Provocation of coronary spasm with ergonovine maleate: New test with results in 57 patients undergoing coronary arteriography

doi:10.1016/0002-9149(77)90060-1

The American Journal of Cardiology

Volume 40, Issue 4, October 1977, Pages 487-491

https://doi.org/10.1016/0002-9149(77)90060-1 Get rights and content

Abstract

Ergonovine maleate (Ergotrate) was given to 57 patients undergoing coronary arteriography for investigation of angina occurring at rest or without provocation when routine study showed normal arteries or insufficient occlusive disease to explain their symptoms. This provocative test induced coronary arterial spasm in 13 patients, 10 of whom had definite Prinzmetal's angina. The spasm was easily reversed with sub-lingually administered nitroglycerin. The spasm was occlusive or nearly occlusive in nine patients, and there was associated reproduction of the chest pain and S-T elevation similar to the spontaneous episodes. One patient with Prinzmetal's angina had S-T depression rather than elevation in association with the chest pain. The other three patients without Prinzmetal's angina had focal narrowing without coronary occlusion, reproduction of the chest pain or electrocardiographic changes. Of the 44 patients who did not demonstrate coronary spasm in response to ergonovine, 29 had normal coronary arteries and 15 had various degrees of atherosclerotic occlusive disease. We conclude that cautious administration of ergonovine maleate during coronary arteriography can be safely used to elicit coronary spasm in some patients who have insufficient fixed occlusive disease to explain their symptoms.

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Vasospastic angina (VSA) is characterized by episodes of rest angina that are responsive to short-acting nitrates and are attributable to coronary artery vasospasm. The condition is underdiagnosed as the provocation test is rarely performed. VSA, the most important component of non-obstructive coronary artery disease, can present with angina, be asymptomatic, or can even present with fatal arrhythmias and cardiac arrest. Although most patients with VSA respond well to vasodilating medications, prognosis does not improve as expected in most patients, suggesting the existence elusive prognostic factors and pathogenesis that warrant further exploration. Moreover, patients with either severe or refractory VSA barely respond to conventional treatment and may develop life-threatening arrhythmias or suffer sudden cardiac death during ischemic attacks, which are associated with immune-inflammatory responses and have been shown to achieve remission following glucocorticoid and immunoglobulin treatments. Our recent work revealed that inflammation plays a key role in the initiation and development of coronary spasms, and that inflammatory cytokines have predictive value for diagnosis. In contrast to the existing literature, this review both summarizes the theoretical and clinical aspects of VSA, and also discusses the relationship between inflammation, especially myocarditis and VSA, in order to provide novel insights into the etiology, diagnosis, and treatment of VSA.
Abnormal epicardial coronary vasomotor reactivity is associated with altered outcomes
2023, Archives of Cardiovascular Diseases
Citation Excerpt :
Whereas coronary atherosclerosis is overwhelmingly predominant, abnormal epicardial coronary vasomotor reactivity (ACVR) is an alternative mechanism of myocardial ischaemia [1,2]. ACVR could be associated with typical variant angina [3], but could also be responsible for more misleading clinical presentations, as demonstrated by studies using ergot derivatives (methylergonovine, methylergometrine) or acetylcholine as a provocative test (PT) [4,5]. PT-induced ACVR is highly prevalent in patients with an acute coronary syndrome (ACS) [6], but PT use varies considerably.
The prevalence and significance of abnormal epicardial coronary vasomotor reactivity (ACVR) in patients with symptoms compatible with myocardial ischaemia remains ill-defined. Our diagnostic strategy is to perform a provocative test (PT) in every patient presenting with chest pain at rest, for whom coronary angiography does not reveal significant epicardial coronary artery disease (≥ 70% stenosis by visual assessment).
To evaluate such a strategy in terms of incidence of ACVR, PT safety and patient outcomes.
The present study was a retrospective observational study with a median clinical follow-up of 5 years. The primary outcome was incidence of ACVR in patients with PT. Risk factors for ACVR and clinical follow-up were obtained, and the rate of major adverse cardiovascular and cerebrovascular events (MACCE; death, cardiovascular mortality, myocardial infarction, stroke and coronary revascularization) was reported.
ACVR was documented in 294 (12.4%) of the 2379 patients with PT, out of the 13,654 patients undergoing angiography. Patients with ACVR were more often female (43.9% vs. 30.0%; P < 0.0001), current smokers (37.4% vs. 8.7%; P < 0.0001) and had a suspected acute coronary syndrome (36.7% vs. 29.1%; P = 0.005) at admittance compared with patients without ACVR. During clinical follow-up, MACCE occurred more frequently in patients with (9.8%) than in those without (3.7%) ACVR (hazard ratio [HR] 4.15, 95% confidence interval [CI] 2.62–6.57; P < 0.0001), including more myocardial infarctions (4.0% vs. 0.4%; HR 17.8, 95% CI 6.41–49.5; P < 0.0001) and more myocardial revascularizations (6.1% vs. 1.1%; HR 9.36, 95% CI 4.67–18.74; P < 0.0001) compared with patients with normal PT at baseline.
ACVR is frequent in patients with symptoms compatible with myocardial ischaemia at rest, with no significant coronary stenosis. PT is a safe strategy to identify a population at high risk of recurrent ischaemic events.
Overview of the pharmacological spasm provocation test: Comparisons between acetylcholine and ergonovine
2017, Journal of Cardiology
Citation Excerpt :
Subsequently, Endo reported the coronary arteriogram and ventriculogram during attack induced by methacholine in Prinzmetal's variant angina in 1976 [19]. Schroeder et al. reported the clinical result of intravenous ER testing in 57 patients in 1977 and Waters et al. also reported the ER testing in coronary care unit in 1980 [20,21]. Curry et al. reported the similarities of ER-induced and spontaneous attacks of variant angina in 1979 [22].
The spasm provocation tests of ergonovine and acetylcholine have been employed in the cardiac catheterization laboratory. Ergonovine acts through the serotogenic receptors, while acetylcholine acts through the muscarinic cholinergic receptors. Different mediators may have the potential to cause different coronary responses. However, there are few reports concerning the coronary response between ergonovine and acetylcholine in the same patients. Acetylcholine is supersensitive for females; spasm provoked by ergonovine is focal and proximal, whereas provoked spasm by acetylcholine is diffuse and distal. We should use both tests as supplementary in the clinic because ergonovine and acetylcholine have self-limitations to induce coronary spasms during daily life. The maximal pharmacological doses, administration methods, and the angiographical positive definition are remarkably different for each institution in the world. We recommend the pharmacological spasm provocation tests as Class I in the guidelines in patients with vasospastic angina throughout the world.
Should an implanted defibrillator be considered in patients with vasospastic angina?
2014, Archives of Cardiovascular Diseases
Citation Excerpt :
Diagnosis remains difficult and is based on combined evidence, especially as coronary artery spasm (CAS) can occur in the absence of any chest pain [6–8]. Per-critical electrocardiographical signs are highly suggestive, but diagnosis is usually confirmed by spasm-provocation tests during coronary angiography [9], with ergonovine or acetylcholine administration [10]. Endothelial dysfunction associated with loss of nitric oxide secretion remains the main physiopathological factor implicated in vasospastic angina [11,12], but other pathways are being explored [13] without any effective alternative treatments.
Vasospastic angina is a frequent and well-recognized pathology with a high risk of life-threatening ventricular arrhythmias and sudden cardiac death. The diagnosis of vasospastic angina requires the combination of clinical and electrocardiographic variables and the results of provocation tests, such as ergonovine administration. Smoking cessation is the first step in the management of vasospastic angina. Optimal medical treatment using calcium-channel blockers and/or nitrate derivatives can provide protection, but life-threatening ventricular arrhythmias may occur despite optimal medical treatment and several years after the start of treatment. In this review, we evaluate the role of implantable defibrillators as a complement to optimal medical management in patients with life-threatening ventricular arrhythmias due to vasospastic angina; this role is not well characterized in the literature or guidelines. We discuss the role of implantable defibrillators in secondary prevention in light of three recent cases managed in our departments and a review of the literature. An implantable defibrillator was implanted in two of the three cases of vasospastic angina with ventricular arrhythmias that we managed. We considered secondary prevention by implantable defibrillator to be justified even in the absence of any obvious risk factor. Ventricular arrhythmias recurred during implantable defibrillator follow-up in the two patients implanted.
In patients with life-threatening ventricular arrhythmias due to vasospastic angina, an implantable defibrillator should be considered because of the risk of recurrence despite optimal medical management.
L’angor spastique est une pathologie fréquente et connue de longue date ayant une morbimortalité non-négligeable. Il existe notamment un risque important de mort subite. Le diagnostic repose sur l’association de signes cliniques, électrocardiographiques et par la confirmation diagnostic par un test de provocation au méthergin. L’arrêt du tabagisme est le point essentiel du traitement. Il est associé à un traitement médicamenteux anti-spastique composé d’inhibiteurs calciques et/ou de dérivés nitrés. Malheureusement cette prise en charge est insuffisante et le risque de mort subite reste présent durant plusieurs années après que le diagnostic ait été porté. Dans cette revue, nous évaluons la place du défibrillateur automatique implantable en sus du traitement médicamenteux chez des patients ayant présenté une mort subite récupérée suite à un spasme coronaire dont la place reste floue.
Nous discutons cette place à la lumière de trois cas que nous avons pris en charge et d’une revue complète de la littérature.
Raynaud's Phenomenon
2012, Vascular Medicine: A Companion to Braunwald's Heart Disease: Second Edition

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^☆: This work was supported in part by Grant HL-5866 and Program Project Grant 1-PO 1-HL-15833 from the National Institutes of Health, Bethesda, Maryland.

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Clinical studyProvocation of coronary spasm with ergonovine maleate: New test with results in 57 patients undergoing coronary arteriography☆

Abstract

Chest

Am J Cardiol

Am J med

Am J Cardiol

Am J Cardiol

Chest

Am J Cardiol

Coronary artery spasm in Prinzmetal's angina. Documentation by coronary arteriography

N Engl J Med

Clinical study
Provocation of coronary spasm with ergonovine maleate: New test with results in 57 patients undergoing coronary arteriography☆