Prognostic value of structural and functional coronary microvascular dysfunction in patients with non-obstructive coronary artery disease; from the multicentre international ILIAS registry

DOI: 10.4244/EIJ-D-22-00043

Coen Boerhout
Coen K.M. Boerhout1, MD; Guus A. de Waard2, MD, PhD; Joo Myung Lee3, MD, PhD; Hernan Meija-Renteria4, MD, PhD; Seung Hun Lee5, MD, PhD; Ji-Hyun Jung6, MD; Masahiro Hoshino7, MD; Mauro Echavarria-Pinto8, MD, PhD; Martijn Meuwissen9, MD, PhD; Hitoshi Matsuo7, MD, PhD; Maribel Madera-Cambero10, MD; Ashkan Eftekhari11, MD, PhD; Mohamed A. Effat12; Tadashi Murai13, MD; Koen Marques2, MD, PhD; Yolande Appelman2, MD, PhD; Joon-Hyung Doh14, MD, PhD; Evald Høj Christiansen11, MD, PhD; Rupak Banerjee15; Chang-Wook Nam16, MD, PhD; Giampaolo Niccoli17, MD, PhD; Masafumi Nakayama7,18, MD, PhD; Nobuhiro Tanaka19, MD, PhD; Eun-Seok Shin20, MD, PhD; Marcel A.M. Beijk1, MD, PhD; Paul Knaapen2, MD, PhD; Javier Escaned4, MD, PhD; Tsunekazu Kakuta13, MD, PhD; Bon-Kwon Koo21, MD, PhD; Tim P. van de Hoef1,2,22, MD; Jan J. Piek1, MD, PhD
1. Department of Cardiology, Amsterdam UMC – location AMC, Amsterdam, the Netherlands; 2. Department of Cardiology, Amsterdam UMC – location VUmc, Amsterdam, the Netherlands; 3. Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 4. Hospital Clínico San Carlos, IDISSC, and Universidad Complutense de Madrid, Madrid, Spain; 5. Division of Cardiology, Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea; 6. Sejong General Hospital, Sejong Heart Institute, Bucheon, Republic of Korea; 7. Gifu Heart Center, Department of Cardiovascular Medicine, Gifu, Japan; 8. Hospital General ISSSTE Querétaro - Facultad de Medicina, Universidad Autónoma de Querétaro, Querétaro, Mexico; 9. Department of Cardiology, Amphia Hospital, Breda, the Netherlands; 10. Tergooi Hospital, Department of Cardiology, Blaricum, the Netherlands; 11. Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; 12. Division of Cardiovascular Health and Diseases, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA; 13. Tsuchiura Kyodo General Hospital, Department of Cardiology, Tsuchiura City, Japan; 14. Department of Medicine, Keimyung University Dongsan Medical Center, Daegu, South Korea; 15. Mechanical and Materials Engineering Department, University of Cincinnati, Cincinnati, OH, USA; and Research Services, Veteran Affairs Medical Center, Cincinnati, OH, USA; 16. Department of Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea; 17. Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Institute of Cardiology, Rome, Italy; 18. Cardiovascular Center, Toda Central General Hospital, Toda, Japan; 19. Department of Cardiology, Tokyo Medical University, Hachioji Medical Center, Tokyo, Japan; 20. Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 21. Department of Internal Medicine, Seoul National University Hospital, Cardiovascular Center, Seoul, Republic of Korea; 22. Department of Cardiology, NoordWest Ziekenhuisgroep, the Netherlands

Background: Coronary microvascular dysfunction (CMD) is an important contributor to angina syndromes. Recently, two distinct endotypes were identified using combined assessment of coronary flow reserve (CFR) and minimal microvascular resistance (MR), termed structural and functional CMD.

Aims: We aimed to assess the relevance of the combined assessment of CFR and MR in patients with angina and no obstructive coronary arteries.

Methods: Patients with chronic coronary syndromes (CCS) and non-obstructive coronary artery disease (fractional flow reserve [FFR] ≥0.80) were selected (N=1,102). Functional CMD was defined as abnormal CFR in combination with normal MR and structural CMD as abnormal CFR with abnormal MR. Clinical endpoints were the incidence of major adverse cardiac events (MACE) and target vessel failure (TVF) at 5-year follow-up.

Results: Abnormal CFR was associated with an increased risk of MACE and TVF at 5-year follow-up. Microvascular resistance parameters were not associated with MACE or TVF at 5-year follow-up. The risk of MACE and TVF at 5-year follow-up was similarly increased for patients with structural or functional CMD compared with patients with normal microvascular function. There were no differences between both endotypes (p=0.88 for MACE, and p=0.55 for TVF).

Conclusions: Coronary microvascular dysfunction, identified by an impaired CFR, was unequivocally associated with increased MACE and TVF rates over a 5-year follow-up period. In contrast, impaired MR was not associated with 5-year adverse clinical events. Moreover, there was no significant difference in the risk of MACE and TVF between a low CFR accompanied by pathologically increased MR (structural CMD) or not (functional CMD). ClinicalTrials.gov: NCT04485234

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coronary flow reservecoronary microvascular dysfunctionhyperaemic microvascular resistanceindex of microvascular resistanceprognosis
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