REVIEW ARTICLESRichard P. Cambria, MD, Section Editor

FromBeD

F.A.Cer

AuthRepWgo

Thetom

0741Pubhttp

804

Design considerations for studies of thebiomechanical environment of the femoropoplitealarteriesFarzana Ansari, MS,a Lindsay K. Pack, BSE,b Steven S. Brooks, MD,b and Tina M. Morrison, PhD,b

Berkeley, Calif; and Silver Spring, Md

Objective: The purpose of this study was to review the available literature regarding the biomechanics of the superficialfemoral artery (SFA) and popliteal artery (PA) in patients with peripheral arterial disease (PAD). Stents are one of manyavailable therapies used to treat patients with PAD. Because stents are permanent implants, they undergo a variety ofdeformations as patients go about their daily activities such as walking, sitting in a chair, or climbing stairs. As a part ofthe marketing application for United States Food and Drug Administration approval, stents need to be evaluated forlong-term durability under a variety of loading modes. The information available in the literature provides direction forsuch evaluation.Methods:We performed a literature search of the PubMed database looking for “key vessel” and “mechanics” (all fields) or“deformation” (all fields) or “flexion” (all fields) or “mechanical environment” (all fields) or “tortuosity” (all fields) or“dynamics” (all fields) or “forces” (all fields), where the “key vessel” was “Femoral Artery,” “Superficial Femoral Artery,”“Popliteal Artery,” and “Femoropopliteal.”Results: Using a decision tree, we found 12 relevant articles that focused solely on the nonradial cyclic deformationsassociated with musculoskeletal motion. Despite the many limitations associated with combining these studies, we learnedthat under walking conditions, the proximal and mid-SFA deforms, on average, by shortening in the axial direction 4.0%,by twisting 2.1�/cm, and by bending 72.1 mm; the distal SFA and proximal PA deform by shortening in the axialdirection 13.9%, by twisting 3.5�/cm, and by being pinched such that the aspect ratio of the lumen changes 4.6%. Thedistal PA deforms by shortening in the axial direction 12.3%, by twisting 3.5�/cm, by bending 22.1 mm, and by beingpinched such that the aspect ratio of the lumen changes 12.5%.Conclusions: A review of the current literature reveals heterogeneous study designs that confound interpretation. Studiesincluded different physiologic settings from young to mature participants, participants with and without disease, andcadavers. Investigators used a range of imaging modalities and definitions of arterial segments, which affected our abilityto compile the data as we learned that deformations vary according to the specific anatomic location within the SFA/PA.As a result of this analysis, we identified design considerations for future studies, because although this work has beenvaluable and significant, there are many limitations with the currently available data such that all we know about theSFA/PA environment is that we don’t know. (J Vasc Surg 2013;58:804-13.)

Despite the abundance of publications on the topics ofsuperficial femoral artery (SFA) and proximal popli-teal artery (pPA) stenting, little is known about the

the Department of Mechanical Engineering, University of California,rkeleya; and the Center for Devices and Radiological Health, Food andrug Administration, Silver Spring.b

received support from the Medical Device Fellowship Program at theenter for Devices and Radiological Health while an intern in the Periph-al Vascular Devices Branch.or conflict of interest: none.rint requests: Tina M. Morrison, PhD, 10903 New Hampshire Ave,O66-1272, Silver Spring, MD 20993 (e-mail: tina.morrison@fda.hhs.v).editors and reviewers of this article have no relevant financial relationshipsdisclose per the JVS policy that requires reviewers to decline review of anyanuscript for which they may have a conflict of interest.-5214/$36.00

lished by Elsevier Inc. on behalf of the Society for Vascular Surgery.://dx.doi.org/10.1016/j.jvs.2013.03.052

biomechanical environment of this arterial segment. Earlypublications of stents used to treat peripheral arterialdisease (PAD) in the SFA/pPA reported fracture rates ashigh as 65%.1 These rates are markedly different thanrecently reported rates of 3.1%,2 which emphasizesa disparity in the information available. This is partlybecause early-generation stents were not designed to with-stand the extreme loading environment of the SFA/pPAgiven that the loading environment was largely unknown.Improvements have been made to make stents moredurable, including finer surface finishes, increased flexi-bility, and longer lengths that reduce the need for overlap-ping. However, despite these enhancements, stents stillfracture at a measurable rate.

The clinical significance of stent fracture remainscontroversial. Studies have reported data suggesting thatstent fractures have a dramatic effect on the patency ofthe vessel. For example, Scheinert et al3 reported an

a b

Fig 1. Illustration summarizing (a) anatomic markers used to clinically define superficial femoral artery (SFA) andpopliteal artery (PA) and subsets and (b) author-defined arterial segments from the authors cited in this review. SeeTable I for the author acronym key. See reference 28 for additional breakdown of the popliteal artery. CFA, Commonfemoral artery.

JOURNAL OF VASCULAR SURGERYVolume 58, Number 3 Ansari et al 805

84.3% patency rate at 12 months for patients without stentfractures compared with a 41.1% patency rate for thosewith stent fractures in first-generation stents. Recentstudies of newer-generation stents for SFA/PA have notconsistently reproduced these findings. Furthermore, notall stent fractures are equal in severity and clinical effects.For example, there appears to be different clinicaloutcomes when a single strut fracture occurs as comparedto a circumferential ring of fractures or a complete separa-tion of the stent components. Moreover, although thesame physiologic factors that contribute to stent fracturecan also independently contribute to restenosis,4,5 a directcausal relationship between stent fracture and clinicaloutcomes, such as restenosis, has not been established.

What is clear, however, from this array of informationis the uniqueness of the biomechanical environment of theSFA/PA compared with other vascular beds. Our suspi-cion is that it stems from the complex deformationsobserved in that region. In addition to the expectedradial distension associated with pulsatile blood flow inarteries are the nonradial deformations, including twist(torsion), bending, pinching (radial compression), axialshortening, and elongation.6 Because these deformations

can negatively affect stents implanted in the SFA/PA,researchers have begun to investigate the magnitudes ofthese deformations during daily activities in patients withPAD.6-26 This work has been valuable and significant,but there are many limitations with the currently availabledata such that we know that we don’t know the SFA/PAbiomechanical environment.

To improve the development and evaluation of stentsand other therapies for treating PAD in the SFA/PA, weneed to have a better understanding of this dynamic vascularbed. This report describes our review of the available pub-lished data on the biomechanical environment of theSFA/PA up to 2012. The reader will be able to take awayan understanding of the current methods of in vivo evalua-tion, the limitations of those methods, the correspondingoutcomes, and design considerations for future studies.

METHODS

This section is divided into four parts: anatomy, wherewe define the SFA/PA; literature search, where we des-cribe the review; nonradial deformation modes, wherewe describe the common deformation modes; and data

Fig 2. A decision tree was used for determining whether an articlehad the appropriate subject matter for the review topic.

JOURNAL OF VASCULAR SURGERY806 Ansari et al September 2013

organization, where we describe how we report theoutcomes from the available studies.

Anatomy

Preliminary review of the sources revealed no clearagreement in the definitions of the different regions of thevasculature in the leg. Therefore, it was important to definethe anatomy of interest before initiating the literature search(Fig 1, a). In the medical literature, the SFA is defined as“extending from the femoral triangle, starting at thecommon femoral artery bifurcation, inferiorly through theadductor canal (AC) where it truncates at the adductorhiatus (AH, the exit of theAC).”27Upon exiting theAC, thePA begins, which continues inferiorly to the poplitealbifurcation, where the anterior tibial artery branches off. Tofacilitate compiling the data into discrete, consistentsegments, we divided the SFA into three regions of equallength: proximal SFA (pSFA), mid-SFA (mSFA), and distalSFA (dSFA). The PA was divided into two regions: theproximal PA (pPA), from theAH to the proximal edge of thepatella, and the distal PA (dPA), down to the center of theknee joint space and continuing down to the poplitealbifurcation.28 We then grouped those segments into moreconcise components: pSFA/mSFA, dSFA/pPA, and dPA.

Literature search

We searched the PubMed database with the followingsearch code: “key vessel” and “mechanics” (all fields) or“deformation” (all fields) or “flexion” (all fields) or“mechanical environment” (all fields) or tortuosity” (allfields) or “dynamics” (all fields) or “forces” (all fields).

The “key vessel” entered for each search was “FemoralArtery,” “Superficial Femoral Artery,” “Popliteal Artery,”and “Femoropopliteal.” The search results yielded 573 arti-cles. Using the decision tree in Fig 2, we determined that 12of these articles specifically addressed the nonradial cyclicdeformations of the SFA/PA.4,6-17 The articles not includedconsisted of computationalmodeling studies, in vitro studiescomparing stent performance with bench-top models,studies of wall compliance as a function of disease, studiesof changes in hemodynamics due to motion, and qualitativeassessments of artery deformation.18-23 The group of articleswas further expanded by including relevant articles orpresentations that were referenced by the 12 articles.24-26

In addition, private correspondence with ArundhutiGanguly, PhD, (e-mail correspondence, July 2011) andAlexander Nikanorov, PhD, (e-mail correspondence, July2011) was used to clarify and supplement published data.

Nonradial deformation modes

As previously mentioned, the goal of the review was tounderstand the deformations that are imposed on a stentimplanted in the SFA/PA during daily activities of patients

with PAD. Four nonradial deformation modes were

discussed in the literature and are summarized below: axialshortening (compression) and elongation, bending,twisting, and pinching. Note that this review does notinclude cyclic radial distension due to blood flow becausethis fatigue mechanism is not cited as most critical inSFA/PA stent fractures.3

Axial shortening and elongation. Axial shorteningand elongation along the length of the vessel is definedas the normalized change in length of the arterial segmentfrom a supine position to a certain degree of flexion. Elon-gation is a positive change in length, whereas shortening isa negative change in length. The mean, maximum, andminimum values (with standard deviations) were recordedwhen provided by the authors.

Bending. The amount of bending or change in curva-ture of the vessel is related to the tortuosity of the vesseland the fulcrum about which the vessel bends. The tortu-osity of the SFA/PA was characterized by the radiusof curvature, as measured along the centerline of thevessel over a specific vessel length. The bending radius(1/curvature) was chosen as the principal parameter forcomparison due to the direct applicability to bench testsfor stent evaluation. Where possible, all data for this defor-mation mode were converted to bending radii along thecenterline. The conversions were as follows:

d Average curvature data were inverted and then con-verted to millimeters.

Table I. List of abbreviations, authors, and referencesfound during literature searcha

Abbreviation Author and year

AG Ganguly et al,7 2011AK Klein et al,8 2009AN 08 Nikanorov et al,9 2008

Nikanorov,25 2008 Stent Summit presentationAN 11 Nikanorov et al,10 2009

Nikanorov,26 2010 TCT presentationCC 06 Cheng et al,11 2006CC 10 Cheng et al,6 2010JD Diaz et al,12 2004HS Smouse et al,13 2005

Smouse,24 2004 TCT presentationNW Wood et al,14 2006PW Wensing et al,15 1994RB Brown et al,16 2009OS Smedby et al,17 1993

TCT, Transcatheter Cardiovascular Therapeutics.aEntries highlighted in bold are those included in the final literature data-base used in data comparison.

JOURNAL OF VASCULAR SURGERYVolume 58, Number 3 Ansari et al 807

d If the bending radius was measured at the inner orouter edge of the artery, the magnitude was convertedto centerline data by adding 2 mm, a conservativeapproximation of the SFA inner lumen radius.29

When possible, we recorded the average and standarddeviation of the minimum bending radius reported overa specified vessel length. Otherwise, we recorded themean bending radius or minimum bending radius. Theranges of the data were also noted, if reported.

Twisting. The amount of twist in an arterial segmentis defined as the change of angular distance between twobranch vessels. Twisting of the vessel was quantifiedbetween the profunda femoris and descending genicularartery (DGA) branch vessels and reported as the degreeof twist per length. The mean and standard deviation ofdegree/length values were recorded, and the maximumand minimum strains were noted, if reported.

Pinching. When the vessel is radially compressed dueto muscle contraction such that the cross-section changesfrom circular to elliptical, the vessel is being pinched orlocally compressed. Thus, the amount of pinching wasquantified as a change in the cross-sectional shape of thearterial segment.

Note that the magnitudes for each mode (except forbending) were taken directly from the references.

Data organization

The definitions of the arterial segments for which thedata were reported in the literature were not the samefor each reference; each definition is shown in Fig 1,b (see the Anatomy section under Results more details).Because of the inconsistency, the data were grouped intothree broad categories (pSFA/mSFA, dSFA/pPA, anddPA in Fig 1, a) to facilitate direct comparison of magni-tudes across the literature database. The magnitude foreach deformation mode was reported for each arterialsegment based on how the authors defined the arterialsegment for their reported data. The grouping scheme is asfollows:

d When the mean values for the individual segmentswere provided (eg, pSFA and mSFA separately), thevalues were averaged to provide a single value for thepaired category.

d When the mean value was presented for only one ofthe paired segments, the single value was recordedfor the paired category (eg, data available only fordSFA were categorized as dSFA/pPA).

d When the mean value was reported for the larger SFAor PA, the value was categorized as pSFA/mSFA ordPA, respectively. No value for dSFA/pPA wasrecorded due to their anatomic inclusion in both ofthe listed arterial segments.

Additionally, an overall maximum and minimum valuefor each deformation within each arterial segment wascalculated using the following methodology:

d For each source, the statistical range was reported as“mean 6 1.5 standard deviations.”

d Author-specific maximum and minimum values wereselected from the calculated statistical range andauthor-reported ranges (if available).

d Overall maximum and minimum values were thenselected from author-specific values.

d For axial shortening, reductions in length were re-ported as positive percentage values. A negative calcu-lated statistical minimum (mean e 1.5 standarddeviations) would suggest elongation. As a result, anyoverall minimums were set to the smallest positiveminimum value for a given segment.

RESULTS

Final literature database

The literature database consisted of 12 articles andthree conference presentations.6-26 Table I lists theauthors of the articles in alphabetical order, along witha legend containing author acronyms and publication yearsfor each source. The presentations were grouped with theassociated article because they typically contained moredata than the article by the same author.

Four of the authors listed in Table I were not included inthe final analysis because the data or methods reported intheir articles were not directly transferrable to the previouslyidentified deformation modes. For example, it was difficultto determine which arterial segments were measured in the1994 article by Wensing et al15 and whether two-dimensional (2D) or three-dimensional (3D) methodswere used to analyze the images. Additionally, Woodet al14 and Smedby et al17 investigated aspects of the SFAin the supine position only; thus, no strain data were avail-able. Diaz et al12 examined the effects of flexion on barePA tortuosity using dynamic angiography. However, themethod to evaluate “hinge points”12 was not directly

Fig 3. Differences in study design variables of image modality (x-axis), physiologic setting (y-axis), and limbpositioning (top) for the eight articles in the final literature database. See Table I for the author acronym key.CT, Computed tomography; MRA, magnetic resonance angiography.

JOURNAL OF VASCULAR SURGERY808 Ansari et al September 2013

transferable to a bend angle as previously presented. Exclu-sion of these four articles reduced the final literaturedatabase to eight articles (listed in bold in Table I).

Variations in study design

Fig 3 presents the different imaging techniques(x-axis), physiologic models (y-axis), and limb positions(box) of the eight articles, as discussed below.

Imaging techniques. Five studies collected andanalyzed 3D reconstructed image data. Three (RB, CC10, CC 06) used magnetic resonance imaging (MRI) toinvestigate one or more deformation modes, AK used 3DX-ray angiography, and AG collected 3D computed tomog-raphy (CT) data. RB restricted the analysis to 2D transverseslices of the MRI data to capture changes of the lumenperimeter due to pinching. The remaining three sources(AN 11, AN 08, HS) used 2D X-ray data, which includedflat-plate X-rays, fluoroscopy, cineangiography, and digitalsubtraction angiography, with views limited to a sagittal sliceof the supine and flexed knee/upper thigh. In general, axialshortening and bending data were extracted with 3D or 2Dimaging modalities. Twist data were only provided bysources using 3D imaging modalities.

Physiologic model. The physiologic state of the SFA/PA widely varied across the studies, ranging from cadavericspecimens to living patients, young to mature patients, anddiseased to healthy arteries. These variations were alsocoupled with a limited number of study participants orcadaveric models, resulting in a small sample size for eachstudy. An average of 10 patients or cadavers were studiedin each publication, with an average of only 13 limbs perstudy to compare for the final review.

Not all arteries were stented. Moreover, in two ofthe four studies that evaluated stented arteries, the

manufacturer of the implanted stents was not provided,nor were we able to determine the relative flexibility ofthe stent design. Furthermore, all four articles with stentedartery data mixed overlapped and nonoverlapped measure-ments to determine average magnitudes in deformations.AG also averaged data from lesions that extended acrossmultiple arterial segments (eg, “mid-thigh” data were aver-aged with data taken from a lesion located “behind theknee”), further confounding the data.

Limb positioning. Seven of the eight studies evalu-ated arterial changes in a supine and flexed position; onlyRB limited their analysis to a relaxed, supine position andhad participants contract the thigh muscles withoutdynamic motion. Of the studies that imposed flexion tosimulate daily activities, the degree of flexion varied tosimulate walking, sitting or stair climbing, or both. Hipand knee bend angles to simulate these leg positionswere also different. AN and HS used 70�/20� and 90�/90� knee/hip bend angles for walking and sitting/stairclimbing, respectively.29 AK and AG approximateda 90�/40� position, also known as a “Fig 4” knee bend.CC used different flexed positions for the 2006 and 2010studies: the younger patients bent their leg into a fetalposition, whereas the older patients flexed to a 90�/40�

bend, respectively.Anatomic definitions. The definition of each arterial

segment was different for each study, as highlighted inFig 1, b. Three articles provided clear anatomic markersto define the start and end points of each arterial segmentevaluated. The remaining articles did not provide cleardefinitions or sufficient details to ascertain where eacharterial segment was anatomically located. None of theauthors in the final database referenced the AH. Only ANused the patella as an end point for the pPA in their studies.

ba

Fig 4. Summary of axial shortening data for (a) walking and (b) sitting/stair climbing positions from the literaturedatabase reports values from each article, as well as the maximum value for stented and bare artery data from the entireliterature database. See Table I for the author acronym key. dPA, Distal popliteal artery; dSFA, distal superficial femoralartery; mSFA, midsuperficial femoral artery; pPA, proximal popliteal artery; pSFA, proximal superficial femoral artery.

Table II. Summary of all nonradial deformation dataa

Variable pSFA/mSFA dSFA/pPA dPA Referencesb

Axial shortening, %Sitting/stair climbing 6.14 (0.4-29.5) 13.9 (1.5-26.0) 12.3 (3.5-18.5) AN 11, AG, HS, AN 08, AK, HS, CC 06Walking 4.0 (0-11.0) 8.1 (1.8-21.5) 7.7 (0-16.5) HS, AN 08, CC 06, AK, HS, AN 08,

AN 11, AG 11Axial twist, �/cm 2.1 (0.1-5.4) - 3.5 (0.6-6.3) AK, CC 10, CC 06Bending radius of

curvature, mm72.1 (19-206) - 22.1 (13.0-33.8) AG, AN 11, HS, CC 10, AK

Local compression (percentchange in aspect ratio), %

- 4.6 (4.5-4.7) 12.5 (12.4-12.6) RB

dPA, Distal popliteal artery; dSFA, distal superficial femoral artery; mSFA, midsuperficial femoral artery; pSFA, proximal superficial femoral artery.aThe mean and range are reported, with maximum and minimum values inclusive of all reported values and mean values 6 1.5 standard deviations.bSee Table I for author key.

JOURNAL OF VASCULAR SURGERYVolume 58, Number 3 Ansari et al 809

AG provided only clinical descriptions (a general approxi-mation of lesion location on the overall limb) and did notspecify the arterial origin.30 HS did not specify the start orend points of each artery, so the marker stents shown in the2005 presentation images were used to approximate arte-rial segments.

The anatomic discrepancies were often associated withthe type of imaging modality used. The use of 3D imagingby AK, CC 10, and CC 06 limited the anatomic markers toarterial branch points because only the artery centerline wasreconstructed for analysis. These branch points do notnecessarily overlap with the muscle and bone markers asused in clinical definitions. For example, the DGA branchesoff the SFA a few centimeters superior to the AH(Fig 1, a).27 Variations among the studies that used 2DX-ray data were mostly due to different choices foranatomic markers or a lack of specifics provided by authors.

Reported data

A summary of the data is in Table II. Below isa discussion of reported values for each nonradial defor-

mation mode.

Axial shortening and elongation. Seven authors re-ported axial shortening. One reported strain for a walkingposition, three reported strain for the sitting/stair climbingposition, and four reported strain for both. AG, CC 06,and AK were the only authors that noted a single instanceof elongation upon flexion; all of the rest of the lesionsexperienced axial shortening. Mean data from these articlesare summarized in Fig 4, with stented and bare artery datademarcated. The maximum reported axial shortening valueof all sources was noted for stented and bare artery data foreach category.

Bending. Six authors quantified bending usinga variety of methodologies for measurement, includingbending radius (fitting a circle to the centerline or inneredge of the vessel), bending angle (approximate anglebetween the start and end of the arterial segment andcentral point), and curvature (inverted radius of curvatureoften averaged over a certain interval spacing for an entirevessel segment).

The interval spacing over which curvature wasmeasured was different for the three sources that measuredcurvature. AK reported the average of curvature over

Fig 5. Bending data are summarized for stented and bare vessels.Adjustments were made to the data to produce centerline bendingradius magnitude, as discussed in the text. Only AG providedmaximum and minimum measurements, with a minimummeasured radius of curvature of 17 mm in the “mid-thigh” region.Also note that the ranges of the magnitudes for the stented andbare overlap were the same. See Table I for the author abbreviationkey. dPA, Distal popliteal artery; mSFA, midsuperficial femoralartery; pSFA, proximal superficial femoral artery.

Fig 6. Summary of axial twist data for the femoropopliteal arteryincludes mean values for each source and maximum measuredvalues from all sources. Only bare artery data are available at thistime. See Table I for the author abbreviation key. dPA, Distalpopliteal artery; mSFA, midsuperficial femoral artery; pSFA,proximal superficial femoral artery.

JOURNAL OF VASCULAR SURGERY810 Ansari et al September 2013

0.5-mm intervals. AG provided individual data points formaximum curvature and minimum bending radius with5-mm spacing. CC 10 used a cost function to calculatean appropriate interval size and reported the maximumchange of curvature for each arterial segment.

As previously stated, the reported bending data wereconverted to provide consistency in the results. Dataprovided by AG were converted to calculate the averageminimum bending radius values and regrouped by clinicaldescriptions of lesion location. Data for pSFA/mSFAincluded data from participants with “upper thigh,” “nearhip,” and “groin” locations, “mid-thigh” locations wereincluded as dSFA/pPA, and “behind the knee/popliteal”data were classified as dPA.

All available sitting/stair climbing data are summarizedin Fig 5. No bending data were available for the dSFA/pPA. Only AN 11 reported a value of 93 mm for dPA(walking), with no data captured forSFA/pPA. CC 06measured the “straightness” of the SFA and found nonotable deviation in young, healthy participants. Becausethese data did not indicate how bent the artery was, theywere not included in Fig 5.

Twisting. Only three authors, who used 3D imagedata, reported twist measured in bare arteries. Fig 6summarizes the data reported.

Pinching (local compression). Pinching was charac-terized geometrically in two studies, both of which evaluatedthe change in the lumen cross-section due to musclecompression. RB determined the change in aspect ratio forbare arterieswas statistically significant for thedSFAandpPA,with a change from 0.88 to 0.77 from a relaxed to a flexedthigh muscle state. AG measured the change in eccentricityfrom supine to a “Fig 4” knee bend for stented arteries, withoverlapped and single-stented lesions. The change ofeccentricity after flexion increased on average by 10%.

DISCUSSION

The SFA/PA segment is different from the othervascular beds, such as coronary and iliac, because it deformssignificantly due to musculoskeletal motion in addition tocardiac pulsatility. Although there appears to be an abun-dance of data from studies conducted to characterize themusculoskeletal motion in the SFA/PA, the differencesand limitations of the studies prohibit the reader fromdrawing conclusions about how the deformations affectstent performance. We need a better, quantitative under-standing of those deformations to improve the develop-ment and evaluation of stents and other therapies fortreating PAD in the SFA/PA. The lack of biomechanicalinformation contributes to the limitations of preclinicalevaluation. As a result, there is no gold standard durabilityand fatigue assessment that adequately predicts clinicalperformance of therapies for PAD.

Small sample sizes required us to pool several differentstudies to evaluate data from a larger host of patients. Theresults from the studies vary widely because of the lack ofuniformity among definitions, imaging modalities, physio-logic setting, and limb positioning.

For example, MRI-based imaging potentially underes-timates the axial and bending deformation in the dSFAbecause the authors used the DGA, which is superior tothe AH, as a cutoff point. Moreover, none of the authorsused the AH as an anatomic marker. Because a significantamount of bending and twisting occurs below the AH,this landmark might be important in defining the differentSFA/PA regions. Only AN specifically isolated the pPA,using an appropriate bone marker (3 cm above the inter-condylar fossa) according to our previously stated defini-tions. Furthermore, these data do not provide a sufficientdescription of how the artery behaves as it transitionsfrom the SFA to the pPA through the AH, nor is there

Table III. Suggested elements for future imaging studiesinvolving arterial deformations

d Use of a single stent design with known mechanical propertiesd Evaluation of the effect of overlapping stentsd Inclusion of data from patients requiring stentsd Use of three-dimensional imaging modalitiesd Standardized approach to applying limb motiond Segmenting the data by specific anatomic location

JOURNAL OF VASCULAR SURGERYVolume 58, Number 3 Ansari et al 811

sufficient evidence to demonstrate whether the pPAundergoes more or less severe deformation than the restof the PA. We further distorted the data because onlyone datum was used in multiple segments due to the lackof consistent terminology. Similar disparities in the avail-able clinical data have spurred working groups to stan-dardize the terminology of the anatomy of the peripheralvasculature.

Limitations of the 2D techniques further confoundedthe data. The authors who used 3D reconstruction wereable to determine changes in length along the centerlinefor axial shortening, providing a more accurate assessmentof strain. 3D reconstruction also captured the bending ofthe artery in all directions, thereby providing a more accu-rate evaluation of vessel tortuosity. Finally, 3D reconstruc-tion captured twisting because the authors were able to usearterial markers (eg, ostia) for tracking between the two legpositions. Unfortunately, vessels are not reconstructed with2D imaging. Thus, the 2D data resulted in a limited view ofthe vasculature during flexion, potentially underestimatingthe minimum bend radius or maximum axial shorteningbecause the SFA/PA can deform out of plane.

In addition, the physiologic setting also varied greatly.There were a variety of vessel types, bare and stented, youngand mature, diseased and healthy, and living and cadaveric.The vessel type affected our ability to compare deformationmagnitudes across different pools of data. Bare arteries(whether older or diseased) tend to be more compliantthan stented arteries; as such, the deformations reportedmight be an overestimation of stented artery deformation.Further, the measurements from stented arteries are diffi-cult to generalize because the type of stent was not alwaysknown, nor did the authors discuss stent flexibility andhow that affected deformation magnitudes. Another incon-sistency was overlapped stents; there was no clear reportingon when overlapped stents were grouped with nonoverlap-ped stents. Moreover, some of the data were collected fromonly young, healthy vessels, which have markedly differentproperties than mature, diseased vessels, including lessdistensibility and flexibility. The twisting data, for example,were collected from bare arteries only.

Limb positioning (ie, the angle to which the hip andknee were bent) likely affected the magnitude of deforma-tion observed. Some studies quantified the deformationunder simulated “walking” hip and knee bends (70�/20�)9,13; others quantified deformation under simulated“stair climbing/sitting” hip and knee bends (90�/90�),6,7,9 and some bends were as extreme as a fetal posi-tion,10 although these patients were young. These differ-ences affected our ability to combine the data collectedfrom multiple studies. Thus, we report magnitudes ofdeformation with large variations, making it difficult topinpoint an accurate representation of the biomechanicalenvironment.

The lack of data at conditions simulating walking orsitting/stair climbing also contributes to our ability todetermine testing conditions that are clinically predictive.To adequately simulate the fatigue modes for accelerated

durability and computational modeling, certain parametersare needed: loading magnitudes, direction, and cyclenumber. When fatigue evaluations are conducted, walkingand sitting/stair climbing loading should both be evalu-ated because it is not evident which simulated activity ismore critical for fatigue. With respect to cycle numbers,walking has been reported to be approximately 10-foldthat of sitting/stair climbing; however, sitting/stair climb-ing consistently results in larger magnitudes of loading.Data are therefore needed to characterize both conditions,which was not captured for each deformation mode.

Although we are not able to report exact magnitudesand cycle numbers for the evaluation of therapies forPAD in the SFA/PA, we can summarize the trends andlimitations in the existing data. The trend in axial short-ening is toward lower magnitudes for stented vesselscompared with bare vessels and higher magnitudes inmore distal regions of the mSFA segment. The data forelongation were not sufficient to conclude any trendsbecause they were not reported in all studies. It is not clearwhether this was because elongation was so small that itwas not measurable or because it was not investigated.

Regarding bending, the trend is toward a smaller radiusof curvature (ie, more bending) in the dSFA/pPA but notbetween stented and bare arteries. We thus conclude thatstented vessels could bend as much as bare vessels if thestent were flexible. However, because many measurementtechniques were used to calculate bending, directlycomparing the results from each study was difficult. Forexample, AK reported mean curvature, which potentiallyunderestimated the severity of the bending, whereas AG re-ported minimum radii of curvature, providing a conserva-tive estimate of bending.

As for twisting, there was no clear trend across thestudies, and all the data are from bare arteries. Note thatbecause arterial branches are used as anatomic markers,all dSFA/pPA data terminate above the AH at the DGA,potentially underestimating the amount of twisting thatoccurs when the SFA exits the AC, becoming the pPA,and traversing the knee joint.

Regarding pinching, AG’s percentage eccentricity andRB’s percentage aspect ratio changes both demonstratea greater deviation in circular shape of the dSFA/pPAthan the pSFA/mSFA and dPA. RB’s data were measuredfrom bare, young arteries, whereas AG’s data includedstented arteries. However, the anatomic locations of AG’sdata are unclear, and the use of both single and overlappedstents muddles the interpretation.

JOURNAL OF VASCULAR SURGERY812 Ansari et al September 2013

Given the heterogeneity of presented studies and thedata collected, several key design considerations, outlinedin Table III, become evident for future studies. It wouldbe valuable to investigate the deformation of unstenteddiseased arteries under flexion and then assess the changeswhen a stent is implanted. Further considerations fora study include adequate sample size, representative patientpopulation, appropriate imaging modalities, walking andsitting/stair climbing positions, and clearly definedanatomic segments.

An important study that could further our know-ledge would include a sufficient number of relativelyhomogeneous patients receiving the same stent type. Asingle stent design with known properties could be usedas a “strain gauge” to help quantify deformations andunderlying forces. The study could additionally considerthe effects of (or completely exclude) overlapping stentsto specifically evaluate overlap regions.

Moreover, with increasing age and subsequent reduc-tion in elasticity, an increase in tortuosity can be seen inolder patients with PAD.15 Thus, to capture data represen-tative of the patient population, patients requiring stentscould be evaluated. This would help address some of thekey disparities in the existing data that stem fromcombining young/old, healthy/diseased, and stented/nonstented individuals.

One way to best quantify the deformation in all direc-tions would be to use 3D imaging methodologies. Bendingand twisting, for example, impose deformations that canoccur out of the imaging plane. To date, our knowledgeof twisting of the SFA/PA has only been evaluated forbare arteries.

It might also be important to include a clearly definedand consistent approach for collecting data that representsboth walking and sitting/stair climbing, or for conditionsthat represent daily activities of patients with PAD. Bycapturing similar data across multiple patients, one canbetter understand the range of motion and forces withinthe population.

Finally, it might also be important to clearly define,analyze, and report the data for the different segments ofthe SFA/PA such that one can discern local deformation.Different regions are expected to deform differently (eg,upper thigh vs behind the knee). Having those data enableevaluation of stents according to conditions expected forspecific indications. Given recent attempts to standardizedefinitions of the peripheral vasculature, it might bepossible to use anatomic definitions that are more easilyidentifiable by using landmarks that are visible with currentimaging (eg, bone markers rather than nonvisible locationsof ligaments).

It is important to note that the clinical significance andconsequence of these complex deformations, especiallywith respect to stent fatigue and fracture, are not wellunderstood. As described above, stent fractures can occuras a result of these complex deformations. However,controversy remains about how significant various fracturetypes are in contributing to clinical sequelae and whether

they are independently associated with and cause clinicalsequelae or are merely a consequence of the initiatingforces that lead to sequelae. If we better understood theclinical significance of fracture types, this would help usbetter define more meaningful acceptance criteria for stentfatigue evaluation, whether from a physical test or a compu-tational simulation, ultimately leading to the design ofmore robust stents.

CONCLUSIONS

A review of the current literature regarding thebiomechanical environment of the SFA/PA reveals hetero-geneous study designs that confound interpretation.The level of heterogeneity limits our understanding ofthe stent deformations and prevents pooling and directcomparisons of the data. The available data demonstratethat deformations vary according to the specific anatomiclocation within the SFA/PA. Further, the amount of defor-mation will vary depending on host factors, such as age,presence of atherosclerotic disease, or the presence orabsence of a stent, inherent to the vessel being studied.Review of the literature revealed trends in understandingthe anatomic and physiologic environment of the vessels,but more importantly, it has provided direction for futurestudy considerations based on inconsistencies in the currentknowledge base. At a minimum, standardization of theanatomic boundaries of the arterial segments is necessary,with landmarks more universally identifiable by theimaging modalities that will be used by future studies.Further, there is a need for standardized flexion anglesfor the measurement of deformation across simulated dailyactivities.

Knowledge from the investigation of the physiologicmilieu of the SFA/PA can be extrapolated to nonclinicalevaluations of stents to design testing that will more closelypredict stent performance in vivo. With the ability topredict stent fracture, it might be possible to discover therelationship between fracture and the clinical sequelaethat are observed and associated with stent fractures and,ultimately, determine causality or the lack of causality. Ulti-mately, with a robust characterization of the biomechanicalenvironment of the SFA/PA, better and safer stents couldbe developed to improve clinical outcomes in an area ofgreat clinical need.

We thank Jennifer Goode, Lisa Lim, and Kenneth Cav-anaugh, of the Peripheral Vascular Devices Branch in theOffice of Device Evaluation at Center for Devices andRadiological Health, for providing their expertise.

AUTHOR CONTRIBUTIONS

Conception and design: TM, LPAnalysis and interpretation: FA, LP, SB, TMData collection: FA, TMWriting the article: FA, LP, SB, TMCritical revision of the article: FA, LP, TMFinal approval of the article: FA, LP, SB, TMStatistical analysis: Not applicable

JOURNAL OF VASCULAR SURGERYVolume 58, Number 3 Ansari et al 813

Obtained funding: TMOverall responsibility: TM

REFERENCES

1. Allie D, Hebert C, Walker C. Nitinol stent fractures in the SFA.Endovascular Today July/August 2004:22-34.

2. Laird J, Katzen BT, Scheinert D, Lammer J, Carpenter J,Buchbinder M, et al. Nitinol stent implantation versus balloon angio-plasty for lesions in the superficial femoral artery and proximal poplitealartery. Circ Cardiovasc Interv 2010;3:267-76.

3. Scheinert D, Scheingert S, Sax J, Piorkowski C, Braunlich S, Ulrich M,et al. Prevalence and clinical impact of stent fractures after femo-ropopliteal stenting. J Am Coll Cardiol 2005;45:312-5.

4. Gray WA, Granada JF. Drug-coated balloons for the prevention ofvascular restenosis. Circulation 2010;121:2672-80.

5. Kandzari DE, Rao SV, Moses JW, Dzavik V, Strauss BH, Kutryk MJ,et al. Clinical and angiographic outcomes with sirolimus-eluting stentsin total coronary occlusions. J Cardiovasc Interv 2009;22:97-106.

6. Cheng C, Choi G, Herfkins R, Taylor CA. The effect of aging ondeformations of the superficial femoral artery resulting from hip andknee flexion: potential clinical implications. J Vasc Interv Radiol2010;21:195-202.

7. Ganguly A, Simons J, Schneider A, Keck B, Bennett NR, Herfkins RJ,et al. In-vivo imaging of femoral artery nitinol stents for deformationanalysis. J Vasc Interv Radiol 2011;22:244-9.

8. Klein A, Chen SJ, Messenger JC, Hansgen AR, Plomondon MR,Carroll JD, et al. Quantitative assessment of the conformational changein the femoropopliteal artery with leg movement. Catheter CardiovascInterv 2009;74:787-98.

9. NikanorovA,SmouseHB,OsmanK,BialasM,ShrivastavaS,SchwartzLB.Fracture of self-expanding nitinol stents stressed in vitro under simulatedintravascular conditions. J Vasc Surg 2008;48:435-40.

10. Nikanorov A, Schillinger M, Zhao H, Minar E, Schwartz LB. Assess-ment of self-expanding nitinol stent deformations implanted into thefemoropopliteal artery [Abstract]. J Vasc Surg 2009;49(5 Suppl):S24.

11. Cheng C, Wilson NM, Hallett RL, Herfkens RJ, Taylor CA. In-vivoMR angiographic quantification of axial and twisting deformations ofthe superficial femoral artery resulting from maximum hip and kneeflexion. J Vasc Interv Radiol 2006;17:979-87.

12. Diaz JA, Villegas M, Tamashiro G, Micelli MH, Enterrios D,Balestrini A, et al. Flexions of the popliteal artery: dynamic angiog-raphy. J Invasive Cardiol 2004;16:712-5.

13. Smouse B, Nikanorov A, LaFlash D. Biomechaical forces in thefemoropopliteal arterial segment. Endovascular Today 2005:60-6.June.

14. Wood NB, Zhao SZ, Zambanin A, Jackson M, Gedroyc W, Thom SA,et al. Curvature and tortuosity of the superficial femoral artery:a possible risk factor for peripheral arterial disease. J App Phys2006;101:1412-8.

15. Wensing PJ, Scholten FG, Buijs PC, Hartkamp MJ, Malk WP,Hillen B. Arterial tortuosity in the femoropopliteal region during kneeflexion: a magnetic resonance angiographic study. J Anat 1995;186:133-9.

16. Brown R, Nguyen TD, Spincemaille P, Prince MR, Wang Y. In-vivoquantification of femoral-popliteal compression during isometric thighcontraction: assessment using MR angiography. J Magn ResonImaging 2009;29:1116-24.

17. Smedby O, Hogman N, Nilsson S, Erikson U, Olsson AG, Walldius G.Two-dimensional tortuosity of the superficial femoral artery in earlyatherosclerosis. J Vasc Res 1993;30:181-91.

18. Adams GJ, Baltazar U, Karmonik C, Bordelon C, Lin PH, Bush RL,et al. Comparison of 15 different stents in superficial femoral arteries byhigh resolution MRI ex vivo and in vivo. J Magn Reson Imaging2005;22:125-35.

19. Choi G, Cheng CP, Wilson NM, Taylor CA. Methods for quantifyingthree-dimensional deformation of arteries due to pulsatile and non-pulsatile forces: implications for the design of stents and stent grafts.Ann Biomed Eng 2009;27:14-33.

20. Ganguly A, Simons J, Schneider A, Keck B, Bennett NR, Herfkens RJ,et al. In vitro imaging of femoral artery Nitinol stents for deformationanalysis. J Vasc Interv Radiol 2011;222:244-9.

21. Klein AJ, Casserly IP, Messnge JC, Carroll JD, Chen SY. In-vivo 3Dmodeling of the femoropopliteal artery in human subjects based onX-ray angiography: methodology and validation. Med Phys 2009;362:289-310.

22. Müller-Hülsbeck S, Schäfer PJ, Charalambous N, Yagi H, Heller M,Jahnke T. Comparison of second-generation stents for application inthe superficial femoral artery: an in vitro evaluation focusing on stentdesign. J Endovasc Ther 2010;176:767-76.

23. Wissgott C, Schmidt W, Behrens P, Schmitz KP, Andresen R.Performance characteristics of modern self-expanding nitinol stentsindicated for SFA. RoFo 2009;181:579-86.

24. Smouse, B, Nikanorov A, LaFlash D. Changes in major peripheralarteries during joint movement before and after stent placement in thecadaver model. Presented at: Transcatheter Cardiovascular Therapeu-tics, September 26-October 4, 2004, Washington, D.C.

25. Nikanorov A. Arterial biomechanical forces and deformations. Pre-sented at: Stent Summit, Cleveland Clinic, July 31-August 2, 2008,Cleveland, Ohio.

26. Nikanorov A. Multiscale modeling for evaluation of peripheral stentmechanical performance. Presented at: Transcatheter CardiovascularTherapeutics, September 21-25, 2010, Washington, D.C.

27. Netter FH. Atlas of human anatomy. 3rd ed. Teterboro, NJ: IconLearning Systems; 2004.

28. Diehm N, Pattynama PM, Jaff MR, Cremonesi A, Becker GJ,Hopkins LN, et al. Clinical endpoints in peripheral endovascularrevascularization trials: a case for standardized definitions. Eur J VascEndovasc Surg 2008;36:409-19.

29. Goswami A. A new gait parameterization technique by means ofcyclogram moments: application to human slop walking. Gait Posture1998;8:15-36.

30. Duda SH, Bosiers M, Lammer J, Scheinert D, Zeller T, Tielbeek A,et al. Sirolimus-eluting versus bare nitinol stent for obstructive super-ficial femoral artery disease: the SIROCCO II trial. J Vasc Interv Radiol2005;16:331-8.

Submitted Nov 6, 2012; accepted Mar 24, 2013.