An observational study in Coronary Artery Disease, Ischaemic Heart Disease and Angina Pectoris, sponsored by University of Oxford. Enrolling by invitation. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-29.
Sponsored by University of Oxford · Observational
EVAREST will identify and validate novel blood and imaging biomarkers of potential value for consistent and accurate interpretation of stress echocardiography. During phase one, blood samples will be collected to assess the impact of cardiac stress on levels of circulating biomarkers and examine whether the measurement of these biomarkers can provide additional prognostic information. Phases one, two and three will also determine whether novel imaging biomarkers can be identified in the echocardiograms that can be used for objective interpretation of the stress echocardiograms. EVAREST will recruit up to 8000 patients (First 500 during phase one, an additional 500 during phase two and an additional 7000 during phase three) from multiple hospitals across United Kingdom, who have been referred for a stress echocardiogram as part of their investigations into ischaemic heart disease. Phase four of the study will continue into a clinical study cohort phase to capture information from all patients referred for a stress echocardiogram in the UK, regardless of the reason for investigation.This registry phase will run for 2 years, recruiting up to 15000 participants.
Study Overview:
EVAREST is a multi-centre observational study comparing accuracy of novel quantitative stress echocardiography biomarkers for prediction of 12 month outcome against standard clinical interpretation.
Coronary artery disease affects 2.3 million people in the UK and is responsible for 66 000 deaths each (BHF, 2018). As such, early diagnosis and intervention is crucial for saving lives and improving people's quality of life. Stress echocardiography is a commonly used, non-invasive imaging test used for detection of prognostically significant coronary artery disease. It allows the detection of regional wall motion abnormalities (RWMAs) which develop when the myocardium is not receiving adequate perfusion and, as such, indicates obstructive coronary artery disease. Average sensitivity and specificity for stress echocardiography is estimated at 81% and 82%, respectively (Geleijnse et al., 2009) in meta-analysis but remains highly subjective (Hoffmann et al., 1996) and subject to operator skill (Picano et al., 1991). Objective, quantifiable biomarkers in blood samples, or from images, acquired during the stress echocardiogram, which predict outcome of patients, could be used to reduce variability of stress echocardiography and ensure consistent and accurate results.
Aims
Phase One
Phase one will investigate the impact of cardiac stress on the levels of circulating biomarkers, in particular, extracellular vesicles. This phase will also assess whether they provide further prognostic information in addition to the echocardiogram. Blood samples will be collected from a cannula (inserted for the standard clinical procedure) before stress, during peak stress and during recovery and analysed to determine whether there were any changes in circulating extracellular vesicles during these three stages and whether these differ between patients with and without ischaemic heart disease.
Phase Two
Phase two continues recruitment for collection of stress echocardiogram images. Data collected during this phase will be compared with the data obtained during phase one to assess the usefulness of incorporating blood biomarkers into assessment of stress echocardiograms. In addition, the images obtained during phase two will be combined with the images collected during phase one to allow for the identification of novel imaging biomarkers which can be used to assist in the identification of patients with prognostically significant coronary disease.
Phase Three
Phase three will expand recruitment to allow evaluation of the generalisability of the imaging biomarkers identified in phase one and two across different healthcare settings, operators, stress protocols, machines and patient groups.
Phase Four
The fourth phase of the study allows for an assessment of all stress echocardiography practise in the UK and the demographics of patients being referred for stress echocardiogram. Phase four will investigate the use of stress echocardiography as a clinical procedure in the UK.
Patients who have been scheduled a stress echocardiogram (using either pharmacological or exercise stress) as part of clinical investigations will be sent a participant information leaflet to read prior to their clinic appointment. When they are in the department, they will be approached by a study investigator to see whether they would be interested in taking part in the study and have the opportunity to ask the investigator any questions so that they fully understand the study. If they are interested in taking part, the process of obtaining informed consent will take place.
Following consent, the images acquired during the stress echocardiogram will be downloaded and anonymised with the participant's unique study ID number. These images will be transferred to the Oxford Research Echocardiography Core Laboratory (ORECL) for further analysis. Relevant medical history will be obtained for each participant as well as the clinician's interpretation of the echocardiogram. One year after the initial stress echocardiogram (range: 11-18 months), the participant will be followed-up to determine whether they underwent any further investigations for ischaemic heart disease (such as coronary angiography, cardiac magnetic resonance imaging, myocardial perfusion scintigraphy or repeat stress echocardiography) or had any coronary events. The participant may also be contacted via telephone to find out whether they were admitted to any other hospital for investigations. For phase one participants only, three blood samples (totalling approximately 40 ml) will be obtained before, at peak stress and after a recovery period, for the assessment of blood biomarkers. These samples will be taken through the cannula inserted as is routine during stress echocardiography. Participants will also give consent for follow-up information to be accessed for up to ten years after their initial stress echocardiogram.
Patient outcomes will be examined by an adjudication committee, blinded to the results of the stress echocardiograms. This committee will be led by a cardiologist and will examine all information obtained for a participant after the follow-up period has concluded. The criteria for confirming the presence of significant coronary artery disease include > 70% stenosis (assessed either via invasive coronary angiography or CT coronary angiography), an FFR \< 0.85 or disease requiring intervention (either by percutaneous coronary intervention (PCI) or coronary artery bypass grafts (CABG)). Other end-points include coronary events (such as myocardial infarction) or death (attributed to coronary artery disease). If a patient has had no further investigations or events since their stress echocardiogram, their outcome will be recorded as normal.
All data obtained will be securely stored in accordance with the General Data Protection Regulations and Data Protection Act (2018) and Caldicott Principles.
4,857 studies on the registry are indexed under Coronary Artery Disease; 890 are open to participants now.
This study's planned enrollment of 23,000 is above the median of 320 across 1,687 observational studies indexed under Coronary Artery Disease.
Browse Coronary Artery Disease studies →University of Oxford is the lead sponsor of 812 studies on the registry; 119 are open to participants now.
Counted across the registry records on this site, refreshed daily.
For phases 1 - 3, patients will be recruited when attending hospital for a stress echocardiogram to investigate the presence of ischaemic heart disease. For phase 4, patients attending hospital for a stress echocardiogram, for any investigation, will be recruited.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants in group 1 will be recruited at their stress echocardiogram appointment. Anonymised versions of the stress echocardiograms will be obtained, in addition to venous blood samples obtained from the cannula inserted as part of the standard clinical procedure. These blood samples will be collected before and after the stress echocardiogram. These participants will be followed up by telephone call after one year to determine whether they had any additional cardiac tests or events outside of their hospital trust. Medical records relating to the participant will be reviewed annually for up to 10 years to identify if the patient has been admitted and obtain health outcome data.
Participants in group 2 will be recruited at their stress echocardiogram appointment. Anonymised versions of the stress echocardiograms will be obtained. These participants will be followed up by telephone call after one year to determine whether they had any additional cardiac tests or events outside of their hospital trust. Medical records relating to the participant will be reviewed annually for up to 10 years to identify if the patient has been admitted and obtain health outcome data.
Participants in group 3 will be recruited at their stress echocardiogram appointment. Anonymised versions of the stress echocardiograms will be obtained. These participants will be followed up by telephone call after one year to determine whether they had any additional cardiac tests or events outside of their hospital trust. Medical records relating to the participant will be reviewed annually for up to 10 years to identify if the patient has been admitted and obtain health outcome data.
Participants in group 4 will be recruited at their stress echocardiogram appointment, regardless of the type of investigation. A simplified data set and an anonymised version of the stress echocardiography report will be collected as a part of this registry phase. Participants will be followed up over a 10-year period.
Assessment of Prognostically Significant CAD
Patients will be followed up one year after their stress echocardiogram to determine whether they have prognostically significant CAD. This is defined as \>70% stenosis assessed by angiography (either via invasive coronary angiography or CT coronary angiography), an FFR\< 0.85 or the intention to revascularize (either via PCI or CABG). Any tests that occur in a ten year period after the stress echocardiogram will also be recorded.
Time frame: Data will be collected for ten years after the patient undergoes the stress echocardiogram.
Examination of Medical Records
Medical records will also be examined to check for any acute coronary syndromes within the year following the stress echocardiogram. Participants will also be contacted by telephone to capture any out-of-hospital events. Further follow-up data will be captured up to 10 years after the patient's initial stress echocardiogram.
Time frame: Data will be collected for ten years after the patient undergoes the stress echocardiogram.
Quantification of Extracellular Vesicles (obtained from blood samples) by Flow Cytometry
The concentration of a comprehensive panel of cell-derived extracellular vesicles (such as erythrocyte, endothelial and platelet-derived extracellular vesicles) will be measured via flow cytometry in both the pre-stress and post-stress blood samples to assess the effect of cardiac stress on their concentration. The concentrations will also be compared between the patients with and without prognostically significant coronary artery disease to determine whether the concentration of extracellular vesicles is affected by coronary artery disease.
Time frame: Blood samples will be obtained before and after the stress echocardiogram. Analysis will be complete one year from the date of the stress echocardiogram
Assessment of Time to Diagnosis
We will assess whether the use of novel imaging and blood biomarkers can reduce the time to diagnosis of prognostically significant CAD.
Time frame: Data will be collected for ten years after the patient undergoes the stress echocardiogram.
Analysis of Potential Cost Savings Through the Use of Novel Biomarkers By the Reduction in Unnecessary Procedures
Health economic assessment will be carried out to determine whether the inclusion of imaging and blood biomarkers in the diagnostic process can ultimately lead to cost reductions through the reduction in unnecessary procedures and treatments.
Time frame: Data will be collected for ten years after the patient undergoes the stress echocardiogram.
Investigation into the use of stress echocardiography as a clinical procedure in the UK.
Analysis of the number and type of stress echocardiograms performed across UK NHS sites as well as demographic information on the patients referred for stress echocardiography and accuracy of stress echocardiography, using follow-up data.
Time frame: Data will be collected for ten years after the patient undergoes the stress echocardiogram.
No study locations are listed for this record.
Plan to share: No
Ran from Mar 2015 to primary completion in Mar 2021, 72 months.
Of 634 non-industry observational studies under Coronary Artery Disease, half reached primary completion within 48 months of starting (the median), counting those still running; a quarter within 23 and three quarters within 122. This study's 72 months is above that.
Counting every sponsor, half of 759 studies reached it within 40 months; a quarter within 21 and three quarters within 87.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
No contact was published for this record. The registry link below has the sponsor’s details.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.