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Ruling Out Acute Coronary Syndromes: Troponin Is Essential, as Is Clinical AssessmentFree Access

Editorial Comment

J Am Coll Cardiol, 74 (7) 855–857
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Introduction

Chest pain is one of the most frequent presenting symptoms reported in the emergency department (ED) (1). The goals of patient evaluation in this setting are the early and accurate diagnosis of an acute coronary syndrome (ACS) (i.e., acute myocardial infarction [AMI] or unstable angina [UA]) to start appropriate therapy as soon as possible and the rule-out of ACS and other potentially serious conditions to allow for a safe discharge. Until recently, the diagnosis of AMI was based on the interpretation of clinical symptoms, the 12-lead electrocardiogram (ECG), and serial measurements of cardiac troponin (cTn) with the use of standard assays. This process was often lengthy but has been significantly shortened by the development of high-sensitivity cTn (hs-cTn) assays. Several algorithms have been validated using both hs-cTn T and I assays with serial testing as early as 1 h after admission (2,3). These algorithms provide excellent sensitivity and negative predictive value (NPV) for AMI and are recommended by the 2015 European Society of Cardiology (ESC) guidelines for non–ST-segment elevation ACS (4). However, it is the prediction of short-term cardiac events rather than only the diagnosis of AMI at the index visit that is important to guide management. In this respect, a study by Mokhtari et al. (5) showed that supplementation of the hs-cTn 0/1 h algorithm with the interpretation of clinical history and the ECG (the so-called extended algorithm) performed better than the hs-cTn–alone algorithm in the prediction of 30-day major adverse cardiac events (MACE) in patients presenting with chest pain.

In this issue of the Journal, Nestelberger et al. (6) aimed to validate, in an external large cohort of patients evaluated for suspected ACS in the ED, the performance of the extended algorithm in the prediction of short-term MACE (death, cardiac arrest, AMI [including the index event], cardiogenic shock, sustained ventricular arrhythmia, or high-grade atrioventricular block) or MACE + UA (angina with coronary revascularization within 24 h) and compare it with that of the ESC hs-cTn 0/1 h algorithm. Analyses were performed in 3,123 patients from the APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation) study with no ST-segment elevation, a clear final diagnosis, and two 0/1 hs-cTn determinations available. Patients judged by the treating physician to have a clinical likelihood for ACS ≥70% or who had a pathologic ECG (ST-segment depression, Q waves, or T-wave inversion) were reclassified as observe or rule-in zones. The extended algorithm reduced the percentage of patients triaged toward rule-out according to the hs-cTn algorithms, maintaining similar MACE rates and resulting in similar NPV. The extended algorithm ruled-in more patients, with a lower positive predictive value. For MACE + UA, the extended algorithm had a higher NPV for rule-out and a lower positive predictive value for rule-in. The authors concluded that the ESC 0/1 h algorithm better balanced efficacy and safety in the prediction of MACE, the extended algorithm for MACE + UA.

This analysis (6) is the largest study assessing the added value of clinical and ECG assessment to the prognostication by hs-cTn algorithms in patients evaluated for chest pain. The authors, who have made major contributions to the knowledge in this area, are to be commended for their thoughtful and comprehensive analysis. Because of the potential implications of the results, some points need to be discussed.

First, if UA had been included as a MACE component, as in the study by Mokhtari et al. (5), the percentage of 30-day MACE would have increased from 17% to 26% and the main conclusion would have been that the extended algorithm performs better than the hs-cTn 0/1 h algorithm in the prediction of this endpoint. Although the prevalence and prognostic implications of UA have been changed by using hs-cTn to the point that it has been suggested removing it from the ACS spectrum (7), the diagnosis of UA is still commonly used and continues to be associated with an increased risk in the era of hs-cTn (8). In fact, in this same cohort, the 1-year rates of future nonfatal AMI were similar in patients with UA versus those with AMI (11.2% vs. 7.9%, respectively) and much higher than in patients with noncardiac chest pain (0.6%) (9). Moreover, by definition, all patients with UA were revascularized, which, along with the concomitant medical therapy administered, likely reduced their risk.

Second, regarding extrapolation of the results to daily practice, it should be underscored that all patients had chest pain/discomfort, that those with end-stage renal failure or equivocal final diagnoses were excluded, and that their median age was lower than in other studies including consecutive patients with suspected ACS (10,11). The accuracy of the hs-cTn algorithm might have been lower in a broader, unselected group of patients (12).

Third, clinical assessment was merely the assignment of a probability of ACS by the treating physician. A more objective evaluation could have been preferable to generalize the results. Although adding formal risk scores may not significantly improve the ability of hs-cTn 0/1 h algorithms to predict AMI or death at 30 days (13,14), their incremental value to predict UA or long-term events has not been reported.

Finally, the usefulness of the 0/1 h algorithm in early presenters is a matter of concern (15). In patients presenting within 2 h from symptom onset, the NPV of both algorithms in this subset was >99%; however, future evidence should support the application of these algorithms in very early presenters.

In conclusion, the study by Nestelberger et al. (6) reinforces the accuracy of hs-cTn 0/1 h algorithms to predict AMI and 30-day AMI-related events. However, a thorough assessment of patient’s history and ECG findings continues to be essential, not only to help differentiate between AMI and other causes of hs-cTn elevation (11,16) but also to identify patients with UA, a condition still associated with a nonnegligible risk.

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Footnotes

The authors’ research is supported by the Instituto de Salud Carlos III, Spain (PI16/00232, and CIBERCV), co-financed by the European Regional Development Fund. Dr. Bardají has participated in educational activities with AstraZeneca, Lilly, and Bristol-Myers Squibb; and has provided consultancy for Bayer. Dr. Barrabés has participated in educational activities with AstraZeneca; and has provided consultancy for Bayer. Dr. Cediel has reported that he has no relationships relevant to the contents of this paper to disclose.