Coronary artery spasm (CAS) is characterized by vasoconstriction of coronary arteries leading to total or subtotal occlusion [1]. Traditionally recognized as a cause of vasospastic angina [2], CAS is also common in patients with chest pain without obstructive disease [3], in those with myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) [4], and it can even lead to sudden cardiac death [1]. In addition, CAS is associated with increased risk of adverse long-term outcomes such as recurrent angina, and particularly with vasospastic angina, major adverse cardiovascular events (MACE) [5,6].

Several possible underlying mechanisms for CAS have been investigated in previous studies [[7], [8], [9]]. These include endothelial dysfunction, vascular smooth muscle cell (VSMC) hyperactivity, inflammation, oxidative stress and autonomic nervous system. Utilizing the underlying mechanisms, acetylcholine (ACH) has been used for provocation of CAS [[10], [11], [12]]. ACH is typically injected in incremental doses until CAS occurs, and the dose of ACH required to elicit spasm can vary among patients [13,14], which could potentially be due to underlying differences in endothelial dysfunction and coronary artery plaque burden.

Although the ACH provocation test using incremental doses is widely utilized, investigations regarding prognostic implications of the dose at which a positive spasm response first occurs remains very limited. One study demonstrated that patients who responded at lower doses had a higher incidence of baseline spasm and more significant vessel narrowing in provocation [15]. This study showed enhanced vulnerability of CAS patients who responded to lower ACH dose. However, at that study, authors did not assess the long-term clinical outcomes of patients based on the first responsive dose. Another study investigated the clinical outcomes of patients with CAS of varying severity; however, the severity classification was not solely defined by the first responsive dose [16].

In this study, we aim to investigate the long-term clinical outcomes of CAS patients based on the initial dose of ACH required to provoke significant CAS.