Crooijmans C, Jansen Tijn P J, Meeder Joan G, Paradies Valeria, de Vos Annemiek M J, Woudstra Pier, Vossenberg Tessel N E, van de Hoef Tim P, Vos Nicola S, Olde Bijvank Els G M, van den Oord Stijn C H, Winkler Patty, Meuwissen Martijn, Widdershoven Jos W M G, Arkenbout E Karin, Stoel Martin G, Appelman Yolande, Beijk Marcel A M, Cetinyurek-Yavuz Aysun, den Ruijter Hester M, Elias-Smale Suzette E, van Royen Niels, Dimitriu-Leen Aukelien C, Damman Peter
Department of Cardiology Radboud University Medical Centre Nijmegen The Netherlands.
Department of Cardiology VieCuri Medical Centre North-Limburg The Netherlands.
J Am Heart Assoc. 2025 Jan 21;14(2):e037913. doi: 10.1161/JAHA.124.037913. Epub 2025 Jan 16.
A coronary function test (CFT) is the recommended diagnostic test to identify coronary vasomotor dysfunction as a cause of symptoms in patients with angina and nonobstructive coronary arteries (ANOCA). Acetylcholine is the commonly used pharmacological agent for spasm provocation. We aimed to investigate an association between severity of symptoms and provocative acetylcholine dose.
We included ANOCA patients undergoing clinically indicated CFT from the Netherlands Registry of Invasive Coronary Vasomotor Function Testing: NL-CFT. Patients with epicardial spasm (n=251) were divided according to acetylcholine spasm triggering dose: low (2-20 mcg, EpiLOW), middle (100 mcg, EpiMIDDLE) or high (200 mcg, EpiHIGH). Patients with microvascular spasm (n=157) were analyzed irrespective of triggering dose. The patient groups were compared to each other and to a control group with negative CFT results (n=101). We assessed mean Seattle Angina Questionnaire angina frequency and summary scores at baseline and follow-up and the proportion of patients improving or deteriorating. An inverse relationship between provocation dosage and angina frequency at baseline was found in epicardial spasm: the lower the triggering dose, the more frequently patients experienced angina (EpiLOW 48±20, EpiMIDDLE 53±21, EpiHIGH 57±19, microvascular spasm 61±21, controls 64±21, overall =0.003). A trend was seen toward most patients improving in the high triggering dose group, and most patients deteriorating in the low triggering dose group.
A significant dose-dependent relationship between spasm provocation and anginal complaints exists. Acetylcholine provocation dose could be incorporated as a risk stratification factor or surrogate outcome in future clinical trials.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT06083155.
冠状动脉功能测试（CFT）是推荐用于识别冠状动脉血管舒缩功能障碍的诊断测试，冠状动脉血管舒缩功能障碍是心绞痛和非阻塞性冠状动脉疾病（ANOCA）患者症状的病因。乙酰胆碱是常用的诱发痉挛的药物。我们旨在研究症状严重程度与诱发乙酰胆碱剂量之间的关联。
我们纳入了来自荷兰有创冠状动脉血管舒缩功能测试注册库（NL-CFT）中接受临床指征CFT的ANOCA患者。根据乙酰胆碱诱发痉挛的剂量，将发生心外膜痉挛的患者（n=251）分为：低剂量组（2-20微克，EpiLOW）、中剂量组（100微克，EpiMIDDLE）或高剂量组（200微克，EpiHIGH）。对发生微血管痉挛的患者（n=157），无论诱发剂量如何均进行分析。将患者组相互比较，并与CFT结果为阴性的对照组（n=101）进行比较。我们在基线和随访时评估了西雅图心绞痛问卷的平均心绞痛发作频率和汇总评分，以及病情改善或恶化的患者比例。在心外膜痉挛患者中，发现诱发剂量与基线时的心绞痛发作频率呈负相关：诱发剂量越低，患者心绞痛发作越频繁（EpiLOW组48±20次，EpiMIDDLE组53±21次，EpiHIGH组57±19次，微血管痉挛组61±21次，对照组64±21次，总体P=0.003）。高诱发剂量组中大多数患者病情改善，低诱发剂量组中大多数患者病情恶化，呈一种趋势。
痉挛诱发与心绞痛症状之间存在显著的剂量依赖关系。乙酰胆碱诱发剂量可作为未来临床试验中的风险分层因素或替代结局指标。
