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

DOI: 10.4244/EIJ-D-22-00270

Bert Vandeloo
Bert Vandeloo1, MD; Daniele Andreini2,3, MD, PhD; Sofie Brouwers4,5, MD, PhD; Takuya Mizukami4,6, MD, PhD; Giovanni Monizzi2, MD; Stijn Lochy1, MD; Niya Mileva4,7, MD; Jean-François Argacha1, MD, PhD; Matthias De Boulle1, MD; Philip Muyldermans1, MD; Marta Belmonte2,4, MD; Jeroen Sonck4, MD, PhD; Emanuele Gallinoro4, MD; Daniel Munhoz4,8,9, MD, PhD; Bram Roosens1, MD, PhD; Daniela Trabattoni2, MD; Stefano Galli2, MD; Ruiko Seki4, MD; Martin Penicka4, MD, PhD; Eric Wyffels4, MD; Saima Mushtaq2, MD, PhD; Sakura Nagumo4,10, MD, PhD; Sofie Pardaens4, MSc, PhD; Emanuele Barbato4,8, MD, PhD; Antonio L. Bartorelli2,3, MD, PhD; Bernard De Bruyne4,11, MD, PhD; Bernard Cosyns1, MD, PhD; Carlos Collet4, MD, PhD
1. Centrum voor Hart- en Vaatziekten (CHVZ), Vrije Universiteit Brussel (VUB), Universtair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium; 2. Centro Cardiologico Monzino, IRCCS, Milan, Italy; 3. Department of Biomedical and Clinical Sciences “Luigi Sacco”, University of Milan, Milan, Italy; 4. Cardiovascular Center Aalst, OLV Clinic, Aalst, Belgium; 5. Department of Experimental Pharmacology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium; 6. Division of Clinical Pharmacology, Department of Pharmacology, Showa University, Tokyo, Japan; 7. Medical Faculty, Medical University Sofia, Sofia, Bulgaria; 8. Department of Advanced Biomedical Sciences University Federico II, Naples, Italy; 9. Department of Internal Medicine, Discipline of Cardiology, University of Campinas (Unicamp), Campinas, Brazil; 10. Department of Cardiology, Showa University Fujigaoka Hospital, Kanagawa, Japan; 11. Department of Cardiology, Lausanne University Hospital, Lausanne, Switzerland

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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