Skip to main content

Advertisement

SpringerLink
Log in

The reliability and utility of on-site CT-derived fractional flow reserve (FFR) based on fluid structure interactions: comparison with FFRCT based on computational fluid dynamics, invasive FFR, and resting full-cycle ratio

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

Fractional flow reserve (FFR) derived off-site by coronary computed tomography angiography (CCTA) (FFRCT) is obtained by applying the principles of computational fluid dynamics. This study aimed to validate the overall reliability of on-site CCTA-derived FFR based on fluid structure interactions (CT-FFR) and assess its clinical utility compared with FFRCT, invasive FFR, and resting full-cycle ratio (RFR). We calculated the CT-FFR for 924 coronary vessels in 308 patients who underwent CCTA for clinically suspected coronary artery disease. Of these patients, 35 patients with at least one obstructive stenosis (> 50%) detected on CCTA underwent both CT-FFR and FFRCT for further investigation. Furthermore, 24 and 20 patients underwent invasive FFR and RFR in addition to CT-FFR, respectively. The inter-observer correlation (r) of CT-FFR was 0.93 (95% confidence interval [CI] 0.85–0.97, P < 0.0001) with a mean absolute difference of − 0.0042 (limits of agreement − 0.073, 0.064); 97.3% of coronary arteries without obstructive lesions on CCTA had negative results for ischemia on CT-FFR (> 0.80). The correlation coefficient between CT-FFR and FFRCT for 105 coronary vessels was 0.87 (95% CI 0.82–0.91, P < 0.0001) with a mean absolute difference of − 0.012 (limits of agreement − 0.12, 0.10). CT-FFR correlated well with both invasive FFR (r = 0.66, 95% CI 0.36–0.84, P = 0.0003) and RFR (r = 0.78, 95% CI 0.51–0.91, P < 0.0001). These data suggest that CT-FFR can potentially substitute for FFRCT and correlates closely with invasive FFR and RFR with high reproducibility. Our findings should be proven by further clinical investigation in a larger cohort.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data Availability

The datasets analyzed during the current study are not publicly available due to privacy reasons, but are available from the corresponding author on reasonable request.

Abbreviations

CAD:

Coronary artery disease

CCTA:

Coronary computed tomography angiography

CFD:

Computational fluid dynamics

CT:

Computed tomography

FFR:

Fractional flow reserve

ICA:

Invasive coronary angiography

iFR:

Instantaneous wave-free ratio

RFR:

Resting full-cycle ratio

References

  1. Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, Van’t Veer M, Klauss V, Manoharan G, Engstrøm T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF, FAME Study Investigators (2009) Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 360:213–224

    Article  CAS  PubMed  Google Scholar 

  2. De Bruyne B, Fearon WF, Pijls NH, Barbato E, Tonino P, Piroth Z, Jagic N, Mobius-Winckler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engström T, Oldroyd K, Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Limacher A, Nüesch E, Jüni P, FAME 2 Trial Investigators (2014) Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med 371:1208–1217

    Article  PubMed  Google Scholar 

  3. Koo BK, Erglis A, Doh JH, Daniels DV, Jegere S, Kim HS, Dunning A, DeFrance T, Lansky A, Leipsic J, Min JK (2011) Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol 58:1989–1997

    Article  PubMed  Google Scholar 

  4. Min JK, Leipsic J, Pencina MJ, Berman DS, Koo BK, van Mieghem C, Erglis A, Lin FY, Dunning AM, Apruzzese P, Budoff MJ, Cole JH, Jaffer FA, Leon MB, Malpeso J, Mancini GB, Park SJ, Schwartz RS, Shaw LJ, Mauri L (2012) Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. JAMA 308:1237–1245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Nørgaard BL, Leipsic J, Gaur S, Seneviratne S, Ko BS, Ito H, Jensen JM, Mauri L, De Bruyne B, Bezerra H, Osawa K, Marwan M, Naber C, Erglis A, Park SJ, Christiansen EH, Kaltoft A, Lassen JF, Bøtker HE, Achenbach S, NXT Trial Study Group (2014) 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 63:1145–1155

    Article  PubMed  Google Scholar 

  6. Patel MR, Nørgaard BL, Fairbairn TA, Nieman K, Akasaka T, Berman DS, Raff GL, Hurwitz Koweek LM, Pontone G, Kawasaki T, Sand NPR, Jensen JM, Amano T, Poon M, Øvrehus KA, Sonck J, Rabbat MG, Mullen S, De Bruyne B, Rogers C, Matsuo H, Bax JJ, Leipsic J (2020) 1-year impact on medical practice and clinical outcomes of FFRCT: the advance registry. JACC Cardiovasc Imaging 13:97–105

    Article  PubMed  Google Scholar 

  7. Hirohata K, Kano A, Goryu A, Ooga J, Hongo T, Higashi S, Fujisawa Y, Wakai S, Arakita K, Ikeda Y, Kaminaga S, Ko BS, Seneviratne SK (2015) A novel CT-FFR method for the coronary artery based on 4D-CT image analysis and structural and fluid analysis. SPIE Med Imaging. 9412:652–666

    Google Scholar 

  8. Kato M, Hirohata K, Kano A, Higashi S, Goryu A, Hongo T, Kaminaga S, Fujisawa Y (2015) Fast CT-FFR analysis method for the coronary artery based on 4D-CT image analysis and structural and fluid analysis. In Proceedings of the American Society of Mechanical Engineers 2015 International Mechanical Engineering Congress and Exposition. ASME, New York. pp. 51124.

  9. Ko BS, Cameron JD, Munnur RK, Wong DTL, Fujisawa Y, Sakaguchi T, Hirohata K, Hislop-Jambrich J, Fujimoto S, Takamura K, Crossett M, Leung M, Kuganesan A, Malaiapan Y, Nasis A, Troupis J, Meredith IT, Seneviratne SK (2017) Noninvasive CT-Derived FFR based on structural and fluid analysis: a Comparison with invasive FFR for detection of functionally significant stenosis. JACC Cardiovasc Imaging 10:663–673

    Article  PubMed  Google Scholar 

  10. Fujimoto S, Kawasaki T, Kumamaru KK, Kawaguchi Y, Dohi T, Okonogi T, Ri K, Yamada S, Takamura K, Kato E, Kato Y, Hiki M, Okazaki S, Aoki S, Mitsouras D, Rybicki FJ, Daida H (2019) Diagnostic performance of on-site computed CT-fractional flow reserve based on fluid structure interactions: comparison with invasive fractional flow reserve and instantaneous wave-free ratio. Eur Heart J Cardiovasc Imaging 20:343–352

    Article  PubMed  Google Scholar 

  11. Abbara S, Blanke P, Maroules CD, Cheezum M, Choi AD, Han BK, Marwan M, Naoum C, Norgaard BL, Rubinshtein R, Schoenhagen P, Villines T, Leipsic J (2016) SCCT guidelines for the performance and acquisition of coronary computed tomographic angiography: a report of the society of cardiovascular computed tomography guidelines committee: endorsed by the North American Society for Cardiovascular Imaging (NASCI). J Cardiovasc Comput Tomogr 10:435–449

    Article  PubMed  Google Scholar 

  12. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15:827–832

    Article  CAS  PubMed  Google Scholar 

  13. Kitagawa T, Yamamoto H, Toshimitsu S, Sasaki K, Senoo A, Kubo Y, Tatsugami F, Awai K, Hirokawa Y, Kihara Y (2017) 18F-sodium fluoride positron emission tomography for molecular imaging of coronary atherosclerosis based on computed tomography analysis. Atherosclerosis 263:385–392

    Article  CAS  PubMed  Google Scholar 

  14. Cury RC, Abbara S, Achenbach S, Agatston A, Berman DS, Budoff MJ, Dill KE, Jacobs JE, Maroules CD, Rubin GD, Rybicki FJ, Schoepf UJ, Shaw LJ, Stillman AE, White CS, Woodard PK, Leipsic JA (2016) CAD-RADS(TM) coronary artery disease reporting and data system. An expert consensus document of the Society of Cardiovascular Computed Tomography (SCCT), the American College of Radiology (ACR) and the North American Society for Cardiovascular Imaging (NASCI). Endorsed by the American College of Cardiology. J Cardiovasc Comput Tomogr. 10(4):269–281

    Article  PubMed  Google Scholar 

  15. Sen S, Escaned J, Malik IS, Mikhail GW, Foale RA, Mila R, Tarkin J, Petraco R, Broyd C, Jabbour R, Sethi A, Baker CS, Bellamy M, Al-Bustami M, Hackett D, Khan M, Lefroy D, Parker KH, Hughes AD, Francis DP, Di Mario C, Mayet J, Davies JE (2012) 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 59:1392–1402

    Article  CAS  PubMed  Google Scholar 

  16. Nozaki YO, Fujimoto S, Aoshima C, Kamo Y, Kawaguchi YO, Takamura K, Kudo A, Takahashi D, Hiki M, Kato Y, Okai I, Dohi T, Okazaki S, Tomizawa N, Kumamaru KK, Aoki S, Minamino T (2021) Comparison of diagnostic performance in on-site based CT-derived fractional flow reserve measurements. Int J Cardiol Heart Vasc 35:100815

    PubMed  PubMed Central  Google Scholar 

  17. Taylor CA, Fonte TA, Min JK (2013) Computational fluid dynamics applied to cardiac computed tomography for noninvasive quantification of fractional flow reserve: scientific basis. J Am Coll Cardiol 61:2233–2241

    Article  PubMed  Google Scholar 

  18. Omori H, Hara M, Sobue Y, Kawase Y, Mizukami T, Tanigaki T, Hirata T, Ota H, Okubo M, Hirakawa A, Suzuki T, Kondo T, Leipsic J, Nørgaard BL, Matsuo H (2021) Determination of the optimal measurement point for fractional flow reserve derived from CTA using pressure wire assessment as reference. AJR Am J Roentgenol 216(6):1492–1499

    Article  PubMed  Google Scholar 

  19. Norgaard BL, Fairbairn TA, Safian RD, Rabbat MG, Ko B, Jensen JM, Nieman K, Chinnaiyan KM, Sand NP, Matsuo H, Leipsic J, Raff G (2019) Coronary CT angiography-derived fractional flow reserve testing in patients with stable coronary artery disease: recommendations on interpretation and reporting. Radiol Cardiothorac Imaging 1(5):e190050

    Article  PubMed  PubMed Central  Google Scholar 

  20. Lee JM, Choi KH, Park J, Hwang D, Rhee TM, Kim J, Park J, Kim HY, Jung HW, Cho YK, Yoon HJ, Song YB, Hahn JY, Nam CW, Shin ES, Doh JH, Hur SH, Koo BK (2019) Physiological and clinical assessment of resting physiological indexes. resting full-cycle ratio, diastolic pressure ratio, and instantaneous wave-free ratio. Circulation 139:889–900

    Article  PubMed  Google Scholar 

  21. Ge J, Erbel R, Rupprecht HJ, Koch L, Kearney P, Görge G, Haude M, Meyer J (1994) Comparison of intravascular ultrasound and angiography in the assessment of myocardial bridging. Circulation 89:1725–1732

    Article  CAS  PubMed  Google Scholar 

  22. Kumar G, Desai R, Gore A, Rahim H, Maehara A, Matsumura M, Kirtane A, Jeremias A, Ali Z (2020) Real world validation of the nonhyperemic index of coronary artery stenosis severity—Resting full-cycle ratio—RE-VALIDATE. Catheter Cardiovasc Interv 96(1):E53–E58

    Article  PubMed  Google Scholar 

  23. Kawaguchi YO, Fujimoto S, Kumamaru KK, Kato E, Dohi T, Takamura K, Aoshima C, Kamo Y, Kato Y, Hiki M, Okai I, Okazaki S, Aoki S, Daida H (2019) The predictive factors affecting false positive in on-site operated CT-fractional flow reserve based on fluid and structural interaction. Int J Cardiol Heart Vasc 23:100372

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This research was supported by the Mochida Memorial Foundation for Medical and Pharmaceutical Research, and a JSPS KAKENHI Grant-in-Aid for Scientific Research (Grant Number 21K08127).

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan

    Yuto Fujii, Toshiro Kitagawa, Hiroki Ikenaga & Yukiko Nakano

  2. Department of Diagnostic Radiology, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan

    Fuminari Tatsugami & Kazuo Awai

Authors
  1. Yuto Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshiro Kitagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroki Ikenaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fuminari Tatsugami
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazuo Awai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yukiko Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YF: Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing—original draft, Visualization. TK: Conceptualization, Methodology, Writing—review & editing, Visualization. HI: Investigation, Data curation. FT: Investigation, Data curation. KA: Supervision. YN: Supervision.

Corresponding author

Correspondence to Toshiro Kitagawa.

Ethics declarations

Conflict of interest

Although not directly influencing the contents of this manuscript, co-author Kazuo Awai has a Collaborative Research Laboratory contract with Canon Medical Systems Corporation. All other authors declare no conflicts of interest associated with this manuscript.

Ethical approval

Ethical approval for this study was given by the Ethical Committee for Epidemiology of Hiroshima University (reference number E-2010). Informed consent was secured via the opt-out route in view of the non-interventional nature of the research and anonymity of the data.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fujii, Y., Kitagawa, T., Ikenaga, H. et al. The reliability and utility of on-site CT-derived fractional flow reserve (FFR) based on fluid structure interactions: comparison with FFRCT based on computational fluid dynamics, invasive FFR, and resting full-cycle ratio. Heart Vessels 38, 1095–1107 (2023). https://doi.org/10.1007/s00380-023-02265-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-023-02265-6

Keywords

Search

Navigation