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

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Recruiting

CT.gov ID

NCT01838148

Collaborator

(none)

4,000

Enrollment

Location

247

Duration (Months)

16.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Angina, Stable Exercise Test Biological Markers SPECT

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

4000 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

May 1, 2004

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2024

Outcome Measures

Primary Outcome Measures

Diagnostic utility of novel biochemical and electrocardiographic signatures [baseline]
Diagnostic utility of biochemical (i.e. cardiac troponin, brain natriuretic peptide) and electrocardiographic signatures alone as well as in combination with the standard 12-lead exercise ECG in the detection of exercise-induced myocardial ischemia, mainly quantified by the area under the receiver operating characteristics curves (AUC ROC) and positive/negative predictive values, respectively.

Secondary Outcome Measures

One year event-free survival [360 days]
Prognostic utility of biochemical (i.e. cardiac troponins, brain natriuretic peptides) and electrocardiographic signatures in the risk prediction for the occurrence of cardiovascular death and acute myocardial infarction
Two year event-free survival [2 years]
Prognostic utility of biochemical (i.e. cardiac troponins, brain natriuretic peptides) and electrocardiographic signatures in the risk prediction for the occurrence of cardiovascular death and acute myocardial infarction
Five year event-free survival [5 years]
Prognostic utility of biochemical (i.e. cardiac troponins, brain natriuretic peptides) and electrocardiographic signatures in the risk prediction for the occurrence of cardiovascular death and acute myocardial infarction
Eight year event-free survival [8 years]
Prognostic utility of biochemical (i.e. cardiac troponins, brain natriuretic peptides) and electrocardiographic signatures in the risk prediction for the occurrence of cardiovascular death and acute myocardial infarction