revised 7 December 2009; accepted 9 December 2009

Abstract

Objectives: We examined the use of point-of-care (POC) testing of cardiac biomarkers against standard core laboratory testing to determine the time-savings and estimate a cost-benefit ratio at our institution. Methods: We prospectively enrolled 151 patients presenting to the emergency department undergoing evaluation for acute coronary syndrome and conducted both central laboratory troponin T (TnT) testing at baseline and 6 hours as well as POC assays of creatine kinase MB, troponin I , and myoglobin at baseline and 2 hours. Sensitivity/specificity was calculated to measure the ability of the POC-accelerated pathway to identify enzyme elevations at rates parallel to our core laboratory. The time-savings were calculated as the difference between the median of the current protocol and the accelerated POC pathway. Results: Troponin T tests were elevated in 12 patients, which were all detected by the accelerated pathway yielding a relative sensitivity of 100%. Time-saving between the accelerated pathway and core laboratory showed a saving of 390 minutes (6.5 hours). The accelerated POC pathway would have benefited 60% (95% confidence interval [CI], 52%-68%) of our patients with an estimated cost of

$7.40 (95% CI, $6.40-$8.70) per direct patient care hour saved.

Conclusion: Our data suggest that the use of an accelerated cardiac POC pathway could have dramatically impacted the care provided to a large percentage of our patients at a minimal cost per direct patient care hour saved.

(C) 2011

Introduction

The appropriate and Timely diagnosis of patients present- ing with chest pain to the emergency department (ED) remains a significant challenge for emergency physicians.

^? Funding: The POC test devices for this project were generously provided by Biosite Inc at the request of the research team.

* Corresponding author. Tel.: +1 718 780 5040; fax: +1 718 780 3153.

E-mail address: [email protected] (R.H. Birkhahn).

More than 8 million patients present for the emergent evaluation of chest pain annually in the United States, with roughly 60% of these patients evaluated for acute coronary syndromes in the inpatient setting [1]. This leaves a tremendous pool of patients in whom early and aggressive cardiac risk stratification could potentially reduce resource use in increasingly busy EDs. Improved diagnostic efficiency may directly translate into time-savings and overall cost- effectiveness not to mention increased patient and hospital staff satisfaction [2-5].

The American College of Cardiology/American Heart Association Task Force guidelines for the management of

0735-6757/$ - see front matter (C) 2011 doi:10.1016/j.ajem.2009.12.007

patients with suspected acute myocardial infarction (AMI) recommends the use of biomarkers of cardiac injury in the early stages of risk stratification, with a turnaround time (TAT) of results within 60 minutes, preferably 30 minutes, to ensure early diagnosis of AMI and appropriate intervention [6,7]. According to the guidelines, diagnosis of AMI is considered when there is rise and/or fall of cardiac biomarkers (preferably troponin) with at least one value above the 99th percentile of the upper reference limit and at least one evidence of myocardial ischemia: symptoms of ischemia, electrocardio- gram (ECG) changes indicative of new ischemia, pathologic Q waves, or imaging evidence of new loss of viable myocardium or new regional Wall motion abnormality [8].

The increasing availability of point-of-care (POC) testing devices to measure cardiac markers has the potential to impact patient flow in the ED. Several studies addressing the impact of POC testing on TAT and patient flow in the ED have been conflicting, and the additional cost associated with bringing this testing to the bedside has not yet been addressed [2,9-12]. The lack of a definitive and efficient diagnostic strategy for non-ST-segment elevation MI has been the number one malpractice burden for ED physicians as patients can be inadvertently discharged from the ED with atypical presentations [13]. On the other hand, conservative evaluation and admission of chest pain patients to monitored cardiac units has been associated with unnecessary costs, resource use, and crowding in the ED, which may be improved upon by earlier and accurate risk stratification of ACS patients.

The purpose of our study was to estimate the impact of implementing POC cardiac biomarker testing in our ED, primarily time-savings and in turn cost-savings, by determining the real-time test availability (defined as TAT) of the accelerated pathway in comparison to the standard laboratory testing.

Methods

Study design

We prospectively enrolled a consecutive sample of patients presenting to the ED for an evaluation of chest pain.

Study setting and population

Adult patients older than 18 years, presenting for the evaluation of chest pain in whom the treating physician made a decision to evaluate with serial cardiac biomarkers, were approached for enrollment in our study. The standing hospital protocol for the evaluation of suspected ACS was 2 troponin T (TnT) enzymes obtained 6 hours apart. Patients were not approached for enrollment if they had an ST- segment elevation on initial ECG or if the treating physician felt that serial cardiac biomarker testing was not needed.

Study protocol

Following informed consent, enrolled patients had orders entered for testing of cardiac markers at enrollment (core laboratory TnT and POC multimarker testing), 2 hours (POC multimarker testing), and 6 hours (core laboratory TnT) measurement. Blood was obtained by the clinical care team by standing order and either transported to the laboratory or analyzed in the ED by the clinical research team. The core laboratory TnT testing was done on the Hitachi Modular Analytics system (Roche Diagnostics Corporation, Indiana- polis, Ind). The POC multimarker testing was performed on the Triage MeterPlus device for creatine kinase MB, troponin I , and myoglobin (Biosite Incoporated, San Diego, Calif).

During the study period, patients with suspected ACS at our institution required admission to a telemetry bed for continuous cardiac monitoring unless they had a nondiag- nostic ECG and at least 2 TnT measurements below the 99th percentile (0.01 ng/mL) at least 6 hours apart.

The manufacturer of the triage cardiac panel quotes cutoff values for POC TnI, myoglobin, and creatine kinase MB of

0.05 ng/mL (99th percentile; coefficient of variation [CV], 25%), 107 ng/mL (95%; CV, 10%), and 4.3 ng/mL (95%;

CV, 10%), respectively [14-17]. In our study, patients who had either POC TnI of 0.1 ng/mL or higher or myoglobin of 150 ng/mL or higher were considered abnormal. Although the use of myoglobin for identifying patients with AMI has been questioned because of its low specificity, our strategy was to use the high sensitivity and early release kinetics to identify patients at low risk of infarction. In this case, the projected “cost” of a false-positive on the multimarker panel was to remain on Telemetry monitoring and verify with serial TnT measurements as per the existing standard of care, whereas the benefit of 2 negative POC tests was an early disposition off of a cardiac monitor (to a regular medical floor, Stress testing, or to home).

Measurements

Within the context of this practice setting, our primary outcome of interest was the time to earliest possible disposition (per our hospital policy for suspected ACS). This policy requires that patients with suspected ACS have 2 negative cardiac biomarkers at least 6 hours apart before disposition off of a monitored bed or performance of a stress test. Patients with confirmed ACS would be monitored in a critical care setting with clinically appropriate interventions. Enrolled patients were observed during their hospital stay to identify any objective cardiac testing performed. Stress testing was considered positive when either ischemia was detected on perfusion imaging or ECG changes occurred during the test period. Patients who had cardiac catheterization were considered positive if a coronary intervention was performed or a cardiac revascularization

was performed or recommended.

Data analysis

Sensitivity and specificity were calculated along with positive and negative predictive values for the POC pathway with regard to an abnormal test in the core laboratory pathway. Time data are presented as medians using 95% confidence intervals (CIs) for both observed and estimated data.

Time-savings, as used for the primary outcome, were calculated as the difference between the availability of the 6-hour TnT and availability of the 2-hour POC test in the accelerated pathway (with the understanding that 4 hours were due solely to the nature of the rapid POC pathway alone). We used this observed time differential in conjunc- tion with available data on hospital and telemetry admission rates to calculate an estimated benefit of implementing this testing strategy in our institution. This was compared with the projected cost of implementing this testing strategy in all patients with an assumption of $20/POC test and

$7/laboratory TnT assay, conditioned on patient volume and accuracy estimates from our sample. For our calcula- tions, we assumed that all patients evaluated in the pathway would still be admitted to the hospital for inPatient evaluation. This provided the most conservative estimate of cost and Time Savings, recognizing a percentage of patients would be able to be discharged from the hospital with or without objective cardiac testing after evaluation in the POC pathway. Reimbursement for assay performance was not considered in this analysis.

All statistics were performed using R-a software environment for statistical computing (R Foundation for Statistical Computing, 2009).

This protocol was reviewed and approved by our institutional review board for clinical research.

Results

There were 151 patients who had both accelerated POC pathway and standard laboratory cardiac biomarker testing (52% male; average age, 65 years). It was determined that 12 patients (8%) had elevated core laboratory TnT upon assessment in the ED. The accelerated pathway identified the 12 patients with elevated TnI and/or myoglobin; thus, there is a relative sensitivity of 100% (95% CI, 74%-100%) for the POC pathway in relation to positive laboratory cardiac biomarkers. If considered separately, TnI was elevated in 10 of the 12 patients, whereas myoglobin was elevated in 11 of the 12 patients.

The accelerated POC pathway also yielded 48 false- positive elevations (32%), as confirmed by negative core laboratory enzyme levels. As for the 91 (60%; 95% CI, 52%- 68%) patients who had normal POC cardiac biomarkers, none were found to be have false negative results as validated by core laboratory results. Based on these results, with 100% sensitivity, the specificity was estimated to be 65% (57%- 73%), with a positive predictive value of 20% (11%-32%), a

Fig. 1 Distribution of TAT using the standard Core laboratory testing of TnT at 6-hour intervals vs an accelerated protocol using POC bedside testing (median values shown). The difference in the median TAT can be accounted for using myoglobin in the POC pathway (4 hours) and by bringing the test to the bedsides (2.5 hours).

negative predictive value of 100% (96%-100%), and an overall accuracy of 68% (60%-76%).

Among the 12 patients who had both positive POC and core laboratory troponins, 9 (75%) underwent cardiac catheterization to further characterize their coronary artery disease. Of these, 6 were found to have stenosis requiring percutaneous coronary intervention, and 1 had triple-vessel disease that required subsequent coronary artery bypass graft. With regard to time to test availability, the average time with core laboratory testing was 660 minutes to the 2nd TnT, whereas it was 270 minutes to the 2nd POC test with the accelerated pathway, which translates into difference of 390 minutes (6.5 hours; P b .00001). Fig. 1 shows the distribution of time to test availability with the standard core laboratory vs the accelerated pathway. It should be emphasized that 4 hours of this difference could be explained using an accelerated POC pathway exploiting the release kinetics of myoglobin and the remaining 2.5-hour differen-

tial was a result of bringing the test to the bedside.

Clinical impact

Our institution has 70 000 ED visits annually with 5% of these visits made for a chief complaint of chest pain that the treating physician initiates an evaluation for ACS with serial cardiac biomarker measurement. This yields a potential pool of 3500 patients per year in whom this accelerated evaluation pathway could be implemented. The cost of 7000 POC tests (at $20/test) would amount to $140 000/y for the

cost of the POC test alone. In addition, our a priori hypothesis assumed that any patient with an abnormal POC test would have testing of TnT in the core laboratory at 6 hours. This would result in an additional TnT measure- ment at 6 hours in the 40% (95% CI, 32%-48%) of patients with an abnormal POC test ($7/test in 1400 patients for a total of $9800/y. The Total cost of implementing an accelerated testing strategy was compared to the existing testing strategy that would require 7000 TnT (at $7/test) for a total of $49 000/y. This results in an estimated incremental cost of $100 800/y (95% CI, $99 000-$103 000) to implement what has been termed the rapid acute cardiac evaluation pathway at our institution.

To estimate the benefit of an accelerated cardiac pathway in our practice environment, we took the observed time-savings of 6.5 hours per patient and multiplied it by the estimated number of patients who would benefit from this pathway per year, 60% (95% CI, 52%-68%) with normal testing or 2100 patients/y. This resulted in a projection of 13 650 (95% CI, 11 800-15 500) direct patient care hours saved in the ED per year or an estimated cost of $7.40 (95% CI, $6.40-$8.70) spent for every hour of direct patient care saved.

Discussion

Traditionally, patients with suspected ACS have been admitted to the hospital for cardiac monitoring; however, the need for this has been called into question in recent studies [18,19]. It has been postulated that with better risk stratification of patients with suspected ACS, it would allow more appropriate use of the telemetry unit. Using a Multimarker approach to identify patients at low risk of cardiac complications would have saved 4 hours when compared to TnT alone. Our results also suggest that there was an additional time-savings in our model of 2.5 hours that was likely due to bringing the test to the bedside.

Previous studies have estimated a time-savings in using bedside testing ranging from 20 to 60 minutes; however, these estimates have been based on a single test [2,12,16,20,21]. The strength of our study was that it was an estimate obtained in vivo in the ED setting. The time that the second blood test was drawn varied widely even though they were ordered via a standard protocol. This variability could be explained by the fact that the ED is a high-stress environment the staff of which is much better at focused, goal-directed interventions occurring over rela- tively short periods rather than delivering routine scheduled care. Consistent with this observation, there was greater variability in the performance of the 6-hour Blood draw than that observed at the 2-hour mark. The research team facilitated the processing of both POC and core laboratory draws but did not provide further encouragement other than to notify the clinical care staff that a blood draw was due per protocol.

Conclusion

Our data suggest that an accelerated cardiac evaluation pathway can be used in suspected ACS to save an average of 6.5 hours by bringing a multimarker approach to the bedside. Directing resources toward identifying patients at lowest risk for ACS complications has the potential to dramatically impact the care delivered to all patients with suspected ACS. The direct cost of this strategy (estimated at $7/h saved) would be more than offset by the reduction in patient workload and presumed patient satisfaction achieved by efficiently risk stratifying patients to an appropriate level of care.

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