HsTroponin in ED Predicts Short-term CV Events

Debra L Beck

August 14, 2019

Measuring high-sensitivity cardiac troponin (hs-cTn) at presentation and after 1 hour not only identifies chest pain patients in the emergency department (ED) who are having an acute myocardial infarction (AMI), but also offers good prediction of short-term major adverse cardiac events (MACE) within 30 days, according to a new analysis.

However, incorporating clinical judgment and electrocardiogram (ECG) findings is better for identifying patients at risk for a MACE end point that includes unstable angina (UA), the researchers also found.

"Allocated for prediction of 30-day MACE, both the Troponin algorithm and the Extended algorithm that included clinical judgment and ECG interpretation had a very high safety for rule-out, while the efficacy was better for the Troponin algorithm," said first author Thomas Nestelberger, MD, from the University of Basel, Switzerland, in an email exchange with theheart.org | Medscape Cardiology. "However, the Extended algorithm is the preferred option for rule-out of MACE + UA."

This latter finding was solely based on unstable angina patients who were missed by the Troponin algorithm, he added, noting that this was not a surprise because the 1-hour Troponin algorithm was not created to identify UA patients.

"The most important finding in our study is that the Troponin algorithm alone is a valuable tool to predict short-term MACE with very high safety and efficacy," said Nestelberger, whereas the Extended algorithm is a "perfect tool" to identify additional patients who need further evaluation, most of whom had unstable angina.

Nestelberger and colleagues published their latest analysis online August 12 in the Journal of the American College of Cardiology.

External Validation

For this report, the researchers aimed to provide external validation in a large prospective multicenter study of performance of the Extended algorithm for the prediction of MACE and MACE + UA.

Although it is mandatory to use the European Society of Cardiology (ESC) hs-cTn 0/1-hour algorithm in conjunction with full clinical assessment and a 12-lead ECG, the best way of combining these diagnostic variables — and the effect of different combinations on diagnostic performance — have not been defined.

This analysis used prospectively collected data from the multicenter APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation) study. APACE showed the predictive accuracy of the ESC hs-cTn 0/1-hour algorithm for ruling out AMI using two measures of high-sensitivity troponin taken within 1 hour. The trial involved 3123 patients who presented to the ED with chest pain and no ST-segment elevation.

In the study, patients underwent routine clinical assessment that included medical history, physical examination, chest radiography, continuous ECG monitoring, and pulse oximetry. Patients judged by the treating physician to have a clinical likelihood for ACS of at least 70% or who had a pathologic ECG (ST-segment depression, Q waves, or T-wave inversion) were reclassified as "observe" or "rule-in."

The primary MACE end point was adjudicated by two independent cardiologists and defined as all-cause death, cardiac arrest, AMI, cardiogenic shock, sustained ventricular arrhythmia, and high-grade atrioventricular block within 30 days, including index events.

The secondary end point was MACE + UA receiving early revascularization within 24 hours. UA was not included in the primary end point because it has a better prognosis than AMI, the researchers note.

Using just the ESC 0/1-hour Troponin algorithm, 60% of patients were ruled out for non-ST-segment MI, compared with 45% for the Extended algorithm, but with similar 30-day MACE rates (0.6% and 0.4%; P = .429).

An additional 16% of patients were ruled in with the 0/1-hour Troponin algorithm, compared with 26% for the Extended algorithm, albeit with a higher positive predictive value (76.6% vs 59%; P < .001).

"These patients with UA have a substantially lower 30-day mortality, including fatal MI, compared with patients with NSTEMI. Therefore, due to these differences, early invasive strategies and dual antiplatelet therapy seem to provide less incremental benefit in some of these patients. However, further evaluation and work-up in these patients may be necessary," he explained in an email.

Reinforces Current Practice

In an editorial accompanying the publication, the coauthors — Germán Cediel, MD, PhD, Hospital Universitari Germans Tiras i Pujol in Badalona, Spain; Alfredo Bardají, MD, PhD, Joan XXIII University Hospital, Tarragona, Spain; and José A. Barrabés, MD, PhD, Universitat Autònoma de Barcelona, CIBERCV, Barcelona — conclude that the new study "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, but also to identify patients with UA, a condition still associated with a non-negligible risk," they write.

"These results do not change clinical practice since the assessment of high sensitivity troponin should be done in patients with suspected AMI, for the majority of cases, in patients with chest pain," said Cediel told theheart.org | Medscape Cardiology in an email exchange. "I think this study reinforces what physicians already do in the emergency department."

Most EDs are using the ESC hs-cTnT/I 0/1-h algorithm, which is currently available for six hs-cTn assays, for early detection or rule-out of AMI, said Nestelberger.

His group has also shown the safety and efficacy of the 0/1-h algorithm using the fifth-generation cardiac troponin T assay (hs-cTnT) that received FDA approval in 2017. FDA-approved use of hs-cTnT differs from European countries in that the lower limit reported is the limit of quantification (6 ng/L) and the 99th percentile upper reference limit (19 ng/L) is slightly higher than that used in Europe.

"Our results extend the Troponin algorithm to apply it for a fast and accurate prediction of short-term MACE in patients presenting with chest pain to an emergency department," said Nestelberger.

"The ESC hs-cTn 0/1-h algorithm has demonstrated its efficacy in the diagnosis of AMI, which is the first question that the clinician in the emergency department wants to answer," he said. "However, in this patient population — those with final diagnosis of AMI — and for those who are discharged early — the rule-out group — it will always be useful to know the probability of the risk of cardiovascular events in the short term, and this is where the message the manuscript sends is relevant."

It is also important "to affirm that unstable angina is part of the spectrum of acute coronary syndrome, being an entity that is associated with an increased risk of adverse events even in the era of the hs-cTn," Cediel added.

To this he added that, lest anyone think their efforts don't matter in a world of increasing algorithmic automation and high-sensitivity testing, a thorough assessment of the patient and ECG findings also continues to be essential.

Nestelberger reports receiving speaker honoraria from Beckman Coulter. Bardají reports that he has participated in educational activities with AstraZeneca, Lilly, and Bristol-Myers Squibb; and has provided consultancy for Bayer. Barrabés reports that he has participated in educational activities with AstraZeneca and has provided consultancy for Bayer. Cediel reports no relationships relevant to the contents of this paper to disclose.

J Am Coll Cardiol. 2019;74:842-854, 855-857. Abstract, Editorial

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