What is fractional flow reserve (FFR)?

What is Fractional Flow Reserve (FFR)?

Fractional flow reserve (FFR) is a pressure-derived physiological index that measures the maximum achievable blood flow in a stenotic coronary artery expressed as a ratio of what the maximum flow would be if that artery were completely normal 1.

Technical Definition and Measurement

FFR is calculated as the ratio of distal coronary pressure (Pd) to proximal aortic pressure (Pa) during maximal pharmacological hyperemia (typically induced by adenosine):

FFR = Pd/Pa 1

This measurement is obtained using a pressure-sensitive coronary wire advanced distal to the stenosis while simultaneously measuring aortic pressure, both under conditions of maximal vasodilation 1.

Physiological Basis

The fundamental principle relies on creating maximal hyperemia to minimize coronary microvascular resistance, establishing an approximately linear relationship between perfusion pressure and blood flow 1. Under these conditions:

• Normal coronary arteries have FFR values of approximately 0.98 ± 0.03 2
• The pressure gradient across a stenosis directly reflects its hemodynamic significance
• FFR accounts for both viscous friction (Poiseuille's Law) and convective acceleration losses (Bernoulli's Law) across the stenosis 1

Clinical Interpretation and Cutoff Values

The clinically significant threshold is FFR ≤0.80, which indicates a hemodynamically significant stenosis that justifies revascularization 3, 1. The evidence shows:

• FFR ≤0.75: Definitively associated with inducible ischemia 2
• FFR 0.75-0.80: "Gray zone" requiring clinical judgment (represents up to 10% of measurements) 3
• FFR >0.80: Stenosis can be safely deferred from revascularization 1

For research purposes, a single cutoff value of 0.80 is recommended 3.

Clinical Advantages Over Angiography

FFR addresses critical limitations of coronary angiography:

• Visual assessment of stenosis severity correlates poorly with physiological significance 1
• Even quantitative coronary analysis (QCA) is commonly discordant with functional significance 1
• FFR is reproducible, specific, and provides well-defined cutoff values with narrow gray zones 3
• It achieves per-segment accuracy with spatial resolution of a few millimeters 3

Guideline Recommendations

FFR-guided management has achieved Class I (Level of Evidence A) recommendations for stable coronary artery disease when prior evidence of ischemia is not available 1. FFR-guided PCI with medical therapy is evidence-based to decrease the need for urgent revascularization compared with optimal medical therapy alone 1.

Important Clinical Caveats

Several situations require careful interpretation:

• Diffuse coronary atherosclerosis: FFR should not be considered a marker of device failure in patients with diffuse disease showing graded, continuous pressure fall along arterial length 3
• Serial stenoses: Limited applicability in vessels with multiple sequential lesions 3
• Acute myocardial infarction: Data are limited and proposed criteria should not currently be extended to this population 3
• Microvascular dysfunction: A diminished hyperemic response can lead to falsely normal FFR values, potentially more prevalent in post-menopausal women 4

Measurement Requirements

The guide wire should be <10% of the minimal lumen area to provide a true gradient that reliably reflects epicardial resistance 3. Standardized 5-step procedures with central core laboratory validation are recommended for clinical trials 3.