Haemodynamic characterisation of different endotypes in coronary artery vasospasm in reaction to acetylcholine

Rutger G T Feenstra; Coen K M Boerhout; Caitlin E M Vink; Janneke Woudstra; Marianne E Wittekoek; Guus A de Waard; Yolande Appelman; Etto C Eringa; Koen M J Marques; Robbert J de Winter; Tim P van de Hoef; Marcel A M Beijk; Jan J Piek

doi:10.1016/j.ijcha.2022.101105

Haemodynamic characterisation of different endotypes in coronary artery vasospasm in reaction to acetylcholine

Int J Cardiol Heart Vasc. 2022 Aug 13:42:101105. doi: 10.1016/j.ijcha.2022.101105. eCollection 2022 Oct.

Affiliations

¹ Amsterdam UMC, Heart Centre, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
² HeartLife klinieken, Utrecht, the Netherlands.
³ Amsterdam UMC, Amsterdam Cardiovascular Sciences, Department of Physiology, Amsterdam UMC, Amsterdam, the Netherlands.
⁴ Maastricht University, Cardiovascular Research Institute Maastricht, Department of Physiology, Maastricht, the Netherlands.

Abstract

Background: Vasoreactivity testing with high-dose acetylcholine is considered vasospasm provocation and low-dose as endothelial function testing.

Aims: To assess the changes in reaction to low- and high-dose acetylcholine in the endotypes of CAS as defined by the Coronary Vasomotor Disorders International Study Group (COVADIS) working group.

Methods: Changes in coronary epicardial diameter, coronary blood flow (CBF) and vascular resistance were determined at low-dose acetylcholine.

Results: A total of 88 ANOCA patients were included in this analysis. In the negative group (n = 14) incremental infusion of acetylcholine produced a progressive increase in CBF (p = 0.008). In reaction to low-dose acetylcholine, the epicardial vasospasm group (n = 30) is characterised by epicardial vasoconstriction that is significantly more severe compared to the microvascular vasospasm group (p = 0.004)(n = 23). The equivocal group (n = 21) is characterised by an increase in CBF and reduction in vascular resistance that are both significantly different compared to the epicardial vasospasm group (p = 0.036 and p = 0.007, respectively). High-dose acetylcholine decreased epicardial diameter and CBF significantly in the epicardial vasospasm, microvascular vasospasm and in the equivocal group (all p < 0.05. Vascular resistance increased significantly in the epicardial vasospasm group (p < 0.001) and equivocal group (p = 0.009).

Conclusion: In reaction to low-dose acetylcholine the negative and equivocal endotype has haemodynamic changes that suggest intact endothelium. In reaction to high-dose acetylcholine the epicardial vasospasm, microvascular vasospasm and equivocal endotype have hemodynamic changes that suggest VSMC-hyperreactivity. These results suggest that the equivocal endotype is a positive test comparable to microvascular vasospasm in the presence of normal endothelial function.

Keywords: ANOCA; ANOCA, angina and no obstructive coronary artery disease; APV, average peak velocity; Acetylcholine; CAS, coronary artery spasm; CBF, coronary blood flow; COVADIS, Coronary Vasomotor Disorders International Study Group; Coronary artery spasm; Haemodynamic changes; ICFT, invasive coronary vasomotor function testing; QCA, quantitative coronary angiography; VSMC, vascular smooth muscle cells.