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P
eripheral arterydisease(PAD)most commonlyresultsfrom atherosclerosis (plaque)of
the arteries that carries blood to the upper and lower extremities, kidneys, and the
splanchniccirculation.However,inthischapter,wefocusonlowerextremityarterialdisease.
Atheroscleroticplaqueisprimarilymadeupofcholesterol,inflammatorytissue,calcium,and
fibroustissue. Over time, they hardenand narrow the arteries, thereby limiting theflow of
blood.Impairedbloodflowtoyourlegscancausepainandnumbness.Thiscanincreasethe
riskofinfection,especiallyindiabeticpatients,andalsopreventhealingafterfootsurgeries.
Inaddition,prolonged,persistentischemiaofthelowerextremitycanleadtogangrene(tissue
death),nonhealingulcers,andeventuallyamputation.
PADisaverycommoncondition affecting 12%to20% ofAmericanswhoare65years
andolder.Itisaleading causeofdisabilityamongpatientswhoare50yearsandolder and
those who have diabetes. PAD affects men and women equally and is more prevalent in
African Americans.1 The Framingham Heart Study and the National Health and Nutrition
ExaminationSurvey (NHANES)haverevealedthattraditionalcoronaryand cerebrovascular
risk factors such as age, diabetes, hypertension,hypercholesterolemia, metabolic syndrome,
andsmokingincreasetheriskofPAD.2Importantly,patientswithPADhavehighcardiacand
cerebrovascular event rates. Interestingly, though, only 10% to 35% of patients with PAD
present with typical features. Most of the patients are either asymptomatic or present with
atypicalsymptoms,whichisassociatedwithfunctionallimitation.OnetotwopercentofPAD
patients present withcritical limb ischemia (CLI) without any warning signs or symptoms.
Giventhe fact that CLI has been associated with a highrate of morbidity and mortality, it
makesitthemostconcerningcategoryamongPAD.Hence,itbecomesofutmostimportanceto
recognizeCLIattheearliest.
The appropriatetreatment may slow disease progressiontosome extent and reduce the
burdenofmorbidityassociatedwithPAD.Treatmentcanbebroadlycategorizedintolifestyle
changes, medical management, endovascular therapy, and surgery. The significant morbidity
andmortalityassociated with PADalong with itsadverse impacton economics makes itan
importantpublichealthproblem.TheoverlapofPADwithcoronaryarterydisease(CAD)has
ledinterventionalcardiologiststobemoreinvolvedinthecareofthesepatients.Finally,inthe
lastfewyears,therehasbeenatremendousgrowthinendovasculartechniquesanddevices,
which has led to the preference of endovascular therapy over surgery when it comes to
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revascularization.
RISKFACTORS
Several risk factors as mentioned earlier have been associated with PAD. Smoking and
diabetesremainthemostimportantones.SmokingisthemainriskfactorforPAD,whichcan
increasetheriskuptofourfold.SmokerswithPADbecomesymptomatic10yearsearlierthan
their nonsmoking counterparts. Abstinence of smoking halts the progression of the disease.
Diabetic patientswho are also smokers are atthe highestrisk for developing PADand its
associatedcomplications,suchasgangrene.Aboutoneinthreepeopleolderthan50whohave
diabeteshavePAD.PADistwiceascommonindiabetics.1DiabeticPADpatientsoftenhave
extensive involvementofinfrapoplitealarteries.PADincreasestheriskofCAD,myocardial
infarction(MI),stroke,andtransientischemicattack.OfthepeoplewhohaveCAD,thereisa
one in three chanceofhaving PAD.The prevalenceoffootulcers rangesfrom 4% to 10%
amongdiabetic patients.3 Annual incidenceofulcers indiabetics ranges from 1% to4.1%,
with a lifetime incidence being as high as 25%. Diabetic foot ulcers frequently become
infected and are a major cause of hospital admissions. In a recent two-center study, PAD
partiallycontributedto30%ofallfootulcers.
4
HISTORYANDPHYSICAL
AthoroughhistoryandphysicalexaminationisabsolutelycriticalinthediagnosisofPADand
also forplanningfurthermanagement.PADpatientsmaypresentwithtypicalclaudicationor
with atypical symptoms on most occasions. Intermittent claudication is defined as a
reproducible discomfort of a group of lower extremity muscles, which is brought on with
exertion and typically relieved with rest. Claudication is derived from the Latin word,
“Claudicato,” which means limp. Atypical symptoms may vary from nonspecific pain,
numbness, aching, or heaviness in the lower extremities. When the arteries of lower
extremitiesstarttodevelopobstructionandresultinreducedbloodflow,therespectivemuscle
group accumulates lactic acid with exertion. This accumulation of lactic acid and other
metabolitescausespain.Withrest,lacticacidandothermetabolitesarewashedawayandthe
patientbecomesfreeofpain.Thelongerthetimeneededforthepaintoberelievedwithrest,
the worseis the obstruction.The presenceoflower extremityresting pain,which improves
whenthelowerextremitiesaredependent,herald CLI.Thepresenceofgangreneandulcers
signifiesCLIandneedsurgentattention.Patientswithahistoryofamputationorfootsurgeries
should undergo comprehensive evaluation with regard to the details of the amputation/foot
surgery,suchasthecauseforitandtherecoveryorhealingphaseofthestump(Table9-1).
Carefulandmeticulousexaminationshouldbeperformedinthesepatients.Bloodpressure
(BP) should be recorded from both the upperextremities as adifference (in systolic blood
pressure[SBP])exceeding20mmHgindicatespotentialinnominate,subclavian,or axillary
occlusive arterial disease. Auscultation over the carotid, subclavian, and renal arteries is
important,asthepresenceofbruitcanbeacluetounderlyingstenosisandisalsoassociated
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Table9-1.
■
■
with higher cardiovascular mortality (especially with carotid bruit).5 The presence of a
pulsatile abdominalmassshouldraisethe suspicionforanabdominal aorticaneurysm. Itis
absolutelyimperativetomakeeveryeffortpossibletopalpatealltheperipheralpulses(radial,
brachial, femoral, popliteal, dorsalis pedis, and posterior tibial). If the pulses are not
palpable, the useofahandheld Doppler shouldbe strongly considered. Thedorsalis pedis
pulsecanbeabsentin8%to12%ofhealthyindividuals,buttheposteriortibialpulseisabsent
in only 2%. The lack of palpable pedal pulses strongly suggests the presence of PAD.
However,thepresenceofapalpablepulsedoesnotexcludePADascollateralbloodflowcan
giverisetoapalpabledistalpulse.6Ifpedalpulsesarenonpalpable,therewouldbeaneedfor
further workup with noninvasive or invasive assessment based onthe clinical presentation.
Expansileandpalpable masses inthefemoralandpoplitealarterialregionsshouldraisethe
suspicionforaneurysms.Capillaryfillingtimeisassessedbysqueezingthegreattoetocause
theskintoblanchandthenlettinggotoseehowlongittakesfortheskintoregainitsoriginal
color.Acapillaryfillingtimeofgreaterthan5secondsisconsideredprolonged.Feetandnails
shouldbeexaminedthoroughlyforanycalluses,discoloration,gangrenouschanges,ulceration,
and infections. The presence of the above should warrant an immediate assessment of the
arterial circulation to the lower extremity. Consultation with a vascular specialist is
recommended. It is important to understand that a large proportion of PAD patients are
asymptomatic.Strictfootcareisveryimportant,especiallysoindiabetics,astheyareproneto
developgangreneandeventuallyamputation.
SiteofPaintoPresumedLevelofObstruction
Siteofpain Presumedlevelofobstruction
Buttockandhip Aortoiliacarterydisease
Impotence Bilateralaortoiliacarterydisease(Leriche)
Thigh Commonfemoraloraortoiliacarterydisease
Uppertwo-thirdsofcalf Superficialfemoralartery
Lowerone-thirdofcalf Poplitealarterydisease
Footclaudication TibialorPeronealarterydisease
ScreeningrecommendedperAmericanHeartAssociation(AHA)asascreeninginitiative
7
recommendsankle-brachialindex(ABI)inasymptomaticindividualswhoare:
Olderthan50yearsofagewithahistoryofdiabetesmellitusorsmoking
Anyoneolderthan65yearsofage
CLASSIFICATIONOFPADPATIENTS
Therearetwotypesofclassificationthatareacceptedinternationallytoclinicallycategorize
thePADpatients.
The Fontaine classification, introduced by René Fontaine in 1954 for chronic limb
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ischemia,8isbasedonsymptomsandwalkingdistance:
StageI:Asymptomatic
StageII:Mildclaudication
StageIIA:Claudicationdistanceofgreaterthan200meters
StageIIB:Claudicationdistanceoflessthan200meters
StageIII:Restpain,mostlyinthefeet
StageIV:Necrosisand/organgreneofthelimb
The more recentclassificationby Rutherford consists of fourgrades and seven categories
9
basedonsymptomalone:
Grade0,Category0:Asymptomatic
GradeI,
Category1:Mildclaudication
Category2:Moderateclaudication
Category3:Severeclaudication
GradeII,Category4:Restpain
Grade III,Category5:Minortissueloss,ischemic ulcerationnotexceedingulcer ofthe
digitsofthefoot
GradeIV,Category6:Majortissueloss,severeischemiculcersorfrankgangrene
OTHERPADDISORDERS
Two diseases needspecialmention becauseoftheiruniquepresentationandcharacteristics.
Leriche syndrome is an atherosclerotic occlusive disease involving the abdominal aortic
bifurcationandmayextendintoboththecommoniliacs.Itisrecognizedwithintermittentthigh
claudication and impotence from hypogastric artery occlusion with decreased flow to the
pudendalartery.Distalpulsesareusuallydiminished.Anytissuelossimpliesdistaldisease,
exceptincaseof“bluetoe”syndromewheremultipletoesareinvolvedfromembolizationof
theiliacplaque.Bluetoeisalsoassociatedwithaorticaneurysms.Angioplastyisthetreatment
ofchoice.
TheotheroneisBergersyndrome,whichisalsoknownasthromboangiitisobliterans.This
inflammatory disease involves the small and medium arteries as well as the veins. The
histopathology is characterized by inflammatory tissue, thrombus, and microabscess. It is
distinctivelyseeninmalesmokers.Typically,thepedalpulsesarenotpalpable.
As mentionedearlier, most of the PADpopulationdo not have any signs or symptoms.
Thus, screening and having a low threshold to perform noninvasive testing are of critical
importance.
VASCULITISOFTHELOWEREXTREMITIES
Vasculitis is inflammatorysystemic or local syndromes, which is the resultof autoimmune-
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mediated inflammation of the blood vessels. There are several types, and a significant
proportionofthesyndromesinvolvethelowerextremityarteries.Theyareknowntopresent
with systemic symptoms such as fever, weight loss, fatigue, malaise, and constellation of
symptoms,dependingonwhichorgansareinvolved.Onphysicalexamination,rash,nodules,
ulcers,andgangrenouschangesofupperandlowerextremitiescanbeidentified.Whenthereis
aconcernforvasculitis,animmediateconsultationtoavascularspecialistiswarranted.
DIAGNOSTICTOOLS
Inthiscurrentera,therearemultiplenoninvasivetoolsandtechniquesavailabletodiagnose
PAD.TheycanbeassimpleastheABItoasophisticatedmagneticresonancearteriography.It
is important to understand the pros and cons of these tests, as a combination of these
investigationsmaybeusedinthePADpopulation.Essentially,thetestingisindividualizedto
thepatients.Nevertheless,ABIremainsthefirstchoiceofinvestigationinscreeningaswellas
indiagnosingPAD.
Ankle-brachialIndex
ABI=HighestSBPinankle(dorsalispedisandposteriortibialarteries)/highestSBPinupper
arm(brachialartery)
This test has 95% sensitivity and 99% specificity to detect PAD. An ABI ≤ 0.90 is
diagnosticofPAD.DependingontheABIvalues,wecanassesstheseverityofPAD.Itisalso
usedtofollowpatientssubsequenttotheirendovascularorsurgicalintervention.Finally,ABI
is an independent multivariate predictor of cardiovascular and cerebrovascular mortality
(Table9-2).
AlternateABIisavariantofthestandard ABI,which isderived bydividingthelowest
SBPoftheankle(eitherdorsalispedisorposteriortibial)bythehighestSBPoftheupperarm.
AnabnormalABIbythismethodimpliesthatthereisanisolatedtibialarterydisease,whichis
notidentified bythe standard ABI as ituses thehigher SBP of the two tibial vessels. Itis
importanttoacknowledgethat both theseforms ofABIs can impacton yourcardiovascular
morbidityandmortality.10SegmentalBP andpulsevolumerecordings(PVRs)maybeuseful
forlocalizingthevascularlesionsinthelowerextremities,andaremostusefulinpatientswho
have abnormal ABI scores at rest. Thus, they help in determining the level and extent of
disease.Thepatientisplaced inasupinepositionandstandard size BPcuffsare placedat
severalsegmentsofthelowerextremity.ThereferenceBPcuffisplacedatthearmlevel.In
thethree-cufftechnique,thereisonecuffaboveandbelowthekneeandattheanklelevel.In
thefour-cufftechnique,twonarrowerBPcuffsareplacedatthethighlevel(thishelpsinthe
differentiationbetweenaortoiliacandsuperficialfemoralartery[SFA]disease).A20mmHg
orgreaterreductioninSBPbetweentwosegmentsisindicativeofaflow-limitinglesion.Itis
importanttonotethatwell-developedcollaterals candiminishthe gradients.Inhypertensive
patients,thegradientsmayfalselyincrease,andinlowcardiacoutputstates,thegradientsmay
falselydecrease.
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Table9-2. InterpretationofABIs
≥0.9–1.4 Normal
>1.4 Calcifiedvessels,whichpromptsfurtherstudies
≤0.9 Diagnosticforocclusivearterialdisease
0.4–0.9 Suggestsarterialobstructionassociatedwithclaudication(mildtomoderate)
<0.4 Multileveldisease(anycombinationofiliac,femoral,ortibialvesseldisease),
associatedwithnonhealingulcers,ischemicrestpain,pedalgangrene
PVRmaybeespeciallyusefulindiabeticpatientswithnoncompressible arteries asitis
lessaffectedbymedialcalcinosisthansegmentalBPrecording.PVRdetectschangesinblood
volumeinthelowerextremitiesandnotthepressures.AnormalPVRwaveformiscomposed
ofasystolic upstrokewith a sharp systolic peakfollowed byadownstrokethat contains a
prominent dicrotic notch. In calcified arteries, BPs are falsely elevated (as they are not
compressiblebytheBPcuff)andthuscanhavenormalABIsandsegmentalpressures.Thus,
thePVRbecomesavaluabletoolindetectingobstructivePADinsuchcalcifiedarteries.Mild
tomoderatediseaseischaracterizedbylossofthedicroticnotchandanoutward“bowing”of
thedownstrokeofthewaveform.Inseveredisease,theamplitudeofwaveformisblunted(Fig.
9-1). As previously mentioned, calcification of the arteries can result in a falsely normal
ankle-brachial pressure index. In addition to PVR, toe-brachial index(TBI) can be used to
assess significant obstructive PAD as the smaller pedal arteries are relatively free from
calcinosis.Thisisdone byplacingapneumaticcuff ononetoe(usuallythe greattoe)and a
photoelectrode on the tip of the toe to obtain a photoplethysmographic (PPG) signal using
infraredlight(anarterialwaveformiscreatedfromthesesignals).Thesignalisproportional
tothequantityofredbloodcellsinthecutaneouscirculation.Thetoecuffisinflateduntilthe
PPGwaveformflattensandthenthecuffisdeflated.Thesystolicpressureisrecordedwhen
thewaveformreestablishes.Pressuregradientof20to30mmHgnormallyexistsbetweenthe
ankleandtoe.NormalTBIvaluesare0.7to0.8.Atoepressureof>30mmHgisrequiredfor
generalwound healing.Indiabetics,toepressures>50mm Hgare neededfor betterwound
healing (as they have capillary dysfunction and thus need greater perfusion pressures to
overcomethisdysfunction).PatientswithaortoiliacdiseasecanhavenormalrestingABIs,but
withexercisetheirABIsfalltoabnormallevels.Hence,exercisestresstestingcanincreasethe
sensitivityofdetectingobstructivePAD.Infact,everyambulatorypatientshouldundergorest
and exercise ABIs. Normally, with exercise the perfusion pressures increase to the lower
extremities. The two most commonlyused exercise protocols are as follows: one involves
walkingon a treadmill ataconstantspeed with nochangeininclineandthe otherprotocol
involves walking onatreadmill at 2 mph at12% inclineforatleast5minutes or until the
symptoms are reproduced.The walking distanceandtime ofonsetof painorsymptoms are
recorded.TheABIsaredoneatrest,1minuteafterexercise,andeveryminutethereafter(upto
5minutes).Thenormal responseis a slightincreaseornochange inABI.Thefallinankle
systolicpressurebymorethan20%frombaselineorbelowabsolute60mmHgthatrequires
morethan3minutestorecoverisabnormal.Thosepatientswhosepostexercisesystolicankle
pressure drops below 50 mm Hg have severe claudication and potentially multivessel or
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inflowdisease.Also,withexercise,thegradientsacrossstenoticlesionsworsen.Patientswith
occlusiveinternaliliacdiseasepresentwithtypicalbuttockclaudicationandcanhavenormal
resting and exercise ABIs.Suchpatientsshouldundergo computed tomography angiography
(CTA)orinvasive angiographytodelineatethediseaseand undergotreatment ifwarranted.
Transcutaneousoxygentensionmeasurement(TcPO2)isanoninvasivediagnosticstudy,which
measuresthepartialpressureofoxygenattheskinsurface.Theelectrodeelementhasaheating
element that raises the temperature of the underlying tissue and results in an increase in
capillaryflowandpartialpressureofoxygen.Thisthenresultsindiffusionofoxygenthrough
theskin,whichcanbemeasuredbytheelectrode.Itisimportanttorememberthatthisdevice
measuresthe underlying oxygentensioninthetissue andnotthearterial oxygentension.As
long as hemodynamic conditions are stable, transcutaneous measurements can be used as a
surrogateofarterialoxygentension.Insimplewords,thistestquantifiestheoxygendelivered
to the microvascular tissue. Importantly, they have a prognostic value in predicting wound
healing.
11
FIGURE9-1.Pulsevolumerecording.
Ultrasonography
UltrasonographycomprisesB-modeimaging,pulsewaveDoppler,continuouswaveDoppler,
andcolorDoppler.Theyarehelpfulinunderstandingtheunderlyinganatomy,hemodynamics,
and lesion morphology. It is cost-effective and can be done in an office setting. They are
extremely useful in diagnosing obstructive PAD, localizing the stenosis, quantifying the
severity ofthe disease, andassessing thepatencyofstents, grafts,andotherinterventions.
12
Hence, they are recommended in the surveillance period postendovascular and surgical
interventions.B-modeultrasonographywiththehelpofcolorDopplerprovidesinformationon
the anatomy of the lesion and also the morphology of the atherosclerotic plaque. Duplex
ultrasonographyhelpsintheaccurateassessmentoftheseverityofstenosisusingpulsedand
continuousDopplertechniques.Therefore,Duplexultrasonographyisaveryimportanttoolin
followinguppatientswhohaveundergoneendovascularandsurgicalinterventions.Theyhelp
intheearlyrecognitionofrestenosis.
13
ComputedTomographyAngiographyandMagneticResonance
Angiography
Inrecentyears,theuseofCTandmagneticresonanceangiography(MRA)intheevaluationof
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PAD has increased. However, this varies from institution to institution, as it is highly
dependent on the resources and theexpertise available to perform these tests andinterpret
them.CTAhasasensitivityandspecificitygreaterthan95%foridentifyingsignificantstenotic
lesions.
14,15
MRAacquiredwithcontrast(gadolinium)produceshigh-resolutionimagesofthe
infrapoplitealvessels.MRAhasasensitivityof90%andaspecificityof97%foridentifying
significantstenoticlesions.16CTAisassociatedwiththerisksseenwithcontrastandradiation
exposure. The MRA test done with gadolinium contrast carries the risk of nephrogenic
systemicfibrosis(especiallysoinpatientswithchronickidneydisease).Itisimportanttonote
that the presence of metallic implants, calcified lesions, and total occlusions results in
distortedimagesandartifactswithCTandMRI.
PeripheralInvasiveArteriography
Peripheral invasive angiography is considered the gold standard for the diagnosis of
obstructive PAD. Invasive arteriography involves the use of radiation and contrast.
Angiogramsperformedwithdigitalsubtractionangiography(DSA)arethepreferredmethod.It
enablestovisualizethelumenbetter.TheDSAhighlightsonlythebloodvesselanditdoesso
byeliminatingthebackgroundbonystructuresusingacomplexcomputerizedalgorithm.During
invasive angiography, in addition to diagnostic angiograms, hemodynamic assessments,
intravascularultrasonography(tovisualizethevesselwallanddefinelesionmorphology),and
variousrevascularizationtherapiescanbeperformed.
AcuteLimbIschemia
Acutelimbischemia(ALI)isthesuddencessationofbloodflowtothelimbs,whichthreatens
theviabilityofthelimbandthepatientpresentswithin14days.TheincidenceofALIisrare
andis approximately 1 to 2 per 10,000 personsper year.Itis characterizedby the six Ps,
whichare pain, pallor,pulselessness, paresthesia, paralysis, and poikilothermia (coolness).
The mostcommon cause is arterial thrombosis, whichcomprises about80%to85% ofthe
total cases. Usually, these patients would have undergone some sort of endovascular or
surgical procedures intherecentpast.Thesecondmostcommoncauseis embolicinorigin,
whichconstitutestherest10%to15%.The mostcommonsource ofembolismiscardiacin
origin(atrialfibrillationwithaleftatrialorleftatrialappendageclot,thrombosedprosthetic
mechanicalvalve,infectiveendocarditiswithsepticemboli,severecardiomyopathywithleft
ventricular thrombus,atrial myxoma, andotherneoplasia whichgive rise to tumor emboli).
The second most common cause of embolism is artery to artery in origin (from an
atherosclerotic aorta or popliteal artery). There are several other causes, which make a
minusculepieceofthewholepie.Itisimportanttorememberthatasignificantproportionof
thesepatientsdonotpresentwiththeclassicsixPs.Therefore,thereneedstobeastrongsense
ofsuspicioninpatientswithapriorhistoryofendovascular/surgicalprocedureswhopresent
with acute severe extremity pain. Such patients warrant a detailed examination of the
circulationwithhandheldDopplersandalsoanassessmentoftheneurologicfunction.When
suspected, it should be treated as an emergency because rapid revascularization is the
cornerstoneforsuccess.Treatmentconsistsofmedical,endovascular,andsurgicalarms.Every
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