Current Methods for Assessing Peripheral Arterial Lesions do not Predict Functional and Haemodynamic Significance

Background: Peripheral arterial disease (PAD) is treated using visual estimation of lesion severity by CT angiography (CTA) and haemodynamic significance on duplex ultrasound (DU). In coronaries, Fractional Flow Reserve (FFR) assesses the functional severity of lesions to inform revascularisation. We related FFR to current standards for assessing peripheral arterial lesions. Methods: Patients with short distance claudication (IC) and critical limb ischaemia (CLI) underwent CTA and DU. Four blinded specialists determined likelihood of lesion significance on CTAs. During angioplasty/stenting, 0.014” dual-sensor guidewires (ComboWire XT®, Phillips- Volcano) were used to measure resting trans-stenotic pressure (Pd/Pa) and FFR by provoking hyperaemia with intra-arterial adenosine. Quantitative Vessel Analysis (Innova IGS, GE Healthcare) was used to analyse %diameter stenosis on intra-operative angiograms (IA DS%). Results: 51 (iliac:22, femoral:29) stenoses in 41 patients with IC (n=30, 59%) and CLI (n=21, 41%) were evaluated. Specialists agreed on haemodynamic significance in only 47% of lesions, with large inter-observer variability (k=0.298 [95% CI, 0.11–0.48]; p<0.005). The median IA DS% was 61% (IQR 48–75%). Pre-treatment median Pd/Pa and FFR were 0.91 (IQR 0.78–0.97) and 0.70 (IQR 0.52–0.87), respectively. DU (R2=0.25; p<0.05) and IA DS% (R2=0.15; p<0.04) correlated poorly with FFR. Measuring FFR unmasked haemodynamic significance in 68% of lesions. The FFR improved significantly after angioplasty/stenting [0.91 (0.80-1.00), P<0.0001]. Conclusions: FFR may better indicate the functional significance of lower limb lesions than current tools. Clinical trials will determine whether FFR will become, as it has in the coronary circulation, the gold standard for making treatment decisions.