Coronary spastic angina (CSA) refers to a transient spastic constriction of the main trunk of the subepicardial coronary artery (coronary artery) and its major branches, resulting in varying degrees of lumen occlusion and transmural or non-transmural ischemia in the innervated myocardial region, which is manifested by ST-segment elevation or depression in the corresponding leads on the electrocardiogram and clinical symptoms of ischemic chest pain [1]. Epidemiological studies have shown that the incidence of CSA is not low, and it is a common disease in Asian countries. 2000, a multicenter study of 2251 patients with angina pectoris in Japan showed that the detection rate of coronary spasm was as high as 40.9%.1 The evolution of the concept from variant angina to vasospastic angina: The concept of variant angina was first proposed by Prinzmetal in 1959. The concept of variant angina was first proposed by Prinzmetal in 1959, and the name reflects the difference between the clinical manifestations of the disease and exertional angina, that is, there are “variations” in risk factors, clinical manifestations, electrocardiographic changes and treatment methods. The core “variation” is “transient ST-segment elevation detected during the onset of resting chest pain”, which is the key to the diagnosis of variant angina. With the development of coronary angiography and drug provocation tests, studies have confirmed that the pathogenesis of variant angina is coronary artery spasm. When incomplete occlusion of coronary spasm leads to non-transmural ischemia, the clinical presentation is chest pain with ST-segment depression; when complete occlusion of coronary spasm leads to transmural ischemia, the clinical presentation is chest pain with ST-segment elevation (i.e., classic variant angina). Surprisingly, ST-segment depression is more common in coronary spasm than in elevation [2-4], and Ong et al [5] found in the CASPAR study that none of the patients with a positive ACH provocation test had the classical phenomenon of “chest pain with transient ST elevation” during telemetry in the CCU. Thus, the concept of variant angina is narrower and corresponds to a rare subtype of vasospastic angina, whereas CAS is broader and more objective, and its nomenclature is more conducive to the diagnosis and treatment of the disease. However, because of the relatively few domestic stimulation tests, the diagnosis of CAS still relies largely on clinical and electrocardiographic features, so the concept of variant angina will continue to be used for a long time in the future.2. Vascular spasm is widely involved in the development of coronary artery disease: originally, it was thought that coronary spasm often occurred on the basis of normal coronary arteries. However, it was found that there are often different degrees of stenosis at the site of coronary spasm. Even when no stenotic lesions (so-called normal coronary arteries) were found on coronary angiography, intravascular ultrasonography showed clear atheromatous lesions at the site of spasm. Further studies found that coronary segments with drug-induced spasm were prone to plaque progression, suggesting that spasm in turn may promote plaque formation. The possible mechanism is that reduced or even stagnant blood flow during coronary spasm activates platelets and the coagulation system, triggering vascular smooth muscle proliferation. As early as the 1970s, it was recognized that coronary spasm is not only a key component of variant angina, but is also involved in the development of many types of acute coronary syndromes such as unstable angina, myocardial infarction, and sudden cardiac death. In many patients with acute myocardial infarction, emergency coronary angiography shows only minimal lesions; or intracoronary injection of nitroglycerin alone can recanalize completely occluded coronary arteries, suggesting that spasm may play an important role.The CASPAR study [5] included 488 patients with chest pain with suspected acute coronary syndromes, and coronary angiography revealed no criminal lesions in 1/3 of patients, of whom 50% had a positive ACH-initiated coronary spasm test was positive. Acute coronary syndromes share a common pathologic basis, i.e., thrombosis after plaque rupture. Coronary spasm may be a major trigger for vulnerable plaque rupture: spasm produces shear forces applied to the coronary lesion, causing endothelial cell rearrangement and fibrous cap wrinkling or rupture, exposing the highly coagulable plaque contents to blood flow and stimulating thrombosis and lumen occlusion. In addition, patients with coronary artery spasm often have alterations such as hypercoagulation, decreased fibrinolytic activity, and activation of platelets and adhesion molecules, which constitute the thrombus-prone state of acute coronary syndrome. The endothelial insufficiency and vasoactive substances released during platelet activation present during the development of acute coronary syndrome can lead to the development of coronary artery spasm. Therefore, in addition to plaque stabilization and antithrombotic therapy, anti-vasospasm therapy is also important for the prevention and treatment of acute coronary syndromes. Although the domestic medical community does not pay enough attention to this, with the widespread use of calcium antagonists (CCB) in hypertension, it may objectively also play a role in the prevention and treatment of coronary spasm.3, vasospastic angina may be an allergic disease: the etiology of coronary spasm varies from person to person, and the pathogenesis is not completely clear, but it is generally believed to be related to vascular endothelial dysfunction, intracellular Ca2 + concentration, oxidative stress, abnormal autonomic tone, and genetic factors. In addition, there is a less familiar mechanism hypothesis, namely, allergic angina. braunwald had earlier speculated that allergic reactions could act on coronary smooth muscle through mediators such as histamine and leukotrienes to induce CSA. kounis and zavras linked classical angina, chest pain and concurrent allergic reactions, increased inflammatory mediators, and proposed “There are two types of Kounis syndrome. type 1 is an acute allergic attack that triggers CAS, with normal or elevated cardiac enzymes and troponin, and the patient often has no risk factors for coronary artery disease. type 2 is an acute allergic attack that triggers plaque erosion or The clinical manifestation is acute myocardial infarction, and patients often have pre-existing coronary atherosclerotic disease. The inflammatory mediators, cytokines and chemokines released during allergic reactions are potent vasospasmogenic substances and are the pathophysiological basis for recurrent acute coronary events and allergic or hypersensitivity reactions in patients with Kounis syndrome. Tsigkas et al [6] and Kumar et al [7] suggested that intracoronary mast cell activation is a novel mechanism of coronary spasm and that there is a threshold for the release of spasmogenic substances (histamine, fibrinolytic enzymes, chymotrypsin, leukotrienes, thromboxane, etc.) that, once exceeded, can trigger CAS and/or plaque rupture. Although clinically allergic reactions rarely result in chest pain or ST-segment changes, Kounis syndrome is not a rare disease and is more likely than expected. Allergic substances such as aspirin, lansoprazole, ACE inhibitors, contrast agents, amoxicillin, ibuprofen, and cefuroxime have been reported [8-15], and placements such as stents can also provoke local hypersensitivity reactions and vasospasm. Therefore, patients with CSA should be carefully questioned about the history of allergic reactions, and antibody and skin tests should be performed if allergy is suspected to be related. In contrast, patients with systemic hypersensitivity reactions should be selectively evaluated for markers of myocardial injury such as cardiac enzymes and troponin. If allergic angina is suspected, mast cell stabilizer therapy may be beneficial [7]. Drug provocation tests are the primary means of diagnosing vasospastic angina: although resting chest pain combined with transient ST-segment elevation is highly specific for the diagnosis of CAS and can be directly diagnosed clinically [16], ST-segment depression is more common than elevation in coronary spasm, and only a very small number of patients have timely ECG examinations and detection of ST-segment elevation. Other conventional diagnostic tools are also of limited value: ambulatory ECG monitoring does not always capture CAS episodes; exercise plate tests are of limited value because they rarely occur during the day [2]; and the probability of detecting spontaneous spasm on conventional coronary angiography is extremely low. Therefore, for a very large proportion of patients, only drug provocation tests at coronary angiography can accurately diagnose CAS, so called “seeing is believing” [4]. In contrast, the duration of action of ACH is extremely short, and the inspired spasm can resolve itself and disappear after 1 to 2 min without the use of nitrates. In contrast, ergometrine induced spasm must be eliminated with nitroglycerin, so it has an effect on the excitation test of another vessel. Therefore, drug provocation tests are often performed with ACH rather than ergometrine [17].Ong et al [18] routinely performed ACH provocation tests in patients with chest pain without significant coronary stenosis in more than 500 cases per year without any complications, noting that the most important safety procedure is to increase the dose of ACH step by step. Because drug provocation tests can provoke uncontrollable vasospasm in extreme cases, leading to lethal arrhythmias or even sudden death [16], the attitude toward provocation tests is conservative in China, where the doctor-patient relationship is in transition. However, given the commonness of coronary spasm and the specificity of treatment, ACH provocation trials should be actively and steadily promoted in China, and eventually ACH provocation trials should be routinely performed in patients with chest pain without significant coronary stenosis to provide conditions for further epidemiological and diagnostic studies of CAS in China. New advances in treatment: drug therapy is the basis, and device therapy is still controversial. Elimination of smoking and other triggers is the prerequisite for treatment, and CCB- and nitrate-based drugs are the cornerstone of treatment. Most patients with coronary artery spasm are effectively treated with medications and have a good prognosis if they are not combined with significant coronary stenosis [19]. However, even with adequate pharmacological treatment, 5%-30% of patients continue to have angina attacks or even myocardial infarction and, in rare cases, sudden arrhythmic death. There is no consensus on whether and when to use stents, buried cardioverter-defibrillators (ICDs), pacemakers and other treatments. In recent years, there have been many reports of coronary stenting for drug-refractory variant angina. Theoretically, since coronary stenotic lesions are likely to be the pathological basis for vasospasm, stent placement in coronary lesion segments, especially those consistent with episodes of ECG or confirmed by drug provocation tests, may be effective in preventing re-spasm and angina attacks. However, there are two major controversies in this approach: the site of spontaneous arterial spasm and the site of stimulated spasm may be different; spasm may occur in the microvasculature rather than in the large subepicardial vessels; Mohri et al [20] analyzed 117 patients with CAS, and although all induced chest pain and ischemic ECG changes, 25% failed to induce spasm in the large subepicardial vessels and concluded that microvascular spasm was present. Therefore, the effectiveness of stent placement to prevent spasm needs to be further verified.The incidence of lethal arrhythmias such as AV block, sinus block, sinus arrest, ventricular tachycardia, and ventricular fibrillation during CSA is as high as 5% to 10% [21]. Coronary spasm may be one of the main causes of sudden cardiac death in patients without organic heart disease. Although a few people still insist on CAS as a drug curable disease and believe that patients with combined arrhythmias (even lethal ones) do not need to be fitted with an ICD [4]. However, pharmacological treatment does not eliminate the occurrence of malignant arrhythmias. Therefore risk stratification may be the key to the problem: screening patients at high risk of sudden death for ICD or pacemaker implantation. Patients with angina-associated syncope and coronary artery spasm with documented severe arrhythmias are now considered to be at greater risk for sudden cardiac death. In addition, diffuse ST-segment elevation on conventional electrocardiograms [2, 22] or vasospasm affecting multiple coronary branches are also likely to provoke ventricular fibrillation and sudden cardiac death. In these high-risk patients, ICD placement may be considered as a precautionary measure.