DebulkingBelowtheKnee:Devices&Techniques

JihadA.Mustapha,MD,FSCAI,FACCAdvancedCardiac&VascularCentersforAmputationPrevention

GrandRapids,MI

DisclosuresBardPeripheralVascular– ConsultantBostonScientific– Consultant,ScientificAdvisory Board,ResearchCardioFlow – Equity,ResearchCardiovascularSystems,Inc.– Consultant,ResearchMedtronic– ConsultantMicromedical Solutions – ChiefMedicalOfficerPhilips– ConsultantPQBypass– ResearchReflowMedical– ChiefMedicalOfficerTerumo - Consultant

AtherectomyDevices

Jetstream™Atherectomy

System(BostonScientific)

PeripheralRotablator™Rotational

AtherectomySystem(BostonScientific)

Diamondback360™,Stealth

360™Atherectomy

System(CardiovascularSystems,Inc)

SilverHawk™,TurboHawk™PlaqueExcision

System(Covidien)

Turbo-Elite™Laser

AtherectomyCatheter

(Spectranetics)

Front-Cutting ü ü N/A

Differential Cutting ü ü ü N/A

ActiveAspiration ü

ConcentricLumens ü ü ü

LesionMorphology:

Calcium ü ü ü ü ü

Soft/FibroticPlaque

ü ü ü

Thrombus ü ü

Sources:EndovascularTodayBuyer’sGuide2014.JETSTREAMSystemBrochure,BostonScientificWebsite,2014.PeripheralRotablator productwebsite,BostonScientific,2014.Diamondback360productwebsite,CSI,2014.Covidienwebsite,DirectionalAtherectomyproducts,2014.Turbo-EliteLaserAtherectomyCatheterInstructionsforUse,May2014.

TheLACIStudies

TheLACITrial:6MonthResults• Lairdetal• 145pt,155criticalischemiclimbs• 423lesions• 41%SFA,15%Popliteal,41%Infrapop• 70%ofPtshadcomboocclusionandstenosis• 29%RutherfordClass4• 71%RutherfordClass5or6• Limbsalvage92%at6months

DEFINITIVELE• StudyDesignandOversight:

• Prospective,non-randomized,globalstudy• 800subjectsenrolledat47centers• CECandSteeringCommitteeoversightandCECadjudicaiton• AngiographicandDuplexcorelaboratoryanalyses

• InclusionCriteria• RCC1-6• ≥50%stenosis• Lesionlengthsupto20cm• ReferenceVessel≥1.5mmand≤7.0mm

• ExclusionCriteria• Severecalcification• In-stentrestenosis• Aneurysmal targetvessel

LesionAssessment

Characteristic Claudication (RCC 1-3)

CLI(RCC 4-6)

All Subjects (RCC 1-6)

Number of Patients 598 201 799Number of Lesions 743 279 1022Mean Length (cm) 7.5 7.2 7.4Baseline Stenosis (%) 73 76 74 Occlusions (%) 17 30 21

Anatomic location based on proximal edge of lesion treatment, % (N)SFA 72% (536) 48% (135) 66% (671)Popliteal 15% (114) 17% (48) 16% (162)Infrapopliteal 13% (93) 34% (96) 18% (189)

CorelabreportedMcKinseyJFetalJACCInterv 2014

PrimaryPatencyinSubgroupsSubgroup Claudicants (n=743) CLI (n=279)

Patency(PSVR < 2.4)

Lesion Length (cm)

Patency(PSVR < 2.4)

Lesion Length (cm)

All (n=1022) 78% 7.5 71% 7.2

Lesion type

Stenoses (n=806) 81% 6.7 73% 5.8

Occlusions (n=211) 64% 11.1 66% 10.3Lesion LocationSFA (n=671) 75% 8.1 68% 8.6

Popliteal (n=162) 77% 6.0 68% 5.4

Infrapopliteal (n=189) 90% 5.5 78% 6.0

PrimaryPatencyinSubgroupsSubgroup Claudicants (n=743) CLI (n=279)

Patency(PSVR < 2.4)

Lesion Length (cm)

Patency(PSVR < 2.4)

Lesion Length (cm)

All (n=1022) 78% 7.5 71% 7.2

By Lesion Length< 4 cm (n=318) 81% 2.2 84% 2.3

4-9.9 cm (n=418) 83% 6.5 62% 6.6≥ 10 cm (n=283) 67% 14.4 65% 15.1SFA Only By Lesion Length< 4 cm (n=184) 78% 2.3 82% 2.3

4-9.9 cm (n=253) 83% 6.5 60% 6.9≥ 10 cm (n=232) 65% 14.6 63% 15.5

JetstreamSystemOverview

ControlPOD ConsoleOver-the-Wire

ApprovedforusewithBSC0.014”300cmThruwayGuidewire

ApprovedforusewithAtherectomyLubricants,suchasRotaglide

XC2.1/3.0mm

XC2.4/3.4mm SC1.85mm

JETSTREAMXCCatheters JETSTREAMSCCatheters

(TibialSizes)(SFA&PoplitealSizes)

SC1.6mm

PatientCharacteristics• 241patients(258lesions)

Overall(N=241)

Age(years),mean± SD 67.1± 9.8Male 66.0%MedicalHistory

Hypertension 82.6%Hypercholesterolemia 66.8%Smoking 50.6%HeartDisease 47.7%Diabetes 41.1%

RaceCaucasian 80.1%AfricanAmerican 16.6%NativeAmerican 2.1%Other 1.2%

LesionCharacteristicsOverall

(N=258lesions)Non-Stenta

(N=165lesions)Stenta

(N=93lesions)Lesionlocation

SuperficialFemoral 75.6% 72.1% 81.7%CommonFemoral 10.9% 15.2% 3.2%Popliteal 13.6% 12.7% 15.1%

Lesionlength,mean± SD 16.4± 13.6cm 14.1± 12.6cm 20.5± 14.4cmCalciumGradeb

0 10.0% 10.2% 9.5%1 16.2% 14.6% 19.0%2 24.1% 17.8% 35.7%3 28.2% 31.8% 21.4%4 19.5% 21.0% 16.7%

LesionRVD,mean± SD 5.7± 0.9mm 5.5± 0.9mm 5.9± 0.9mmOcclusion(100%stenosis) 36.1% 28.7% 50.0%Pre-treatmentstenosisestimate,mean± SD 91.1%± 9.8% 90.2%± 10.0% 92.7%± 9.4%

aPost hocanalysisofpatientswhoreceivedanddidnot receiveadjunctivestents.bCalcium grading:0=novisiblecalcification;1=one individual segmentofvesselcalcificationrepresenting<25%ofthelengthoftheentiresegment;2=aggregatecalcificationrepresenting<50%ofthesegmentlength;3=aggregatecalcificationrepresenting>50%ofthesegmentlength;4=densecircumferentialcalcificationalong thesegmentlength.

Procedures• 98.3%proceduralsuccess(≤30%residualdiameterstenosispost-procedure)

• 84patients(35%)receivedadjunctivestents

• Stentplacementperformedatoperator’sdiscretion

• Embolicprotectionusedin22.4%ofcases

Post-treatmentstenosisestimate,mean± SDOverall

(N=258lesions)Non-Stent

(N=165lesions)Stent

(N=93lesions)Post-Jetstream 44.4%± 20.0% 38.5%± 16.2% 54.8%± 22.0%PostAdjunctiveTreatment 9.8%± 11.4% 11.6%± 11.7% 6.6%± 10.2%

Proceduretime: 73.4± 37.5minTotalJetstreamruntime: 4.7± 3.5 min

NumberofPassesBladesDown: 2.0± 1.5BladesUp: 1.8± 1.4

UniqueMechanismofActionPreferential Sanding

• Elastichealthytissue“gives”andisnotaffectedbydiamond grit

• Diseasedtissueprovides resistanceandallowsgritto“sand”theplaque

Compliant TissueDiseased TissueDiamond Grit

No detrimental effectEffective plaque removal

• 6monthdata• 124patientsforinfrapopliteal revascularization(201lesions)• Claudicants55%• CLI45%• TreatmentOAeitherstandaloneorwithadjuctive Rx

`

LIBERTY360• Prospective,observational,multi-centerclinicalstudytoevaluateacuteandlong-termclinical,functionalandeconomicoutcomesofendovasculardeviceinterventioninpatientswithdistaloutflowperipheralarterialdisease(PAD)

• Noinclusionandexclusion• Independentcorelaboratoryanalysesandadjudications

• Angiographic• DuplexUltrasound• SixMinuteWalkTest• HealthEconomics

• Includesseparateanalysesfor• Claudicants• Criticallimbischemia(RB4and5)• Criticallimbischemia(RB6)

DeviceUsagebyLesionBalloonand/oratherectomywerepreferreddevices.

*BailoutstentgroupisasubsetofStentgroup.Bailoutstentdefinedasstentplacedduetoanangiographiccomplicationorsub-optimalresult(>50%stenosis).CoreLabreportedlesions.Patientswithreportedvaluesmaybelessthantotalnumberofpatientsenrolledineacharm.

ComparisonbetweenRutherfordcategoriessignificant(p<0.05)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Balloon Atherectomy Stent Bailoutstent*

Rutherford2-3(N=599) Rutherford4-5(N=754) Rutherford6(N=145)

MajorAdverseEvents(MAEs)to6MonthsHighfreedomfrom6-MonthMajorAdverseEvents(MAE),indicatingevenRC6subjectscanbetreatedwithPVI.

Kaplan-MeiermethodusedtoobtainestimateoffreedomfromMAE.Greenwood’smethodusedtoobtainthe95%confidenceintervalfortheestimate.PairwiseLog-RankP-valuesat180-Days:RC2-3vs.RC4-5,P<0.0001;RC2-3vs.RC6,P<0.0001;RC4-5vs.RC6,P=0.0453

MajorAdverseEventdefinedas:

v Death(within30daysoftheindexprocedure)

v Unplannedmajoramputationofthetargetlimb(abovetheankle)

v Clinically-drivenTVR(inclusiveofTLR)ofthetargetlimb

499 484 450 414589 554 479 40699 87 67 54

0 30 90 180

Time to MAE (Days)

0.5

0.6

0.7

0.8

0.9

1.0

Surv

ival

Pro

babi

lity

2-3: Claudicants4-5: CLI

6: CLI

6: CLI4-5: CLI2-3: ClaudicantsBaseline Rutherford Classification

Product-Limit Survival EstimatesWith Number of Subjects at Risk and 95% Confidence Limits

499 484 450 414589 554 479 40699 87 67 54

0 30 90 180

Time to MAE (Days)

0.5

0.6

0.7

0.8

0.9

1.0

Surv

ival

Pro

babi

lity

2-3: Claudicants4-5: CLI

6: CLI

6: CLI4-5: CLI2-3: ClaudicantsBaseline Rutherford Classification

+ Censored

Product-Limit Survival EstimatesWith Number of Subjects at Risk and 95% Confidence Limits

6-MonthFreedomfromMAEs

(PointEstimateand95%ConfidenceIntervals)Kaplan-MeiermethodusedtoobtainestimateoffreedomfromMAE.Greenwood’smethodusedtoobtainthe95%confidenceintervalfortheestimate.

60% 65% 70% 75% 80% 85% 90% 95% 100%

Rutherford6

Rutherford4-5

Rutherford2-3

73.7%

81.2%

92.6%

AtRisk 54

Events 23

Censored 22

AtRisk 406

Events 102

Censored 81

AtRisk 414

Events 35

Censored 50

6-Month RC2-3vs.RC4-5 RC2-3vs.RC6 RC4-5 vs.RC6

Hazard Ratio P Hazard Ratio P Hazard Ratio P

MAE 0.40[0.29,0.56] <0.0001 0.26[0.16,0.41] <0.0001 0.63[0.42,0.95] 0.0271

6-MonthFreedomfromMAEComponents

PointEstimateand95%ConfidenceIntervalsKaplan-MeiermethodusedtoobtainestimateoffreedomfromMAE.Greenwood’smethodusedtoobtainthe95%confidenceintervalfortheestimate.

RC2-3 RC4-5 RC6

Atrisk 445 485 61

Events 1 18 11

Censored 53 86 27

70% 80% 90% 100% 70% 80% 90% 100% 70% 80% 90% 100%

85.1%

95.3%

97.1%

87.1%

96.8%

99.8%

85.1%

83.1%

93.0%

ForcalculationofMAErate,deathcappedat30days.

Death MajorAmputation TVR

RC2-3

RC2-3 RC4-5 RC6

Atrisk 446 498 66

Events 14 26 13

Censored 39 65 20

RC2-3 RC4-5 RC6

Atrisk 414 411 59

Events 33 91 12

Censored 52 87 28

RC4-5

RC6

CoxproportionalhazardsmodelidentifiesnodifferencebetweenanyRCgroup/armat6months.

Phoenixcatheter• 5Fr,OTW,frontcuttingatherectomy

• Rotationalspeed10000RPM

• DebriswithdrawnthroughArchimedesscrewsystem

• EASEtrial>100patients,0.8%embolicevents

Pantheris

• VISIONtrial• 130pts• 55(24monthresults)

• 91.4%treatedstandalonePantheris

• 9.6%DCB• 5.1%stent

• 82%freedomfromTLRat24months

DEFINITIVEARStudyDesign

GeneralandAngiographicCriteria

Assessment

Lesionseverelycalcified?

Guidewirepassage,enrollment&Randomization

DAART*(N=48)

DCB(N=54)

GuidewirePassage&Enrollment

DAART*(N=19)

No

Yes

Registryarmforseverelycalcifiedlesionscreatedtolimitbail-outstenting(andthereforevariables)inrandomizedarm.

*DirectionalAtherectomy+Anti-RestenoticTherapy

Purpose:assessandestimatetheeffectoftreatingavesselwithdirectionalatherectomy +DCB(DAART)comparedtotreatmentwithDCBalone

ClinicalLimitations&UnmetNeeds

CalciumasaBarrier LongerLesionLengthCalcium Limits Vessel Expansion1

Calcium May Limit Drug Effect2Increasedlesionlengthisanindependent

predictorofdecreasedpatency5.

1FreedMS,ManualofInterventionalCardiology,2FanelliDEBELLUM,3Laird,CCI,June2010,4SMARTControlIFU,5Matusumura,DURABILITYIIJVS,July2013,6Davaine,

EuropeanJournalofVascularandEndovascularSurgery44(2012)

BaselineLesionCharacteristicsPerCoreLab

BaselineCharacteristics DAART(N=48)

DCB(N=54)

p-Value* DAARTSevereCa++Arm

(N=19)

LesionLength(cm) 11.2 9.7 0.05 11.9

DiameterStenosis 82% 85% 0.35 88%

Referencevesseldiameter(mm) 4.9 4.9 0.48 5.1

Minimumlumendiameter(mm) 1.0 0.8 0.34 0.7

Calcification 70.8% 74.1% 0.82 94.7%

Severecalcification 25.0% 18.5% 0.48 89.5%

*p-valueforDAARTandDCBgroups

KeyStudyOutcomeat12Months- AngiographicPatencyshowssimilarpattern

82.490.9

58.3

71.8 68.8

42.9

0102030405060708090

100

AllPatients Lesions>10cm AllSevereCa++

DAART

DCB

N=34N=39 N=22N=16 N=24N=7

Resultsforallpatientswhoreturnedforangiographicfollow-up

What’soutthereandwhattochoose?• Severaldevicesnowavailablefordebulking

• Criticalquestionremainsisdebulkingpartofvesselprep“all”or“some”ofthetime

• Eachdevicehascompellingdata

• Somebetterforcalcificdisease

• Somebetterforeaseofuse

• ThereisnoquestionthatinsomecaseseitherforDCBorstentingadebulkingstrategyiscriticaltoobtainbestinitialandprobablylong-termoutcomes

• Combinedtherapyappearcompellingthoughnotfullytested