Bringing Physiology to the Peripheral Vessels: Where and How to Start?

Article blog

Dr. Chadi Alraies, MD FACC, Director, Interventional Cardiology Research Detroit Medical Center

Burden of PAD in CAD Patients

Peripheral artery disease (PAD) has a prevalence of 12% to 15% in subjects over 65 years of age and affects between 8 and 10 million people.1,2

 It is not uncommon for the peripheral arterial disease to coexist with coronary artery disease (CAD) owing to a high prevalence of similar atherosclerotic risk factors, including smoking, hyperlipidemia, diabetes, and hypertension. The peripheral arterial disease is usually diagnosed with non-invasive testing, including ankle-brachial index and ultrasound to evaluate velocity and vessel stenosis.3 However, angiographic assessment of the vessel stenosis could be challenging and doesn’t correlate with the non-invasive results. Therefore, there is an increased interest in evaluating vessel patency using intravascular physiology and imaging. In this article, we will highlight the utility of pressure wires in the peripheral arteria bed to evaluate the severity of the disease and assess post-treatment values.

Physiology Assessment for CAD

It has been shown in multiple studies in the coronary intervention literature that physiology helps decision-making and treatment strategy in CAD patients.  

As shown in the coronary physiology literature, fractional flow reserve was able to defer 25% of patients who were referred for coronary intervention to be treated medically due to normal values. Coronary FFR/iFR can predict clinical significance of the lesions so intervention is done on lesions that are flow limiting and causing symptoms. Furthermore, coronary physiology has been shown to predict future events, evaluate acute results, and predict near term outcome. Patients with PAD are referred to the cath lab for peripheral intervention due to claudication symptoms or critical limb ischemia with abnormal ultrasound or ankle-brachial index results.  These patients often undergo peripheral angiogram to further assess disease severity and location.

Limitation of Non-invasive Assessment of PAD

The standard of care for critical limb ischemia evaluation is done before and during the procedure. Preprocedural assessment include ankle-brachial index, duplex scan to demonstrate occlusions, CT angiogram, MRA and perfusion imaging. Although these tests are readily available and required to evaluate underlying PAD, these modalities have limitations due to calcification, availability, and chronic kidney disease. Therefore, patients with abnormal results or those with classic symptoms often subject to invasive angiography to further delineate the disease severity and, if indicated, intervention of the lesion.

Physiology and Imaging for PAD

Currently there is lack of intravascular evaluation tools in the cath lab for PAD patients. Indeed, PAD is often a diffuse disease which makes it hard to properly treat culprit segments. Moreover, PAD is often associated with severe calcification which could lead to abnormal non-invasive results but, it is not flow limiting and doesn’t require intervention if properly assessed with invasive modalities. Conversely, patients with severe claudication symptoms often have normal non-invasive testing which preclude these patients from intervention that could improve pain, lifestyle and healing.3 This led to the need for better intraprocedural evaluation tool which helps providers treat culprit lesions in large above the knee or below the knee vascular bed.


Peripheral FFR/iFR is useful in PAD patients due to the nature of the disease. PAD is often a diffuse eccentric disease process which makes angiographic angulation difficult. Pressure wire has the potential to be used to evolute intervention site as well as proximal and distal vascular bed post intervention. This is a critical step that can be utilized to guarantee good results post-intervention. FFR has been shown to help quality supply-demand mismatch in chronic limb ischemia and help determine procedural success. Several studies demonstrated a significant correlation between post-exercise ABI and peripheral FFR at hyperemia in patients with isolated aortoiliac lesions.4,5 

Physiology Assessment of PAD Lesions

Experts have suggested specific techniques to use coronary pressure wire in the periphery to evaluate lesion severity. There are uncertainties related to the wire length, normalization location, hyperemic agent, and indices cutoff. For lesions in the iliac and above the knee, the wire length is enough to measure pullback.

For below-the-knee assessment, wire length would be enough, and pedal access or antegrade access might be needed to use the wire successfully. Regarding the hyperemic agent, intravenous adenosine (140 µg/kg/min) is the recommended agent. It is the preferred route when a pressure pullback is needed. 

However, adenosine is associated with a decrease in systemic pressure by 10-20%, accompanied with burning sensation and AV nodal block. 


In summary, endovascular therapies need to catch up to their coronary counterparts by improving intraprocedural physiologic evaluation, redesign equipment to allow assessment for lesions below the knee, and study pre and post-intervention FFR cutoff, which correspond to wound healing and claudication resolution.

  1. Criqui MH, Fronek A, Barrett-Connor E, Klauber MR, Gabriel S, Goodman D. The prevalence of peripheral arterial disease in a defined population. Circulation. 1985;71(3):510-515.
  2. Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999–2000. Circulation. 2004;110(6):738-743.
  3. Aboyans V, Criqui M, Abraham P, et al. American Heart Association Council on peripheral vascular disease; council on epidemiology and prevention; council on clinical cardiology; council on cardiovascular nursing; council on cardiovascular radiology and intervention, and council on cardiovascular surgery and anesthesia. Measurement and interpretation of the ankle-brachial index: a scientific statement from the American Heart Association. Circulation. 2012;126(24):2890.
  4. Hioki H, Miyashita Y, Miura T, et al. Diagnostic value of peripheral fractional flow reserve in isolated iliac artery stenosis: a comparison with the post-exercise ankle-brachial index. Journal of Endovascular Therapy. 2014;21(5):625-632.
  5. Fukunaga M, Fujii K, Kawasaki D, et al. Vascular flow reserve immediately after infrapopliteal intervention as a predictor of wound healing in patients with foot tissue loss. Circulation: Cardiovascular Interventions. 2015;8(6):e002412.



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