At the start of this study (in 2013), the Rotterdam-Rijnmond region in the western part of the Netherlands holds a population of 1.1 mio. The region has a total of 10 hospitals, two of which (Erasmus MC and Maasstad Ziekenhuis) offer a 24/7 primary PCI service for MI patients. The majority of patients with acute ischaemic chest pain have their first medical contact with a paramedic of the ambulance crew—it should be noted that, in the Netherlands a medical doctor is not present on the ambulance. The paramedic performs a brief physical examination and provides an initial diagnosis, which is mainly based on an automated analysis of the ECG. All ambulances in the region are equipped with the Corpuls 3 defibrillator/monitoring system, in which Biosigna HES PRO ECG-interpretation software (algorithm Rev. 2.2) was implemented. Patients with a confirmed evolving MI are then transported to a PCI hospital, whereas the remaining patients are transported to the nearest non-PCI hospital.

In November 2013, the Corpuls devices on the ambulances in the Rotterdam-Rijnmond region were equipped with modems which enabled transmission of the ECGs for online interpretation by an ECG expert: the on-call cardiologist or cardiology resident in one of the two PCI hospitals (Erasmus MC and Maasstad Ziekenhuis). Since then, the ECG protocol for pre-hospital MI diagnosis in patients with acute ischaemic chest pain (which is a prerequisite) is as follows (Fig. 1).

The existing protocol remained unchanged for patients with an ECG showing ST elevation ≥200 µv in ≥2 adjacent anterior leads, or ≥100 µv in ≥2 non-anterior leads (Category 2). They are directly transported to a PCI hospital, as they meet the STEMI criteria and need immediate revascularisation. The ambulance staff sends an alert to the PCI hospital, and transmits the ECG for completion of the medical record.

With respect to the treatment of other patients, the existing protocol was extended. ECGs that do not meet the STEMI criteria, but still show total ST deviation ≥800 µv (Category 3) must now be transmitted for online interpretation by the ECG expert. In accordance with the advice of the ECG expert, provided by telephone within 5 min, the patient is then transported to the on-call PCI hospital for immediate angiography, possibly followed by revascularisation, or to a non-PCI hospital for further evaluation by a cardiologist. For patients with an ECG that cannot be interpreted by the ECG-interpretation software because of conduction disorders (Category 1), as well as for patients with abnormal ECGs, but not showing evident acute ischaemic changes (Category 4), the ECG expert offers online supervision as a service that is not mandatory.

We monitored the revised protocol during the 1‑year period from December 2013 to November 2014. Transmitted ECGs and primary data were collected by the ambulance personnel, including age, sex, ECG transmission date and time, and the diagnostic classification that was generated by the Corpuls device. Secondary data were collected by the first author (SA), based on a review of hospital medical records, and included medical history, risk factors, reperfusion time, final discharge diagnosis, and other pertinent clinical outcomes. All data were recorded in a dedicated database.

The patients whose ambulance ECG did not meet the STEMI criteria were the population of main interest (Categories 1, 3, and 4). Still, we also collected information on patients who met the STEMI criteria (Category 2), and whose ECGs were transmitted.

The revised protocol was developed to increase the early rule-in of MIs, and to increase the number of patients undergoing ‘primary’ PCI within the recommended 90-minutes window (PCI_90min), in particular in those patients who initially did not meet the STEMI criteria. PCI_90min was therefore defined as the main study endpoint. PCI delay was defined as the time difference between the acquirement of the ECG (time zero) and the wire crossing. The revised protocol also aimed to avoid unnecessary patient burden, invasive diagnostics (coronary catheterisation) and treatments. From this perspective, we considered patients who were immediately transported to a PCI centre but did not undergo PCI during the initial hospitalisation as ‘false positives’. Consequently, PCI_{hospitalisation} was defined as the secondary endpoint. PCI_90min is an inappropriate endpoint in this respect, since it will be influenced by logistic delays.

We classified patients according to their final diagnosis as acute MI (STEMI), NSTEMI, unstable angina pectoris (UAP), or ‘other’. The diagnostic and treatment criteria that were used by the treating physicians were based on prevailing European Society of Cardiology guidelines [8‐10]. This study was embedded in the clinical practice of the ambulance service and hospitals in the Rotterdam-Rijnmond region, and we accepted the final diagnosis made by the treating cardiologist. We derived this information from the hospital discharge letter, and we did not install an adjudication board to evaluate diagnoses and treatment decisions.

We compared baseline characteristics between the four diagnostic categories. Continuous variables are presented as mean value ± standard deviation (SD) and categorical variables are presented as numbers and percentages.

PCI_90min and PCI_{hospitalisation} are reported in relation to the diagnostic category. We conducted logistic regression analyses to examine the relation between diagnostic category and patient characteristics as predictor variables, and PCI_{hospitalisation} as outcome (Category 2 patients are excluded from this analysis). Results are presented as unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (CI). These analyses might be useful to identify patient categories in which the diagnostic system was apparently and definitely—as by judgment of the treating physician—unsuccessful.

This is an observational study. For the purpose of this study, patients were not subject to acts, or imposed to any mode of behaviour, other than standard treatment. For that reason, according to Dutch law, written informed consent for a patient to be enrolled in this study was not necessary. This study was conducted in accordance with the privacy policy of the Erasmus MC, and according to the Erasmus MC regulations for the appropriate use of data in patient-oriented research.

The study cohort comprised 1,421 patients with a mean age of 62 ± 17 years, and 67% were men (Table 1). A total of 345 patients met the STEMI criteria (Category 2 patients). As compared with the other categories (1, 3, 4), patients from Category 2 were younger (mean age 57 versus 61–68 years), whereas the percentage of men was higher (76 versus 61–72%). Furthermore, these patients had a somewhat more favourable cardiovascular disease risk profile, as fewer patients had hypertension (37 versus 58–64%), hypercholesterolaemia (29 versus 43–47%), diabetes mellitus (11 versus 22–25%) and a history of coronary artery disease (CAD) (17 versus 32–43%).

As Table 2 demonstrates, a total of 287 (83%) of Category 2 patients were directly transported to a PCI hospital. The reasons why the remaining 17% stayed home or were transported to a non-PCI hospital were not recorded. The final diagnosis acute MI with STEMI was made in 222 (77%). Twelve patients (4%) had NSTEMI (the cardiac enzymes were positive without further increased STEMI abnormalities on the ECG) or UAP. Other diagnoses included pre-existing STEMI abnormalities on the ECG, pericarditis, costo-myalgia or cardiomyopathy. In STEMI patients, PCI_{hospitalisation} was performed in 211 (95%) cases, whereas 73% had PCI_90min. A total of 8 (67%) NSTEMI/UAP patients had PCI_{hospitalisation}, and 25% had PCI_90min.

After online consultation with the ECG expert, 735 (68%) Category 1, 3 and 4 patients were directly transported to a PCI hospital for catheterisation and further treatment. A total of 209 (28%) were diagnosed with acute MI and 132 (18%) patients were diagnosed NSTEMI (positive cardiac enzyme) or UAP. An indication for PCI was present in 189 acute MI patients. The remaining patients had contraindication for PCI because of advanced age, multiple physical comorbidities or had an indication for coronary artery bypass grafting (CABG) treatment. PCI_90min was performed in 63% and 15% of acute MI and NSTEMI/UAP patients, respectively. The percentage of patients with a final diagnosis of acute MI ranged from 42% in Category 1 to 22% in Category 4, whereas, in these acute MI patients, PCI_90min ranged from 53% (Category 4) to 70% (Category 3). Fig. 2 shows details of time delays between ECG transmission and PCI treatment. Apparently, delays were longer for patients with an initial ECG that did not meet the STEMI criteria.

Table 3 shows determinants of PCI_{hospitalisation}. Patients presenting with an initial ECG that shows rhythm or conduction disturbances, which for that reason could not be analysed by the ECG-interpretation software, had considerably higher odds to receive PCI_{hospitalisation} than those with abnormal, but interpretable ECGs (49 versus 30%, OR_adjusted 2.7). Interestingly, patients with a history of atrial fibrillation had apparently lower odds for PCI_{hospitalisation} than patients with normal rhythm (20 versus 41%, OR_adjusted 0.25). Women had lower odds than men (31 versus 42%, OR_adjusted 0.56), whereas elderly patients had higher odds (OR_adjusted 1.04 per year). Also smoking status and a positive family history of CAD appeared to be related to PCI_{hospitalisation} treatment.

As by design, our study has several limitations that need to be mentioned. First, the telephone conversation between the ambulance paramedic and the on-call ECG expert was neither protocolised nor reported. As a result, we could not evaluate the factors that actually affected the reason for acceptance or refusal for immediate transportation to the PCI centre. This is particular relevant for patients living in the zip code area of the PCI-capable hospital. Most likely, the threshold to undergo early CAG in these patients is lower than for their counterparts living at further distance. Second, it is possible that the phone call, in which the clinical condition was discussed, led to the admission, and not the transmitted and reviewed ECG per se. Unfortunately, however, we are not able to disentangle the influence of both phenomena. Third, we did not follow up the patients who stayed at home, or who were transported to a non-PCI centre. We appreciate that patients who ultimately had MI might still have been missed in the prehospital phase, but, consequently, we cannot quantify their number. This is particularly the case for patients who were labelled by the ECG-interpretation software as Category 1 or 4. Fourth, we did not measure clinical outcomes. Thus—apart from the fact that our study is not a randomised trial—we are not able to demonstrate the benefit of the revised diagnostic system in terms of patient outcomes.

In conclusion, by applying the modified pre-hospital triage protocol for patients with acute ischaemic chest pain in the Rotterdam-Rijnmond region, during a 1-year period, over 100 acute MI patients with an initially inconclusive ECG received primary PCI within 90 min. The ‘false positive’ rate of 64% is considered acceptable. Still, further research is warranted to improve the specificity of the triage protocol, so that unnecessary burden to the patient and the system will be avoided.