SpringerLink
Log in

Pd/Pa fluctuation with continuous ATP administration indicates inaccurate FFR measurement caused by insufficient hyperemia

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

Abstract

Continuous intravenous adenosine triphosphate (ATP) administration is the standard method for inducing maximal hyperemia in fractional flow reserve (FFR) measurements. Several cases have demonstrated fluctuations in the ratio of mean distal coronary pressure to mean arterial pressure (Pd/Pa) value during ATP infusion, which raised our suspicions of FFR value inaccuracy. This study aimed to investigate our hypothesis that Pd/Pa fluctuations may indicate inaccurate FFR measurements caused by insufficient hyperemia. We examined 57 consecutive patients with angiographically intermediate coronary lesions who underwent fractional flow reverse (FFR) measurements in our hospital between November 2016 and September 2018. Pd/Pa was measured after continuous ATP administration (150 μg/kg/min) via a peripheral forearm vein for 5 min (FFRA); and we analyzed the FFR value variation in the final 20 s of the 5 min, defining ‘Fluctuation’ as variation range > 0.03. Then, 2 mg of nicorandil was administered into the coronary artery during continued ATP infusion, and the Pd/Pa was remeasured (FFRA+N). Fluctuations were observed in 23 of 57 patients. The cases demonstrating discrepancies of > 0.05 between FFRA and FFRA+N were observed more frequently in the fluctuation group than in the non-fluctuation group (12/23 vs. 1/34; p < 0.0001). The discrepancy between FFRA and FFRA+N values was smaller in the non-fluctuation group (mean difference ± SD; −0.00026 ± 0.04636 vs. 0.02608 ± 0.1316). Pd/Pa fluctuation with continuous ATP administration could indicate inaccurate FFR measurements caused by incomplete hyperemia. Additional vasodilator administration may achieve further hyperemia when Pd/Pa fluctuations are observed.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Data availability

The data that support the findings of this study are not openly available. However the data are available from the corresponding author upon reasonable request.

References

  1. Pijls NH, Van Gelder B, Van der Voort P, Peels K, Bracke FA, Bonnier HJ, el Gamal MI (1995) Fractional flow reserve. a useful index to evaluate the influence of an epicardial coronary stenosis on myocardial blood flow. Circulation 92:3183–3193

    Article  CAS  PubMed  Google Scholar 

  2. Tonino PA, Fearon WF, De Bruyne B, Oldroyd KG, Leesar MA, Ver Lee PN, Maccarthy PA, Van’t Veer M, Pijls NH (2010) Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation. J Am Coll Cardiol 55:2816–2821

    Article  PubMed  Google Scholar 

  3. De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PA, Piroth Z, Jagic N, Möbius-Winkler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engström T, Oldroyd KG, Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Jüni P, Fearon WF, FAME 2 Trial Investigators (2012) Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med 367:991–1001

    Article  PubMed  Google Scholar 

  4. Tanaka N, Nakamura M, Akasaka T, Kadota K, Uemura S, Amano T, Shiode N, Morino Y, Fujii K, Hikichi Y, CVIT-DEFER Registry Investigators (2017) One-year outcome of fractional flow reserve-based coronary intervention in Japanese daily practice-CVIT-DEFER registry. Circ J 81:1301–1306

    Article  PubMed  Google Scholar 

  5. Toth GG, Johnson NP, Jeremias A, Pellicano M, Vranckx P, Fearon WF, Barbato E, Kern MJ, Pijls NH, De Bruyne B (2016) Standardization of fractional flow reserve measurements. J Am Coll Cardiol 68:742–753

    Article  PubMed  Google Scholar 

  6. Johnson NP, Johnson DT, Kirkeeide RL, Berry C, De Bruyne B, Fearon WF, Oldroyd KG, Pijls NHJ, Gould KL (2015) Repeatability of fractional flow reserve despite variations in systemic and coronary hemodynamics. JACC Cardiovasc Interv 8:1018–1027

    Article  PubMed  Google Scholar 

  7. Matsumoto H, Nakatsuma K, Shimada T, Ushimaru S, Mikuri M, Yamazaki T, Matsuda T (2014) Effect of caffeine on intravenous adenosine-induced hyperemia in fractional flow reserve measurement. J Invasive Cardiol 26:580–585

    PubMed  Google Scholar 

  8. Wilson RF, Wyche K, Christensen BV, Zimmer S, Laxson DD (1990) Effects of adenosine on human coronary arterial circulation. Circulation 82:1595–1606

    Article  CAS  PubMed  Google Scholar 

  9. Seto AH, Tehrani DM, Bharmal MI, Kern MJ (2014) Variations of coronary hemodynamic responses to intravenous adenosine infusion: implications for fractional flow reserve measurements. Catheter Cardiovasc Interv 84:416–425

    Article  PubMed  Google Scholar 

  10. Zhang Y, Wernly B, Cao X, Mustafa SJ, Tang Y, Zhou Z (2021) Adenosine and adenosine receptor-mediated action in coronary microcirculation. Basic Res Cardiol 116:22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ho MF, Low LM, Rose’Meyer RB (2016) Pharmacology of the adenosine A3 receptor in the vasculature and essential hypertension. PLoS ONE 11:e0150021

    Article  PubMed  PubMed Central  Google Scholar 

  12. Bender SB, Tune JD, Borbouse L, Long X, Sturek M, Laughlin MH (2009) Altered mechanism of adenosine-induced coronary arteriolar dilation in early-stage metabolic syndrome. Exp Biol Med (Maywood) 234:683–692

    Article  CAS  PubMed  Google Scholar 

  13. Zhou Z, de Wijs-Meijler D, Lankhuizen I, Jankowski J, Jankowski V, Jan Danser AH, Duncker DJ, Merkus D (2013) Blunted coronary vasodilator response to uridine adenosine tetraphosphate in post-infarct remodeled myocardium is due to reduced P1 receptor activation. Pharmacol Res 77:22–29

    Article  CAS  PubMed  Google Scholar 

  14. De Bruyne B, Pijls NH, Bartunek J, Kulecki K, Bech JW, De Winter H, Van Crombrugge P, Heyndrickx GR, Wijns W (2001) Fractional flow reserve in patients with prior myocardial infarction. Circulation 104:157–162

    Article  PubMed  Google Scholar 

  15. Kofflard MJ, Michels M, Krams R, Kliffen M, Geleijnse ML, Ten Cate FJ, Serruys PW (2007) Coronary flow reserve in hypertrophic cardiomyopathy: relation with microvascular dysfunction and pathophysiological characteristics. Neth Heart J 15:209–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jang HJ, Koo BK, Lee HS, Park JB, Kim JH, Seo MK, Yang HM, Park KW, Nam CW, Doh JH, Kim HS (2013) Safety and efficacy of a novel hyperaemic agent, intracoronary nicorandil, for invasive physiological assessments in the cardiac catheterization laboratory. Eur Heart J 34:2055–2062

    Article  CAS  PubMed  Google Scholar 

  17. Tanaka N, Takahashi Y, Ishihara H, Kawakami T, Ono H (2015) Usefulness and safety of intracoronary administration of nicorandil for evaluating fractional flow reserve in Japanese patients. Clin Cardiol 38:20–24

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kato D, Takashima H, Waseda K, Kurita A, Kuroda Y, Kosaka T, Kuhara Y, Ando H, Maeda K, Kumagai S, Sakurai S, Suzuki A, Toda Y, Watanabe A, Sato S, Fujimoto M, Mizuno T, Amano T (2015) Feasibility and safety of intracoronary nicorandil infusion as a novel hyperemic agent for fractional flow reserve measurements. Heart Vessel 30:477–483

    Article  Google Scholar 

  19. Markham A, Plosker GL, Goa KL (2000) Nicorandil. an updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects. Drugs 60:955–974

    Article  CAS  PubMed  Google Scholar 

  20. Ishibuchi K, Fujii K, Otsuji S, Takiuchi S, Hasegawa K, Tamaru H, Ishii R, Yasuda S, Nakabayashi S, Yamamoto W, Kusumoto H, Taniguchi Y, Kakishita M, Shimatani Y, Higashino Y (2019) Utility and validity of intracoronary administration of nicorandil alone for the measurement of fractional flow reserve in patients with intermediate coronary stenosis. Circ J 83:2010–2016

    Article  CAS  PubMed  Google Scholar 

  21. Takami H, Sonoda S, Muraoka Y, Sanuki Y, Kashiyama K, Fukuda S, Oginosawa Y, Tsuda Y, Araki M, Otsuji Y (2017) Impact of additional intracoronary nicorandil administration during fractional flow reserve measurement with intravenous adenosine 5’-triphosphate infusion. J Cardiol 69:119–124

    Article  PubMed  Google Scholar 

  22. Matsumoto H, Mikuri M, Masaki R, Tanaka H, Ogura K, Arai T, Sakai R, Oishi Y, Okada N, Shinke T (2020) Feasibility of intracoronary nicorandil for inducing hyperemia on fractional flow reserve measurement: comparison with intracoronary papaverine. Int J Cardiol 314:1–6

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the work of past and present members of our laboratory.

Funding

The authors declare no conflicts of interest associated with this manuscript.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757, Asahimachidori, Chuo-ku, Niigata, 951-8510, Japan

    Shintaro Yoneyama, Makoto Hoyano, Kazuyuki Ozaki, Ryutaro Ikegami, Naoki Kubota, Takeshi Okubo, Takao Yanagawa, Takakuni Kurokawa, Takumi Akiyama, Yuzo Washiyama, Takeshi Kashimura & Takayuki Inomata

Authors
  1. Shintaro Yoneyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Makoto Hoyano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuyuki Ozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ryutaro Ikegami
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naoki Kubota
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takeshi Okubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takao Yanagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takakuni Kurokawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Takumi Akiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yuzo Washiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Takeshi Kashimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Takayuki Inomata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shintaro Yoneyama.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Authorship inclusion criteria

This manuscript has been read and approved by all the authors, the requirements for authorship as stated above have been met, and each author believes that this manuscript represents honest work.

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

Yoneyama, S., Hoyano, M., Ozaki, K. et al. Pd/Pa fluctuation with continuous ATP administration indicates inaccurate FFR measurement caused by insufficient hyperemia. Heart Vessels (2024). https://doi.org/10.1007/s00380-024-02438-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00380-024-02438-x

Keywords

Search

Navigation