Fractional flow reserve-guided management in stable coronary disease and acute myocardial infarction: recent developments

Colin Berry, David Corcoran, Barry Hennigan, Stuart Watkins, Jamie Layland, Keith G Oldroyd, Colin Berry, David Corcoran, Barry Hennigan, Stuart Watkins, Jamie Layland, Keith G Oldroyd

Abstract

Coronary artery disease (CAD) is a leading global cause of morbidity and mortality, and improvements in the diagnosis and treatment of CAD can reduce the health and economic burden of this condition. Fractional flow reserve (FFR) is an evidence-based diagnostic test of the physiological significance of a coronary artery stenosis. Fractional flow reserve is a pressure-derived index of the maximal achievable myocardial blood flow in the presence of an epicardial coronary stenosis as a ratio to maximum achievable flow if that artery were normal. When compared with standard angiography-guided management, FFR disclosure is impactful on the decision for revascularization and clinical outcomes. In this article, we review recent developments with FFR in patients with stable CAD and recent myocardial infarction. Specifically, we review novel developments in our understanding of CAD pathophysiology, diagnostic applications, prognostic studies, clinical trials, and clinical guidelines.

Keywords: Coronary revascularization; Fractional flow reserve; Medical therapy; Myocardial infarction; Stable angina.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Figures

Figure 1
Figure 1
Systemic and coronary vascular beds that influence FFR. Ao, aortic pressure; Pa, arterial pressure proximal to stenosis; Pd, coronary pressure distal to epicardial stenosis; Pv, venous pressure; Qc, collateral blood flow; Rc, collateral resistance; Rs, epicardial coronary stenosis; FFR, fractional flow reserve; IMR, index of microvascular resistance; CFR, coronary flow reserve.
Figure 2
Figure 2
Angina associated with inducible ischaemia, non-obstructive epicardial coronary artery disease and microvascular dysfunction revealed by guidewire-based diagnostic tests with FFR, CFR, and IMR. A 70-year-old male presented to the Chest Pain Service with a 2-month history consistent with Canadian Cardiovascular Society class II angina and hypertension. A treadmill exercise tolerance test disclosed angina and ST-segment depression in leads II, III, aVF, and V3–V6 at 6 min 52 s at Stage 3 of the Bruce protocol. The patient was invited to participate in the CE-MARC2 clinical trial (NCT01664858). Written informed consent was obtained and he was then randomly assigned to the management according to the National Institute of Clinical Excellence guideline-95. Based on a pre-test likelihood of coronary artery disease of 60–90%, the patient was referred directly for invasive management. Coronary angiography revealed multiple plaques (white arrows) in the left (white arrow) and right (yellow arrow) coronary arteries. The FFR in all three major epicardial arteries was >0.90, ruling out flow-limiting stenoses in these arteries. The IMR and CFR were 31 and 1.4 in the left circumflex artery and 25 and 2.1 in the right coronary artery, consistent with microvascular dysfunction. The haemodynamic display from guidewire-based physiological testing in the right coronary artery shows recordings of pressure (upper panel) measured from the guide catheter in the aorta (red, Ao) and guidewire-based distal coronary pressure (green, Pd), and thermodilution curves (lower panel) using serial intra-coronary injections of 3 mL of saline at room temperature at rest (blue thermodilution curves, three curves, mean 0.55 s) and then during adenosine stress [orange thermodilution curves with one highlighted in green (active measurement, 0.22 s, mean 0.26 s) during a 41 s measurement period (x-axis)]. There is a modest ‘left-shift’ in the thermodilution transit times indicating a reduced vasodilator response of the coronary microcirculation to intravenous adenosine, consistent with a degree of microvascular dysfunction. The patient was treated medically with 75 mg of aspirin, 40 mg of simvastatin, and angina medications. Permission obtained, Prof. John Greenwood, Principal Investigator for the CE-MARC2 trial. RCA, right coronary artery; LCA, left coronary artery; FFR, fractional flow reserve; CFR, coronary flow reserve; IMR, index of microcirculatory resistance.
Figure 3
Figure 3
Prognostic importance of fractional flow reserve values below and above the ischaemic zone (0.75–0.80).
Figure 4
Figure 4
FAME-2 long-term follow-up. Cumulative incidence of the primary endpoint (death, myocardial infarction, or urgent revascularization) and its components.
Figure 5
Figure 5
Impact of fractional flow reserve disclosure on treatment decisions based on standard angiography-alone in the FAMOUS-NSTEMI clinical trial.

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