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  • Review Article
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Fractional flow reserve as a surrogate for inducible myocardial ischaemia

A Correction to this article was published on 15 October 2013

This article has been updated

Abstract

Documentation of inducible myocardial ischaemia, related to the coronary stenosis of interest, is of increasing importance in lesion selection for percutaneous coronary intervention (PCI). Fractional flow reserve (FFR) is an easily understood, routine diagnostic modality that has become part of daily clinical practice, and is used as a surrogate technique for noninvasive assessment of myocardial ischaemia. However, the application of a single, discrete, cut-off value for FFR-guided lesion selection for PCI, and its adoption in contemporary revascularization guidelines, has limited the requirement for a thorough understanding of the physiological basis of FFR. This limitation constitutes an obstacle for the adequate use and interpretation of this technique, and also for the understanding of new and future modalities of physiological functional intracoronary testing. In this Review, we revisit the fundamental elements of coronary physiology in the absence or presence of coronary artery disease. We provide insight into three essential characteristics of FFR as a diagnostic tool in contemporary clinical practice—the theoretical framework of FFR and its associated limitations; the characteristics and role of FFR as a surrogate for noninvasively assessed myocardial ischaemia; and the requirement and associated caveats of potent vasodilatory drugs to induce maximal vasodilatation of the coronary vascular bed.

Key Points

  • Fractional flow reserve (FFR) is an invasive technique that was introduced as a surrogate for noninvasive assessment of inducible myocardial ischaemia

  • FFR is the physiological index of choice to evaluate functional lesion severity, because it is cost-effective and its use has unequivocal clinical benefit to patients with stable coronary artery disease

  • The relationship between FFR and inducible myocardial ischaemia and, therefore, the accuracy of FFR to identify ischaemia-generating stenoses, as based on a single, predefined cut-off value, can differ between patients

  • FFR is based on a simplified, theoretical framework of the coronary circulation, which has important consequences for appropriate use and interpretation that should be considered in daily clinical practice

  • The technique to measure FFR should adhere to methods used in validation studies, especially the methods used to achieve maximal vasodilatation, to ensure appropriate lesion selection for percutaneous coronary intervention

  • Full physiological investigation of a coronary lesion requires simultaneous assessment of intracoronary pressure and flow, thereby separating the contributions of epicardial and microvascular resistance to reduced blood flow

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Figure 1: The coronary pressure–flow relationship.
Figure 2: Diagram of stenosis flow field.
Figure 3: The relationship between stenosis pressure drop and flow velocity.
Figure 4: The coronary pressure–flow relationship in the absence and presence of stenosis.
Figure 5: Effect of changes in hyperaemic microvascular resistance on FFR and CFVR.
Figure 6: Relationship between coronary flow velocity and the distal:aortic pressure ratio during the vasodilatory response to adenosine.

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Change history

  • 15 October 2013

    In the version of this article originally published, the arrows in figure 5 were mislabelled. 'Increase in MR' and 'Decrease in MR' on the figure were swapped. This error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

The authors gratefully acknowledge the skilled assistance of Froukje Nolte MSc, of the Department of Biomedical Engineering and Physics at the Academic Medical Center of the University of Amsterdam, with the preparation of the figures. T. P. van de Hoef, M. Siebes, J. A. E. Spaan and J. J. Piek are funded by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 224495 (euHeart project), and by grants from the Dutch Heart Foundation (2006B186, 2000.090, and D96.020). J. E. Davies (FS/05/006) is a British Heart Foundation fellow.

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T. P. van de Hoef researched data for the article. All the authors discussed the content, wrote the article, and reviewed and edited the manuscript.

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Correspondence to Tim P. van de Hoef.

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J. E. Davies declares that he is a consultant for Volcano Corporation and holds intellectual property pertaining to iFR technology which is under license to Volcano Corporation.

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van de Hoef, T., Meuwissen, M., Escaned, J. et al. Fractional flow reserve as a surrogate for inducible myocardial ischaemia. Nat Rev Cardiol 10, 439–452 (2013). https://doi.org/10.1038/nrcardio.2013.86

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