ReviewA Practical Guide for Fractional Flow Reserve Guided Revascularisation
Introduction
Coronary artery disease (CAD) is a major cause of morbidity and mortality in Australia with the highest level of health care expenditure among any disease groups [1]. Management of stable CAD typically comprises medical therapy alone or in combination with revascularisation. The presence and extent of myocardial ischaemia determines prognosis and benefit from revascularisation [2], [3]. In non-ischaemic lesions revascularisation offers no benefit and is potentially harmful [4].
Non-invasive ischaemia assessment is performed in <50% of cases referred to invasive angiography [5]. Accordingly, revascularisation is performed in lesions with ischaemia localised on prior non-invasive functional testing or on lesions deemed visually significant on invasive coronary angiography. However, this approach of angiographic guided revascularisation in patients with objective ischaemia on prior stress testing failed to provide additional benefit when compared with optimal medical therapy alone when tested in a large randomised trial setting [6]. This may be explained by the limited capacity of both non-invasive stress testing and invasive coronary angiography to predict lesion specific ischaemia, resulting in non-ischaemic lesions being stented, and ischaemic lesions left unrevascularised. This is particularly important in patients with multivessel disease, intermediate stenoses or side branch disease [7], [8], [9].
The introduction of invasive fractional flow reserve (FFR) has equipped interventionists with the ability to accurately determine vessel and lesion specific ischaemia. FFR has been demonstrated in several large randomised trials to improve cardiovascular outcomes when applied to guide percutaneous coronary intervention (PCI) [4], [10], [11]. The instantaneous wave free ratio (iFR) is an emerging resting index of functional stenosis severity which has been demonstrated to be non-inferior to FFR in guiding PCI [12], [13]. Despite evidence for cost effectiveness, FFR remains a tool which is only performed in less than 20% of lesions prior to revascularisation in Australia [14].
This article aims to review the science of FFR, the evidence for its clinical application, its use (and reasons for underutilisation) in the Australian health system, the practicalities on how FFR may be applied in lesion subsets and the emerging application of iFR in mainstream practice.
Section snippets
Principles of Fractional Flow Reserve
Fractional flow reserve assesses the haemodynamic significance of a coronary stenosis and is defined as the ratio of the mean perfusion pressures distal to a stenosis (Pd), obtained via a coronary pressure wire, divided by the mean aortic pressure (Pa) as assessed from the guiding catheter. It is performed under vasodilator induced maximal hyperaemia, a state in which microvascular resistance is minimised and constant, and coronary flow becomes proportional to perfusion pressure [15]. For
Fractional Flow Reserve Guided Revascularisation
The outcomes of randomised trials evaluating the use of FFR to determine lesion specific ischaemia and guide revascularisation of lesions identified have been summarised in Table 1. The DEFER study demonstrated the safety of deferring PCI in coronary stenosis with an FFR ≥ 0.75, with improved outcomes and reduced costs compared to PCI guided by angiography alone [4]. In patients with multi-vessel disease (Figure 2), the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME)
Uptake and Barriers to the Use of Fractional Flow Reserve in the Australian Health System
Despite robust clinical evidence and guideline recommendations, FFR in Australia is used in one in twenty coronary angiograms and one in five PCI [14]. Potential reasons for low uptake include concerns regarding increasing the duration of the procedure, reduced steerability of the FFR wire and patient discomfort associated with hyperaemia. A significant factor limiting broader use of FFR is the lack of financial reimbursement for the pressure wire. There is currently no government reimbursement
Tips and Pitfalls of Fractional Flow Reserve Use in the Catheterisation Laboratory
A recommended systematic approach in performing FFR has been summarised in Table 2. We have also highlighted below a number of pertinent tips, which will help facilitate FFR integration into clinical practice. 1) Willingness and efficiency in use of pressure wires in any catheterisation laboratory depends on staff familiarity with the technology, including its connections, drawing up of adenosine and adequate venous access. For this reason, easy-to-follow protocols and adequate training to the
Left Main Disease
Data from a meta-analysis of six studies involving 525 patients demonstrated the safety of FFR guided deferral of intermediate left main coronary artery (LMCA) stenosis. Long-term outcomes in such patients for whom revascularisation is deferred based on FFR are favourable and similar to the revascularisation group in terms of overall mortality and subsequent myocardial infarction [40].
Visual-functional mismatch between invasive angiography and FFR is commonly observed, in particular reverse
Future Directions
Technical advances are rapidly addressing potential barriers to the uptake of FFR measurement in the catheterisation laboratory. To address the issues of reduced steerability and pressure drift, a rapid exchange FFR microcatheter with fibre-optic pressure sensor has recently been developed [58]. The optical pressure sensor is associated with less signal drift compared to piezo resistive sensors on conventional wires, however, its use is limited as the microcatheter has a relatively large
Conclusion
Fractional flow reserve is a well validated, highly reproducible, cost effective technique that improves clinical outcomes and has become the reference standard for the assessment of lesion-specific ischaemia. The benefits of FFR extend broadly and include assessment of LMCA, bifurcation lesions, tandem stenoses and patients with acute coronary syndrome (ACS). Integration into Australian clinical practice remains challenging and is limited by a lack of adequate remuneration. Non-adenosine based
Declarations of Interest
A/Prof Ko has been an invited speaker at symposiums sponsored by St Jude Medical, Pfizer, Bristol Myers, Squibb, Eli Lilly and Novartis. Dr Yong has received minor honoraria from St Jude Medical.
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