Overcrowding in the emergency department is an increasing problem in hospitals worldwide. Point-of-care Troponin (POC cTn) testing combined with a well investigated risk stratification tool (HEART-score) used in the ambulance may contribute to more rapidly diagnostics of ruling in or ruling out myocardial infarctions (MI) and subsequently reduce unnecessary hospital admissions, total admission time and costs. However, the applicability of the POC cTn and the HEART-score in the pre-hospital setting remains unclear. This study will evaluate this applicability.

Co-primary Objectives:

1. To evaluate the interobserver agreement of the HEART-score performed by ambulance personnel compared to the HEART-score performed by emergency physicians.

2. To evaluate the diagnostic performance of a strategy based on a pre-hospital HEART-score (with POC cTn testing) or combined with an adjuvant single hs-cTn test at the emergency department to rule-in or rule-out acute coronary syndrome (ACS).

3. To evaluate the diagnostic performance of (serial) POC cTn testing or combined with hs-cTn testing compared to (serial) hs-cTn testing to rule-in or rule-out MI.

4. To investigate the feasibility of using the pre-hospital HEART-score and POC cTn in the 0/1 hour algorithm to rule-out ACS.

   Secondary Objectives:

5. To evaluate the occurrence of major adverse cardiac events (MACE) in all included patients with a follow up time of 30 days from first medical contact.

6. To evaluate the patient reported outcome measures (PROMs) in all chest pain patients transported to the hospital at baseline and at 30 days

7. To perform a cost-analysis of an early diagnostic strategy using the pre-hospital HEART-score

Study design: A prospective, observational, single multicentre study Study population: Total number of patients needed for analysis: n=650 Inclusion criteria: - All out-of-hospital chest pain patients visited by an ambulance

• Transportation to a hospital with working diagnosis NSTE-ACS
• Age ≥ 18 years Exclusion criteria: - Comatose state, hemodynamic instability or shock
• Electrocardiographic ST-segment elevation in the pre-hospital setting treated as STEMI
• No pre-hospital 12-lead electrocardiogram performed or available
• An obvious non-cardiac cause for the chest pain (trauma, etc.)
• Suspicion of aortic dissection or pulmonary embolism
• Cognitive impairment
• Pregnancy
• Suspicion of COVID-19 by ambulance

Study procedures: The HEART-score and the POC cTn will be calculated in all included patients in the pre-hospital phase. Simultaneously, a venous blood sample will be drawn from the venous access site for later hs-cTn testing. Outcomes of any pre-hospital study measurements (i.e. pre-hospital POC cTn results or calculated pre-hospital HEART-scores) are blinded to the physicians at the ED and will not affect usual care. According to current practice, all patients will be transported to the hospital for further evaluation. At the emergency department (ED) all included patients will undergo regular hs-cTn testing and HEART-score assessment performed by emergency physicians (standard care), and an extra venous blood sample will be drawn for this study. Additional cTn tests (POC and hs-cTn) will be performed in the laboratory.

Main study parameters/endpoints:

1. HEART-score agreement (interobserver variability between pre-hospital and in-hospital HEART-score assessment)

2. Final diagnosis of NSTE-ACS at discharge

3. Myocardial infarction at discharge

   Secondary study parameters/endpoints:

4. Composite endpoint (cardiovascular mortality, myocardial infarction, urgent revascularisation) at 30 days

5. Angina frequency and stability, physical limitations, treatment satisfaction, quality-of-life, cardiac anxiety and depression (SAQ, PHQ-4)

Follow-up: Total follow-up duration is 30 days after initial presentation. Other demographic and clinical parameters at baseline will be taken into account.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All patients will undergo a POC cTn test performed by ambulance personnel. In all patients, two venous blood samples will be drawn in the pre-hospital phase (1x) and at the emergency department (1x). Besides the minimal risks of performing a POC finger prick test, no other risks are involved with study participation. All patients will be asked to fill in questionnaires (i.e. SAQ, PHQ-4) at baseline and at follow-up.

Inclusion Criteria:

• All out-of-hospital chest pain patients visited by an ambulance
• Transportation to a hospital with working diagnosis NSTE-ACS
• Age ≥ 18 years

Exclusion Criteria:

• Comatose state, hemodynamic instability or shock
• Electrocardiographic ST-segment elevation in the pre-hospital setting
• No pre-hospital 12-lead electrocardiogram performed or available
• An obvious non-cardiac cause for the chest pain (trauma, etc.)
• Suspicion of aortic dissection or pulmonary embolism
• Cognitive impairment
• Pregnancy

Patients with suspected acute coronary syndrome. Total number of patients needed for analysis: n=650

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