What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Angina with nonobstructive coronary arteries (ANOCA) (n=947). Intervention: Comprehensive interventional diagnostic procedure (IDP). Primary outcome: Prevalence of coronary endotypes (epicardial vasospasm, microvascular spasm, and coronary microvascular dysfunction) and their distribution by age and sex.

What does this research mean for the field?

Coronary vasospasm and coronary microvascular dysfunction frequently coexist in patients with ANOCA, exhibiting distinct age- and sex-related distribution patterns where microvascular spasm is more prevalent in women and CMD is linked to older age and female sex. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

June 11, 2026Journal of the American Heart AssociationOpen Access

Comprehensive Endotyping of Patients With Angina and Nonobstructive Coronary Arteries: A Report From the J‐CMD

Q: What are the key findings of this study?

Among patients with ANOCA, epicardial vasospasm was present in 49.4%, and the coexistence of coronary microvascular dysfunction with coronary spasm was significantly more common in women than men (10.8% vs 6.0%).

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Key result

Epicardial vasospasm affects ~49% of ANOCA patients, with CMD-spasm overlap occurring twice as often in women.

n=947

Why the study?

Despite recommendations for comprehensive invasive testing in ANOCA, prospective data on the prevalence and interplay of coronary vasospasm and CMD endotypes remain limited.

Key Points

To investigate the prevalence, clinical correlations, and overlap of epicardial vasospasm, microvascular spasm, and coronary microvascular dysfunction in patients with angina and nonobstructive coronary arteries.
Analyzed data from the prospective, multicenter nationwide J-CMD registry (UMIN000047609) comprising 947 patients (527 women and 420 men) with angina and nonobstructive coronary arteries.
Patients underwent standardized intracoronary functional testing, including acetylcholine- or ergonovine-based spasm provocation and coronary flow reserve assessment.
Epicardial vasospasm was diagnosed in 49.4% (468 patients) and microvascular spasm in 20.0% (189 patients), with microvascular spasm occurring significantly more frequently in women than in men (23.9% versus 15.0%, P=0.003).
Coronary microvascular dysfunction (LAD CFR <2.0) was present in 13.6% (129 patients), coexisting with epicardial vasospasm in 38.0% and microvascular spasm in 25.6% of affected individuals.
Coexistence of coronary microvascular dysfunction and coronary spasm was significantly higher in women than in men (10.8% versus 6.0%, P=0.011), with endotype distribution varying significantly across age tertiles in women (P=0.019) but not in men (P=0.456).

Study Design

Type

Cross-Sectional (n=947)

Multicenter

Yes

Structured PICO

Population

947 patients with angina and nonobstructive coronary arteries who underwent comprehensive interventional diagnostic procedures in a Japanese multicenter registry.

Exposure

Comprehensive interventional diagnostic procedure (IDP) including spasm provocation testing (intracoronary acetylcholine or ergonovine) and physiological microvascular functional assessment (bolus thermodilution for CFR and IMR).

Outcome

Prevalence, clinical correlations, and overlap of epicardial vasospasm, microvascular spasm, and coronary microvascular dysfunction (defined as CFR <2.0) endotypes stratified by sex and age.

In patients with ANOCA, comprehensive invasive physiological testing demonstrates that coronary vasospasm and microvascular dysfunction are highly prevalent and frequently coexist, highlighting the need for accurate endotyping to guide tailored therapy.

Limitations

Observational, cross-sectional nature demonstrates associations but not causality, preventing determination of prognostic implications.
Recruitment from specialized centers may introduce selection bias toward patients with more severe or refractory symptoms.
Coronary microvascular dysfunction definition relied solely on a CFR <2.0 without incorporating IMR.
Conducted exclusively in a Japanese population, which may limit generalizability to other ethnic groups with different vasospasm susceptibility.
Sequence of spasm provocation testing and microvascular functional assessment was not standardized.
Physiological assessment was limited to the left anterior descending artery, potentially underestimating microvascular dysfunction in other territories.
Testing sequence (spasm provocation vs. vasodilator-based functional assessment) was not prespecified and left to operator discretion
Multivessel spasm provocation testing was performed at operator discretion and not systematically in all patients
Specific hyperemic agent used for physiological assessment was not systematically recorded

Implication

Endotype coexistence varies by sex in ANOCA; extends observational data but leaves open therapeutic implications.

Abstract

BACKGROUND: Angina with nonobstructive coronary arteries (ANOCA) is frequently driven by coronary vasospasm and coronary microvascular dysfunction (CMD). Despite recommendations for comprehensive invasive testing to phenotype ANOCA, prospective data on the prevalence and interplay of these endotypes remain limited. We aimed to investigate the prevalence, clinical correlations, and overlap of epicardial vasospasm, microvascular spasm, and CMD, defined by a coronary flow reserve <2.0. METHODS: We analyzed the data from a prospective, multicenter nationwide registry of the J-CMD (Japanese Association of Coronary Microvascular Dysfunction; UMIN000047609). Patients with ANOCA underwent standardized intracoronary functional testing, including acetylcholine-based spasm provocation and coronary flow reserve assessment. The distribution of the endotypes (epicardial vasospasm, microvascular spasm, isolated CMD, and CMD with spasm) was investigated according to sex and age tertiles. RESULTS: =0.011). While microvascular spasm was more prevalent in women, CMD was associated with older age, female sex, hypertension, and diabetes. Intriguingly, the prevalence of these endotypes varied with age in women, a pattern not observed in men. CONCLUSIONS: Among patients with ANOCA, coronary vasospasm and CMD were prevalent and frequently coexisted, demonstrating distinct sex- and age-related patterns. These findings offer novel insights into the heterogeneous pathophysiology of ANOCA and reinforce the importance of comprehensive invasive assessment in establishing a precise diagnosis and guiding targeted therapy.

Discussion

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Published by Journal of the American Heart Association · CC BY-NC-ND

Cite This Study

Hada et al. (2026) conducted a cross-sectional in Angina with nonobstructive coronary arteries (ANOCA) (n=947). Comprehensive interventional diagnostic procedure (IDP) was evaluated on Prevalence of coronary endotypes (epicardial vasospasm, microvascular spasm, and coronary microvascular dysfunction) and their distribution by age and sex. Among patients with ANOCA, epicardial vasospasm was present in 49.4%, and the coexistence of coronary microvascular dysfunction with coronary spasm was significantly more common in women than men (10.8% vs 6.0%).

synapsesocial.com/papers/6a2a508980c8f91e7f39d107 https://doi.org/10.1161/jaha.125.048016

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Implication

Endotype coexistence varies by sex in ANOCA; extends observational data but leaves open therapeutic implications.

Comprehensive Endotyping of Patients With Angina and Nonobstructive Coronary Arteries: A Report From the J‐CMD

Key Points

Study Design

Structured PICO

Limitations

Implication

Abstract

Discussion

Figures from the paper

Cite This Study

Comprehensive Endotyping of Patients With Angina and Nonobstructive Coronary Arteries: A Report From the J‐CMD

Key Points

Study Design

Structured PICO

Limitations

Implication

Abstract

Discussion

Figures from the paper

Cite This Study

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