Does One Negative Troponin Measurement Rule Out Acute Coronary Syndrome?

By Michael H. Crawford, MD, Editor. Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco

SYNOPSIS: Using a common clinical chest pain algorithm plus a point-of-care troponin measurement for low-risk patients, researchers reported significantly lower healthcare costs. Also, this approach did not seem to result in more major adverse cardiovascular events.

SOURCE: Camaro C, Aarts GWA, Adang EMM, et al. Rule-out of non-ST-segment elevation acute coronary syndrome by a single, pre-hospital troponin measurement: A randomized trial. Eur Heart J; 2023 Feb 9:ehad056. doi: 10.1093/eurheartj/ehad056. [Online ahead of print].

With the advent of point-of-care (POC) rapid troponin measurements, it is possible to identify low-risk patients for acute coronary syndrome (ACS) prehospital and reduce unnecessary emergency department (ED) visits. However, prehospital rule-out of ACS has not been tested in a randomized trial. Camaro et al designed and conducted the ARTICA trial in which they assessed the major adverse cardiac events (MACE) and healthcare costs of this strategy.

ARTICA was conducted in five ambulance regions of the Netherlands with a combined population of about 2.5 million people. It involved 112 ambulances and 552 paramedics. These paramedics were trained in how to determine the components of the HEAR score (History, ECG, Age and Risk factors) and complete a case report form that automatically calculated the HEAR score. The inclusion criteria for the study were low-risk chest pain patients (HEAR score of 3 or lower) for whom symptoms onset at least two hours before ambulance presentation. The paramedics could transmit the ECG to a cardiologist if there was any doubt. Patients suspected of other diagnoses, such as pulmonary embolism or aortic dissection, were excluded.

After obtaining informed consent, patients were randomized to the prehospital or standard ED rule-out strategy. In the prehospital strategy, researchers conducted a POC troponin measurement. If the score was high, patients were transferred to the ED. If the score was normal, patients were referred to their primary care doctor. After 30 days, all patients were followed-up by phone or email, and any hospital data were collected. The primary outcome was estimated healthcare costs at 30 days. MACE at 30 days was a secondary outcome ascertained in both strategy groups and in the population ruled out by either strategy.

From 2019 to 2022, 1,138 patients were screened and 866 randomized (mean age, 54 years; 57% were women). In the total randomized population, 97% ruled out. Among the prehospital group, 15 patients ruled in; in the ED group, 12 were ruled in. Among the total population, MACE rates within 30 days were comparable between the prehospital and ED groups (3.9% vs. 3.7%). Among those who ruled out, MACE occurred in 0.5% of the prehospital patients and 1% of the ED patients. Healthcare costs were significantly lower in the prehospital group (€1,349 vs. €1,960; P < 0.001). The authors concluded using a prehospital POC troponin measurement in low-risk patients for ACS lowered healthcare costs without increasing MACE rates.

COMMENTARY

Most patients evaluated in the ED for chest pain syndromes are not diagnosed with ACS. Most EDs use a triage protocol to weed out low-risk patients. Still, these patients often are put in chest pain units for serial troponins or stress testing before discharge. Camaro et al examined the cost-savings and safety of a prehospital POC troponin added to the HEAR score to identify patients who do not need to be evaluated in an ED. The results demonstrated considerable cost-savings.

Most of the cost difference between the two strategies is driven by the cost of the ED visit and subsequent testing. Although MACE rates between the two groups basically were the same, this does not really test the safety of the prehospital evaluation because those with a positive POC troponin were transported to the ED. Also, the trial was not powered for safety endpoints since there were few MACEs. A better measure of safety in this study was the frequency of MACE in those for whom ACS was ruled out. This analysis showed the incidence of 30-day MACE was 0.5% in the prehospital group and 1% in the ED group. Thus, despite the fact this work was not powered for safety, the prehospital strategy likely is safe.

The major limitation of this study is the question of applicability to other health systems. The Netherlands operates a well-developed ambulance system, with short driving distances to EDs. Also, their paramedics are highly trained and tend to score patients higher on the HEAR score than ED physicians. The authors suggested an alternative would be taking patients at low risk to primary care urgent care clinics. This makes sense to me, since I occasionally see a new patient with chest pain in my clinic. If they are at low risk of an ACS diagnosis, I have sent a stat troponin to the lab. If negative, I sent the patient home.

Another downside to the prehospital strategy is the fact the ambulance spends more time at the pickup site. However, when total time to when the ambulance was available for another call was analyzed, the average time was shorter for the prehospital strategy, probably because 92% of these patients were not transported to the ED. In addition, the POC troponin test is less sensitive than the high-sensitivity troponin tests run at the hospital lab, so high-risk patients could be missed.

To account for this weakness, patients with chest pain for less than two hours were excluded from the trial because the expected frequency of a falsely negative troponin test is expected to be high. Realistically, this strategy probably would not be widely applicable in the United States, but certain dense cities with highly developed ambulance systems and well-trained paramedics could make it work.