Inducing Hyperaemia
The debate regarding the clinical challenges with adenosine continues and is mainly focused on patient discomfort, cost and additional procedural time. The reality is that most patients, with the exception of those with severe asthma, tolerate adenosine15 and use of intracoronary adenosine in particular is associated with little additional procedural time or cost while preserving diagnostic accuracy. Other agents including regadenoson and nicorandil are also options for inducing hyperaemia and in some situations may be preferable to adenosine.16 There are theoretical concerns that some of the agents used to induce hyperaemia may introduce haemodynamic disturbances including hypotension and bradycardia, which may alter FFR and lesion classification. This was not borne out in a recent study which demonstrated no significant differences in FFR between a variety of hyperaemic agents and routes of administration.16 A strong correlation was found between IV adenosine/ATP and IC nicorandil (r=0.962; p< 0.001 with a classification agreement of 91.2 %). Similarly, IV adenosine and IV regadenoson compared well (r=0.990; p<0.001 with a classification agreeement of 100 %).16
Cost
The technology itself remains reasonably expensive; however, it is likely to become significantly cheaper with increased competition as new wires from alternative manufacturers come to the market. In addition, a pressure-sensing microcatheter is now commercially available. It is important to note that FFR guidance reduces inappropriate PCI and increases quality of life and is therefore cost effective in patients scheduled for multi-vessel PCI despite the associated expense of the pressure wire and hyperaemic agents.17
Grey-Zone FFR Values
The original validation study as well as many subsequent reports confirmed a very high concordance for non-invasive evidence of ischaemia with FFR values ≤0.75.3,5 However, in order to improve sensitivity and minimise the risk of under-treatment an FFR cut-off value of ≤0.80 was adopted in the FAME and FAME 2 trials.3,4 This has resulted in the de facto creation of a so-called FFR grey-zone between 0.75 and 0.80 within which the need to perform revascularisation is unclear and there may in fact be over-treatment. Indeed, preliminary data from our group suggests that only one-third of patients with grey-zone FFRs have perfusion abnormalities in the corresponding artery when assessed using stress MRI.18 All 33 grey-zone stenoses in a recent study were found to be non-ischaemic using a combined reference standard of hyperaemic stenosis resistance index and myocardial perfusion scintigraphy.19 Another recent study assessed 3-year clinical outcomes in 150 patients with intermediate coronary lesions. Of these patients 56 had FFR 0.75–0.80 while the remaining 94 patients had FFR >0.80.20 Although target vessel revascularisation was higher in the patients with FFR 0.75–0.80 (14 % versus 3 %; p=0.020), there was no difference in rates if death or MI. This finding is consistent with the relationship between FFR and prognosis outlined above12 and emphasises that although there is a need for subsequent revascularisation in this group, they require careful consideration of the risk:benefit ratio of intervention.