{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T17:10:56Z","timestamp":1792257056036,"version":"4.4.0"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">A coronary function test (CFT) is\u00a0the 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We included ANOCA patients undergoing clinically indicated CFT from the Netherlands Registry of Invasive Coronary Vasomotor Function Testing: NL\u2010CFT. Patients with epicardial spasm (n=251) were divided according to acetylcholine spasm triggering dose: low (2\u201320\u2009mcg, EpiLOW), middle (100\u2009mcg, EpiMIDDLE) or high (200\u2009mcg, 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\u2010up 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\u00b120, EpiMIDDLE 53\u00b121, EpiHIGH 57\u00b119, microvascular spasm\u00a061\u00b121, controls 64\u00b121, overall\n              <jats:italic>P<\/jats:italic>\n              =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.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">A significant dose\u2010dependent 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT06083155.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.037913","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T03:40:11Z","timestamp":1737085211000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Angina Severity and Symptom Improvement Are Associated With Diagnostic Acetylcholine Provocation Dose in Vasospastic Angina"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9253-5154","authenticated-orcid":false,"given":"C.","family":"Crooijmans","sequence":"first","affiliation":[{"name":"Department of Cardiology Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9615-9491","authenticated-orcid":false,"given":"Tijn P. J.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3261-9361","authenticated-orcid":false,"given":"Joan G.","family":"Meeder","sequence":"additional","affiliation":[{"name":"Department of Cardiology VieCuri Medical Centre North\u2010Limburg The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3513-7819","authenticated-orcid":false,"given":"Valeria","family":"Paradies","sequence":"additional","affiliation":[{"name":"Department of Cardiology Maasstad Hospital Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4613-6774","authenticated-orcid":false,"given":"Annemiek M. J.","family":"de Vos","sequence":"additional","affiliation":[{"name":"Department of Cardiology Catharina Hospital Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5870-9923","authenticated-orcid":false,"given":"Pier","family":"Woudstra","sequence":"additional","affiliation":[{"name":"Department of Cardiology Medical Centre Leeuwarden Leeuwarden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1122-2429","authenticated-orcid":false,"given":"Tessel N. E.","family":"Vossenberg","sequence":"additional","affiliation":[{"name":"Department of Cardiology Medical Centre Leeuwarden Leeuwarden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0682-0619","authenticated-orcid":false,"given":"Tim P.","family":"van de Hoef","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Centre Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3977-1403","authenticated-orcid":false,"given":"Nicola S.","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Cardiology Onze Lieve Vrouwe Gasthuis Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Els G. M.","family":"Olde Bijvank","sequence":"additional","affiliation":[{"name":"Department of Cardiology Haaglanden Medical Centre Den Haag The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1717-451X","authenticated-orcid":false,"given":"Stijn C. H.","family":"van den Oord","sequence":"additional","affiliation":[{"name":"Department of Cardiology Rijnstate Hospital Arnhem The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6150-535X","authenticated-orcid":false,"given":"Patty","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zuyderland Hospital Heerlen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5421-5205","authenticated-orcid":false,"given":"Martijn","family":"Meuwissen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Amphia Hospital Breda The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3721-0901","authenticated-orcid":false,"given":"Jos W. M. G.","family":"Widdershoven","sequence":"additional","affiliation":[{"name":"Department of Cardiology Elisabeth Tweesteden Hospital Tilburg The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0109-2792","authenticated-orcid":false,"given":"E. Karin","family":"Arkenbout","sequence":"additional","affiliation":[{"name":"Department of Cardiology Tergooi Medical Center Hilversum The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4321-7328","authenticated-orcid":false,"given":"Martin G.","family":"Stoel","sequence":"additional","affiliation":[{"name":"Department of Cardiology Medical Spectrum Twente Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-7105","authenticated-orcid":false,"given":"Yolande","family":"Appelman","sequence":"additional","affiliation":[{"name":"Department of Cardiology Amsterdam University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7984-3021","authenticated-orcid":false,"given":"Marcel A. M.","family":"Beijk","sequence":"additional","affiliation":[{"name":"Department of Cardiology Amsterdam University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4024-8775","authenticated-orcid":false,"given":"Aysun","family":"Cetinyurek\u2010Yavuz","sequence":"additional","affiliation":[{"name":"Department of IQ Health Science Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9762-014X","authenticated-orcid":false,"given":"Hester M.","family":"den Ruijter","sequence":"additional","affiliation":[{"name":"Laboratory of experimental Cardiology University Medical Centre Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1351-1582","authenticated-orcid":false,"given":"Suzette E.","family":"Elias\u2010Smale","sequence":"additional","affiliation":[{"name":"Department of Cardiology Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6136-8640","authenticated-orcid":false,"given":"Niels","family":"van Royen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9131-9903","authenticated-orcid":false,"given":"Aukelien C.","family":"Dimitriu\u2010Leen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9284-7967","authenticated-orcid":false,"given":"Peter","family":"Damman","sequence":"additional","affiliation":[{"name":"Department of Cardiology Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for NL\u2010CFT","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa503"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001168"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehae177"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4244\/EIJ-D-21-00971"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.03.385"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.09.006"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4244\/EIJ-D-21-00402"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab653"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2023.06.043"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2023.02.043"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2021.02.079"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3791\/54295-v"},{"key":"e_1_3_2_14_2","first-page":"2565","article-title":"International standardization of diagnostic criteria for vasospastic angina","volume":"38","author":"Beltrame JF","year":"2017","unstructured":"Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN; Coronary Vasomotion Disorders International Study G . International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38:2565\u20132568.","journal-title":"Eur Heart J"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2017.08.068"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)00397-9"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.113.000752"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.7478"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.4244\/EIJ-D-21-00875"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.020535"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcin.2021.10.003"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.124.037913","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T12:04:01Z","timestamp":1737547441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.124.037913"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,21]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,1,21]]}},"alternative-id":["10.1161\/JAHA.124.037913"],"URL":"https:\/\/doi.org\/10.1161\/jaha.124.037913","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,21]]},"assertion":[{"value":"2024-09-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e037913"}}