Functional assessment of intermediate severity (50-75%) coronary lesions with fractional flow reserve (FFR) has now become routine practice in many catheterization laboratories. Several randomized trials and observational studies have shown that FFR-guided revascularization improves outcomes, results in fewer stents implanted, and is cost-effective.^1-4 While the utility of invasive hemodynamic assessment in the coronary system has proven to be useful, evidence for such an approach with peripheral arterial lesions is severely lacking. As the field of peripheral intervention moves toward less stenting in this era of increasing scrutiny of cardiovascular procedures, a reliable objective method for determining the need for revascularization will be necessary.

Practically speaking, most operators determine the need for revascularization based on symptoms, noninvasive studies, and the two-dimensional arteriogram performed in various projections. However, ankle- and toe-brachial indices, segmental pressure measurements, and pulse volume recordings do not offer the granularity needed to identify ischemia-provoking lesions. Duplex ultrasonography is less accurate at sites of highly calcific plaque and serial stenoses. Often, lesions of intermediate severity are discovered in tandem or at multiple levels during angiography, and the question again arises as to which lesion is primarily responsible for a patient's symptoms. It is well accepted that angiographic percent stenosis does not correlate well with functional significance.^5-8 More importantly, these noninvasive tests are rarely available during invasive procedures. Current American and European guidelines, therefore, recommend translesional pressure gradient assessment (with or without induced hyperemia) at the time of diagnostic lower extremity arteriogram when the significance of an intermediate obstruction is ambiguous.^9,10 It is the opinion of the authors of this Expert Analysis article that every effort should be made to measure gradients under maximal hyperemia as resting gradients in the peripheral arterial system are often not substantial. As with the coronary circulation, if maximal hyperemia is not achieved, then stenosis severity may be underestimated.

Despite recommendations from major societies, there is no consensus on what constitutes a significant pressure gradient or which pressure parameter(s) most accurately predicts functional severity in the peripheral arterial system. Most evidence is derived from studying aortoiliac stenoses. Early investigations suggested a peak systolic gradient of at least 20 mm Hg or a mean gradient of greater than 10 mm Hg during peak hyperemia induced by either exercise or vasodilator infusion.^7,11,12 These cut-points, however, were established with relatively large (4 to 5 French) fluid-filled catheters with low frequency response resulting in erroneous measurements. Moreover, they were not compared with a reference standard for functional assessment. Recent studies suggest that FFR (obtained via 0.36 mm diameter pressure sensor wires) more accurately assesses hemodynamic severity in comparison with systolic gradients and correlates well with Doppler peak systolic velocity.^13,14 However, a threshold for significance (with an appropriately selected gold-standard) is yet to be established with this high-fidelity technology.

Assessment of translesional pressure gradients might also be useful in the post-intervention setting, though there is very little evidence to support such an approach at the present time. As there can be significant inter- and intra-observer variability with angiographic assessment, comparison of pre- and post-intervention gradients may offer an objective means to determine the adequacy of revascularization. For example, in one study that compared provisional stenting after angioplasty versus primary stenting for short iliac artery lesions, the hemodynamically-guided provisional stenting approach avoided stenting in 63% of cases while achieving the same acute and long-term procedural success rate.¹⁵ Hemodynamic assessment after angioplasty might also help separate flow-limiting dissections and recoils that may need further intervention from non-flow-limiting lesions that may simply be observed. Finally, post-intervention gradients may also be able to prognosticate and predict outcomes such as long-term patency rates, improvement in functional capacity, improvement in quality of life, and wound healing.

Since the 1950s, the fields of vascular medicine and surgery have touted the merits of invasive functional assessment of lower extremity arterial disease; however, technical limitations precluded practical applications. Now that small-diameter pressure sensor wires are commonplace in the catheterization laboratory, physicians should capitalize on this opportunity and demand more objective data on which to base treatment decisions.

References

1. Bech GJ, De Bruyne B, Pijls NH, et al. Fractional flow reserve to determine the appropriateness of angioplasty in moderate coronary stenosis: a randomized trial. Circulation 2001;103:2928-34.
2. De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med 2012;367:991-1001.
3. Fearon WF, Yeung AC, Lee DP, Yock PG, Heidenreich PA. Cost-effectiveness of measuring fractional flow reserve to guide coronary interventions. Am Heart J 2003;145:882-7.
4. Tonino PA, De Bruyne B, Pijls NH, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213-24.
5. Fischer JJ, Samady H, McPherson JA, et al. Comparison between visual assessment and quantitative angiography versus fractional flow reserve for native coronary narrowings of moderate severity. Am J Cardiol 2002;90:210-5.
6. Thiele BL, Strandness DE Jr. Accuracy of angiographic quantification of peripheral atherosclerosis. Prog Cardiovasc Dis 1983;26:223-36.
7. Udoff EJ, Barth KH, Harrington DP, Kaufman SL, White RI. Hemodynamic significance of iliac artery stenosis: pressure measurements during angiography. Radiology 1979;132:289-93.
8. Breslau PJ, Jorning PJ, Greep JM. Assessment of aortoiliac disease using hemodynamic measures. Arch Surg 1985;120:1050-2.
9. European Stroke O, Tendera M, Aboyans V, et al. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J 2011;32:2851-906.
10. Rooke TW, Hirsch AT, Misra S, et al. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:1555-70.
11. Moore WS, Hall AD. Unrecognized aortoiliac stenosis. A physiologic approach to the diagnosis. Arch Surg 1971;103:633-8.
12. Wesolowski SA, Martinez A, Domingo RT, et al. Indications for aortofemoral arterial reconstruction: a study of borderline risk patients. Surgery 1966;60:288-98.
13. Lotfi AS, Sivalingam SK, Giugliano GR, Ashraf J, Visintainer P. Use of fraction flow reserve to predict changes over time in management of superficial femoral artery. J Interv Cardiol 2012;25:71-7.
14. 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. J Endovasc Ther 2014;21:625-32.
15. Tetteroo E, Haaring C, van der Graaf Y, van Schaik JP, van Engelen AD, Mali WP. Intraarterial pressure gradients after randomized angioplasty or stenting of iliac artery lesions. Dutch Iliac Stent Trial Study Group. Cardiovasc Intervent Radiol 1996;19:411-7.

Keywords: Angiography, Angioplasty, Ankle, Ankle Brachial Index, Catheterization, Consensus, Constriction, Pathologic, Coronary Circulation, Hemodynamics, Hyperemia, Iliac Artery, Quality of Life, Stents, Systole, Vasodilator Agents, Wound Healing, Aneurysm

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