Invasive Endotyping in Patients With Angina and No Obstructive Coronary Artery Disease: A Randomized Controlled Trial

Abstract

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: https://www.clinicaltrials.gov ; Unique identifier: NCT03477890

Sex-Specific Associations of the Plasma-Proteome with incident Coronary Artery Disease

“…Men are more likely to suffer from intraplaque haemorrhage secondary to neovessel-rupture, whereas women more often present with coronary microvascular dysfunction (CMD) and subsequent angina with non-obstructive coronary arteries. [56][57][58] This is noteworthy, considering that female hormone signalling has been associated with CMD, 59 while oestrogen replacement therapy has not been found effective to halt classical obstructive atherosclerotic plaque progression in post-menopausal women with ischaemic heart disease. 60,61 The findings of our present study further substantiate the concept that in the development of CAD, both sexes exhibit numerous common risk factors in addition to sex-specific mechanisms.…”

Prevalence of Abnormal Coronary Function in Patients With Angina and No Obstructive Coronary Artery Disease on Coronary Computed Tomography Angiography: Insights From the CorCTA Trial

“…In addition, although prevalent, ANOCA remains a heterogeneous syndrome and its underlying mechanisms are much less clear than current 'endotypes' would suggest. With CorMicA and now CorCTA, Sidik, Berry, and colleagues 12 have raised the bar for future work in this arena, challenging us to incorporate coronary microvascular assessments into rigorous trials to optimize discovery and tailor interventions in the forthcoming global pandemic of cardiometabolic disease.…”

“…In this issue of Circulation , Sidik et al 12 shed light on this important question with results of the CorCTA trial. Carried out in Scotland and funded by the British Heart Foundation, CorCTA is a successor to the CorMicA trial, 13 a 2018 blinded randomized controlled trial in which 151 patients (74% women, median age 61 years) with angina and no obstructive CAD on invasive angiography (<50% diameter stenosis and/or fractional flow reserve >0.8) underwent coronary function testing using guidewire-based assessment of coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) during adenosine infusion for evaluation of microvascular angina followed by acetylcholine provocation testing for vasospastic angina.…”

Mechanisms Matter: Combining Invasive Metrics to Better Define Microvascular Dysfunction

“…Currently, there are no therapies for MVD proven to reduce MACE. In Sidik et al, 5 patients underwent guideline-directed therapy following an invasive study, which fundamentally consisted of stopping beta blockers and adding CCBs and nitrates. The result was a statistically insignificant, but clinically depressing, 50% increase in MACE.…”