Review
A Practical Guide for Fractional Flow Reserve Guided Revascularisation

https://doi.org/10.1016/j.hlc.2017.09.017Get rights and content

The presence and extent of myocardial ischaemia is a major determinant of prognosis and benefit from revascularisation in patients with stable coronary artery disease. Fractional Flow Reserve (FFR) is accepted as the reference standard for invasive assessment of ischaemia. Its ability to detect lesion specific ischaemia makes it a useful test in a wide range of patient and lesion subsets, with FFR guided intervention improving clinical outcomes and reducing health care costs compared to assessment with coronary angiography alone. This article will review the basic principles in FFR, practical tips in FFR guided revascularisation and the role of emerging non-hyperaemic indices of ischaemia.

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.

References (63)

  • A. Ladwiniec et al.

    The haemodynamic effects of collateral donation to a chronic total occlusion: Implications for patient management

    Int J Cardiol

    (2015)
  • S.J. Kang et al.

    Intravascular ultrasound-derived predictors for fractional flow reserve in intermediate left main disease

    JACC Cardiovasc Interv

    (2011)
  • W.F. Fearon et al.

    The impact of downstream coronary stenosis on fractional flow reserve assessment of intermediate left main coronary artery disease: Human validation

    JACC Cardiovasc Interv

    (2015)
  • H.L. Kim et al.

    Clinical and physiological outcomes of fractional flow reserve-guided percutaneous coronary intervention in patients with serial stenoses within one coronary artery

    JACC Cardiovasc Interv

    (2012)
  • B.K. Koo et al.

    Physiologic assessment of jailed side branch lesions using fractional flow reserve

    J Am Coll Cardiol

    (2005)
  • S.L. Chen et al.

    Randomized comparison of FFR-guided and angiography-guided provisional stenting of true coronary bifurcation lesions: The DKCRUSH-VI trial (double kissing crush versus provisional stenting technique for treatment of coronary bifurcation lesions VI)

    JACC Cardiovasc Interv

    (2015)
  • F. Cuculi et al.

    Impact of microvascular obstruction on the assessment of coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve after ST-segment elevation myocardial infarction

    J Am Coll Cardiol

    (2014)
  • A. Ntalianis et al.

    Fractional flow reserve for the assessment of nonculprit coronary artery stenoses in patients with acute myocardial infarction

    JACC Cardiovasc Interv

    (2010)
  • C.W. Nam et al.

    Relation of fractional flow reserve after drug-eluting stent implantation to one-year outcomes

    Am J Cardiol

    (2011)
  • S.K. Agarwal et al.

    Utilizing Post-Intervention Fractional Flow Reserve to Optimize Acute Results and the Relationship to Long-Term Outcomes

    JACC Cardiovasc Interv

    (2016)
  • A. Jeremias et al.

    Multicenter core laboratory comparison of the instantaneous wave-free ratio and resting Pd/Pa with fractional flow reserve: The RESOLVE study

    J Am Coll Cardiol

    (2014)
  • N.P. Johnson et al.

    Continuum of Vasodilator Stress from Rest to Contrast Medium to Adenosine Hyperemia for Fractional Flow Reserve Assessment

    JACC Cardiovasc Interv

    (2016)
  • C. Berry et al.

    VERIFY (VERification of instantaneous wave-free ratio and fractional flow reserve for the assessment of coronary artery stenosis severity in everyday practice): A multicenter study in consecutive patients

    J Am Coll Cardiol

    (2013)
  • Australian Institute of Health and Welfare

    Health-care expenditure on cardiovascular diseases 2008–09

    (2014)
  • R. Hachamovitch et al.

    Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction

    Circulation

    (1998)
  • L.J. Shaw et al.

    Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy

    Circulation

    (2008)
  • G.J.W. Bech et al.

    Fractional Flow Reserve to Determine the Appropriateness of Angioplasty in Moderate Coronary Stenosis: A Randomized Trial

    Circulation

    (2001)
  • G.A. Lin et al.

    Frequency of stress testing to document ischemia prior to elective percutaneous coronary intervention

    JAMA

    (2008)
  • W.E. Boden et al.

    Optimal medical therapy with or without PCI for stable coronary disease

    N Engl J Med

    (2007)
  • G. Toth et al.

    Evolving concepts of angiogram: Fractional flow reserve discordances in 4000 coronary stenoses

    Eur Heart J

    (2014)
  • P.A.L. Tonino et al.

    Fractional flow reserve versus angiography for guideing percutaneous coronary intervention

    N Engl J Med

    (2009)
  • Cited by (0)

    View full text