Coronary microvascular dysfunction in patients with stable coronary artery disease: The CE-MARC 2 coronary physiology sub-study

David Corcoran, Robin Young, David Adlam, Alex McConnachie, Kenneth Mangion, David Ripley, David Cairns, Julia Brown, Chiara Bucciarelli-Ducci, Andreas Baumbach, Rajesh Kharbanda, Keith G Oldroyd, Gerry P McCann, John P Greenwood, Colin Berry, David Corcoran, Robin Young, David Adlam, Alex McConnachie, Kenneth Mangion, David Ripley, David Cairns, Julia Brown, Chiara Bucciarelli-Ducci, Andreas Baumbach, Rajesh Kharbanda, Keith G Oldroyd, Gerry P McCann, John P Greenwood, Colin Berry

Abstract

Background: In patients with angina undergoing invasive management, no obstructive coronary artery disease (NOCAD) is a common finding, and angina may persist following percutaneous coronary intervention (PCI). Coronary microvascular dysfunction may be relevant. We aimed to assess the proportion of patients presenting with suspected CAD who had coronary microvascular dysfunction.

Methods: Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC 2) was a prospective multicenter randomised controlled trial of functional imaging versus guideline-based management in patients with suspected CAD. Invasive coronary angiography was protocol-directed. Fractional flow reserve (FFR) and parameters of microvascular function (coronary flow reserve (CFR), index of microcirculatory resistance (IMR), resistance reserve ratio (RRR)) were measured in major epicardial coronary arteries with ≥40-≤90% diameter stenosis. An FFR value ≤0.80 indicated the presence of obstructive CAD.

Results: 267/1202 (22.2%) patients underwent angiography and 81 (30%) patients had FFR measured. 63 (78%) of these patients had microvascular function assessed in 85 arteries (mean age 58.5 ± 8.2 years; 47 (75%) male). 25/63 (40%) patients had NOCAD, and of these, 17 (68%) had an abnormality ≥1 parameter of microvascular function (abnormal IMR (≥25), abnormal CFR (<2.0), and abnormal RRR (<2.0) occurred in 10 (40%), 12 (48%), and 11 (44%), respectively). 38/63 (60%) patients had obstructive epicardial CAD. Of these patients, 15/38 (39%), 20/38 (53%), and 12/38 (32%) had an abnormal IMR, CFR and RRR, respectively.

Conclusions: Coronary microvascular dysfunction is common in patients with angina. Invasive assessment of microvascular function may be informative and relevant for decision-making in patients with both NOCAD and obstructive epicardial CAD.

Clinical trial registration: ClinicalTrials.gov Identifier: NCT01664858.

Keywords: Angina; Coronary artery disease; Coronary microvascular dysfunction; Stable ischaemic heart disease.

Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram. CONSORT flow diagram of patients enrolled in the CE-MARC 2 microvascular sub-study. Of 1202 patients enrolled into the CE-MARC 2 trial, 267 (22.2%) underwent invasive coronary angiography and 119 (45%) of these patients had an indication for FFR measurement. Thirty-eight (32%) of these patients did not have FFR measured for the following reasons: severe obstructive CAD, n = 15; urgent invasive management, n = 3; clinical and technical factors, n = 20. Eighty-one patients had FFR measured in at least one coronary artery (115 vessels) and additional parameters of microvascular function were available for 63/81 (78%) patients in 85 vessels. Overall, 63 patients had coronary microvascular function assessed, including 22, 18 and 23 patients randomised to CMR-guided, MPS-guided and NICE management-guided care, respectively. FFR = fractional flow reserve.
Fig. 2
Fig. 2
Abnormal invasive coronary microvascular function test results. Abnormal IMR, CFR and RRR on a per-patient and per-vessel basis. FFR = fractional flow reserve, IMR = index of microcirculatory resistance, CFR = coronary flow reserve, RRR = resistance reserve ratio.

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