Acute Coronary Syndrome

Zahir Kanjee, MD, MPH

Joshua M. Liao, MD, MSc

Is there an evidence-based approach to differentiating NSTE-ACS from noncardiac causes of chest pain on initial evaluation?

Clinical prediction tools can outperform individual historical, examination, and ECG findings. These tools (e.g., HEART and TIMI scores) can be helpful in differentiating NSTE-ACS from noncardiac chest pain.

This question was studied in a 2015 systematic review¹ that evaluated all potentially relevant articles from January 1995 to July 2015. Authors included studies meeting three criteria: (1) presentation to the ED with suspected ACS, (2) clear descriptions of diagnostic testing (including history, physical, ECG, overall assessment, and clinical prediction tools including the HEART score and the TIMI score (Table 13.1), and (3) adequate listing of outcomes (either hospital discharge diagnosis or subsequent significant cardiovascular event).

To focus primarily on using available tools to differentiate patients at point of first contact, the review excluded studies (1) in which

assessment was initiated after acquisition of serial ECGs/troponins, (2) among patients at disproportionately high, intermediate, or low probability of ACS, and (3) using high-sensitivity troponin assays, which were not routinely available in the United States at the time of study. Fifty-eight articles were included in the final analysis.

TABLE 13.1 Clinical Decision Tools to Assess ACS

Clinical Prediction Tool	Variable	High-Risk Score Value	+LR for ACS	Low-Risk Score Value	+LR for ACS
HEART score Scores five variables on scale of 0-2 to give score 0-10	History: 0 points for history incompatible with ACS, 1 point for history potentially compatible with ACS, and 2 points for history strongly suggestive of ACS EKG: 0 points for normal ECG, 1 point for ECG with nonspecific repolarization abnormalities, and 2 points for ECG with ST depression or transient ST elevation Age: 0 points for < 45 years, 1 point for 45-65 years, and 2 points for > 65 years Risk factors: 0 points for no risk factors, 1 point for 1-2 risk factors, and 2 points for ≥ 3 risk factors or known CAD Troponin: 0 points for normal troponin level, 1 point for 1-3 × upper limit of normal, and 2 points for >3 × upper limit of normal	7-10	13 (95% CI 7.0-24)	0-3	0.20 (95% CI 0.13-0.30)
TIMI score Assesses for presence of seven variables to give score 0-7	Age ≥ 65 years ≥ 3 cardiac risk factors Known CAD Aspirin use ≥ 2 episodes of angina in preceding 24 hours ST-segment elevation or depression ≥ 0.5 mm Elevation in cardiac biomarkers	5-7	6.8 (95% CI 5.2-8.9)	0-1	0.31 (95% CI 0.23-0.43)
ACS, acute coronary syndrome; CAD, coronary artery disease; LR, likelihood ratio. Data from Backus BE, Six AJ, Kelder JC, et al. A prospective validation of the HEART score for chest pain patients at the emergency department. Int J Cardiol. 2013;168(3):2154; Antman EM, et al. The TIMI Risk Score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. J Am Med Assoc. 2000;284(7)835-842; and Faranoff AC, et al. Does this patient with chest pain have acute coronary syndrome? The rational clinical examination systematic review. J Am Med Assoc. 2015;314(18):1955-1965.

The authors found several commonly used predictors of ACS to be of mild to moderate utility. Mildly helpful to rule in ACS were a history of an abnormal stress test (+LR 3.1, 95% CI 2.0-4.7) and pain radiating to both arms (+LR 2.6, 95% CI 1.8-3.7). More useful were ST depression (+LR 5.3, 95% CI 2.1-8.6) or “ischemic” ECG (+LR 3.6, 95% CI 1.6-5.7). However, each of these findings was limited by poor sensitivity and resultant poor ability to rule out ACS. Clinicians’ overall impression of whether a patient had ACS prior to seeing their ECG and troponin was somewhat more diagnostic (“definite” ACS + LR 4.0, 95% CI 2.5-6.6; “definitely not” ACS + LR 0.36, 95% CI 0.05-2.8).

Formal decision tools were superior for predicting ACS. A high HEART score (7-10) was associated with +LR 13 (95% CI 7.0-24) for ACS, high TIMI score (5-7) with +LR 6.8 (95% CI 5.2-9.0). Low HEART score (0-3) was associated with +LR 0.20 (95% CI 0.13-0.30), low TIMI score (0-1) with +LR 0.31 (95% CI 0.23-0.43). Study caveats include the use of revascularization, which can be affected by measurement bias, as an outcome in many studies.

The first patient is a 44-year-old man with hypertension who presents with a single episode of chest pain. The episode was potentially consistent with ACS by history. His only medication is amlodipine and aspirin. His ECG has nonspecific repolarization abnormalities, and his troponin is negative. You find him to have a TIMI score of 1 and a HEART score of 3 (both low risk). Based on his low risk for ACS, you discharge him from observation after a second troponin and ECG several hours later. Working with his primary care physician, you arrange for an outpatient stress test within 48 hours of discharge.

The second patient is a 67-year-old man with a hyperlipidemia, hypertension, and family history of early coronary disease who presents with three episodes that are strongly suggestive of ACS by history in the last 24 hours. After two sublingual nitroglycerin tablets, his pain is resolved. His medication list includes hydrochlorothiazide, pravastatin, and aspirin. ECG shows 1 mm ST depressions in anterior leads as well as nonspecific T-wave inversions. His repeat troponin
is within normal limits. You calculate his TIMI and HEART scores as 5 and 8, respectively (both high risk). You diagnose this patient with unstable angina and admit him to an inpatient telemetry bed.

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