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

https://doi.org/10.1016/j.jacc.2014.07.973Get rights and content
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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.

Key Words

fractional flow reserve
meta-analysis
prognosis
threshold

Abbreviations and Acronyms

CABG
coronary artery bypass grafting
CAD
coronary artery disease
CI
confidence interval
FFR
fractional flow reserve
MACE
major adverse cardiac event(s)
MI
myocardial infarction
PCI
percutaneous coronary intervention

Cited by (0)

Dr. Johnson has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; signed nonfinancial, nondisclosure agreements with St. Jude Medical and Volcano Corporation to discuss coronary physiology projects; and received significant institutional research support from both companies. Drs. Lai and Zhu have received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis. Dr. Barbato has received institutional consultancy fees and research support from St. Jude Medical. Dr. Hamilos has received consulting fees from St. Jude Medical. Dr. Jensen has received grant support from St Jude Medical, Terumo, and Biosensors. Dr. Koo has received institutional research support from St. Jude Medical. Dr. Palop has received research grants from Abbott Vascular, Terumo; and Medtronic; and honoraria for advisory panels and presentations from Medtronic, Abbott Vascular, Boston Scientific, Terumo, Volcano, St. Jude, Eli Lilly and AstraZeneca. Dr. Muller has received research support from the Fondation Vaudoise de Cardiologie, Lausanne, Switzerland; and has received honoraria for presentations from St. Jude Medical and Medtronic. Dr. Van Belle has served as a consultant for St. Jude Medical and received speaker's fees and honoraria from Volcano and St. Jude Medical. Dr. Fearon has received research support from St. Jude Medical and Medtronic; speaker’s fees from Medtronic; and owns minor stock options in HeartFlow Inc. Dr. Pijls has served as a consultant to St. Jude Medical and HeartFlow Inc; and has received institutional grant support from St. Jude Medical. Dr. De Bruyne has received consulting fees and research support from St. Jude Medical; his consulting fees are passed to Cardiovascular Research Center Aalst, a not-for-profit organization. Dr. Gould has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; signed nonfinancial, nondisclosure agreements with St. Jude Medical and Volcano Corporation to discuss coronary physiology projects; 510(k) applicant for cfrQuant, a software package for quantifying absolute flow using cardiac positron emission tomography, and all royalties will go to a University of Texas scholarship fund, as the University of Texas has a commercial, nonexclusive agreement with Positron Corporation to distribute and market cfrQuant in exchange for royalties, but Dr. Gould retains the ability to distribute cost-free versions to selected collaborators for research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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