Prognostic value of fractional flow reserve: Linking physiologic severity to clinical outcomes

Nils P. Johnson, Gábor G. Tóth, Dejian Lai, Hongjian Zhu, Göksel Açar, Pierfrancesco Agostoni, Yolande Appelman, Fatih Arslan, Emanuele Barbato, Shao Liang Chen, Luigi Di Serafino, Antonio J. Domínguez-Franco, Patrick Dupouy, Ali M. Esen, Özlem B. Esen, Michalis Hamilos, Kohichiro Iwasaki, Lisette O. Jensen, Manuel F. Jiménez-Navarro, Demosthenes G. KatritsisSinan A. Kocaman, Bon Kwon Koo, Ramón López-Palop, Jeffrey D. Lorin, Louis H. Miller, Olivier Muller, Chang Wook Nam, Niels Oud, Etienne Puymirat, Johannes Rieber, Gilles Rioufol, Josep Rodés-Cabau, Steven P. Sedlis, Yasuchika Takeishi, Pim A.L. Tonino, Eric Van Belle, Edoardo Verna, Gerald S. Werner, William F. Fearon, Nico H.J. Pijls, Bernard De Bruyne, K. Lance Gould

Research output: Contribution to journalArticle

269 Citations (Scopus)

Abstract

Background Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.

Objectives The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.

Methods Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.

Results A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.

Conclusions FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy. (J Am Coll Cardiol 2014;64:164154).

Original languageEnglish
Pages (from-to)1641-1654
Number of pages14
JournalJournal of the American College of Cardiology
Volume64
Issue number16
DOIs
StatePublished - 21 Oct 2014

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Anatomy
Meta-Analysis
Therapeutics
Confidence Intervals

Keywords

  • fractional flow reserve
  • meta-analysis
  • prognosis
  • threshold

Cite this

Johnson, N. P., Tóth, G. G., Lai, D., Zhu, H., Açar, G., Agostoni, P., ... Gould, K. L. (2014). Prognostic value of fractional flow reserve: Linking physiologic severity to clinical outcomes. Journal of the American College of Cardiology, 64(16), 1641-1654. https://doi.org/10.1016/j.jacc.2014.07.973
Johnson, Nils P. ; Tóth, Gábor G. ; Lai, Dejian ; Zhu, Hongjian ; Açar, Göksel ; Agostoni, Pierfrancesco ; Appelman, Yolande ; Arslan, Fatih ; Barbato, Emanuele ; Chen, Shao Liang ; Di Serafino, Luigi ; Domínguez-Franco, Antonio J. ; Dupouy, Patrick ; Esen, Ali M. ; Esen, Özlem B. ; Hamilos, Michalis ; Iwasaki, Kohichiro ; Jensen, Lisette O. ; Jiménez-Navarro, Manuel F. ; Katritsis, Demosthenes G. ; Kocaman, Sinan A. ; Koo, Bon Kwon ; López-Palop, Ramón ; Lorin, Jeffrey D. ; Miller, Louis H. ; Muller, Olivier ; Nam, Chang Wook ; Oud, Niels ; Puymirat, Etienne ; Rieber, Johannes ; Rioufol, Gilles ; Rodés-Cabau, Josep ; Sedlis, Steven P. ; Takeishi, Yasuchika ; Tonino, Pim A.L. ; Van Belle, Eric ; Verna, Edoardo ; Werner, Gerald S. ; Fearon, William F. ; Pijls, Nico H.J. ; De Bruyne, Bernard ; Gould, K. Lance. / Prognostic value of fractional flow reserve : Linking physiologic severity to clinical outcomes. In: Journal of the American College of Cardiology. 2014 ; Vol. 64, No. 16. pp. 1641-1654.
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title = "Prognostic value of fractional flow reserve: Linking physiologic severity to clinical outcomes",
abstract = "Background Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.Objectives The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.Methods Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.Results A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95{\%} confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20{\%} fewer adverse events and 10{\%} better angina relief.Conclusions FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy. (J Am Coll Cardiol 2014;64:164154).",
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language = "English",
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Johnson, NP, Tóth, GG, Lai, D, Zhu, H, Açar, G, Agostoni, P, Appelman, Y, Arslan, F, Barbato, E, Chen, SL, Di Serafino, L, Domínguez-Franco, AJ, Dupouy, P, Esen, AM, Esen, ÖB, Hamilos, M, Iwasaki, K, Jensen, LO, Jiménez-Navarro, MF, Katritsis, DG, Kocaman, SA, Koo, BK, López-Palop, R, Lorin, JD, Miller, LH, Muller, O, Nam, CW, Oud, N, Puymirat, E, Rieber, J, Rioufol, G, Rodés-Cabau, J, Sedlis, SP, Takeishi, Y, Tonino, PAL, Van Belle, E, Verna, E, Werner, GS, Fearon, WF, Pijls, NHJ, De Bruyne, B & Gould, KL 2014, 'Prognostic value of fractional flow reserve: Linking physiologic severity to clinical outcomes', Journal of the American College of Cardiology, vol. 64, no. 16, pp. 1641-1654. https://doi.org/10.1016/j.jacc.2014.07.973

Prognostic value of fractional flow reserve : Linking physiologic severity to clinical outcomes. / Johnson, Nils P.; Tóth, Gábor G.; Lai, Dejian; Zhu, Hongjian; Açar, Göksel; Agostoni, Pierfrancesco; Appelman, Yolande; Arslan, Fatih; Barbato, Emanuele; Chen, Shao Liang; Di Serafino, Luigi; Domínguez-Franco, Antonio J.; Dupouy, Patrick; Esen, Ali M.; Esen, Özlem B.; Hamilos, Michalis; Iwasaki, Kohichiro; Jensen, Lisette O.; Jiménez-Navarro, Manuel F.; Katritsis, Demosthenes G.; Kocaman, Sinan A.; Koo, Bon Kwon; López-Palop, Ramón; Lorin, Jeffrey D.; Miller, Louis H.; Muller, Olivier; Nam, Chang Wook; Oud, Niels; Puymirat, Etienne; Rieber, Johannes; Rioufol, Gilles; Rodés-Cabau, Josep; Sedlis, Steven P.; Takeishi, Yasuchika; Tonino, Pim A.L.; Van Belle, Eric; Verna, Edoardo; Werner, Gerald S.; Fearon, William F.; Pijls, Nico H.J.; De Bruyne, Bernard; Gould, K. Lance.

In: Journal of the American College of Cardiology, Vol. 64, No. 16, 21.10.2014, p. 1641-1654.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prognostic value of fractional flow reserve

T2 - Linking physiologic severity to clinical outcomes

AU - Johnson, Nils P.

AU - Tóth, Gábor G.

AU - Lai, Dejian

AU - Zhu, Hongjian

AU - Açar, Göksel

AU - Agostoni, Pierfrancesco

AU - Appelman, Yolande

AU - Arslan, Fatih

AU - Barbato, Emanuele

AU - Chen, Shao Liang

AU - Di Serafino, Luigi

AU - Domínguez-Franco, Antonio J.

AU - Dupouy, Patrick

AU - Esen, Ali M.

AU - Esen, Özlem B.

AU - Hamilos, Michalis

AU - Iwasaki, Kohichiro

AU - Jensen, Lisette O.

AU - Jiménez-Navarro, Manuel F.

AU - Katritsis, Demosthenes G.

AU - Kocaman, Sinan A.

AU - Koo, Bon Kwon

AU - López-Palop, Ramón

AU - Lorin, Jeffrey D.

AU - Miller, Louis H.

AU - Muller, Olivier

AU - Nam, Chang Wook

AU - Oud, Niels

AU - Puymirat, Etienne

AU - Rieber, Johannes

AU - Rioufol, Gilles

AU - Rodés-Cabau, Josep

AU - Sedlis, Steven P.

AU - Takeishi, Yasuchika

AU - Tonino, Pim A.L.

AU - Van Belle, Eric

AU - Verna, Edoardo

AU - Werner, Gerald S.

AU - Fearon, William F.

AU - Pijls, Nico H.J.

AU - De Bruyne, Bernard

AU - Gould, K. Lance

PY - 2014/10/21

Y1 - 2014/10/21

N2 - Background Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.Objectives The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.Methods Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.Results A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.Conclusions FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy. (J Am Coll Cardiol 2014;64:164154).

AB - Background Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.Objectives The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.Methods Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.Results A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.Conclusions FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy. (J Am Coll Cardiol 2014;64:164154).

KW - fractional flow reserve

KW - meta-analysis

KW - prognosis

KW - threshold

UR - http://www.scopus.com/inward/record.url?scp=84907982178&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2014.07.973

DO - 10.1016/j.jacc.2014.07.973

M3 - Article

C2 - 25323250

AN - SCOPUS:84907982178

VL - 64

SP - 1641

EP - 1654

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 16

ER -