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From bench to practice: fractional flow reserve

Session presentations
Basic Sciences, Pharmacology, Genomics and Cardiovascular Pathology

This session, dedicated to fractional flow reserve (FFR), a pressure derived index of stenosis severity, was held 2 days before the presentation of a landmark study in the field at the ESC congress in Munich, namely the FAME II trial. This fact may explain the great interest demonstrated by the audience, with numerous questions posed to the presenters in the session.

Nico Pijls presented a comprehensive review of the experimental basis of FFR. A key aspect of the acceptance of FFR is the simplicity of its technique, facilitated by a simplified model of coronary circulation that makes it possible to draw conclusions on the restriction of myocardial blood supply caused by coronary stenoses. After performing a historical review of the use of pressure to assess stenosis severity, Dr Pijls highlighted the differences between trans-stenotic pressure gradients and FFR, a hyperemic trans-stenotic pressure gradient. The stability of FFR measurements in shifting haemodynamic conditions was emphasised.

One of the most important aspects of FFR is adequate performance of the technique. Emmanuele Barbato proposed a very useful checklist of conditions for accurate FFR measurements. The importance of achieving adequate coronary hyperemia, the avoidance of catheter pressure damping as a consequence of engagement in the vessel (particularly in left main or ostial stenosis), and the special value of FFR in small vessels was discussed. His presentation included numerous excellent examples illustrating how improper technique may lead to major errors in stenosis assessment unless they are identified and corrected in a timely manner.

Francois Schiele, from Besançon, France, performed a critical review of the available decision-making trials using FFR (DEFER and FAME). He highlighted some of the differences between the trials reported to date, namely DEFER and FAME. While DEFER used an FFR cut-off of 0.75 and enrolled only stable patients, in FAME the FFR cut-off was 0.80 and both stable and unstable patients were randomised. This allowed conclusions on the safety of clinical decision making in both coronary syndromes (acute and non-acute), keeping in mind that interrogation of the culprit artery in myocardial infarction remains a contra-indication for FFR. The FAME II trial was born in the post-COURAGE era, which cast major doubts as to the benefit of coronary revascularisation in patients with stable angina, compared to medical treatment. However, further data based on the COURAGE nuclear substudy and study-level meta-analysis investigating this issue suggested that PCI results in better patient outcome than medical treatment if adequate identification of patients with ischemia is performed. FAME II was designed to demonstrate this concept. However, in the view of the presenter, the premature interruption of the trial could limit the conclusions of the trial.

The final presentation, by Justin Davies, provided a glimpse into the future of pressure-derived indices of stenosis severity. Despite all the accumulated evidence on the benefit of using FFR in clinical practice, its rate of uptake of use remains very low, about 6%. In the view of the presenter, the development of an adenosine free index of stenosis severity would contribute to simplifying the technique, at low costs, and increased safety of the examination. Dr Davies presented the concept of instantaneous wave free ratio (iFR), defined as the translesional pressure ratio over a specific interval of the cardiac cycle (the wave-free period) without the need for concomitant adenosine administration. Data from the ADVISE study and the ADVISE registry (published online the opening day of the ESC congress) that support the value of iFR to assess coronary stenoses, compared with FFR, was reviewed. In addition, favourable (South Korean study) and unfavourable (VERIFY registry) comparisons of iFR and FFR were also presented. The limitations of further comparisons were highlighted on the grounds of the impact that frequency distribution and intra-technique variability have on the classification agreement of diagnostic tests that use a dichotomous classification (significant/non-significant) of disease. The possibility of using a combined iFR / FFR approach to limit the use of adenosine to stenoses with iFR values close to the diagnostic cutoff (0.90) was presented.

In summary, a great session on coronary physiology demonstrating that this type of assessment, born in the bench of the physiology lab, has become a way to improve outcomes in patients with coronary artery disease.




From bench to practice: fractional flow reserve

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.