Original Research

DOI: 10.4244/EIJ-D-25-00277

Chest pain patterns and coronary microvascular function in non-obstructive coronary artery disease

Kai Nogami1, MD; Yoshihisa Kanaji2, MD, PhD; Takumi Toya3, MD; Jaskanwal Deep Singh Sara1, MBChB; Claire E. Raphael1, MBBS, PhD; Rajiv Gulati1, MD; Abhiram Prasad1, MD; Tsunekazu Kakuta2, MD, PhD; Lilach O. Lerman1, MD, PhD; Amir Lerman1, MD

Abstract

Background: Coronary microvascular dysfunction (CMD) is a common cause of chest pain (CP) in patients with angina and non-obstructive coronary arteries (ANOCA). Although both CMD and CP have distinct classifications, the relationship between them remains insufficiently understood.

Aims: This study investigated the relationship between CMD and CP patterns and their prognostic impact in ANOCA patients.

Methods: Serial patients with ANOCA who underwent coronary reactivity testing were enrolled. CP patterns were categorised as exertional, resting, or both. Endothelium-dependent CMD was defined as a <50% change in coronary blood flow (CBF) with intracoronary acetylcholine infusion and endothelium-independent CMD as a coronary flow reserve (CFR) <2.5 during adenosine-induced hyperaemia. Microvascular function and prognosis were compared between patients with exertional CP and resting CP.

Results: Among 1,264 patients, the median age was 52 years, and 65.3% were women; 23.7% had exertional CP, 27.0% resting CP, and 49.4% both. Exertional CP patients had a lower CFR and a higher prevalence of endothelium-independent CMD compared to resting CP patients (2.8 vs 3.0; p=0.014, 32.1% vs 24.4%; p=0.034). Exertional CP patients showed a significantly lower CBF increase in response to acetylcholine (38.2% vs 50.7%; p=0.015). Survival analysis over a median 7-year follow-up revealed that endothelium-independent CMD significantly increased risk in exertional CP patients (p=0.002) but not in resting CP patients (p=0.388).

Conclusions: ANOCA patients with exertional CP demonstrated worse microvascular function than those with resting CP, with endothelium-independent CMD showing a significant prognostic impact. Exertional CP patients may benefit more from treatment strategies specifically targeting CMD.

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Volume 21 Number 17
Sep 1, 2025
Volume 21 Number 17
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