Invasive endotyping in patients with angina and no obstructive coronary artery disease: a randomized controlled trial

Sidik, N. P. et al. (2023) Invasive endotyping in patients with angina and no obstructive coronary artery disease: a randomized controlled trial. Circulation, (doi: 10.1161/CIRCULATIONAHA.123.064751) (PMID:37795617) (Early Online Publication)

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BACKGROUND: We investigated the usefulness of invasive coronary function testing to diagnose the cause of angina in patients with no obstructive coronary arteries. METHODS: Outpatients referred for coronary computed tomography angiography in 3 hospitals in the United Kingdom were prospectively screened. After coronary computed tomography angiography, patients with unobstructed coronary arteries, and who consented, underwent invasive endotyping. The diagnostic assessments included coronary angiography, fractional flow reserve (patient excluded if ≤0.80), and, for those without obstructive coronary artery disease, coronary flow reserve (abnormal <2.0), index of microvascular resistance (abnormal ≥25), and intracoronary infusion of acetylcholine (0.182, 1.82, and 18.2 μg/mL; 2 mL/min for 2 minutes) to assess for microvascular and coronary spasm. Participants were randomly assigned to disclosure of the results of the coronary function tests to the invasive cardiologist (intervention group) or nondisclosure (control group, blinded). In the control group, a diagnosis of vasomotor angina was based on medical history, noninvasive tests, and coronary angiography. The primary outcome was the between-group difference in the reclassification rate of the initial diagnosis on the basis of coronary computed tomography angiography versus the final diagnosis after invasive endotyping. The Seattle Angina Questionnaire summary score and Treatment Satisfaction Questionnaire for Medication were secondary outcomes. RESULTS: Of 322 eligible patients, 250 (77.6%) underwent invasive endotyping; 19 (7.6%) had obstructive coronary disease, 127 (55.0%) had microvascular angina, 27 (11.7%) had vasospastic angina, 17 (7.4%) had both, and 60 (26.0%) had no abnormality. A total of 231 patients (mean age, 55.7 years; 64.5% women) were randomly assigned and followed up (median duration, 19.9 [12.6–26.9] months). The clinician diagnosed vasomotor angina in 51 (44.3%) patients in the intervention group and in 55 (47.4%) patients in the control group. After randomization, patients in the intervention group were 4-fold (odds ratio, 4.05 [95% CI, 2.32–7.24]; P<0.001) more likely to be diagnosed with a coronary vasomotor disorder; the frequency of this diagnosis increased to 76.5%. The frequency of normal coronary function (ie, no vasomotor disorder) was not different between the groups before randomization (51.3% versus 50.9%) but was reduced in the intervention group after randomization (23.5% versus 50.9%, P<0.001). At 6 and 12 months, the Seattle Angina Questionnaire summary score in the intervention versus control groups was 59.2±24.2 (2.3±16.2 change from baseline) versus 60.4±23.9 (4.6±16.4 change) and 63.7±23.5 (4.7±14.7 change) versus 66.0±19.3 (7.9±17.1 change), respectively, and not different between groups (global P=0.36). Compared with the control group, global treatment satisfaction was higher in the intervention group at 12 months (69.9±22.8 versus 61.7±26.9, P=0.013). CONCLUSIONS: For patients with angina and no obstructive coronary arteries, a diagnosis informed by invasive functional assessment had no effect on long-term angina burden, whereas treatment satisfaction improved. REGISTRATION: URL:; Unique identifier: NCT03477890

Item Type:Articles
Additional Information:This study was funded by the British Heart Foundation (FS/17/26/32744, RE/18/6134217) and supported by the Chief Scientist Office of the Scottish Government.
Status:Early Online Publication
Glasgow Author(s) Enlighten ID:McConnachie, Professor Alex and Stanley, Miss Bethany and Mahrous Abouzaid, Dr Ahmed and McEntegart, Dr Margaret and Carrick, Dr David and Corcoran, Dr David and Bradley, Dr Conor and Morrow, Dr Andrew and Berry, Professor Colin and Heggie, Mr Robert and Young, Dr Robin and Lang, Professor Ninian and Roditi, Dr Giles and Wu, Professor Olivia and Sykes, Dr Robert and Sidik, Ms Novalia
Authors: Sidik, N. P., Stanley, B., Sykes, R., Morrow, A. J., Bradley, C. P., Mcdermott, M., Ford, T., Roditi, G., Hargreaves, A., Stobo, D., Adams, J., Byrne, J., Mahrous, A., Young, R., Carrick, D., McGeoch, R., Corcoran, D., Lang, N. N., Heggie, R., Wu, O., McEntegart, M. B., McConnachie, A., and Berry, C.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Health Economics and Health Technology Assessment
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Circulation
Publisher:American Heart Association
ISSN (Online):1524-4539
Published Online:05 October 2023
Copyright Holders:Copyright © 2023 American Heart Association, Inc.
First Published:First published in Circulation 2023
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
174109The conundrum of angina in patients without obstructive coronary disease: a randomised controlled pilot trial of routine testing of coronary function.Colin BerryBritish Heart Foundation (BHF)FS/17/26/32744School of Cardiovascular & Metabolic Health
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217SCMH - Cardiovascular & Metabolic Health