Table of Contents
Year : 2020  |  Volume : 5  |  Issue : 1  |  Page : 3-4

A new contestant enters the race for noninvasive fractional flow reserve evaluation, iFRCT

1 Department of Radiology and Radiological Science, Division of Cardiovascular Imaging, Medical University of South Carolina, Charleston, SC, USA
2 First Department of Medicine-Cardiology, University Medical Centre Mannheim, Mannheim, Germany

Date of Submission14-Mar-2020
Date of Acceptance16-Mar-2020
Date of Web Publication4-Apr-2020

Correspondence Address:
Prof. U Joseph Schoepf
Department of Radiology and Radiological Science, Division of Cardiovascular Imaging, Medical University of South Carolina, Charleston, SC
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cp.cp_8_20

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How to cite this article:
Bayer II R, Baumann S, Schoepf U J. A new contestant enters the race for noninvasive fractional flow reserve evaluation, iFRCT. Cardiol Plus 2020;5:3-4

How to cite this URL:
Bayer II R, Baumann S, Schoepf U J. A new contestant enters the race for noninvasive fractional flow reserve evaluation, iFRCT. Cardiol Plus [serial online] 2020 [cited 2020 Sep 26];5:3-4. Available from:

The assessment of the functional significance of coronary artery disease (CAD) has been an important topic in both invasive and noninvasive cardiac imaging over the past decade. While invasive coronary angiography remains the gold standard for coronary artery luminal assessment, the decision to proceed with revascularization is no longer governed by subjective visual assessment of luminal stenosis. Prior data have demonstrated significant interobserver variability in the interpretation of coronary angiograms, while others have demonstrated a poor correlation between visual angiographic assessment and objective lesion-specific ischemia.[1],[2] It was with the Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention trial that patient outcomes were improved when fractional flow reserve (FFR) was utilized to guide coronary revascularization.[3] In addition, it has been demonstrated that coronary lesions without hemodynamic functional significance, as determined by FFR, can have intervention safely deferred. Within this patient population, the annual rates of myocardial infarction are <1%.[4] As such, FFR has a Class I indication for the assessment of lesion-specific ischemia to guide revascularization by the European Society of Cardiology and Class IIa recommendation for the American College of Cardiology.[5],[6]

In addition to FFR, an instantaneous wave-free ratio (iFR) is an alternative invasive method to assess the functional significance of coronary stenoses. FFR utilizes adenosine to reduce and minimize intracoronary resistance. Under these conditions, minimized and constant intracoronary resistance, pressure, and flow are proportional. Thus, decreased pressure across a coronary lesion corresponds to a decrease in the flow.[7] Utilizing similar principles, iFR utilizes an interval of time during diastole when intracoronary resistance is constant and low, similar to conditions obtained with adenosine infusion. During this time interval, the transtenotic pressure gradients reflect the functional significance of the stenosis.[7] These iFR pressure gradients are obtained without the need for intravenous adenosine administration. Prior studies have demonstrated that a revascularization strategy guided by iFR is noninferior to FFR.[8],[9] As such, iFR also carries a Class I indication for the assessment of lesion-specific ischemia by the European Society of Cardiology.[5]

While FFR and iFR allow for the assessment of lesion-specific ischemia once the patient has proceeded for invasive evaluation, many patients undergo invasive angiography only to reveal nonobstructive disease. As such, a method to determine the functional significance of coronary lesions prior to invasive angiography is attractive. This would allow for more efficient use of catheterization laboratories, focusing resource utilization on patients where intervention is appropriate. This is the premise behind coronary CT angiography (CCTA)-derived FFR. Noninvasive CT-based FFR utilizes methods such as computational fluid dynamics (FFRCFD-CT) and artificial intelligence-based machine learning (FFRML-CT) to calculate FFR values from standard CCTA datasets. FFRCFD-CT has demonstrated high diagnostic accuracy for the diagnosis of functionally significant CAD when compared to invasive FFR.[10] In addition, FFRML-CT has been shown to have a similar performance in detecting lesion-specific ischemia when compared to FFRCFD-CT.[11] Most importantly, in clinical practice, CCTA with selective FFRCFD-CT had similar outcomes to that of planned ICA while resulting in lower costs.[12] More recently, given the increased use of iFR, FFRML-CT has been shown to have excellent diagnostic performance when compared to iFR.[13]

The article by Zhang et al.[14] seeks to expand the existing evidence of noninvasive FFR utilizing a new technique that calculates a CCTA-derived iFR (iFRCT). In this article, iFRCT was compared to invasive FFR in 114 patients with 115 myocardial bridges (MBs). Their results demonstrated good diagnostic accuracy of iFRCT with a sensitivity of 0.90, a specificity of 0.73, and an accuracy of 0.79 when compared to invasive FFR.

The concept of iFRCT, as presented, represents an interesting and novel technique for the noninvasive evaluation of hemodynamically significant CAD. It is interesting that the authors elected to evaluate this technique in patients with myocardial bridging and not more traditional atherosclerotic coronary lesions. An MB is often considered a normal variant, and invasive functional assessment of MBs remains a source of controversy.[15] In addition, there are data that suggest because of the changes in intracoronary pressure related to vessel compression during systole that FFR may be less accurate in determining real hemodynamic significance when compared to iFR.[15] This would suggest that in this particular patient population, a more appropriate comparison of iFRCT might have, in fact, been invasive iFR itself. Moreover, one of the benefits to iFR is that infusion of adenosine, which can result in adverse procedural symptoms (chest pain, shortness of breath, etc.), is not needed.[9] However, with noninvasive CT-derived FFR (FFRCFD-CT and FFRML-CT), hyperemia is simulated and similarly does not require the infusion of adenosine. Given that both FFRCFD-CT and FFRML-CT have shown high diagnostic performance when compared to invasive reference standards, the benefit of an iFRCT approach remains unclear. Furthermore, the authors state that the modeling software for iFRCT is complex and time consuming but do not provide the time required to obtain results or how this compares to the other noninvasive FFR techniques. Finally, the study represents a small single-center trial and will require additional larger prospective trials to validate the results.

  References Top

Nallamothu BK, Spertus JA, Lansky AJ, Cohen DJ, Jones PG, Kureshi F, et al. Comparison of clinical interpretation with visual assessment and quantitative coronary angiography in patients undergoing percutaneous coronary intervention in contemporary practice: The Assessing Angiography (A2) project. Circulation 2013;127:1793-800.  Back to cited text no. 1
Fischer JJ, Samady H, McPherson JA, Sarembock IJ, Powers ER, Gimple LW, et al. Comparison between visual assessment and quantitative angiography versus fractional flow reserve for native coronary narrowings of moderate severity. Am J Cardiol 2002;90:210-5.  Back to cited text no. 2
Pijls NH, Fearon WF, Tonino PA, Siebert U, Ikeno F, Bornschein B, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) study. J Am Coll Cardiol 2010;56:177-84.  Back to cited text no. 3
Pijls NH, van Schaardenburgh P, Manoharan G, Boersma E, Bech JW, van't Veer M, et al. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER Study. J Am Coll Cardiol 2007;49:2105-11.  Back to cited text no. 4
Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. The Task Force on myocardial revascularization of the European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS). G Ital Cardiol (Rome) 2019;20:1-61S.  Back to cited text no. 5
Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol 2011;58:e44-122.  Back to cited text no. 6
Sen S, Escaned J, Malik IS, Mikhail GW, Foale RA, Mila R, et al. Development and validation of a new adenosine-independent index of stenosis severity from coronary wave-intensity analysis: Results of the ADVISE (ADenosine Vasodilator Independent Stenosis Evaluation) study. J Am Coll Cardiol 2012;59:1392-402.  Back to cited text no. 7
Götberg M, Christiansen EH, Gudmundsdottir IJ, Sandhall L, Danielewicz M, Jakobsen L, et al. Instantaneous wave-free ratio versus fractional flow reserve to guide PCI. N Engl J Med 2017;376:1813-23.  Back to cited text no. 8
Davies JE, Sen S, Dehbi HM, Al-Lamee R, Petraco R, Nijjer SS, et al. Use of the Instantaneous wave-free ratio or fractional flow reserve in PCI. N Engl J Med 2017;376:1824-34.  Back to cited text no. 9
Nørgaard BL, Leipsic J, Gaur S, Seneviratne S, Ko BS, Ito H, et al. Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: The NXT trial (analysis of coronary blood flow using CT angiography: Next steps). J Am Coll Cardiol 2014;63:1145-55.  Back to cited text no. 10
Tesche C, De Cecco CN, Baumann S, Renker M, McLaurin TW, Duguay TM, et al. Coronary CT angiography-derived fractional flow reserve: Machine learning algorithm versus computational fluid dynamics modeling. Radiology 2018;288:64-72.  Back to cited text no. 11
Douglas PS, De Bruyne B, Pontone G, Patel MR, Norgaard BL, Byrne RA, et al. 1-year outcomes of FFRCT-guided care in patients with suspected coronary disease: The PLATFORM study. J Am Coll Cardiol 2016;68:435-45.  Back to cited text no. 12
Baumann S, Hirt M, Schoepf UJ, et al. Correlation of machine learning computed tomography-based fractional flow reserve with instantaneous wave free ratio to detect hemodynamically significant coronary stenosis [published online ahead of print, 2019 Oct 29]. Clin Res Cardiol 2019.  Back to cited text no. 13
Zhang XY, Zhou F, Tang CX, Xu PP, Zhou CS, Zhang LJ. Diagnostic performance of coronary computed tomography angiography-derived instantaneous wave-free ratio for myocardial bridge. Cardiol Plus 2020;5:33-41.   Back to cited text no. 14
  [Full text]  
Tarantini G, Barioli A, Nai Fovino L, Fraccaro C, Masiero G, Iliceto S, et al. Unmasking myocardial bridge-related ischemia by intracoronary functional evaluation. Circ Cardiovasc Interv 2018;11:e006247.  Back to cited text no. 15


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