Original Contribution

Application of the TIMI risk score in ED patients with cocaine-associated chest pain

Maureen Chase MD*, Aaron M. Brown BS, Jennifer L. Robey RN, Kara E. Zogby RN, Frances S. Shofer PhD, Lauren Chmielewski BS, Judd E. Hollander MD

Department of Emergency Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA

Received 6 January 2007; revised 26 February 2007; accepted 2 March 2007

Abstract

Objective: The TIMI risk score has been validated as a risk stratification tool in emergency department (ED) patients with potential acute coronary syndrome. The goal of this study was to assess its ability to predict adverse cardiovascular outcomes in cocaine-associated chest pain.

Methods: This was a prospective cohort study of ED patients with chest pain with cocaine use. Data included demographics, medical history, and TIMI risk score. The main outcomes were acute myocardial infarction, revascularization, or death within 30 days of ED presentation.

Results: There were 261 patient visits. Patients were 43.2+8 years old, 73% male, 92% black, and 75% smokers. There were 33 patients with the Composite outcome. The incidence of 30-day outcomes according to TIMI score is as follows: TIMI 0, 3.7% (95% CI, 0.1-8.3); TIMI 1, 13.2% (5.7-20.7); TIMI 2, 17.1% (4.3-29.8); TIMI 3, 21.4% (4.4-38.4); TIMI 4, 20.0% (0.1-43.6); TIMI 5/6, 50.0% (0.1-100).

Conclusions: The TIMI risk score has no clinically useful predictive value in patients with cocaine- associated chest pain.

D 2007

Introduction

Recent reports from the Substance Abuse and Mental Health Services Administration estimate that there are more than 2 million people who have used cocaine in the past month [1]. As a consequence, cocaine accounts for 1 of every 5 drug-related emergency department (ED) visits, generating approximately 250000 visits each year for complaints related to its use [2]. Chest pain is the most frequently encountered symptom among cocaine users presenting to the ED [3].

* Corresponding author. Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. Tel.: +1 617 781 2298; fax: +1 617 754 2350.

E-mail address: [email protected] (M. Chase).

Cocaine increases the baseline risk of acute myocardial infarction (AMI) by 24 times in the first hour after use [4], and 1 of every 4 nonfatal myocardial infarctions (MIs) in patients aged 18 to 45 is related to frequent cocaine use [5]. Approximately 6% of patients with cocaine-associated chest pain sustain an AMI [6,7].

Identification and risk stratification of patients with potential acute coronary syndrome (ACS) is difficult in the best of circumstances. One method used to risk-stratify patients with potential ACS in terms of potential adverse cardiovascular outcomes is the TIMI risk score. Derived and validated to predict 14-day outcomes in trials of patients with unstable angina and non-ST-segment elevation MI [8-12], the tool uses 7 variables to risk-stratify patients with respect to outcomes. The TIMI score has been proven a

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reliable and valid means for risk-stratifying ED patients with chest pain of all causes [2,13] as well as helping to guide treatment of those patients with readily identified ACS [9,10]. The TIMI risk score predicts AMI, revascularization, and death within 30 days, even when applied at the time of ED presentation [2,13]. However, cocaine users were either not addressed or specifically excluded in these previous analyses, and there are no published risk stratification schemes for patients with cocaine-associated chest pain.

Table 1 Baseline characteristics of study population

Patient characteristics n (%)

Asian

Hispanic

Chest pain onset (minutes) Chest pain duration (minutes) cardiac risk factors Hypertension

Diabetes

Elevated cholesterol Family history of CAD Tobacco use

Past Medical History Coronary artery disease Congestive heart failure Angina

Myocardial infarction Undiagnosed chest pain TIMI Risk Factors

Age z65

Known coronary stenosis Cardiac risk factors z3 Aspirin use in prior 7 days

Anginal events z2 over past 24 hours ST segment deviation

Elevated cardiac markers Initial ECG impression Normal

Nonspecific

Early repolarization Abnormal, not diagnostic Ischemia, known to be old Ischemia, not known to be old Suggestive of MI

Other ECG findings

ST segment elevation z1 mm Q waves

Left bundle branch block Right bundle branch block Cardiac enzymes

Ordered Elevated

2 (b1)

3 (1)

240 (IQR 60-960)

180 (IQR 30-720)

114 (44)

37 (14)

28 (11)

53 (20)

196 (75)

55 (21)

33 (13)

47 (18)

56 (22)

27 (10)

4 (2)

44 (17)

61 (23)

54 (21)

83 (32)

39 (15)

54 (21)

97 (37)

46 (17)

19 (7)

76 (29)

8 (3)

9 (3)

6 (2)

41 (16)

17 (6)

1 (b1)

1 (b1)

241 (92)

54 (22)

All values are reported as absolute number and percent

frequency occurrence unless otherwise noted. IQR = interquartile range.

The goal of this study was to evaluate the ability of TIMI risk score to predict the composite outcome of 30-day AMI, revascularization, or death in patients who presented to the ED with cocaine-associated chest pain.

Materials and methods

This was a prospective observational cohort study of consecutively enrolled patients who presented to the ED with chest pain in the setting of cocaine use. The goal of this study was to assess the predictive value of the TIMI risk score on adverse outcomes in this patient population. The study protocol was approved by the institutional committee on research involving human subjects at our institution.

This study was conducted at the Hospital of the University of Pennsylvania. The ED served an urban population with approximately 52000 adult patient visits per year during the study period. Trained research assistants were available to enroll study participants 16 hours a day, 7 days a week.

Patients 18 years or older who presented to the ED with chest pain and received an electrocardiogram (ECG) were enrolled. Eligible patients were identified by either a self- reported history of cocaine use within the prior 7 days or the results of a urine toxicology test revealing cocaine metabolites. All Treatment decisions, including toxicologic urine testing, were at the discretion of the treating physician and independent of study enrollment.

All core criteria in the Standardized reporting guidelines

[14] were collected, including demographic characteristics, medical and cardiac history, characteristics of chest pain and related symptoms, presenting ECG interpretation, and treatment. Treating physicians calculated the TIMI risk score for each patient. Each positive variable (age N65 years, 2 or more risk factors for coronary artery disease, known coronary artery stenosis, ST-segment deviation on present- ing ECG, 2 or more anginal events in prior 24 hours, use of aspirin in prior 7 days, and elevated serum cardiac markers) received a single point, and each point was added to determine the total TIMI risk score. If data were missing or not obtained, a score of zero was assigned for that variable, in keeping with clinical practice.

Investigators followed the hospital course of admitted patients daily. Primary outcomes were all-cause mortality, AMI, or revascularization via percutaneous coronary inter- vention or coronary artery bypass surgery within 30 days of ED presentation. The diagnosis of AMI was determined

using the European Society of Cardiology/American Col- lege of Cardiology criteria and included AMI during the initial hospitalization as well as within 30 days [15]. This is consistent with prior studies on the TIMI risk score in ED patients [2,13]. Data recorded on hospitalized patients included any Cardiovascular complications, serial cardiac

Age (y)	43.2 F 8
Female sex	70 (27)
Male sex	191 (73)
Race
African American	241 (92)
Caucasian	15 (6)

Table 2 Relative risk of composite outcome for each TIMI risk score component
TIMI variable	Outcomes, n (%)	Relative risk	95% CI
Age z65 y	0 (0)	-	-
Prior CAD	9 (20.4)	1.8	0.91-3.56
z3 Cardiac risk factors	7 (11.5)	0.9	0.40-1.86
ST-segment deviation	9 (23.1)	2.1	0.97-4.12
Aspirin use	9 (16.7)	1.4	0.71-2.81
z2 Anginal events in 24 h	10 (12.0)	0.9	0.47-1.82
elevated cardiac biomarkers	23 (42.6)	8.8	4.51-17.21

marker results, cardiac diagnostic testing, and final diagno- sis. Follow-up was conducted at 30 days from initial presentation for each patient via direct telephone contact with patients or their health care proxies.

Continuous data are presented as either means with SDs or medians with interquartile ranges based upon the distribution of the data. Categorical data are presented as the percentage of frequency of occurrence. The relationship between the TIMI risk score and the composite outcome was analyzed using v² testing and the Cochran-Armitage trend test. Because troponin has been found to be a more specific marker for myocardial ischemia than creatine kinase-MB (CK-MB) in patients with cocaine-associated chest pain [16], subanalysis was also performed excluding patients diagnosed with an AMI by elevated CK-MB level in the absence of elevated troponin I level. All analyses were performed using SAS statistical software (Version 9.1; SAS Institute, Cary, NC).

Results

During the study period, there were 261 qualifying patient visits. The mean patient age was 43.2 F 8 years, and the study population was 73% male, 92% black, and 6% white. Other patient characteristics at the time of presenta- tion are presented in Table 1.

There were 213 patients who reported cocaine use in the preceding 7 days. Of the 118 patients who had toxicologic screening, 113 were found to have cocaine metabolites in their urine. There were 204 patients admitted to the hospital;

1 (0.4%) patient had immediate cardiac catheterization, 31 (12%) patients were admitted to the intensive care unit, 161 (62%) patients were monitored in telemetry floor beds, 10 (4%) patients were admitted to an unmonitored floor bed, and 1 (0.4%) patient was transferred to another facility. There were 53 (20%) patients who were discharged from the ED, and 4 (1%) patients left against medical advice.

Thirty-day follow-up was completed on 238 (91%) patients. In total, there were 33 patient encounters resulting in one or more of the events in our composite outcome. During index hospitalization, 29 patients had an AMI, and

4 underwent revascularization via percutaneous coronary intervention. There were no coronary artery bypass surgeries during initial hospitalization. Two patients died. Upon 30-

day follow-up, there were 27 patients who were rehospi- talized, and 2 had AMI. There were no additional deaths or revascularization procedures at 30 days.

The incidence of each TIMI variable in our study cohort was as follows; older than 65 years, 1.5%; known coronary stenosis, 16.9%; 3 or more cardiac risk factors, 23.4%; aspirin use in the prior 7 days, 20.7%, 2 or more anginal events over 24 hours, 31.8%; ST-segment deviation on presenting ECG, 14.9%; positive cardiac markers, 20.7%. The only variable found to have a significant relationship with the composite outcome was elevated cardiac markers (Table 2).

The incidence of 30-day death, AMI, and revasculariza- tion according to TIMI score is as follows: TIMI 0, 3.7% (95% CI, 0.1-8.3); TIMI 1, 13.2% (5.7-20.7); TIMI 2, 17.1%

(4.3-29.8); TIMI 3, 21.4% (4.4-38.4); TIMI 4, 20.0% (0.1-

43.6); TIMI 5/6, 50.0% (0.1-100). A significant relationship (v² = 0.02) was observed between TIMI risk score and adverse outcomes, but the TIMI score failed to categorize patients into discrete strata of risk (Fig. 1). Most adverse outcomes occurred in patients with low TIMI risk scores.

Exclusion of patients with AMI with elevated CK-MB level without elevated troponin I level did not significantly alter this relationship. The incidence of adverse outcomes in relation to TIMI risk score in this subset of patients is as follows: TIMI 0, 1.2% (95% CI, 0.1-4.2); TIMI 1, 3.3%

(0.1-7.5); TIMI 2, 9.8% (0.1-20.1); TIMI 3, 17.9% (1.9-

33.8); TIMI 4, 6.7% (0.1-22.6); TIMI z5, 25% (0.1-79.9).

Fig. 1 Study population according to TIMI risk score and composite outcome.

Discussion

Based on reports of accelerated atherosclerosis in patients with cocaine abuse, it is not unreasonable to assume that the same factors that predispose patients with traditional chest pain to adverse cardiac events would contribute to higher risk for patients with cocaine-associ- ated chest pain. The TIMI risk score stratification has proven reliable in patients with actual and potential ACS [2,8,10-13]. However, the results of our study do not support its use for risk stratification in patients with cocaine-associated chest pain. Although we did observe a relationship between TIMI risk score and rate of adverse outcomes, almost half of the observed events occurred in patients with a TIMI risk score V1. Patients with a TIMI risk score of zero had a 3.7% incidence of adverse outcomes, which is more than twice that reported in patients with chest pain unrelated to cocaine use who have a TIMI risk score of zero [13].

The overall outcome rate in this study was 12.6% and

includes 31 AMIs. The incidence of AMI in this study is twice that reported in 2 previous studies [6,7]. These unpredictable and disparate rates of cardiovascular out- comes in cocaine users highlights the challenge of identi- fying those with cocaine-associated chest pain who are at risk. The overall TIMI risk score failed to stratify our study population, and we found only a single variable in the TIMI risk score, elevated cardiac markers, to be independently associated with adverse outcomes. This strong association was also noted in previous studies [2,12,13].

There are several potential limitations of our study design that merit discussion. First, the study cohort was limited in size. Our study population was primarily younger, male, tobacco smoking, and black. Although these same patient demographics are consistent with previous cocaine chest pain reports, our results may not be easily generalized to other patient populations who use cocaine.

Also, 9% of our study cohort was lost to follow-up. These patients had similar distribution of demographic character- istics and TIMI risk scores as compared with our study cohort. Therefore, it is unlikely that additional events in patients lost to follow-up would have changed the observed findings in this study.

We conclude that all but one of the TIMI variables and the overall TIMI risk score cannot be used to adequately predict all-cause mortality, MI, or urgent revascularization by 30 days in patients with cocaine-associated chest pain. This is in contrast to patients with chest pain unrelated to cocaine use.

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