Elsevier

The Lancet

Volume 351, Issue 9110, 18 April 1998, Pages 1165-1169
The Lancet

Early Report
Angina pectoris caused by coronary microvascular spasm

https://doi.org/10.1016/S0140-6736(97)07329-7Get rights and content

Summary

Background

Microvascular angina can occur during exercise and at rest. Reduced vasodilator capacity of the coronary microvessels is implicated as a cause of angina during exercise, but the mechanism of angina at rest is not known. Our aim was to test the hypothesis that primary hyperconstriction (spasm) of coronary microvessels causes myocardial ischaemia at rest.

Methods

Acetylcholine induces coronary artery spasm in patients with variant angina. We tested the effects of intracoronary acetylcholine at graded doses in 117 consecutive patients with chest pain (at rest, during exertion, or both) and no flow-limiting (>50%) organic stenosis in the large epicardial coronary arteries. We also assessed the metabolism of myocardial lactate during acetylcholine administration in 36 of the patients by measurement of lactate in paired blood samples from the coronary artery and coronary sinus vein.

Findings

Of the 117 patients, 63 (54%) had large-artery spasm, 29 (25%) had microvascular spasm, and 25 (21%) had atypical chest pain. The 29 patients with microvascular spasm developed angina-like chest pain, ischaemic electrocardiogram (ECG) changes, or both spontaneously (two patients) or after administration of acetylcholine (27 patients) without spasm of the large epicardial coronary arteries. Testing of paired samples of arterial and coronary sinus venous blood showed that lactate was produced during angina attack in nine of 11 patients with microvascular spasm. There was more women (p < 0·01) and fewer coronary risk factors (p < 0·01) in patients with microvascular spasm than in those with large-artery spasm.

Interpretation

Coronary microvascular spasm and resultant myocardial ischaemia may be the cause of chest pain in a subgroup of patients with microvascular angina.

Introduction

Angina pectoris occurs in patients with angiographically normal or slightly diseased coronary arteries and no coronary artery spasm. Such patients have a generic diagnosis of microvascular angina or syndrome X.1, 2 Blunted coronary-vasodilator responses to metabolic and pharmacological stimuli have been shown in selected cases of microvascular angina.3, 4, 5, 6 Inadequate micro-vascular dilation in response to increased demand for myocardial oxygen could account for exercise-induced myocardial ischaemia in these patients.4, 7 A large proportion of patients with syndrome X, however, have angina at rest.8 We postulate that primary microvascular hyperconstriction (spasm) could be the cause of myocardial ischaemia in this group of patients.

Acetylcholine can induce coronary artery spasm with high sensitivity and specificity in patients with variant angina caused by spasm of the large epicardial arteries.9, 10 The aim of our study was to test the hypothesis that myocardial ischaemia might result from spasm of the coronary microvessels in a subgroup of patients with microvascular angina. Because visualisation of spasms of the coronary microvessels by conventional arteriography is difficult, we examined whether intracoronary administration of acetylcholine induced chest pain, ischaemic ST changes, or both without spasm of the epicardial artery in patients who had a history of chest pain and angiographically normal or slightly diseased coronary arteries. We also assessed the metabolism of myocardial lactate during acetylcholine administration.

Section snippets

Methods

The study protocol was approved by the Institutional Human Research Committee of Kyushu University. We obtained written informed consent from each patient before enrolment.

Between September, 1994, and January, 1997, consecutive patients admitted to our department for chest pain underwent diagnostic coronary arteriography. Cardiac catheterisation was done in the fasting state after administration of oral diazepam 5 mg. All cardiovascular drugs, apart from sublingual nitroglycerin, were

Results

We enrolled 117 consecutive patients (58 men, 59 women, median age 63 [IQR 54–68] years) with chest pain at rest, on exertion, or both and no flow-limiting (>50%) organic stenosis of the large epicardial coronary arteries. We classified the patients as having large-artery spasm, microvascular spasm, or atypical chest pain. 63 (54%) patients had large-artery spasm—ie, coronary artery spasm in one or more of the large epicardial coronary segments, spontaneously (six patients) or after

Discussion

Of 117 consecutive patients who had a history of chest pain at rest, on exertion, or both without atherosclerotic stenosis of greater than 50% in the large epicardial coronary arteries, we identified 29 in whom myocardial ischaemia probably resulted from microvascular spasm. The myocardial-lactate-extraction ratio was examined in 11 of these patients and production of lactate was confirmed in nine patients, which indicates that they developed myocardial ischaemia.

Acetylcholine is used to induce

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