Percutaneous coronary intervention versus medical therapy in patients with angina and grey-zone fractional flow reserve values: a randomised clinical trial

Abstract

Introduction: There is conflicting evidence regarding the benefits of percutaneous coronary intervention (PCI) in patients with grey zone fractional flow reserve (GZFFR artery) values (0.75-0.80). The prevalence of ischaemia is unknown. We wished to define the prevalence of ischaemia in GZFFR artery and assess whether PCI is superior to optimal medical therapy (OMT) for angina control.

Methods: We enrolled 104 patients with angina with 1:1 randomisation to PCI or OMT. The artery was interrogated with a Doppler flow/pressure wire. Patients underwent Magnetic Resonance Imaging (MRI) with follow-up at 3 and 12 months. The primary outcome was angina status at 3 months using the Seattle Angina Questionnaire (SAQ).

Results: 104 patients (age 60±9 years), 79 (76%) males and 79 (76%) Left Anterior Descending (LAD) stenoses were randomised. Coronary physiology and SAQ were similar. Of 98 patients with stress perfusion MRI data, 17 (17%) had abnormal perfusion (≥2 segments with ≥25% ischaemia or ≥1 segment with ≥50% ischaemia) in the target GZFFR artery. Of 89 patients with invasive physiology data, 26 (28%) had coronary flow velocity reserve <2.0 in the target GZFFR artery. After 3 months of follow-up, compared with patients treated with OMT only, patients treated by PCI and OMT had greater improvements in SAQ angina frequency (21 (28) vs 10 (23); p=0.026) and quality of life (24 (26) vs 11 (24); p=0.008) though these differences were no longer significant at 12 months.

Conclusions: Non-invasive evidence of major ischaemia is uncommon in patients with GZFFR artery. Compared with OMT alone, patients randomised to undergo PCI reported improved symptoms after 3 months but these differences were no longer significant after 12 months.

Trial registration number: NCT02425969.

Keywords: combined pressure and doppler flow coronary wire; fractional flow reserve; percutaneous coronary intervention; stress perfusion MRI.

Conflict of interest statement

Competing interests: There was no industry sponsorship of this trial. CB has undertaken research, consulting and lectures for Abbott Vascular, Opsens and Coroventis based on contracts with The University of Glasgow. KGO has received speaker fees from Abbott Vascular, Boston Scientific and Biosensors. BH has received honoraria from Philips Volcano for consultancy.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

GZFFR flowchart. ‘Screening FFR’ used any pressure wire system for basic FFR assessment without flow indices. All subsequent measurements involved the Combowire device to assess indices of pressure, flow and resistance. FFR, fractional flow reserve; GzFFR, grey zone; OMT, optimal medical therapy; PCI, percutaneous coronary intervention and optimal medical therapy group; Pd/Pa, resting pressure gradient; QCA, quantitative coronary angiography; STEMI, ST elevation myocardial infarction.

Figure 2

Consort flow diagram for the GZFFR trial. *One patient died at 65 days postrandomisation following a witnessed fall with traumatic intracranial haemorrhage, another died at 51 days postrandomisation from metastatic lung cancer diagnosed during the MRI performed as part of the study and the third died of pulmonary emboli post resection of a chronic benign meningioma at 84 days postrandomisation. Combowire, combined pressure and Doppler flow wire; FFR, fractional flow reserve; GZFFR, grey zone; OMT, optimal medical therapy; PCI, percutaneous coronary intervention and optimal medical therapy group.

Figure 3

This patient had a moderately severe mid left circumflex lesion with GZFFR physiology with reduced CFVR of 1.5 pre-PCI which improved to a CFVR of 4 post-PCI. The stenosis resistance HSR reduced following PCI with improved FFR. GZFFR coronary lesion in mid circumflex indicated by blue arrow before PCI (upper panel) and after PCI with coronary physiology data in the left panel. CFVR, coronary flow velocity reserve; FFR, fractional flow reserve; GZFFR, grey zone; HSR, Hyperaemic Stenosis Resistance Index.