ABSTRACT: Purpose: To describe a novel technique coupling the use of a pressure-wire gradient measurement with and without hyperemia (induced with an external blood pressure cuff inflated to 20 mmHg above the systolic blood pressure for 1 minute on the affected calf). Case: A 70-year-old patient presented with lifestyle-limiting lower-extremity calf claudication. He underwent angiography, which revealed left superficial femoral artery stenosis. Angioplasty of the lesion improved the angiographic appearance, but a residual pressure gradient could be elicited with provocative hyperemia testing. This prompted stenting, which resolved the differential. Conclusions: Pressure-wire gradient detection with and without provocative hyperemia testing using our novel approach may prove to be a useful adjunct in the diagnosis and treatment of lower extremity occlusive disease.

VASCULAR DISEASE MANAGEMENT 2015;12(9):E166-E172

Key words: hyperemia, peripheral vascular intervention, fractional flow reserve

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A 70-year-old patient presented with lifestyle-limiting claudication. He previously had stents placed in his external iliac arteries bilaterally as well as his right distal superficial femoral artery, but he had persistent claudication of the left calf. On presentation, he had an abnormal ankle-brachial index (ABI) of 0.68 on the left. Duplex ultrasound revealed an elevated left superficial femoral artery peak systolic velocity of 384 cm/s with otherwise normal flow velocities.

Upon angiography, the left common femoral, profunda femoral, and superficial femoral (SFA) arteries were all patent proximally. By the mid-thigh, heavy calcification resulted in significant stenosis and plaque burden of the SFA with the greatest degree of stenosis at Hunter’s canal (at least 90% diameter stenosis) (Figures 1 and 2). The popliteal artery, anterior tibial artery, and posterior tibial arteries were patent. 

A resting peak systolic pressure gradient between the proximal SFA and proximal popliteal artery was 32 mmHg and was 0.88 when given as a ratio (Figure 3). Upon provocative testing with a blood pressure cuff on the calf inflated to 20 mmHg above the systolic blood pressure for 1 minute and then deflated, the pressure gradient was 58 mmHg with a ratio of 0.64 (Figure 4). These measurements were obtained with a 0.014˝ Verrata Pressure Wire (Volcano Corporation). The lesion was balloon-dilated with a 6 mm x 100 mm balloon with subsequent resolution of the lesion pressure differential (Figure 5). Post-angioplasty at rest without hyperemia, the pressure gradient was 5 mmHg with a ratio of 0.96. Repeat testing with hyperemia revealed a pressure difference of 19 mmHg and a ratio of 0.88 (Figure 6). 

Intravascular ultrasound (IVUS) confirmed the size, extent, and length of the plaque. Stenting of this lesion thus required two Zilver PTX (Cook Medical) stents.  A 6 mm x 80 mm stent was placed in the distal SFA, and a 7 mm x 80 mm stent was placed just proximal to the first. The stents were post-dilated with a 6 mm angioplasty balloon with an excellent angiographic and hemodynamic result (Figure 7). Completion hyperemia measurements showed a pressure gradient of 1 mmHg and a ratio of 1.0 (Figure 8, Table 1).  

On follow-up evaluation the patient had resolution of his claudication with normal pedal pulses on examination. His ABI is normal now at 1.02 on the left. He has duplex evidence of normal flow velocities of the SFA stents as well.

Discussion

Fractional flow reserve (FFR) measurement and its technique have previously been described for assessment of lesion severity in the coronary vasculature.¹ The pressure gradient across the lesion is obtained with the use of a pressure wire distal to the lesion (Pd) and compared to aortic pressure (Pa). While measurements of pressure gradients using pressure wires correlate with those obtained by catheter alone in the periphery, catheter-based measurements tend to overestimate the pressure gradients.² In the coronary bed, FFR is calculated using the difference in mean blood pressure measurements and reported using the ratio Pd:Pa. Clinical significance is defined as an FFR less than 0.8.³ The Society for Cardiovascular Angiography and Interventions recommends using a threshold value of 0.8 for the FFR in the coronary vasculature.⁴ Values under this threshold likely represent ischemia-producing lesions and should be treated, whereas those values obtained that are greater than 0.8 likely do not represent ischemia. Not only is FFR measurement cost effective when compared to a strategy of stenting or a strategy of adjuvant testing to further determine ischemia,⁵ but FFR measurement also may predict long-term patency in the coronary bed^6,7 as well as in hemodialysis access dysfunction.⁸ An FFR of less than 0.9 (i.e. a residual pressure gradient) indicates a suboptimal effect with a higher likelihood of long-term restenosis.^3,9-12 In contrast, an FFR greater than 0.9, especially if greater than 0.95, was associated with a lower rate of adverse outcome.¹³ Certainly, extrapolation of this information would be consistent with previous peripheral data suggesting that normalization of the ABI to above 0.9 is predictive of improved outcomes.¹⁴

This technique has been used in the lower extremity but with limited applicability because the “therapeutic threshold” has not been objectively established. Despite noninvasive and angiographic assessment, establishing the clinical and hemodynamic significance of a lesion, the Pd:Pa ratio may still be calculated above 0.9. This creates too narrow a separation between lesions that are or are not hemodynamically significant. This window may be broadened by using the systolic pressure difference instead of the mean pressure values. The addition of hyperemia causes transient arterial vasodilation, further increasing the difference between Pa and Pd. 

Reactive hyperemia in the coronary bed is typically induced by intracoronary infusion of adenosine, nitroglycerine, or verapamil.^15-17 A single report described the use of using intra-arterial adenosine to induce hyperemia and simulate physiologic demand in the leg.¹⁸ Fortunately, the lower extremity is easily accessible for hyperemic testing by mechanically inducing transient ischemia with inflation of a blood pressure cuff placed around the calf. This creates reactive distal vasodilation and simulation of physiologic demand without the risk of sequelae due to pharmacologic infusions.

This difference in technique is not only one of convenience and reduction of sequelae but also one that attempts to accommodate the difference in vascular beds under scrutiny. It is important to recognize that the physiology and the need for hyperemia differ in the periphery compared to the coronary vessels. In the coronary system, maximal vasodilation helps reduce the influence of collateralization. In contrast, in the periphery, the intent is to evaluate for residual or undiagnosed stenoses in a more dynamic or “demand” state. As a result, the technique we propose herein is different than that previously described for the coronary vessels.

Reactive hyperemia is not necessary diagnostically for lesions that are obvious, but it may prove of greater utility in discerning the quality and normalcy of flow after angioplasty (especially drug-coated balloon). The interventionalist may therefore be able to better make a decision regarding provisional secondary treatment (i.e. stent, atherectomy, additional PTA) based on an objective endpoint compared to the subjective information obtained with traditional angiography. Additionally, the individual significance of each of tandem lesions may be better discerned using this technique. By combining the use of pressure wire measurements of a pressure gradient with reactive hyperemic testing, this novel approach allows for the on-table evaluation of the success of intervention prior to conclusion of the procedure and therefore improved decision-making regarding extent of treatment.

This approach does not add significant time to the procedure (approximately 1 minute for each assessment) or expense (with the exception of a pressure wire). No systemic sequelae have been identified, contrary to the significant potential side effects with pharmacologic intravascular administration such as atrioventricular block, chest pain, or dyspnea.¹⁹ Further evaluation of this novel technique to elucidate its utility and role in routine angiography is warranted. 

Editor’s note: Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no financial relationships or conflicts of interest regarding the content herein. 

Manuscript received November 16, 2014; provisional acceptance given February 12, 2015; final version accepted June 15, 2015. 

Address for correspondence: Issam Koleilat, MD, Greenville Health System, Surgery, 701 Grove Road, Greenville, SC 29605, United States. Email: ikoleilat@gmail.com.

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