Appendix 1. Secondary endpoints - http;//links.lww.com

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1 | P a g e Appendix 1. Secondary endpoints

1) Potential influence on troponin assays

The potential reduction in the number of troponin tests was defined as the difference between the number of tests actually conducted, and the theoretical number of troponin tests that would be required if the HEAR score or the 2-step HEAR-T strategy had been strictly applied. It was estimated as follows:

Let us consider n patients in the study (1 ≤ i ≤ n). This sample is divided into three theoretical groups based on the 2-step HEAR-T strategy (1 ≤ j ≤ 3), with nj patients in each group. The first group comprises patients with a low risk HEAR score, who theoretically do not need a bioassay (j = 1). The second group is defined for patients with a HEAR score > 1 but a HEART score below 4, or HEAR score > 1 and a HEART score above 3 and chest pain onset more than six hours ago (j = 2). They theoretically need a single troponin test. In the last group, we have the other patients, theoretically requiring repeated troponin assays (j = 3). See supplementary Figure 1

Thus, the computation formula of the number of patients diagnosed with the pathway in order to save one troponin test (𝛥𝑎̅̅̅̅) is defined as follows:

∆𝑎̅̅̅̅ = 𝑛 𝑛₂+ 2 ∗ 𝑛₃− 𝐴

where A is the number of troponin assay actually performed in the first 24hrs. of admission in all patients of the study and nj is the number of patients in group j.

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2 | P a g e Supplementary Figure1. Decisional algorithm to determine the theoretical number of troponin

measurements using 2-step HEAR-T strategy.

2) Potential influence on ED length of stay

For the potential reduction of the LOS, we assumed that the LOS in the ED was driven by the number of troponin tests performed. A theoretical LOS was calculated using the median LOS of patients that had no, one or more than one troponin test. These theoretical LOSs were imputed according to the required number of troponin measurements: none when the HEAR score was < 2; one when the HEART score was <4; one when the HEART score was ≥ 3 and chest pain onset was more than six hours ago;

or more than one when the HEART score was ≥ 3 and chest pain onset was less than six hours ago. The LOS potential reduction was defined as the difference between the actual LOS and the theoretical LOS.

See online appendix for more details on secondary outcome calculation.

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3 | P a g e The theoretical length of stay in the ED for each group is defined by 𝜏_𝑘, and the real length of stay for one patient is defined by 𝑡_𝑖𝑘.

Thus, the computation formula of the mean reduction in length of stay in the ED (𝛥𝑡̅̅̅) is defined as follows:

∆𝑡̅̅̅ =^∑ ^∑ ^(𝜏^𝑘^−𝑡^𝑖𝑘⁾

3 𝑘=1 𝑛𝑘 𝑖=1

𝑛

Based on actual practice, we chose to define the values of 𝜏_𝑘 by the following rules:

𝜏₁ : median length of stay of patients without troponin test.

𝜏₂ : median length of stay of patients with a single troponin test.

𝜏₃ : median length of stay of patients with more than one troponin test.

Each value of 𝜏_𝑘 was computed from the patients of the study.

In patients with a HEAR score ≥2 but without a troponin test, the value of the assay was considered below the normal threshold for HEART score calculation.

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4 | P a g e Appendix 2. Patients with negative 2-step HEAR-T strategy and MACE

Case 1 – 35yo male Obese and smoker

Exertional chest pain, rated totally atypical

Tall T-wave on admittance ECG, rated normal ECG

Recurrent chest pain 2 hours after admission revealing ST-elevation myocardial infarction.

First troponin 9x 99^th percentile, Δ +250% 6 hours later

Diagnosed with MI and treated with PCI on the left anterior descending and left circumflex artery

HEAR score <2 and Low risk HEART score Case 2 – 52yo male

Hypertension and family history of coronary disease

Brutal chest pain at rest, but recent history of exertional chest pain, rated as having some atypical elements

ECG considered normal

Troponin undetectable on admittance and 3hrs. later No wall motion anomalies on cardiac echography GRACE score < 140

Stress test clinically positive

Impassable ostial obstacle on the circumflex artery on percutaneous angiogram Multi aneurysmal artery on coronary CT angiogram

Treated by CABG

HEAR score ≥2 and Low risk HEART score

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5 | P a g e Appendix 3. Mean theoretical reduction in emergency department length of stay stratified by centers.