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Prospective Validation of a Biomarker-Based Rule Out Strategy for Functionally Relevant Coronary Artery Disease
Joan E Walter1, Ursina Honegger1, Christian Puelacher1,2
1Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland.
Insights
A single high-sensitivity cardiac troponin I (hs-cTnI) blood test can safely rule out significant coronary artery disease (CAD) in about 10% of patients. This strategy advances non-invasive CAD assessment for improved patient care.
Area of Science:
- Cardiology
- Biomarker Research
- Diagnostic Strategies
Background:
- Coronary artery disease (CAD) diagnosis often requires invasive procedures.
- High-sensitivity cardiac troponin I (hs-cTnI) shows promise for non-invasive CAD assessment.
- A validated, multi-step approach is needed to implement hs-cTnI for CAD rule-out.
Purpose of the Study:
- To prospectively develop and validate a rule-out strategy for functionally significant CAD using hs-cTnI.
- To assess hs-cTnI performance in serum and plasma across different measurement platforms.
- To establish a clinical platform for hs-cTnI-based CAD risk stratification.
Main Methods:
- A 3-step prospective study involving patients without known CAD referred for myocardial perfusion imaging (MPI-SPECT/CT).
- Cohorts for validation (serum), correlation (serum/plasma), and application (plasma) using research and clinical assay systems.
- Functional CAD adjudicated by expert MPI-SPECT/CT interpretation and coronary angiography.
Main Results:
- Functionally relevant CAD was identified in 21% of patients.
- In the validation cohort, hs-cTnI distinguished CAD, enabling rule-out in 14% with 95% sensitivity.
- Serum and plasma hs-cTnI correlated strongly (r=0.921) with similar diagnostic accuracy; low plasma hs-cTnI (<0.5 ng/L) ruled out CAD in 10% in the application cohort.
Conclusions:
- A single resting plasma hs-cTnI measurement can safely rule out functionally relevant CAD in approximately 10% of patients without known CAD.
- This hs-cTnI-based strategy offers a potential non-invasive approach for CAD risk stratification.
- Implementation on a clinical platform supports the bedside application of hs-cTnI for CAD rule-out.
Background:
This study aimed to prospectively advance a rule-out strategy for functionally significant coronary artery disease (CAD) by use of high-sensitivity cardiac troponin I (hs-cTnI) from bench to bedside, by application of a 3-step approach: validation in serum, correlation in plasma, and application on a clinical platform.
Methods:
Patients without known CAD referred for rest/stress myocardial perfusion single-photon emission tomography/computer tomography (MPI-SPECT/CT) were assigned to 3 consecutive cohorts: validation, correlation, and application. Functionally relevant CAD was adjudicated with the use of expert interpretation of MPI-SPECT/CT and, if available, coronary angiography. In the validation cohort resting hs-cTnI was measured in serum before stress testing with the research Erenna system, in serum and plasma in the correlation cohort with the research Erenna system, and in plasma in the application cohort with the clinical Clarity system.
Results:
Overall, functionally relevant CAD was adjudicated in 21% (304/1478) of patients. In the validation cohort (n = 613), hs-cTnI concentrations were significantly higher in patients with functionally relevant CAD (median 2.8 ng/L vs 1.9 ng/L, P < 0.001) as compared to patients without functionally relevant CAD and allowed a rule out with 95% sensitivity in 14% of patients. In the correlation cohort (n = 606), hs-cTnI concentrations in serum and plasma strongly correlated (Spearman r = 0.921) and had similar diagnostic accuracy as quantified by the area under the receiver operating characteristic curve (0.686 vs 0.678, P = 0.425). In the application cohort (n = 555), very low hs-cTnI plasma concentrations (< 0.5 ng/L) ruled out functionally relevant CAD with 95% sensitivity in 10% of patients.
Conclusions:
A single resting plasma hs-cTnI measurement can safely rule out functionally relevant CAD in around 10% of patients without known CAD.
