Original Article
Integrated Coronary Physiology in Percutaneous Intervention: A new paradigm in interventional cardiology

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Coronary angiography has provided an unrivalled appreciation of coronary anatomy fostering a far greater appreciation of the extent of atherosclerotic disease. However, the subjectivity of coronary angiography at determining the extent of plaque has been exposed with IVUS. Indices of coronary physiology have provided valuable adjunctive information as to the physiological importance of specific lesions. Fractional flow reserve is an established method for evaluating the significance of epicardial stenoses. Fractional flow reserve guided percutaneous coronary intervention is associated with improved outcomes when compared to a conventional angiographic guided strategy, particularly in intermediate lesions. The use of coronary physiology in the cath lab represents a new avenue to guide appropriate patient specific revascularisation strategies. This review examines the theory and evidence for fractional flow reserve and its use in percutaneous coronary intervention.

Introduction

Coronary angiography has done much to improve our understanding of coronary artery disease providing an unrivalled appreciation of coronary anatomy. Indeed it is the cornerstone for determining the presence and extent of coronary artery disease. Following Gruenzigs’ first percutaneous balloon angioplasty in 1977 the growth of percutaneous coronary intervention (PCI) with the use of stents has been exponential. Figures from Europe show that the number of stents implanted increased from 3000 in 1992, to 777,000 in 2004 [1]. However, despite a reduced mortality in patients with acute coronary syndromes (ACS) [2] the use of PCI in patients with stable coronary disease has not been associated with a similar mortality advantage, but has been shown to improve symptoms of angina compared with optimal medical therapy alone [3]. Such equivocal results may be ascribed to the inherent subjectivity that coronary angiography provides in determining the severity of coronary stenoses, with significant inter and intra-observer variability between reporting physicians [4], [5], and that angiography does not provide complete information on the haemodynamic significance of a stenosis. Recent guidelines recommend the demonstration of ischaemia prior to stenting in elective, stable patient subgroups [6]. However, decisions to revascularise lesions are largely based on coronary angiography alone without reference to the physiological importance of the lesion with prior non-invasive testing [7]. This can result in inappropriate stent implantation with potentially morbid complications [8]. The severity of a lesion and its haemodynamic impact is determined primarily by the severity of the stenosis, however other factors such as lesion length are also important [9]. There are many different methods that can be employed to evaluate lesion severity including non-invasive investigations such as exercise stress tests, myocardial perfusion scans, and the emerging coronary computed tomography (CT) as well as invasive assessments such as intravascular ultrasound and pressure derived methods that include fractional flow reserve.

This review will examine the evidence and clinical utility for the use of assessment of fractional flow reserve (FFR), a validated invasive physiological tool that accurately determines lesion severity at the time of coronary angiography and discuss its role in specific patient populations.

Section snippets

Coronary Angiography – “A Shadow of the Truth”

Autopsy and intravascular ultrasound studies have demonstrated the shortcomings of coronary angiography in determining extent of atherosclerotic disease [10]. Coronary arteries are three-dimensional structures and fluoroscopic coronary angiography only provides a planar silhouette of the contrast filled lumen. The coronary angiographic severity of lesions is also described in relation to a distal ‘normal’ reference segment [11]. Necropsy studies have demonstrated that in patients with

Fractional Flow Reserve

With the potential but real complications of unnecessary PCI, being certain of a lesions need for revascularisation assumes significant importance. To be able to assess this at the time of coronary angiography is highly advantageous. Gould has made a significant contribution to our understanding of coronary physiology by demonstrating that resting myocardial blood flow remains normal until an epicardial stenosis reaches ≥85% and that hyperaemic blood flow reduces with a >50% stenosis [15].

Measuring Fractional Flow Reserve (FFR) in the Cath Lab (Figs. 2 and 3)

FFR is a simple cath lab based tool whose technique shares similar characteristics to percutaneous intervention and as such should only be undertaken by interventional cardiologists who have undergone the necessary training.

Validation of Fractional Flow Reserve (FFR)

Following initial exploratory work in animal models [22], numerous clinical studies comparing FFR with non-invasive stress tests established an ischaemic FFR threshold of ≤0.75 [23], [24]. Pijls and colleagues looked at 41 consecutive patents with an intermediate lesion on coronary angiography and compared FFR with exercise bicycle stress testing, dobutamine stress echocardiography and thallium scintigraphy [23]. All patents with an FFR value ≤0.75 demonstrated reversible myocardial ischaemia

Outcomes with Fractional Flow Reserve (FFR) Guided Strategy

The first major randomised trial to use FFR values to determine treatment strategy was the DEFER (deferral vs performance of PCI of non-ischaemia-producing stenoses) trial [28]. The study looked at a group of 325 patients who were scheduled to undergo elective PCI of an intermediate lesion without prior stress testing. All patients underwent FFR evaluation. If FFR was ≥0.75 the patients were randomised to deferral vs performance of PCI. The five-year results of this landmark study were

Post MI/scar

In the acute phases of an acute myocardial infarction, oedema and capillary plugging can limit the recruitable hyperaemic response of the microcirculation. This can theoretically lead to falsely elevated FFR values in the acute myocardial infarction setting and so FFR values early in the course of an AMI need to be interpreted carefully. More remotely, De Bruyne and colleagues looked at the impact of FFR on patients who had previously had an AMI  six days ago [25]. They demonstrated that FFR

Left Main Stem Disease

Reliable evaluation of left main stenoses is often difficult with the consequences of mislabelling severity potentially disastrous. Although no randomised data are available, prospective single centre studies have shown the usefulness of FFR in this population. In patients with intermediate or equivocal left main lesions and an FFR value of ≥0.8, medical treatment rather than surgical revascularisation was safe and associated with a similar prognosis to patients who had been revascularised for

Conclusion

We can clearly see that utilising FFR in PCI, particularly when encountering intermediate lesions, leads to improved patient selection. In order to determine the ischaemic significance of a lesion, using an FFR ischaemic threshold of ≤0.8 has been shown to be associated with improved patient outcomes and is more cost effective when compared solely to an angiographic driven strategy. Increasing integration of coronary physiology into the cath lab will lead to better decision making by guiding

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