Characterization of different phenotypes of microvascular dysfunction and their impact on angina severity in patients with chronic angina without apparent obstructive coronary artery disease

Around half of the patients undergoing coronary angiography for angina and/or myocardial ischemia are found to have non-obstructive coronary artery disease (CAD). Coronary microvascular dysfunction (CMD) is increasingly recognized as a key contributor to angina and ischemic symptoms in this population.

This study aims to evaluate coronary physiology and microvascular function in patients with angina and ischemia who do not present with obstructive CAD.

The MiVa registry is a prospective, multicenter study in Italy enrolling patients with angina and ischemia detected by non-invasive testing, who were referred for coronary angiography and found to have non-obstructive CAD. All patients underwent an invasive assessment of coronary physiology, including measurements of coronary flow reserve (CFR), index of myocardial resistance (IMR) and fractional flow reserve (FFR). Acetylcholine provocation testing was strongly recommended.

Between September 2022 and November 2024, 400 patients were enrolled (46% female; mean age 64 ± 10 years) in 16 Italian institutions. The most prevalent cardiovascular risk factors were dyslipidemia (78%), hypertension (75%), family history of CAD (31%), and obesity (25%). The mean values of coronary physiological indices were CFR (2.9 ± 1.1), IMR (24 ± 19), and FFR (0.88 ± 0.08). CMD was diagnosed in 47% of patients. Based on pathophysiological classification, 37% had structural CMD (CFR <2.5, IMR >25), 28% had initial structural CMD (CFR >2.5, IMR >25), and 35% had functional CMD (CFR <2.5, IMR <25). Acetylcholine provocation testing was performed in 42% of patients, of whom 49% had a positive response. Specifically, 39% exhibited epicardial spasm, while 12% had microvascular spasm. Regarding angina perception, the Seattle Angina Questionnaire (SAQ7) score was 62.0 ± 18.3 in structural CMD, 64.1 ± 18.5 in initial structural CMD, 58.9 ± 18.2 in functional CMD, and 60.9 ± 16.8 in patients with non-cardiac pain (NCP). Patients with vasospastic angina (VSA) had a significantly lower SAQ7 scores (57.3 ± 16.5) compared to those with any form of CMD (63.1 ± 17.9, p<0.05), indicating more severe symptom perception in this subgroup. Interestingly, patients with both CMD and VSA (CMD + VSA) exhibited an even lower SAQ7 score (55.2 ± 19.6), suggesting an additive burden of symptoms. Furthermore, the invasive assessment of the coronary physiology leaded to a significant improvement of the medical therapy, potentially influencing both symptoms persistence and quality of life.

Microvascular dysfunction is present in nearly half of the patients with angina and ischemia referred for coronary angiography without obstructive CAD. These findings highlight the importance of coronary microvascular assessment in this population to better understand mechanisms underlying ischemic symptoms and guide targeted therapeutic strategies.For image description, please refer to the figure legend and surrounding text.