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Multicenter Study
. 2023 Feb 6;18(13):e1090-e1098.
doi: 10.4244/EIJ-D-22-00270.

Diagnostic performance of exercise stress tests for detection of epicardial and microvascular coronary artery disease: the UZ Clear study

Bert Vandeloo  1 , Daniele Andreini  2   3 , Sofie Brouwers  4   5 , Takuya Mizukami  4   6 , Giovanni Monizzi  2 , Stijn Lochy  1 , Niya Mileva  4   7 , Jean-François Argacha  1 , Matthias De Boulle  1 , Philip Muyldermans  1 , Marta Belmonte  2   4 , Jeroen Sonck  4 , Emanuele Gallinoro  4 , Daniel Munhoz  4   8   9 , Bram Roosens  1 , Daniela Trabattoni  2 , Stefano Galli  2 , Ruiko Seki  4 , Martin Penicka  4 , Eric Wyffels  4 , Saima Mushtaq  2 , Sakura Nagumo  4   10 , Sofie Pardaens  4 , Emanuele Barbato  4   8 , Antonio L Bartorelli  2   3 , Bernard De Bruyne  4   11 , Bernard Cosyns  1 , Carlos Collet  4
Affiliations
Multicenter Study

Diagnostic performance of exercise stress tests for detection of epicardial and microvascular coronary artery disease: the UZ Clear study

Bert Vandeloo et al. EuroIntervention. .

Abstract

Background: Cardiac stress tests remain the cornerstone for evaluating patients suspected of having obstructive coronary artery disease (CAD). Coronary microvascular dysfunction (CMD) can lead to abnormal non-invasive tests.

Aims: We sought to assess the diagnostic performance of exercise stress tests with indexes of epicardial and microvascular resistance as reference.

Methods: This was a prospective, single-arm, multicentre study of patients with an intermediate pretest probability of CAD and positive exercise stress tests who were referred for invasive angiography. Patients underwent an invasive diagnostic procedure (IDP) with measurement of fractional flow reserve (FFR) and index of microvascular resistance (IMR) in at least one coronary vessel. Obstructive CAD was defined as diameter stenosis (DS) >50% by quantitative coronary angiography (QCA). The objective was to determine the false discovery rate (FDR) of cardiac exercise stress tests with both FFR and IMR as references.

Results: One hundred and seven patients (137 vessels) were studied. The mean age was 62.1±8.7, and 27.1% were female. The mean diameter stenosis was 37.2±27.5%, FFR was 0.84±0.10, coronary flow reserve was 2.74±2.07, and IMR 20.3±11.9. Obstructive CAD was present in 39.3%, whereas CMD was detected in 20.6%. The FDR was 60.7% and 62.6% with QCA and FFR as references (p-value=0.803). The combination of FFR and IMR as clinical reference reduced the FDR by 25% compared to QCA (45.8% vs 60.7%; p-value=0.006).

Conclusions: In patients with evidence of ischaemia, an invasive functional assessment accounting for the epicardial and microvascular compartments led to an improvement in the diagnostic performance of exercise tests, driven by a significant FDR reduction.

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Conflict of interest statement

D. Andreini reports receiving research grants from GE Healthcare and Bracco. T. Mizukami reports receiving consulting fees from Zeon Medical, research grants from Boston Scientific, and speaker fees from Abbott, CathWorks, and Boston Scientific. N. Mileva reports receiving speaker fees from Abbott. D. Munhoz reports receiving research grants provided by the CardioPaTh PhD program. E. Barbato reports receiving speaker's fees from Boston Scientific, Abbott, GE Healthcare, Insight Lifetech, and OpSens. B. De Bruyne reports receiving consultancy fees from Boston Scientific and Abbott, research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott, and owning equity in Siemens, GE Healthcare, Philips, HeartFlow, Edwards Lifesciences, Bayer, Sanofi, and Celyad. B. Cosyns reports receiving consulting fees from Philips and Boehringer Ingelheim, participation on the Board of Novartis and Pfizer; is President of the EACVI; and is a board member of the ESC and the Belgian Society of Cardiology. C. Collet reports receiving research grants from Biosensors International, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott, and consultancy fees from HeartFlow, OpSens, Abbott, and Philips. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Study flowchart.
In 14 patients, invasive physiology measurements were not performed because of either a total occlusion or sub-occlusive lesion. CABG: coronary artery bypass graft surgery; FFR: fractional flow reserve; IMR: index of microvascular resistance; PCI: percutaneous coronary intervention
FIgure 2
FIgure 2. The relationship of fractional flow reserve with diameter stenosis and index of microvascular resistance.
A) The correlation between FFR and diameter stenosis is shown. B) The relationship between FFR and IMR is presented. FFR: fractional flow reserve; IMR: index of microvascular resistance
Figure 3
Figure 3. Distribution of invasive coronary physiology findings.
Overall, in 54.2% of patients, evidence of haemodynamically significant epicardial or microvascular disease was found. In 16.8% of patients, coronary microvascular dysfunction (IMR ≥25) was observed. In 33.7%, a significant lesion based on FFR (≤0.80) was detected, whereas in 3.7% an alteration of both epicardial and microvascular domains was noticed. FFR: fractional flow reserve; IMR: index of microvascular resistance
Central illustration
Central illustration. Study protocol and main results.
The study protocol included symptomatic patients with an intermediate probability of coronary artery disease (CAD) and evidence of ischaemia. The study was to determine the diagnostic accuracy of exercise stress testing using both FFR and IMR as clinical references. Approximately half of the patients had evidence of epicardial or microvascular CAD. An invasive diagnostic procedure accounting for both epicardial and microvascular compartments improved the diagnostic performance of exercise tests through a significant reduction in the false discovery rate. The bottom of the figure shows the individual results of the index of microvascular resistance, fractional flow reserve, and quantitative coronary angiography. The red icon represents abnormal tests based on the metric-specific cut-offs. CAD: coronary artery disease; DS%: percentage diameter stenosis; FFR: fractional flow reserve; IMR: index of microvascular resistance; QCA: quantitative coronary angiography
Figure 4
Figure 4. Case example of a positive exercise test and coronary microvascular dysfunction.
A 54-year-old male with dyslipidaemia presenting with typical angina. A) The exercise test with an electrocardiogram in rest and during exercise. The test was considered positive due to ST depression of 2 mm and chest pain during exercise. B) Coronary angiography showed no obstructive coronary artery disease. The invasive diagnostic protocol showed an FFR of 0.89 and an IMR of 38. Therefore, the patient was diagnosed with microvascular angina. FFR: fractional flow reserve; IMR: index of microvascular resistance
See this image and copyright information in PMC

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