Clinical Value of Coronary microvascular dysfunction (CMD) and Vasospastic Angina (VSA) Testing: JACC Advances November 2025

Coronary microvascular dysfunction (CMD) and vasospastic angina (VSA) are common and clinically important contributors to chest pain in patients with non-obstructive coronary arteries, and invasive physiologic testing offers meaningful guidance during routine care. The FlowLab study, published in JACC Advances, showed that CMD/VSA testing is practical to perform, integrates smoothly into standard catheterization workflows, and frequently influences management at the time of the procedure. For clinicians, this reinforces the value of looking beyond angiography when evaluating persistent angina.

Angina with non-obstructive coronary arteries (ANOCA) – Cardiologists’ Challenge

Angina with non-obstructive coronary arteries (ANOCA) is a familiar challenge in cardiovascular practice. These patients often continue to experience symptoms despite “normal” angiograms, leading to uncertainty regarding the true cause of their discomfort. CMD and VSA are recognized mechanisms behind these presentations, but they are often missed because they cannot be seen on standard imaging. The study provided a timely look at how U.S. centers are incorporating coronary functional testing into everyday practice and how such testing improves diagnostic clarity for complex angina.

Study Overview

In this multicenter, real-world assessment, clinicians performed CMD and VSA testing whenever they felt it clinically appropriate, making the results directly relevant to daily patient care rather than controlled research environments. Fourteen U.S. centers participated, using bolus thermodilution to measure coronary flow reserve (CFR) and index of microcirculatory resistance (IMR), with optional acetylcholine provocation for vasospasm. Operators had full discretion over when to perform these evaluations—before or after angiography, or alongside other physiologic assessments. This flexible approach ensured that the data reflected true practice patterns rather than trial-specific protocols. A total of 253 procedures were included in the analysis.

Key Findings

The results revealed how frequently clinically meaningful abnormalities are present in patients with nonobstructive coronary disease.

• Impaired CFR was seen in 43% of the cohort, while 28% had elevated IMR—both markers of CMD. Vasospasm testing, performed in roughly half the patients, identified positive responses in 57%, highlighting how commonly vasospastic mechanisms contribute to symptoms.
• CMD and VSA occurred individually or in combination, explaining why standard angiography alone often fails to provide a full diagnostic picture.
• Importantly, functional testing had direct therapeutic consequences. Patients with elevated IMR were much more likely to receive additional antianginal therapy (61% vs 29%), and preventive measures were frequently intensified based on physiologic abnormalities rather than angiographic appearance.

Testing itself was efficient, typically completed in about ten minutes and easily incorporated into various procedural workflows.

Potential Clinical Implications for Interventionalists

Clinically, the implications are significant. Relying solely on angiography leaves many patients without a clear diagnosis, potentially prolonging symptoms and contributing to repeated evaluations. By integrating CMD and VSA testing into routine invasive pathways, clinicians can identify the true drivers of ischemic symptoms and tailor treatment accordingly. Although the study reflects real-world variability and observational limitations, the consistent presence of physiologic abnormalities and the immediate shift in management they prompt—supports the growing role of coronary functional testing in modern chest pain evaluation. The FlowLab experience underscores that in many patients, the answers lie beyond the angiogram, and targeted physiologic assessment helps bridge that diagnostic gap.

Reference: Bergmark BA, Shah S, Toleva O, Maksoud A, Kearney KE, Kobayashi Y, Fahed AC, Hashim H, Sharma A, Blair J, Chehab BM, Kanakadandi U, Jaffer FA, Jeremias A, Gross DA, Baljepally R, Ali ZA, Reddy G, Shlofmitz E, Moussa I, Zhang S, Murphy SA, Ahmed S, Spinelli J, Meinen J, Rapoza RJ, Sabatine MS. Multicenter Prospective Assessment of Coronary Microvascular Dysfunction: Primary Results of the FlowLab Study. JACC Adv. 2025 Sep 26;4(11 Pt 1):102179. doi: 10.1016/j.jacadv.2025.102179. Epub ahead of print. PMID: 41014809; PMCID: PMC12510197.