Chronic deep venous occlusions: Case planning, recanalization

and stent technique

Michael K. W. Lichtenberg, FESC German Venous Center Arnsberg, Germany

Conflict of Interest - Disclosure

Within the past 12 months, I or my spouse/partner have had a financial

interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

1. Honoraria for lectures: CR Bard, Veniti, AB Medica, Volcano, Optimed

GmbH, Straub Medical, Terumo, Biotronik, Veryan

2. Honoraria for advisory board activities: Veniti, Optimed GmbH, Straub

Medical, Biotronik, Veryan, Boston Scientific

3. Participation in clinical trials: Biotronik, CR Bard, Veryan, Straub Medical,

Veniti, TVA Medical, Boston Scientific, LimFlow

4. Research funding: Biotronik, Boston Scientific, Veryan, Veniti, AB Medica

Complexity of Venous Hemodynamics

Artery Vein

• Low-pressure

• Low-velocity

• Large-volume

• Low-resistance converging pipe

system

• Phasic flow

• High compliance

• Valves

• High-pressure

• High-velocity

• Small-volume

• High-resistance diverging pipe

system

• Pulsatile flow

• Stiffer vessel walls

C6, 58 year female, postthrombotic syndrome

Sinus XL Stent (22 x 80 mm) 4 x Veniti Stents (16 x 120 mm + 14 x 60 mm)

• Venous outflow obstruction plays an important role in clinical expression of CVD, particularly pain 1,3-4

• Ulcerated limbs have a high rate of obstruction (37-52%) 5-6

• In limbs with obstruction, ulcers occur rarely with isolated obstruction (4%), more often in association with reflux (30%) 1

• Treatment results in impressive clinical relief of pain, swelling, VCSS, VDS and QoL, even when associated reflux is left untreated 1-3

• Treatment results in healing of ulcers, despite untreated reflux, in 55-58% of the patients 1,3,6

What has ilio-caval vein stenting shown us?

1Neglén et al, J Vasc Surg 2003;38:879-85 2Hartung et al, J Vasc Surg 2005;42:1138-44 3Neglén et al, J Vasc Surg 2007;46:979-90

4Delis KT et al. Ann Surg 2007, 245:130-9 5Marston et al, J Vasc Surg 2011, 53:1303-8 6Alhalbouni S et al, Ann Vasc Surg. 2012, 26:185-9

How do I find patients with ilio-femoral venous obstruction?

• Awareness – Think obstruction!

• Specific clinical signs and symptoms

severe C3, C4-6

abdominal collaterals, atypical vv, early vv

recurrence

typical venous claudication

venous “visceral” type of pain/discomfort

postthrombotic disease

pain out of proportion to lesion

no detectable lesion explaining symptoms

Morphological Studies

• Duplex Doppler scanning (including pelvic outflow)

• Ascending venogram

• Transfemoral antegrade venogram

• CT-V, MR-V or IVUS

Morphological diameter/ area stenosis >50% is considered significant.

Intravascular Ultrasound

• Evaluation of lumen diameter and stenosis

• Evaluation of thrombus, fibrotic tissue and scare tissue

• Evaluation of compression

• Intervention without contrast dye

Peter Neglen 2002 Journal of Vascular Surgery:

„In comparison to standard venography IVUS

appears to be superior for identify morphologic

changes of iliac venous outflow obstruction“

Visions® PV .035 Digital IVUS Catheter

Product Overview

• 60 mm field of view, free of wire artifact - 10 MHz

• 90 cm working length

• Over-the-wire design

• 0.035” guide wire compatible

• Min. Sheath 8.5 F

• New radiopaque and inked centimeter markers

*

12

Visions® PV .035

IVUS Catheter

Radiopaque

Markers

Venous obstruction

Can the patient be stented? Assess the “Landing Zones”

Attempt to assess the central and peripheral extent of the disease before the intervention is scheduled using DUS, venogram, CTV, MRV etc.

1. Central “landing zone” a. Is the IVC patent? b. Does the disease involve the IVC? c. Is the potential outflow of the stent system appropriate? d. Is the contralateral venous outflow compromised?

2. Peripheral “landing zone” a. Is the CFV involved? b. Is there a potential landing zone in the CFV above the profunda-

femoral vein confluence? c. Is there a sufficient inflow from the periphery to sustain patency of a

stent placed in the pelvic outflow?

Tips and trick for access

• Ipsilateral femoral vein

• Ultrasound guided access

• Vein is usually post-thrombotic scarred

• Orientation can be difficult

• Stiff hydrophilic guidewire (Terumo)

• Dilators 6,8,10 F

• Extra support, long sheaths

• Different projections

Recanalization

• Exchange for superstiff guidewire

• Advance PTA ballons (10,12,14,16,18 mm)

• Predilatation is eminent

• Standard inflation pressure is 6 – 12 atm (PAINFULL !!!!)

• No rupture risk !

Stenting

Double barrel Apposition Fenestration Bifurcation

Significant body of clinical work • Existing stents…Wallstent

• Good success treating obstructive component of many venous disorders

Current generation of stents being studied • VIVO Trial – Zilver Vena (Cook Medical)

• VIRTUS Trial – VICI VENOUS STENT (VENITI, Inc.)

Venous Stenting is Not New

19

• Self-expandable

• Crush resistant across length of stent

• Sufficient chronic outward force

• Sufficient wall coverage

• Flexibility sufficient to resist kink at physiological angles

• Durability allowing repeated shortening, twisting, and bending at the groin

• Minimal foreshortening on deployment and balloon dilation

• Predictable, consistent deployment

Venous Stent Attributes

Flexibility

Lumen quality

Strength

Stent options !

Boston

Wallstent Optimed

Cook

Zilver Vena Veniti Vici

Optimed

Sinus

obliquus

Bard

Venovo

VIVO (EU) Trial VIRTUS Trial

VERNACULAR Trial Sinus Obliquus-01-NIS

Upcoming: Medtronic, Gore, ab Medica, INTACT, Abbott Vascular

Venovo® Stent 14 x 120 mm and 14 x 80 mm on both CIV and EIV

Closed Cell Open Cell

Design Attributes • All struts interconnected • Not all struts interconnected

Performance

Crush Resistance ++ + Flexibility + ++ Coverage ++ +

Performance Characteristics

Radial Force and Crush Resistance

0.146

0.049

0.030

BARD VENOVO 14X160 N=20

OPTIMED SINUS VENOUS 14X80

N=3

COOK ZILVER VENA 14X100

N=2

Rad

ial R

esis

tive

Fo

rce

at

1m

m o

vers

ize

(N

/mm

)

Radial Resistive Force

2.65

1.94

1.18

BARD VENOVO 14X160 N=20

OPTIMED SINUS VENOUS 14X80

N=3

COOK ZILVER VENA 14X100

N=3

Loca

l Co

mp

ress

ion

Fo

rce

(N

)

Crush Resistance

Bench testing may not be indicative of clinical performance. Different test

methods may yield different results. Competitive testing samples represent

commercially available venous stents with CE mark as of June 2014.

This product is not available for sale in the US

Stent Flexibility

1.29

0.62

0.43

BARD VENOVO 14X160 OPTIMED SINUS VENOUS 14X80

COOK ZILVER VENA 14X100

3 P

oin

t B

end

ing

Stif

fnes

s (N

)

Bard

Cook Optimed

Bench testing may not be

indicative of clinical

performance. Different test

methods may yield different

results. Competitive testing

samples represent

commercially available venous

stents with CE mark as of June

2014.

Bard N=20

Optimed Sinus Venous N=3

Cook Zilver Vena N=3

This product is not available for sale in the US

Results from VIVO-EU, a Prospective Study of

the Zilver® VenaTM Venous Stent in the Treatment

of Symptomatic Iliofemoral Outflow Obstruction

Michael Lichtenberg, M.D. and

Jennifer McCann-Brown, Ph.D., RAC

1Klinikum Arnsberg, Germany; 2Cook Research Incorporated

On behalf of the Investigators:

Christoph Binkert, M.D.

Narayan Karunanithy, M.D.

Gerard O`Sullivan, M.D.

Marta Ramirez Ortega, M.D.

28

Real World Patient Population

29

Medical History Reported

(N=35)

Clotting disorder (family history) 14.3% (5)

Bleeding diathesis/coagulopathy 14.3% (5)

Pulmonary embolism (history or current)

20.0% (7)

Deep vein thrombosis (DVT) 62.9% (22)

Acute DVT Acute DVT on Chronic DVT

Chronic DVT

40.9% (9/22) 9.1% (2/22)

50.0% (11/22)

DVT (family history) 28.6% (10)

History of cancer 8.6% (3)

Currently undergoing treatment 33.3% (1/3)

Acute DVT Acute DVT on Chronic DVT

Chronic DVT

40.9% (9/22) 9.1% (2/22)

50.0% (11/22)

Baseline Lesion Data

30

Vessel location(s) Site Reported

(n=35) Core Lab

(n=34)

Side treated

Left

Right

94.3% (33)

5.7% (2)

94.1% (32)

5.9% (2)

Lesion Location

Common iliac vein 57.1% (20) 55.9% (19)

External iliac, common iliac veins 22.9% (8) 14.7% (5)

Common femoral, external iliac, common iliac

veins 20.0% (7) 20.6% (7)

Common femoral vein 0% (0) 5.9% (2)

Femoral, common femoral, external iliac,

common iliac veins 0% (0) 2.9% (1)

Lesion Characteristics

Lesion Length (mm; Mean ± SD) 106 ± 69 (n=35)

(range: 20-256 mm)

89.3 ±58.6 mm (n=31)

(range: 5.6-219.9)

Total Occlusion 12.9% (4/31)1 22.6% (7/31)

Lesion data are consistent with previous reports for this population.

1A determination of total occlusion could not be made in four patients. .

Major Adverse Events

Major Adverse Event Frequency (n=35)

Procedural bleeding requiring transfusion 0

Procedure- or device-related death 0

Clinically-driven target lesion reintervention for occlusion1 1

Stent migration requiring intervention 0

Procedure- or device-related symptomatic pulmonary embolism2 1

Procedure-related uncorrectable perforation 0

Procedure-related flow-limiting dissection of the target vessel 0

Total 2

1 A clinically-driven reintervention for occlusion at 155 days post-procedure. Edema and a pre-reintervention INR of 1.1; the occlusion was treated by thrombolysis, balloon angioplasty, and additional stent placement.

2 A symptomatic pulmonary embolism one day post-procedure, categorized as possibly related to the study procedure and managed by a change in medication. No additional clinical sequelae reported.

31

Venous Clinical Severity Score Improved Following Treatment

32

Four patients did not complete 12-month follow-up due to unrelated death (n=1), withdrawal (n=1), or lost-to-follow-up (n=2). Patients with any reintervention (n=5) in the stented vessel were excluded from subsequent assessment of venous clinical symptoms.

Venous Disability Score Improved Following Treatment

33

Four patients did not complete 12-month follow-up due to unrelated death (n=1), withdrawal (n=1), or lost-to-follow-up (n=2). Patients with any reintervention (n=5) in the stented vessel were excluded from subsequent assessment of venous clinical symptoms.

VICI 14 x 120 mm

VIRTUS Feasibility Trial Design

Objective Assess safety & effectiveness in achieving patency of target venous lesion through 12-M post stent placement

Safety MAEs @ 30 days

Effectiveness Primary Patency @ 12-M

Principal Investigators

Dr. William Marston Dr. Mahmood Razavi

Study Design Prospective, multicenter, single arm non-randomized, up to 45 sites worldwide

Patient Population

200 subjects with clinically significant chronic non-malignant obstruction of the iliofemoral venous segment – first 30 were feasibility.

Etiologies: Post Thrombotic (75%); Non Thrombotic (25%)

Core Labs

Venography: Syntactx IVUS: St. Lukes DUS: VasCore/MGH X-Ray: Syntactx

Non-thrombotic

Post-thrombotic

Image Courtesy of Mr. Stephen Black

Image Courtesy of Mr. Mahmood Razavi

Demographics & Medical History Female 24 (80%) Male 6 (20%)

Age 44.4 ±14.1 years

CEAP* Baseline

0 3% (pain by VCSS Score of ≥2)

1 0%

2 0%

3 47%

4 40%

5 7%

6 3%

Etiology

PTS 63%

NIVL 37%

Target Lesion Location

Lesion1 Location

Patients N = 30

Left N = 25 (83%)

Right N = 5 (17%)

CIV lesions 26/30 (87%)

EIV lesions 18/30 (60%)

CIV & EIV lesions 15/30 (50%)

Lesions that extended into CFV2

9/30 (30%)

Average Target Lesion Length

11.9 ±6.7 cm

1. Some patients have more than 1 lesion or lesion extends in multiple vein segments 2. No lesions were isolated to the CFV alone

Patency by Duplex Ultrasound (Corelab Analysis)

Courtesy of Dr. Ediberto Soto-Cora

Patency Results of Feasibility Cohort (N=30)

Primary Patency1 Secondary

Patency

1- M 93% 100%

6 – M 90% 100%

12 – M 93% 97%

Patency Results at 12-Months (Site Reported)

Primary Patency1

Secondary Patency

Full Cohort (N=30) 87%

(26/30) 97%

(29/30)

Etiology

NIVL 37% 100% (11/11) 100% (11/11)

PTS 63% 79% (15/19) 95% (18/19)

All patients enrolled in the study will be followed until study completion

Patency by Lesion Etiology (Site Reported)

Courtesy by Dr Michael Sadek

VCSS Pain Scale

45% had “substantial symptomatic improvement” (VCSS ≥2 ) @12-M

CIVIQ-20

Arnsberg Venous Registry VENITI VICI VENOUS STENT® System

Objective Assess safety & effectiveness in achieving patency of target venous lesion through 36 months post stent placement (VENITI VICI Stent)

Effectiveness Primary Patency @ 12-M

Principle Investigators Dr. Michael Lichtenberg Dr. Rick de Graaf

Study Design Ongoing prospective, single arm, single center non-randomized registry FU 1 (4 weeks), FU 2 (6 months), FU 3 (12 months), FU 4 (24 months), FU 5 (36 months)

Patient Population Subjects with clinically significant chronic non-malignant obstruction of the iliofemoral venous segment

Demographics N=90

Age in years (mean ± SD [range])

57.4 ± 16.4 [19-84]

Gender Male Female

47.8% (N=43) 52.2% (N=47)

Ethnicity Caucasian

100% (N=90)

Medical history N=90

Coagulation disorder 4.4% (N=4)

Pulmonary embolism 24.4% (N=22)

Deep vein thrombosis 47.8% (N=43)

History of cancer 14.4% (N=13)

Lesion analysis N=90

Sides treated Both Left Right

7.8% (N=7) 74.4% (N=67) 17.8% (N=16)

Lesion location(s)

Left: Common iliac vein External iliac vein Common femoral vein Common iliac vein, external iliac vein Common iliac vein, external iliac vein, common femoral vein External iliac vein, common femoral vein Right: Common femoral vein Common iliac vein External iliac vein Common iliac vein, external iliac vein Common iliac vein, external iliac vein, common femoral vein External iliac vein, common femoral vein Both: External iliac (R), common iliac (L) vein External iliac (R), common iliac (L), external iliac (L) vein Common iliac (R+L), external iliac (L) vein Common iliac (R+L), external iliac (R+L), common femoral (L) vein Common iliac (R+L), external iliac (R+L), common femoral (R+L) vein

37.8% (N=34) 4.4% (N=4) 2.2% (N=2) 17.8% (N=16) 8.9% (N=8) 3.3% (N=3) 2.2% (N=2) 3.3% (N=3) 6.7% (N=6) 1.1% (N=1) 1.1% (N=1) 3.3% (N=3) 1.1% (N=1) 2.2% (N=2) 2.2% (N=2) 1.1% (N=1) 1.1% (N=1)

64 / 90 (71%) patients: Postthrombotic

26 / 90 (29%) patients: NIVL

Effectiveness analysis

0

10

20

30

40

50

60

70

80

90

100

FU 4 w FU 6 mo FU 12 mo

% Patentcy analysis

NIVL PTS

N=50 N=82 N=21

100 % 100 % 100 %

97% 90 % 87 %

9.2

5.4 4.9

4.2

0

2

4

6

8

10

12

14

Baseline FU1 FU2 FU3

Mean VCSS score (±SD)

N=90 N=82 N=50 N=21

9.2

5.4 4.9

4.2

Claudication, Pain, Swelling,

Ulceration improvemnt

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

Baseline FU1 FU2 FU3

Mean CEAP score (±SD)

N=90 N=82 N=50 N=21

3.6

2.6 2.7

2.4

The BARD® VENOVO™ Venous Stent Study – A Prospective, Non-Randomized, Multi-Center, Single-Arm Study of the

Treatment of Iliofemoral Occlusive Disease – an Assessment for Effectiveness and Safety (VERNACULAR)

Study Design

Type of Study

Prospective, multi-center, global, single-arm, non-randomized study

Number of Sites Up to 35

Number of Subjects 170

Primary Endpoint Follow Up 12-Months Post-Procedure

Follow-Up Intervals 30-Days and 6-, 12-, 24-, & 36-Months

Post-Procedure.

8 European Sites Dr. Gerard O‘Sullivan

University College Hospital Galway

Dr. Stephen Black St. Thomas, London

Prof. Luis Miguel Izquierdo Lamoca,

Hospitales Universitarios Montepríncipe, Madrid

Dr. Rick de Graaf Maastricht Universitair

Medisch Centrum+ Maastricht

Prof. Salah Dine Qanadli Centre Hospitalier

Universitaire Vaudois. Lausanne

Prof. Thomas Zeller Universitäts-

Herzzentrum Freiburg Bad Krozingen

Dr. Houman Jalaie Uniklinik RWTH, Aachen

Dr. Michael Lichtenberg Klinikum Arnsberg

Primary Endpoint Efficacy:

Primary Patency rate at 12 months defined as

Freedom from TVR

Freedom from thrombus occlusion and stenosis > 50% as measured by DUS.

THANK YOU FOR YOUR ATTENTION

21 y, female, descending DVT in May – Thurner syndrome.

KAHN et al. Determinants of health-related quality of life during the 2 years following deep vein thrombosis. Journal of Thrombosis and Haemostasis 2009, 6: 1105–1112

Standard Treatment vs. CDT

Enden T, et al: CaVenT Study

– Follow-Up 24 months:

– Number needed to treat: 7

Lancet. 2012 Jan 7;379(9810):31-8.

Long-Term Results using Catheter-directed Thrombolysis in 103 Lower Limbs

with Acute Iliofemoral Venous Thrombosis

N. Bækgaard, R. Broholm, S. Just, M. Jørgensen, L.P. Jensen

European Journal of Vascular and Endovascular Surgery , Volume 39, Issue 1, Pages 112-117 (January 2010)

All patients with patent veins and normal valve

function

showed no sign of dermal pigmentation,

ulceration or venous

claudication at follow-up

1 major

bleeding

complication

• 2. Indications for early thrombus removal

• 2.1. We suggest a strategy of early thrombus removal in selected patients meeting the following criteria:

• (a) a first episode of acute iliofemoral deep venous thrombosis

• (b) symptoms <14 days in duration

• (c) a low risk of bleeding

• (d) ambulatory with good functional capacity and an acceptable life expectancy (Grade 2C)

AngioJet® EKOS® Peripheral

Infusion System Trellis™ System

M. Lichtenberg (Hrsg.), C. Tiefenbacher, M. Katoh, P. Minko, E. Minar, C. Wissgott, A. Storck, B. Hailer: Thrombektomie: medikamentös, mechnisch, operativ. Uni-med Verlag,

2013

Early Clot Removal Many Choices – None Perfect!

6 – 10

French

Aspirex® (Rotational thrombectomy) Indigo System ® (Penumbra)

Overall, the 2-year data supported the use of standard therapy/anticoagulation

alone in most DVT patients

PCDT was not shown to prevent postthrombotic syndrome (PTS) and was

associated with increased bleeding.

However, PCDT was shown to reduce early DVT symptoms as well as PTS

severity

The PCDT arm saw a statistically significant higher rate of major bleeding

within 10 days (1.7% vs 0.3%; P = .049),

Leg pain and leg swelling were significantly improved in patients who received

PCDT vs no-PCDT: (leg pain, 10 days: -1.62 vs -1.29; P = .019; 30 days: -2.17

vs -1.83; P = .026) (leg swelling, 10 days: -0.26 vs +0.27; P = .024; 30 days: -

0.74 vs -0.28; P = .051).

2-Year ATTRACT Data The difference in PTS severity was almost entirely seen in the

iliofemoral DVT patients with moderate/severe PTS seen in

18.4% of PCDT patients versus 28.2% in the no-PCDT group

THANK YOU FOR YOUR ATTENTION

Chronic deep venous occlusions: Case planning, recanalization

and stent technique

Michael K. W. Lichtenberg, FESC German Venous Center Arnsberg, Germany