Prehospital Risk Stratification in Acute Coronary Syndromes- Feasibility Trial
Phase: NA
Conditions: Acute Coronary Syndrome, Non-ST Elevation Myocardial Infarction (nSTEMI)
Sponsor: Sorlandet Hospital HF

Prehospital risk stratification in Acute Coronary Syndrome (PreACS-study)  
Feasibility trial October 2017- October 2018  
 
1. Version October 2017, Last revised (only document format and statistic 
description) v.2.1; 28.12.2019 
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Project plan 
Prehospital risk stratification in Acute Coronary Syndrome 
(PreACS-study) 
-a pilot trial (part I) 
 
 
A study approved by the Norwegian regional ethics committee (REK# 2017/ 701). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Prehospital risk stratification in Acute Coronary Syndrome (PreACS-study)  
Feasibility trial October 2017- October 2018  
 
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description) v.2.1; 28.12.2019 
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1. Introduction 
Acute coronary syndrome (ACS) is a common cause of death in industrialized countries 
and accounts for a large proportion of hospital admissions1-6. The term ACS includes 
unstable angina pectoris and acute myocardial infarction (AMI). Approximately 13 000 
Norwegians are diagnosed annually with acute myocardial infarction, and of these the 
30-day mortality rate is 10 %7.   
 
Several studies have shown that early coronary angiography and percutaneous coronary 
intervention (PCI) reduce the risk of death and recurrent cardiovascular events after 
AMI, and guidelines from the European Society of Cardiology (ESC) recommend such 
treatment to all patients8, 9. Timing of coronary angiography and revascularization are 
today primarily guided by electrocardiogram (ECG)8, 10. The benefit of urgent 
revascularization is well documented in ST-elevation myocardial infarction (STEMI), 
where most patients have an acute occlusion of a coronary artery11. Because an acute 
coronary occlusion in most cases causes a process of irreversible myocardial damage 
that starts within minutes, urgent revascularization is particularly important in this 
subset of patients. In non-ST-elevation myocardial infarction (NSTEMI) coronary 
angiography is recommended within 2 or 24 hours depending on risk stratification8. 
Urgent coronary angiography is recommended for patients with very high-risk features, 
such as hemodynamic instability, refractory chest pain or life-threatening arrhythmias8. 
However, NSTEMI probably shares the same pathophysiology as STEMI since acute 
coronary occlusion is a common finding at coronary angiography also in patients with 
NSTEMI12-14. At coronary angiography, 25-55% of patients with NSTEMI have an 
occlusion of the culprit coronary artery, and ECG has limited sensitivity for identification 
of acute coronary occlusions13, 15, 16. As a consequence, many patients with NSTEMI are 
at risk of extensive myocardial injury due to delayed revascularization9, 17. Only 22% of 
patients (<80 years of age) with NSTEMI underwent coronary angiography within 24 
hours in Norway in 2014, and 24% of the patients were not offered this examination at 
all18.  
 
 
In Norway, few hospitals offer emergency coronary angiography and PCI in suspected 
AMI. In order to perform earlier invasive evaluation and treatment of NSTEMI, patients 
with suspected AMI must be evaluated for admission directly to a hospital with PCI 
facilities. However, early prehospital risk stratification of patients with suspected 
NSTEMI is challenging because decision making based on clinical features and ECG is 
inadequate14. Detection of regional differences in myocardial function by means of 
echocardiography can help distinguishing between NSTEMI with and without coronary 
occlusion14, 19 Routine echocardiography in the emergency department is recommended 
in the NSTEMI-ACS ESC guidelines8, but has never been evaluated in the ambulance 
service. Telemedical digital transmission of cardiac ultrasound images from ambulances 

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to hospital specialists could make this feasible and may improve the diagnostic 
precision. 
 
Cardiac troponin is central in defining AMI20. European guidelines recommend cardiac 
biomarkers to be measured at presentation in all patients with suspected AMI8, 10. 
Cardiac troponin has today the greatest sensitivity and accuracy of all biomarkers in 
AMI. Point-of-care test of cardiac troponin applied in the prehospital setting may also be 
a valuable tool for optimizing diagnosis and treatment in patients with suspected 
NSTEMI21, 22. 
 
2. Objectives and specific aims 
 
The main objective of this study is in a randomized controlled trial to test the effects of 
prehospital risk stratification by echocardiography and Troponin T testing in patients 
with suspected acute coronary syndrome compared with conventional in-hospital 
evaluation, with time delay to coronary revascularization and AMI-size as primary 
outcomes (Part II – to be completed upon achievement of results from the feasibility 
study). 
 
But, before being able to conduct that, a feasibility study (Part I – described in this 
project plan) of prehospital echocardiography examination with wireless transmission 
to a specialized heart Centre and point-of-care troponin testing conducted by 
paramedics has to be completed. The quality of echocardiographic images exploring 
whether semi-automatic myocardial deformation analyses (strain) conducted by 
paramedics in a prehospital setting can attain necessary precision, will be assessed, as 
well as the feasibility of prehospital troponin testing performed by paramedics. 
 
3. Methods and study organization 
 
3.1 Materials and Methods 
 
3.1.1 Study design  
 
A feasibility study of prehospital echocardiographic examination and point-of-care 
troponin analysis, conducted by paramedics, in patients with suspected acute 
coronary syndrome.  
 
3.1.2 Study population 
Inclusion criteria: 
• Patients presenting to the medical dispatch center (AMK) with chest pain; 

Prehospital risk stratification in Acute Coronary Syndrome (PreACS-study)  
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Norwegian medical index criteria A10.2- A10.11 
• Men and women 
• Age ≥ 18 
• Informed consent for participation 
• Examined by paramedics in a prehospital setting due to newly onset (<12 hours) 
chest pain (lasting for >20 min) and suspected AMI 
 
Exclusion criteria: 
• Any condition which interfere with the ability to cooperate 
• Hemodynamic instability 
• Severe mental disorder 
• Pregnancy or breast-feeding 
• STEMI 
• Obvious non-cardiac origin of the chest pain 
 
 
3.1.2 Study plan 
The trial will be conducted at Sørlandet Hospital, Arendal, Norway. One acute care 
ambulance in Agder county will be equipped with a high-end cardiac ultrasound scanner 
(Vivid IQ, GE Ultrasound) with wireless communication to the cardiac 
centre/cardiologist, and a point-of-care troponin T quantitative analysis kit (Cobas 
H232, Roche Diagnostics). Four paramedics will be offered a comprehensive hands-on 
(5 hours) course in cardiac ultrasound image acquisition by an echo-technician and a 
cardiologist. Similar, a short (2 hours) course will be given in point-of-care troponin 
analysis.  
 
Up to 50 patients meeting the inclusion/exclusion criteria will be included 
consecutively. Cardiac ultrasound images over three heart cycles from five standard 
projections will be sampled and transferred to the hospital, and a troponin- T analysis 
will be done before/during transport to hospital. A cardiologist will be consulted 
immediately for cardiac ultrasound image interpretation, for interpretation of the 
troponin T value, ECG and symptoms, and for a clinical decision of further treatment.  
 
Feasibility of the concept will be evaluated according to the following functionality 
criteria: 
• Time intervals from patient inclusion to images achieved 
• Imaging quality according to the manufacturer  
• Communication between paramedic and cardiologist established 
• Image transfer and interpretation by cardiologist functional 
• Technical problems addressed and solved in collaboration with manufacturer  

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When the concept is proven fully functional on five NSTEMI patients, the evaluation 
board will reconsider further inclusion needs. If possible, the feasibility study is then 
ended and summed up. 
 
 
 
Figure 1. Study plan 
 
 
 
3.1.3 Outcome measures 
 
- 
Feasibility of prehospital cardiac ultrasound examination and point-of-care 
troponin T analysis by paramedics in patients with suspected acute coronary 
syndrome  
- 
Quality of prehospital echocardiography images in patients with suspected acute 
coronary syndrome  
- 
Time spent on prehospital echocardiography examination and point-of-care 
troponin T analysis in patients with suspected acute coronary syndrome  
 
3.1.4 Data handling and storage 
The following records are collected in a secure electronic database (e-CRF) at Sørlandet 
Hospital, which is responsible for the data protection.  
• Name, national identification number, gender and address 
• Comorbidity including previous cardiovascular disorders, cardiac risk factors and 
medication 
• Date and time of symptoms and first medical contact, and the various time delays 
to examination, hospitalization, treatment and discharge from hospital 
• ECG findings, laboratory values and results of echocardiographic examinations  
• Results of coronary angiogram 
• Treatments received (PCI and medication) 
Prehospital 
screening
Included
Echocardiography 
and troponin T test
Clinical decision
PCI hospital
Local hospital
Not included
(STEMI/
Local hospital/PCI 
hospital according to 
clinical guidelines

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• Complications, new cardiovascular events and death until discharge from 
hospital 
 
The prehospital echocardiographic examination will be transferred and stored at a local 
image server. No personal records are stored at this server, but a unique study number 
is provided as a link to patient social security number.  
 
3.1.5 Statistical analysis 
Continuous variables would be presented as median (min and max value /interquartile 
range (IQR)), and categorical variables are presented as counts and percentages of total 
count.  To assess the demographic differences between the groups with and without 
NSTEMI the Fisher exact test would be used for categorical variables, the two-sided t-
test for normal distributed continuous variables, and the two sided Mann-Whitney U-
test  for non-normal distributed continuous variables. Shapiro-Wilk normality to be 
used together with qq-plot to determine normality. Further, the Levene’s test to test for 
heteroscedastic (difference in variance) in the two groups compared. The result of this 
test determines if the equal variance t-test or Welsh-test will be used. A p-value < 0.05 
could be considered statistically significant. Statistical analyses will be performed 
using R. 
 
3.2 Organization 
The trial is conducted at Sørlandet Hospital Thrust foundation in collaboration with the 
Norwegian Air Ambulance Foundation, Norwegian University of Science and Technology 
(NTNU), St. Olavs Hospital, University of Oslo and Oslo University Hospital. 
 
The research group has considerable expertise in prehospital medicine and cardiology, 
and extensive research experience with risk stratification in patients with acute 
coronary syndromes, particularly ultrasound imaging in this population. 
 
3.2.1 Research group 
Name 
Title 
Institution 
Study role 
Jarle Jortveit 
MD, PhD, 
HoD 
Sørlandet Hospital, Arendal 
Project leader & co-supervisor  
Kristi Grønvold 
Bache 
PhD, HoD 
Norwegian Air Ambulance 
Foundation 
Main supervisor 
Roy Olsen 
MD, PhD 
Sørlandet Hospital, Arendal 
Co-supervisor  
Lars Jacobsen 
MD, HoD 
Sørlandet Hospital, Arendal 
PhD candidate  
Jo Røislien 
Professor 
Norwegian Air Ambulance 
Foundation & University of 
Stavanger  
Statistician 
Bjørnar Grenne  
MD, PhD 
NTNU & St. Olavs Hospital, 
Trondheim 
Study participant and main supervisor 
candidate II (if study part II is realized) 

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Benthe Sjøli  
MD, PhD 
Sørlandet Hospital, Arendal 
Study participant and future co-
supervisor candidate II (if study part II 
is realized) 
Trond Helge 
Lislevand 
MD 
Sørlandet Hospital, Arendal 
Study participant and PhD candidate II 
(if study part II is realized) 
Thor Edvardsen 
Professor 
dr. med 
Oslo University Hospital & 
University of Oslo, Oslo 
Study participant 
Tom Helge Vik 
Tollefsrud 
Paramedic 
Sørlandet Hospital HF 
Study participant 
Harald Brunvand 
MD, PhD 
Sørlandet Hospital, Arendal 
Study participant 
Slobodan Calic 
MD 
Sørlandet Hospital, Arendal 
Study participant 
Sunniva Bakke 
Archer 
MD 
Sørlandet Hospital, Arendal 
Study participant 
Thusego 
Motswakadikgwa 
MD 
Sørlandet Hospital, Arendal 
Study participant 
Mi Nguyen 
MD 
Sørlandet Hospital, Kristiansand 
Study participant 
Daniela Melichova 
MD 
Sørlandet Hospital, Arendal 
Study participant 
Sigve Karlsen 
MD 
Sørlandet Hospital, Arendal 
Study participant 
Thomas Dahlslett 
MD 
Sørlandet Hospital, Arendal 
Study participant 
 
 
3.3 Finance 
The technical ultrasound infrastructure is supported cost-free by GE Ultrasound. 
The study has received an innovation grant from Helse Sør-Øst (NOK 498 000,-). 
PhD candidate I receives a PhD grant by Norwegian Air Ambulance Foundation, Oslo, 
Norway. 
 
If study part II (the randomized controlled trial) is realized, the PhD candidate II will be 
funded by Centre for Innovative Ultrasound Solutions (CIUS), Norwegian University of 
Science and Technology, Trondheim, Norway 
 
3.4 Progression plan 
 
Year 
Activities 
Publications 
2017 
Establishment of study infrastructure 
Training of paramedics 
Patient inclusion  
 
2018 
Final patient inclusion  
Data analysis and writing of papers 
International presentation 
Paper 1 
2019 
Data analysis and writing of papers 
International presentation 
Paper 2 
2020 
Writing of paper 
Paper 3 

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PhD dissertation 
 
 
Planned publications:  
The results of this project will be published in level 1 and 2 international peer-reviewed 
journals, with corresponding presentations at scientific meetings. 
 
The following papers are planned: 
1. Feasibility of echocardiographic image transfer from road ambulances in patients 
with acute coronary syndrome. 
2. Echocardiography by paramedics in patients with acute coronary syndrome 
3. Prehospital point-of-care troponin analysis in patients with acute coronary 
syndrome 
 
 
4. User involvement 
A Patient Advisory Committee consisting of three patients will be established. The 
committee will contribute to regular evaluation of the practical performance of the 
project and modifications of it within the protocol frames.  
 
5. Ethics and legal aspects 
Participation in the study will depend on informed consent by the patient. This study is 
an acute diagnostic- and stratification study of patients in a potentially life-threatening 
emergency situation, and we therefore apply for retrospective collection of written 
consent in hospital. The patient (or next of kin) included in the study will be informed 
about the study, and an oral consent in the prehospital acute phase will be obtained 
when possible. In the cardiac unit, before discharge, a dedicated cardiologist especially 
assigned, will be in charge of collecting written consent from all included patients (or 
next of kin). The principal investigator and the PhD-candidate will follow up obtaining 
consent (see attached consent text). Participation is voluntarily and the patient’s 
decision will not influence further treatment except for the explicit tests performed as 
part of the study. Patients who decline participation will receive standard care. 
Prehospital ECG is performed routinely in patients with chest pain and will be acquired 
and analysed before echocardiography and troponin to identify patients with STEMI, 
who need immediate revascularization and are excluded from this study. A request for 
approval by the Regional committee for research ethics will be sent. Data Protection 
official (NSD) approval will be applied too.  

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