Microvascular Dysfunction in Patients with Positive Coronary CT Angiography: Implications of Invasive Physiological Studies

Both European and US clinical guidelines recommend coronary CT angiography as the starting diagnostic study when coronary artery disease is suspected. However, a considerable proportion of these patients, when referred to invasive coronary angiography, do not show angiographically obstructive lesions. 

In this context, coronary microvascular dysfunction has surged as pathophysiological explanation for angina patients with no significant lesions.  This diagnosis might allow personalized treatment and improved quality of life. The invasive procedure consists of measuring coronary flow reserve and microvascular resistance rate with specific guidewires and software.  

This study, based on the Dan-NICAD cohort, included patients sent to invasive coronary angiography suspected of >50% disease at CT angiography. The aim was to assess and compare clinical and procedural characteristics — including perfusion images with Rb-PET and SA questionnaires— across different CAD subtypes:

• “Disease Free”, defined as >30% absence of stenosis with normal physiological parameters.
• “Microvascular Dysfunction”, when fractional flow reserve was >0.80 and, even so, there was <2.5 coronary flow reserve and/or microvascular resistance index ≥ 25.
• “Obstructive Epicardial Disease”, with >90% stenosis or ≤ 0.80 fractional flow reserve.
• “Concomitant”, when ≤ 0.80 fractional flow reserve and microvascular resistance index ≥ 25 coexist. 

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561 symptomatic patients were assessed with angio CT suggesting >50% epicardial stenosis. Mean patient age was 63 and 31% were women. Isolated microvascular dysfunction was diagnosed in 23%. However, when applying a three vessel invasive physiological protocol, and not only when stenosis was ≥30%, prevalence increased by 35%, while the proportion of patients classified as “disease free” dropped from 44 to 28%. This finding highlights the importance of a broader physiological assessment, since when limited to segments with intermediate stenosis overlooks a significant number of patients with microvascular alterations. 

Vessels with microvascular dysfunction identified by invasive physiology showed myocardial flow values under stress and PET-derived myocardial flow reserve were comparable to those of disease free vessels. In contrast, vessels with obstructive epicardial disease presented the expected reduction in stress-induced blood flow and reserve, which suggests a normal PET does not rule out the presence of microvascular dysfunction.

As regards symptoms, assessed with SAQ at kickoff and after 3 months, there were no significant differences in absolute scores between groups. However, after adjusting for baseline angina frequency, the probability of freedom from symptoms was lower in patients with microvascular dysfunction and higher in patients receiving revascularization for epicardial obstructive disease, vs. disease free patients. 

Conclusions

In symptomatic patients referred to coronary angiography after suspicious angio CT, we will often find microvascular dysfunction. Unlike obstructive CAD, it may occur with normal Rb-PET stress studies. At followup, it has been associated to lower freedom from angina vs. disease free patients, while epicardial revascularization tends to improve symptoms. 

Original Title: Coronary microvascular disease in patients referred to coronary angiography following coronary computed tomography angiography.

Reference: Westra J, Rasmussen LD, Karim SR, Jensen RV, Ejlersen JA, Gormsen LC, Bøttcher M, Eftekhari A, Winther S, Christiansen EH. Coronary microvascular disease in patients referred to coronary angiography following coronary computed tomography angiography. EuroIntervention. 2025 Sep 1;21(17):e1005-e1014. doi: 10.4244/EIJ-D-24-01155. PMID: 40887988; PMCID: PMC12378605.