Prognostic Value of Fractional Flow Reserve Linking Physiologic Severity to Clinical Outcomes

Nils P. Johnson; Gabor G. Toth; Dejian Lai; Hongjian Zhu; Goksel Acar; Pierfrancesco  Agostoni; Yolande Appelman; Fatih Arslan; Emanuele Barbato; Shao-Liang Chen; Luigi Di Serafino; Antonio J. Dominguez-Franco; Patrick Dupouy; Ali M. Esen; Ozlem B. Esen; Michalis Hamilos; Kohichiro Iwasaki; Lisette O. Jensen; Manuel F. Jimenez-Navarro; Demosthenes G. Katritsis; Sinan A. Kocaman; Bon-Kwon Koo; Ramon Lopez-Palop; Jeffrey D. Lorin; Louis H. Miller; Olivier Muller; Chang-Wook Nam; Niels Oud; Etienne Puymirat; Johannes Rieber; Gilles Rioufol; Josep Rodes-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

doi:10.1016/j.jacc.2014.07.973

Prognostic Value of Fractional Flow Reserve Linking Physiologic Severity to Clinical Outcomes

Nils P. Johnson^*, Gabor G. Toth, Dejian Lai, Hongjian Zhu, Goksel Acar, Pierfrancesco Agostoni, Yolande Appelman, Fatih Arslan, Emanuele Barbato, Shao-Liang Chen, Luigi Di Serafino, Antonio J. Dominguez-Franco, Patrick Dupouy, Ali M. Esen, Ozlem B. Esen, Michalis Hamilos, Kohichiro Iwasaki, Lisette O. Jensen, Manuel F. Jimenez-Navarro, Demosthenes G. KatritsisSinan A. Kocaman, Bon-Kwon Koo, Ramon Lopez-Palop, Jeffrey D. Lorin, Louis H. Miller, Olivier Muller, Chang-Wook Nam, Niels Oud, Etienne Puymirat, Johannes Rieber, Gilles Rioufol, Josep Rodes-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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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. (C) 2014 by the American College of Cardiology Foundation.

Original language	English
Pages (from-to)	1641-1654
Number of pages	14
Journal	Journal of the American College of Cardiology
Volume	64
Issue number	16
DOIs	https://doi.org/10.1016/j.jacc.2014.07.973
Publication status	Published - 21 Oct 2014

Keywords

fractional flow reserve
meta-analysis
prognosis
threshold
PERCUTANEOUS CORONARY INTERVENTION
COLLATERAL BLOOD-FLOW
ARTERY-DISEASE
INTRAVASCULAR ULTRASOUND
STENOSIS SEVERITY
NATURAL-HISTORY
MEDICAL THERAPY
FOLLOW-UP
ANGIOGRAPHY
REVASCULARIZATION

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10.1016/j.jacc.2014.07.973

http://www.ncbi.nlm.nih.gov/pubmed/25323250

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Johnson, N. P., Toth, G. G., Lai, D., Zhu, H., Acar, G., Agostoni, P., Appelman, Y., Arslan, F., Barbato, E., Chen, S.-L., Di Serafino, L., Dominguez-Franco, A. J., Dupouy, P., Esen, A. M., Esen, O. B., Hamilos, M., Iwasaki, K., Jensen, L. O., Jimenez-Navarro, M. F., ... 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

@article{b45e427beab34f57823d8821edf017a8,

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. (C) 2014 by the American College of Cardiology Foundation.",

keywords = "fractional flow reserve, meta-analysis, prognosis, threshold, PERCUTANEOUS CORONARY INTERVENTION, COLLATERAL BLOOD-FLOW, ARTERY-DISEASE, INTRAVASCULAR ULTRASOUND, STENOSIS SEVERITY, NATURAL-HISTORY, MEDICAL THERAPY, FOLLOW-UP, ANGIOGRAPHY, REVASCULARIZATION",

author = "Johnson, {Nils P.} and Toth, {Gabor G.} and Dejian Lai and Hongjian Zhu and Goksel Acar and Pierfrancesco Agostoni and Yolande Appelman and Fatih Arslan and Emanuele Barbato and Shao-Liang Chen and {Di Serafino}, Luigi and Dominguez-Franco, {Antonio J.} and Patrick Dupouy and Esen, {Ali M.} and Esen, {Ozlem B.} and Michalis Hamilos and Kohichiro Iwasaki and Jensen, {Lisette O.} and Jimenez-Navarro, {Manuel F.} and Katritsis, {Demosthenes G.} and Kocaman, {Sinan A.} and Bon-Kwon Koo and Ramon Lopez-Palop and Lorin, {Jeffrey D.} and Miller, {Louis H.} and Olivier Muller and Chang-Wook Nam and Niels Oud and Etienne Puymirat and Johannes Rieber and Gilles Rioufol and Josep Rodes-Cabau and Sedlis, {Steven P.} and Yasuchika Takeishi and Tonino, {Pim A. L.} and {Van Belle}, Eric and Edoardo Verna and Werner, {Gerald S.} and Fearon, {William F.} and Pijls, {Nico H. J.} and {De Bruyne}, Bernard and Gould, {K. Lance}",

year = "2014",

month = oct,

day = "21",

doi = "10.1016/j.jacc.2014.07.973",

language = "English",

volume = "64",

pages = "1641--1654",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier USA",

number = "16",

}

Johnson, NP, Toth, GG, Lai, D, Zhu, H, Acar, G, Agostoni, P, Appelman, Y, Arslan, F, Barbato, E, Chen, S-L, Di Serafino, L, Dominguez-Franco, AJ, Dupouy, P, Esen, AM, Esen, OB, Hamilos, M, Iwasaki, K, Jensen, LO, Jimenez-Navarro, MF, Katritsis, DG, Kocaman, SA, Koo, B-K, Lopez-Palop, R, Lorin, JD, Miller, LH, Muller, O, Nam, C-W, Oud, N, Puymirat, E, Rieber, J, Rioufol, G, Rodes-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

TY - JOUR

T1 - Prognostic Value of Fractional Flow Reserve Linking Physiologic Severity to Clinical Outcomes

AU - Johnson, Nils P.

AU - Toth, Gabor G.

AU - Lai, Dejian

AU - Zhu, Hongjian

AU - Acar, Goksel

AU - Agostoni, Pierfrancesco

AU - Appelman, Yolande

AU - Arslan, Fatih

AU - Barbato, Emanuele

AU - Chen, Shao-Liang

AU - Di Serafino, Luigi

AU - Dominguez-Franco, Antonio J.

AU - Dupouy, Patrick

AU - Esen, Ali M.

AU - Esen, Ozlem B.

AU - Hamilos, Michalis

AU - Iwasaki, Kohichiro

AU - Jensen, Lisette O.

AU - Jimenez-Navarro, Manuel F.

AU - Katritsis, Demosthenes G.

AU - Kocaman, Sinan A.

AU - Koo, Bon-Kwon

AU - Lopez-Palop, Ramon

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 - Rodes-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. (C) 2014 by the American College of Cardiology Foundation.

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. (C) 2014 by the American College of Cardiology Foundation.

KW - fractional flow reserve

KW - meta-analysis

KW - prognosis

KW - threshold

KW - PERCUTANEOUS CORONARY INTERVENTION

KW - COLLATERAL BLOOD-FLOW

KW - ARTERY-DISEASE

KW - INTRAVASCULAR ULTRASOUND

KW - STENOSIS SEVERITY

KW - NATURAL-HISTORY

KW - MEDICAL THERAPY

KW - FOLLOW-UP

KW - ANGIOGRAPHY

KW - REVASCULARIZATION

U2 - 10.1016/j.jacc.2014.07.973

DO - 10.1016/j.jacc.2014.07.973

M3 - Article

C2 - 25323250

SN - 0735-1097

VL - 64

SP - 1641

EP - 1654

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 16

ER -

Prognostic Value of Fractional Flow Reserve Linking Physiologic Severity to Clinical Outcomes

Abstract

Keywords

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