Biochemical and Electrocardiographic Signatures in the Detection of Exercise-induced Myocardial Ischemia

NCT ID: NCT01838148

Last Updated: 2025-07-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 4000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2025-12-31

Brief Summary

The primary aim is to perform the largest study worldwide to evaluate novel biochemical and electrocardiographic signatures alone as well as in combination with the standard 12-lead exercise ECG in the detection of exercise-induced myocardial ischemia (diagnostic endpoint). The secondary aim is to evaluate these innovative tools in the risk prediction for the occurrence of cardiovascular death and acute myocardial infarction during long-term follow-up.

Detailed Description

Background: The detection of coronary artery disease (CAD) is one of the most important tasks in medicine. Exercise-induced myocardial ischemia is the pathophysiological hallmark of stable CAD. Currently, sophisticated imaging techniques including coronary angiography, rest/stress myocardial perfusion single-photon emission computed tomography (SPECT), and coronary CT-scanning are required to accurately detect CAD. Unfortunately, these techniques are associated with inherent risks due to substantial radiation exposure, intraarterial or intravenous application of iodinated contrast media, mechanical complications, require referral to a specialist, and are very costly. In addition, most of them provide anatomical but not functional information. For clinical practice, functional information that differentiates lesions that cause exercise-induced myocardial ischemia from functionally irrelevant lesions is critical. Exercise electrocardiography (ECG) is a widely used simple and non-invasive functional test, which however has imperfect sensitivity and specificity (both below 75%) in the detection of CAD. Novel cardiac biomarkers as well as novel computer-based quantitative approaches to analyse the ECG signal recorded during exercise offered by advances in information technology and signal processing may provide incremental value to the exercise ECG and thereby improve clinical care.

Aim: The primary aim is to perform the largest study worldwide to evaluate novel biochemical and electrocardiographic signatures alone as well as in combination with the standard 12-lead exercise ECG in the detection of exercise-induced myocardial ischemia (diagnostic endpoint). The secondary aim is to evaluate these innovative tools in the risk prediction for the occurrence of cardiovascular death and acute myocardial infarction during long-term follow-up.

Methodology: We will enroll approximately 4200 consecutive patients with suspected exercise induced myocardial ischemia referred for rest/ergometry myocardial perfusion SPECT. SPECT findings (complemented by coronary angiography and fractional flow reserve [FFR, if availabe] findings in patients who obtain both investigations) are used to adjudicate and quantify the presence of myocardial ischemia (the primary diagnostic end point). Clinical long-term follow-up will be obtained at 1 year, 2 years, 5 years and 8 years to record death, cardiovascular death, and acute myocardial infarction as well as coronary revascularisation.

Investigational tests: Venous blood samples will be collected before exercise stress testing for the determination of biochemical signatures possibly associated with myocardial ischemia including high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, B-type natriuretic peptide, IL-6, and cardiac microRNA. In addition, continuous ECG signals are recorded using 12 leads (16 leads in a subset of patients) and 24-bit amplitude resolution with 8000 Hz sampling frequency before, during and after the stress test. Novel methods of computer-based ECG signal-processing technology will be used to decipher electronic markers of myocardial ischemia and to develop improved software algorithms for automated ECG interpretation. All investigational tests will be performed in a blinded fashion.

Potential Significance: We hypothesize that biochemical and electrocardiographic signals of myocardial ischemia will significantly improve the non-invasive detection of exercise-induced myocardial ischemia. This would markedly improve the initiation of treatment in affected patients and thus advance medical management of patients with suspected CAD. In addition, this approach would help to simplify (exercise ECG versus myocardial SPECT) the non-invasive detection of exercise-induced myocardial ischemia and help to avoid the inherent health hazards associated current radiologic imaging procedures.

Conditions

Coronary Artery Disease; Angina, Stable; Exercise Test; Biological Markers; SPECT

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Patients presenting with suspected exercise-induced myocardial ischemia referred for rest/ergometry myocardial perfusion SPECT

Exclusion Criteria

• Age < 18 years
• Pregnancy
• Unable or unwilling to give informed consent
• Symptoms at rest or minor exertion

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Mueller, Prof. Dr. MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

University Hospital Basel

Basel, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Christian Mueller, Prof. Dr. MD

Role: CONTACT

Christian.Mueller@usb.ch

+ 41 61328 65 49

Facility Contacts

Christian Mueller, Prof. Dr. MD

Role: primary

References

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Reference Type: DERIVED

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Other Identifiers

BASEL VIII

Identifier Type: -

Identifier Source: org_study_id