Contrast Fractional Flow Reserve (cFFR): A pragmatic response to the call for simplification of invasive functional assessment

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Highlights

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    Hyperaemia for FFR can be costly, time consuming, unpleasant for the patient and possibly associated with side effects. Thus, new alternative indexes have been developed.

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    Among these alternative indexes, contrast-FFR (cFFR) shows the best correlation with FFR but has not yet been tested in randomised, controlled trial with clinical end-points.

  • •

    Compared to a hybrid approach with any resting index, avoidance of adenosine is greatest with cFFR

  • •

    If positive results of cFFR will be confirmed also on clinical endpoints, cFFR will represent a cheap, safe and effective alternative to FFR.

Abstract

Aim

To review the current approaches to simplify functional assessment of coronary stenosis with particular regard for contrast Fractional Flow Reserve (cFFR).

Methods and results

Maximal hyperaemia to assess FFR is perceived as time-consuming, costly, unpleasant for the patient and associated with side effects. Resting indexes, like Pd/Pa and iFR, have been proposed to circumvent the use of vasodilators as well as an approach based on the administration of contrast medium to induce coronary vasodilation, the cFFR. Contrast FFR can be obtained quickly, at very low cost in the absence of substantial side effects. Among these alternative indexes, cFFR shows the best correlation with FFR, reduces the use of adenosine even more than a hybrid resting approach but has not yet been tested in a randomized, controlled trial with clinical end-points.

Conclusion

cFFR represents a cheap, safe and effective alternative to FFR, able to facilitate the dissemination of a functional approach to myocardial revascularization.

Section snippets

From coronary flow reserve to fractional flow reserve

Our knowledge of coronary physiology stems from the seminal studies by Lance Gould et al. [1] who first assessed the quantitative haemodynamic relationship between lumen reduction and Coronary Flow Reserve (CFR). They studied 12 consecutive dogs who underwent a progressive occlusion of the left circumflex coronary artery inducing hyperaemia by the intra-coronary (i.c.) injection of Sodium Diatrizoate, a high osmolality contrast medium. Their data demonstrated that resting coronary flow is not

Vasodilator agents for hyperaemia

The most potent stimulus to hyperaemia is reactive hyperaemia to coronary occlusion that was used in past to clinically validate CFR [12]. However the need for a more practical method to induce hyperaemia for clinical purposes lead to introduction of papaverine [13] and then of intra-venous (i.v.) adenosine [14]. I.v. administration of adenosine at 140 μg/Kg/min is considered the best combination between hyperaemia and side effects (including dyspnoea, chest pain, hypotension, flushing, anxiety

Resting indexes: Pd/Pa and iFR

In the attempt to obviate the need for the administration of vasodilator agents, attention has been paid to the possible use of resting indexes. Mamas et al. [26] investigated the relationship between resting Pd/Pa and FFR obtained during maximal hyperaemia. They retrospectively analysed 528 consecutive FFR (in which maximal hyperaemia was obtained by i.v. adenosine 140 μg/Kg/min) performed in 483 patients over a 2-year period. The authors demonstrated that resting Pd/Pa has a significant

cFFR: the “The egg of Columbus” [45]

The hyperaemic potential of radiographic contrast media is well recognized since 60s. In addition to potentially cardio-toxic effects, such as ischemic ST-depression, arrhythmias and LV function depression, all ionic contrast media showed the ability to induce a significant coronary hyperaemia [46]. On this basis, some years later, Lance Gould used Sodium Diatrizoate to induce hyperaemia in his pivotal studies of CFR [1]. More recently, the availability of non-ionic contrast media with a very

Conclusions

Pharmacological hyperaemia for FFR assessment is time-consuming, costly, frequently unpleasant for the patient and sometimes associated with serious side effects. On the contrary cFFR can be quickly obtained, at very low cost, in the absence of substantial side effects. Among alternative indexes, cFFR shows the best correlation with FFR but has not been yet tested in a randomized trial with clinical end-points [59]. If accuracy of cFFR were translated in favourable results on clinical

Conflicts of interest

A.M.L. received speaking honoraria from St. Jude Medical/Abbott and from Bracco Imaging, F.C., F.L.P. and M.A. have no conflicts of interest.

References (59)

  • 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)
  • J. Escaned et al.

    Prospective assessment of the diagnostic accuracy of instantaneous wave-free ratio to assess coronary stenosis relevance: results of ADVISE II international, multicenter study (ADenosine vasodilator independent stenosis evaluation II)

    JACC Cardiovasc. Interv.

    (2015)
  • T. Härle et al.

    Comparison of instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) - first real world experience

    Int. J. Cardiol.

    (2015)
  • M. Van't Veer et al.

    Comparison of different diastolic resting indexes to iFR: are they all equal?

    J. Am. Coll. Cardiol.

    (2017)
  • K.L. Gould et al.

    Approximate Truth

    J. Am. Coll. Cardiol.

    (2017)
  • S.V. Guzman et al.

    Cardiac effects of intracoronary arterial injections of various roentgenographic contrast media

    Am. Heart J.

    (1959)
  • 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)
  • P. Van Wyk et al.

    The utility of contrast medium fractional flow reserve in functional assessment of coronary disease in daily practice

    Heart Lung Circ.

    (2018)
  • Y. Kanaji et al.

    Efficacy of pressure parameters obtained during contrast medium-induced submaximal hyperemia in the functional assessment of intermediate coronary stenosis

    Int. J. Cardiol.

    (2016)
  • Y. Kobayashi et al.

    The influence of lesion location on the diagnostic accuracy of adenosine-free coronary pressure wire measurements

    JACC Cardiovasc. Interv.

    (2016)
  • S. Vijayan et al.

    Assessing coronary blood flow physiology in the cardiac catheterisation laboratory

    Curr. Cardiol. Rev.

    (2017)
  • N.H. Pijls et al.

    Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty

    Circulation

    (1993)
  • G.J.W. Bech et al.

    Fractional flow reserve to determine the appropriateness of angioplasty in moderate coronary stenosis: a randomized trial

    Circulation

    (2001)
  • P.A.L. Tonino et al.

    Fractional flow reserve versus angiography for guideing percutaneous coronary intervention

    N. Engl. J. Med.

    (2009)
  • B. De Bruyne et al.

    Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease

    N. Engl. J. Med.

    (2012)
  • G. Montalescot et al.

    2013 ESC guidelines on the management of stable coronary artery disease

    Eur. Heart J.

    (2013)
  • B. De Bruyne et al.

    Coronary flow reserve calculated from pressure measurements in humans. Validation with positron emission tomography

    Circulation

    (1994)
  • C.W. White et al.

    Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis?

    N. Engl. J. Med.

    (1984)
  • R.F. Wilson et al.

    Intracoronary papaverine: an ideal coronary vasodilator for studies of the coronary circulation in conscious humans

    Circulation

    (1986)

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