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Volume 62
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Review

Non-Invasive Assessment of Coronary Microvascular Dysfunction: From Flow Quantification to Clinical Decision Making

by
Panagiotis Theofilis
1,*,†,
Athanasios Sakalidis
1,2,†,
Kyriakos Dimitriadis
1,
Paschalis Karakasis
3,
Aggelos Papanikolaou
1,
Panagiotis Iliakis
1,
Aikaterini Vordoni
1,
Panayotis K. Vlachakis
1,
Panagiotis Tsioufis
1,
Eleni Adamopoulou
1,
Vasileios Panoulas
2,
Konstantinos Aznaouridis
1,
Konstantinos Tsioufis
1 and
Dimitris Tousoulis
1
1
First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 11527 Athens, Greece
2
Harefield Hospital, Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 7EH, UK
3
Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642 Thessaloniki, Greece
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Medicina 2026, 62(10), 1954; https://doi.org/10.3390/medicina62101954
Submission received: 24 August 2026 / Revised: 15 September 2026 / Accepted: 8 October 2026 / Published: 9 October 2026
(This article belongs to the Section Cardiology)
Versions Notes

Abstract

Coronary microvascular dysfunction (CMD) is a major mechanism of myocardial ischemia and adverse cardiovascular outcomes in patients with angina or dyspnea, both in the absence and in the presence of obstructive coronary artery disease. Because the coronary microcirculation cannot be visualized directly with routine angiography, diagnosis depends on physiological assessment. Non-invasive imaging has moved beyond relative perfusion analysis toward quantification of resting and hyperemic myocardial blood flow and flow reserve. Positron emission tomography (PET) remains the most extensively validated non-invasive method and provides robust absolute flow measurements with strong prognostic evidence. Quantitative stress cardiovascular magnetic resonance (CMR) is rapidly maturing, combining high-resolution perfusion mapping with ventricular and tissue characterization without ionizing radiation. Transthoracic Doppler echocardiography offers an accessible, radiation-free estimate of coronary flow velocity reserve, whereas myocardial contrast echocardiography can assess myocardial blood volume and replenishment kinetics. Dynamic cadmium-zinc-telluride single-photon emission computed tomography and stress computed tomography perfusion extend flow quantification to more widely available platforms, although standardization and outcome validation remain less developed. Across modalities, interpretation requires attention to the adequacy of vasodilator stress, resting hemodynamics, diffuse epicardial atherosclerosis, scar, and technical factors. A reduced flow reserve is not synonymous with isolated microvascular disease and cannot identify acetylcholine-provoked vasospasm. This review provides a clinically oriented framework for selecting, performing, interpreting, and reporting non-invasive CMD testing; examines the evidence, strengths, and limitations of each modality; and defines situations in which invasive coronary function testing remains necessary. Future progress will depend on cross-platform standardization, automated quality control, disease- and sex-specific reference ranges, and prospective trials linking imaging-defined endotypes to effective treatment strategies.
Keywords: coronary microvascular dysfunction; myocardial blood flow; myocardial flow reserve; positron emission tomography; cardiovascular magnetic resonance; echocardiography; SPECT; CT perfusion; INOCA; ANOCA coronary microvascular dysfunction; myocardial blood flow; myocardial flow reserve; positron emission tomography; cardiovascular magnetic resonance; echocardiography; SPECT; CT perfusion; INOCA; ANOCA

Share and Cite

MDPI and ACS Style

Theofilis, P.; Sakalidis, A.; Dimitriadis, K.; Karakasis, P.; Papanikolaou, A.; Iliakis, P.; Vordoni, A.; Vlachakis, P.K.; Tsioufis, P.; Adamopoulou, E.; et al. Non-Invasive Assessment of Coronary Microvascular Dysfunction: From Flow Quantification to Clinical Decision Making. Medicina 2026, 62, 1954. https://doi.org/10.3390/medicina62101954

AMA Style

Theofilis P, Sakalidis A, Dimitriadis K, Karakasis P, Papanikolaou A, Iliakis P, Vordoni A, Vlachakis PK, Tsioufis P, Adamopoulou E, et al. Non-Invasive Assessment of Coronary Microvascular Dysfunction: From Flow Quantification to Clinical Decision Making. Medicina. 2026; 62(10):1954. https://doi.org/10.3390/medicina62101954

Chicago/Turabian Style

Theofilis, Panagiotis, Athanasios Sakalidis, Kyriakos Dimitriadis, Paschalis Karakasis, Aggelos Papanikolaou, Panagiotis Iliakis, Aikaterini Vordoni, Panayotis K. Vlachakis, Panagiotis Tsioufis, Eleni Adamopoulou, and et al. 2026. "Non-Invasive Assessment of Coronary Microvascular Dysfunction: From Flow Quantification to Clinical Decision Making" Medicina 62, no. 10: 1954. https://doi.org/10.3390/medicina62101954

APA Style

Theofilis, P., Sakalidis, A., Dimitriadis, K., Karakasis, P., Papanikolaou, A., Iliakis, P., Vordoni, A., Vlachakis, P. K., Tsioufis, P., Adamopoulou, E., Panoulas, V., Aznaouridis, K., Tsioufis, K., & Tousoulis, D. (2026). Non-Invasive Assessment of Coronary Microvascular Dysfunction: From Flow Quantification to Clinical Decision Making. Medicina, 62(10), 1954. https://doi.org/10.3390/medicina62101954

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