High-sensitive cardiac Troponin T and exercise stress test for evaluation of angiographically significant coronary disease

https://doi.org/10.1016/j.ijcard.2019.04.019Get rights and content

Highlights

  • Resting hs-cTnT levels are higher in patients with angiographically verified CAD than those without.

  • Resting hs-cTnT levels alone or combined with exercise stress test results provide increased accuracy in diagnosis of CAD.

  • Resting hs-cTnT is correlated with extent of atherosclerotic burden verified by coronary angiography and using Gensini score.

Abstract

Background

Exercise stress test (EST) has a moderate precision for diagnosis of CAD and could potentially obtain improved accuracy if adding a reliable cardiac biomarker to the test.

Objective

We aimed to investigate resting levels and change in hs-cTnT during EST in patients with and without angiographically significant CAD. Moreover, we intended to explore the additive value of hs-cTnT to EST results in diagnosis of stable CAD. We hypothesized that hs-cTnT would be higher in CAD patients and increase diagnostic precision of EST.

Method

Patients presenting with symptoms of stable CAD, performed a maximal EST on a bicycle ergometer. Venous blood samples were taken at rest and within 5 min post-exercise. All patients underwent coronary angiography. Significant CAD was defined as having ≥75% stenosis in one or more segments of the coronary arteries.

Results

Out of the 297 participants, significant CAD was found in 111 (37%) patients.

Patients with significant CAD compared to without, had higher resting levels of hs-cTnT (median 8.1 vs 5.0 ng/L) and no significant difference in exercise-induced change (median 0.5 vs 0.3 ng/L), p < 0.001 and p = 0.086 respectively. Combined resting hs-cTnT with EST had higher predictive value for significant CAD than EST alone, AUC = 0.751 vs. AUC = 0.637. In an adjusted multivariable regression analysis, resting hs-cTnT >6.0 ng/L was predictive for having significant CAD, OR 2.55 (CI 95% 1.40, 4.65 p = 0.002).

Conclusion

In patients with suspected stable CAD, hs-cTnT has a predictive value alone, as well as added to a diagnostic EST for CAD.

Introduction

In contemporary clinical practice, high-sensitive cardiac troponin assays are preferably used for risk stratification and clinical diagnosis of acute coronary syndrome (ACS). In the general population, among patients with chest pain and known stable coronary artery disease (CAD), high-sensitive cardiac Troponin T (hs-cTnT) has recurrently shown to be of prognostic importance [1,2,3]. Whether ischemia per se, without evident myocardial injury, may cause leakage of troponins is an ongoing debate and different pathophysiological mechanisms have been suggested [4,5].

To recognize stable CAD, before it evolves into an unstable state, is essential for patients at risk. Although imaging diagnostic techniques are advancing, peri-procedural complications and expenses of these techniques are nevertheless still of concern [6]. Exercise stress test (EST) is a cost-effective diagnostic tool and with low risk of complications, however, the test is known to be of suboptimal diagnostic precision for detecting obstructive CAD. Selection of patients for referral to invasive diagnostic procedures remains a challenge for clinicians.

Previously, studies have reported on increased baseline troponin levels in patients with stable CAD compared to those without [5,7,8].

Similarly, troponins have been shown to predict obstructive CAD among stable patients [9]. Exercise-induced troponin secretion among healthy individuals has been described [10,11], whereas for exercise-induced change in troponin levels, among patients with suspected CAD without concomitant cardiac disease, sparse data is available and especially using coronary angiography as the diagnostic tool.

In this study we aimed to investigate resting and exercise-induced change of hs-cTnT in patients with suspected stable CAD, without other known cardiac disease. Furthermore, we intended to explore whether hs-cTnT in combination with the EST would increase sensitivity and specificity of EST for the diagnosis of CAD.

Section snippets

Study population

Patients referred for exercise stress testing or coronary angiography due to symptoms suggestive of CAD, were enrolled in the CADENCE study (clinicaltrials.gov NCT01495091), at the Department of Cardiology, Oslo University Hospital Ullevaal, Oslo Norway. Patients were eligible for the study if they had symptoms indicative of ischemic heart disease, were ≥18 years of age and had a Morise risk score ≥ 9 points, indicating intermediate to high risk of cardiovascular disease [12]. Exclusion

Demographic data and coronary angiography

Of the 327 patients initially enrolled in the study, 15 patients had previously had CABG, 9 patients resigned before completing the study protocol and 6 patients were found to have ≥1 exclusion criteria not seen prior to inclusion. The remaining patients (n = 297) constituted the present study sample. Of the total population 111 patients (37%) were found to have significant CAD, of which 86 patients were re-vascularized. In the group without significant CAD (<75% stenosis) 8 patients were

Discussion

In the present study of 297 participants with suspected CAD, we found significantly higher levels of hs-cTnT at rest and during exercise stress test in patients with angiographically verified CAD. Moreover, resting hs-cTnT combined with EST results, had a better discriminatory value, than that of EST alone, for predicting angiographically significant CAD. In fact, measurement of resting value of hs-TnT alone seems to discriminate angiographically significant CAD better than EST.

To our

Limitations

Several considerations concerning circulating troponin levels should be accounted for. As we discussed previously, time point for assessment of exercise induced troponin elevations may be questioned as we did not collect blood samples at time points beyond 5 min post-exercise, why we may have missed a later rise in troponin increment. As well the know low precision of the hs-cTnT assay at low concentration is a central limitation. Neither did we evaluate cardiac Troponin I and it remains to be

Conclusion

In our patients with suspected stable CAD and no other known concomitant cardiac disease, resting hs-cTnT alone as well as when added to a diagnostic exercise stress test, had a significant predictive value for angiographically verified significant CAD. Hs-cTnT was found related to extent of coronary artery disease and a cut-off level of 6.0 ng/L may be used to differentiate between patients with negative and positive exercise stress test results.

Acknowledgement

The authors thank Department of Cardiology and Section for Cardiology Intervention at Oslo University Hospital, for their support during patient inclusion. We would like to thank Vibeke Kjær and Charlotte Holst Hansen, for their help during patient inclusion. Sissel Aakra and Vibeke Bratseth at Center for Clinical Heart Research, as well as Department of Medical Biochemistry at Oslo University Hospital Rikshospitalet, are acknowledged for laboratory assistance. Miriam Langseth, contributed to

Ethics approval and consent to participate

All participants have given written informed consent to participate. The study has been conducted in accordance with the Declaration of Helsinki, and the Regional Ethics Committee in South Eastern Health Region in Norway approved the protocol.

Conflict of interest

The authors declare that they have no competing interests.

Financial support

This study was financially supported by University of Oslo and the Stein Erik Hagen Foundation for Clinical Heart Research, Oslo, Norway.

Authors' contributions

J. Cwikiel was involved in patient inclusion, interpretation

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