Peter A. Schneider, M.D.University of California San Francisco

Disclosure

Peter A. Schneider, MD

.................................................................................

I have the following potential conflicts of interest to report:

Consulting: Philips, Medtronic, Boston Scientific, Intact, PQ Bypass,

Cagent, Silk Road Medical, Surmodics, Profusa, CSI

Open Surgical Repair

Surgical bypass

Gold standard

- Autogenous or prosthetic bypass 1

- Better patency than EVTs

- Traditionally recommended for complex femoropopliteal lesions, e.g. TASC C and D lesions

- Concerns: highly invasive, high risk of perioperative complications, long post-operative hospital stays, longer patient recovery, not as cost-effective as EVTs 5

Endovascular Treatments (EVTs) 3

Percutaneous transluminal angioplasty

Plain old balloon angioplasty - lower long-term patency, especially in long lesions

Drug-coated balloon - limited success with heavily calcified lesions and the active pharmaceutical may increase all-cause

mortality 6

Stenting

Bare metal or Stent Graft – foreign object with the risk of fracture and migration

Atherectomy

High rates of restenosis and risk of distal embolization

1 Cheung C, Rogers A, McMonagle MP. Case of lower limb revascularisation using composite sequential bypass graft with a ‘diamond’ intermediate anastomosis. BMJ Case Reports. 2018;2018:bcr-2017-223749; 2 Image from: https://www.virchicago.com/peripheral-artery-disease/; 3 Hiramoto JS, Teraa M, de Borst GJ, Conte MS. Interventions for lower extremity peripheral artery disease. Nature Reviews Cardiology. 2018;15(6):332-350; 4 Image from: http://www.crosscountycardiology.com/atherectomy/; 5 Adam DJ, Beard JD, Cleveland T, et al. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet. 2005;366(9501):1925-1934; 6

Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, Karnabatidis D. Risk of death following application of Paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2018;7(24):e011245.

Current Treatment Options for Treatment of Long SFA Lesions

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Zilv

er P

TX

1

Via

ba

hn

25

2

Lu

ton

ix6

Eve

rflex

14

1-Y

ear

Pat

en

cy

1 P100022/S020; 2P040037/S060; 3 P120002 ; 4 P140010/S037; 5 P070014/S010; 6 P130024; 7 Rocha‐Singh, Krishna J., et al. "Patient‐level Meta‐analysis Of 999 Claudicants Undergoing Primary Femoropopliteal Nitinol Stent Implantation." Catheterization and Cardiovascular Interventions 89.7 (2017): 1250-

1256.; 8 P040037; 9 P160025; 10 P120020; 11 P140028; 12 P140002; 13 P160004; 14 P110023 15 Estimated avg. interpolated assuming normal distribution.

15 Lumsden AB, Morrissey NJ. Randomized controlled trial comparing the safety and efficacy between the FUSION BIOLINE heparin-coated vascular graft

and the standard expanded polytetrafluoroethylene graft for femoropopliteal bypass. Journal of vascular surgery. 2015;61(3):703-712.e701.

FDA-Approved SFA Devices for

Treatment of Long Lesions

12M Primary Patency

59.5%

0

10

20

30

40

Lesi

on

Le

ngt

h (

cm) “Long Lesions” 20.6 cm

Drug eluting stent

Stent graft

Bare metal stent

Drug-coated balloon

Other

Loss of patency in open surgical repair is 100% luminal loss

67.0%

N 181 62 3 151 46 77 248 16 33 18 36 13 72 24 82

Lesion Length (cm)15

21.5 26.5 18.4 28.7 19.2 26.8 15.2 12.3 15.9 14.5 19.0 17.9 18.0 16.5 37.1

Goal:

• To investigate the safety and effectiveness of the PQ Bypass DETOUR System as a percutaneous femoropopliteal bypass intervention through 2-year follow-up

Methods:

• 78 patients with 82 long-segment (>100mm) femoropopliteal lesions

• Procedure using the DETOUR system

• Safety endpoints include major adverse events (MAEs), clinically driven target vessel revascularization (CD-TVR), and major amputation

• Effective endpoints include primary patency, assisted primary patency, and secondary patency

DETOUR I Trial

Device Components and Procedure

TORUS Stent Graft• Self-expanding, flexible, composite structure comprised of a

nitinol wire frame encapsulated in an ePTFE film

• Synthetic conduit used to create a fully-percutaneous bypass

Labeled Device Diameter (mm)

Recommended Vessel

Diameter (mm)

Available Device Nominal Lengths (mm)

5.5 5.0 – 5.5 200

6.0 5.6 – 6.0 100, 150, 200

6.7 6.1 – 6.7 100, 150, 200

PQ Snare• Over-the-wire endovascular snare composed of

radiopaque dual-nitinol caged scaffolds, 95cm in length• Support to the femoral vein, destination and snare for

guidewire• Nitinol cages deploy to a maximum of 11 mm at apex• Compatible with a 7Fr Sheath and 0.014” guidewire

PQ Crossing Device• Spring-loaded guidewire with a 0.025” Nitinol

needle and 15mm throw• Create anastomoses between artery and vein • 8Fr compatible device• 135 cm working length• Dual 0.014” guidewire ports

Step 1: Proximal AnastomosisSpecialized crossing device and snare create arteriovenous connection above proximal margin of the lesion

Step 2: Distal AnastomosisSpecialized crossing device and snare create arteriovenous connection below distal margin of the lesion

Step 3: Graft DeploymentStent graft bypass exits artery, travels within femoral vein, adjacent to occlusion and reenters artery at the site of reconstitution

Safety and Effectiveness Outcomes

1-Year 2-Year

Primary Patency 81±4% 81±4%

Assisted Primary Patency 82±4% 82±4%

Secondary Patency 90±4% 90±3%

1-Year 2-YearMajor Adverse Events 13/80 (16.3%) 14/78 (17.9%)

Death 1/79 (1.3%) 3/72 (4.2%)CD-TVR 12/79 (15.2%) 12/76 (15.8%)Target limb amputation 0/79 (0.0%) 1/73 (1.4%)

Primary Safety Endpoints

Primary Effectiveness Endpoints

Symptomatic Deep Vein Thrombosis (DVT)

Non-occlusive venous material associated with the graft: i.e Benign EndoVenous Graft

Associated Material (EGAM)

Pulmonary Embolism (PE)

Venous Luminal Occupancy by the Torus Stent Graft and Venous Changes Over Time

Clinical Considerations Specific to Occupancy of the Deep Venous

System with a TORUS Stent Graft

DVT vs. EGAM• Symptomatic Deep Vein Thrombosis:

2 of 81 cases (2.5%)• Occlusive blood clot/thrombus within a deep

vein, as confirmed by an imaging study (e.g. DUS) or direct visualization (e.g. intra-op)

• Distinct from the presence of mild fibrin/graft associated thrombotic material with no hemodynamic impact

• Intentional occupancy of a duplicated deep vein by the graft would not constitute a DVT

• Benign EndoVenous Graft Associated Material (EGAM)• Accumulation of nonobstructive material

measuring >0.9 mm in greatest thickness adherent to the external surface of the venous component of the Torus stent graft, as determined by DUS

• This material is not associated with hemodynamic significance and may be composed of fibrin or mixture of other components

Image from: https://pt.wikipedia.org/wiki/Trombose_venosa_profunda

PE was defined in the protocol as: blockage of an artery of the lungs diagnosed using CT pulmonary angiography, lung ventilation/perfusion scan

Venous thrombus within a PQ Bypass limb may behave differently than standard DVTs regarding embolic risk. Hypotheses include:

a) The graft material provides a nidus to which the thrombus is strongly adherent

b) A significant component of the occlusive material may be fibrin rather than typical soft thrombus

c) Hemodynamics of the deep venous system are altered by the presence of the stent, resulting in less embolization

Through 24 months of follow-up in DETOUR 1, only 2 Subjects Developed Ipsilateral

Symptomatic DVTPatient 1 Patient 2

Age/Gender 73/Male 50/Male

Time to Event 5 months, 16 days 27 days (at 1-month follow-up)

Observation • Symptoms of pulling in left thigh and left ankle swelling

• DUS performed 10 days after inguinal hernia repair and revealed occlusive venous thrombus (dual antiplatelet therapy had been held in the pre- and peri-op period)

• Symptoms of mild pre-tibial edema• DUS performed as part of routine 30-day

follow-up and demonstrated occlusive venous thrombus in addition to occlusion of the proximal right AT artery

Site Left distal femoral vein, and popliteal vein Right mid and distal femoral vein, and popliteal vein

Rutherford Category 3 3

ABI 0.8 0.6

VCSS/Villata 1/1 (Baseline 1/1) 2/2 (Baseline 0/0)

Complications None None

Treatment Rivaroxaban Rivaroxaban

All subjects enrolled in DETOUR 1 had femoral venous diameters of 10mm or greater. As such, event the largest

TORUS stent grafts had

Even with use of the largest TORUS grafts, venous luminal preservation remains High

While some subjects were noted to have increases in vein diameter following PQ Bypass over time, this pattern of

accommodation was not universal

Protocol-defined: Primary, Primary-Assisted, and Secondary Patency

73%(58/82)

80%(64/82)

94%(75/82)

0.0%

20.0%

40.0%

60.0%

80.0%

100.0%

PSVR < 2.5 without TLR

Revascularization of 50% to 99%

stenoses

Primary Patency

Primary Assisted Patency

SecondaryPatency

Revascularization of 100% occlusion

Independently adjudicated by Cleveland Clinic Core Laboratory and Syntactx CEC1

*Core lab data were used when available; site reported data and/or clinical presentation were used otherwise. Two (2) patients did not have sufficient follow-up images, and two (2) patients are in, or have exited 12 M follow up window with no clinical complaints – visits pending.

Discussion and Conclusion

Conclusions:

1. Low DVT rate

• Non-occlusive lesions in the vein may be EGAM and not true DVTs

2. PEs are unlikely to result from the placement of a PQ Bypass graft

3. Significant venous luminal preservation is achieved, even with occupancy of the femoral and popliteal veins with a TORUS stent graft

Areas for Future Investigation:

• Measure thickness of all non-occlusive venous material

• Track changes in vein diameter over time

• Track changes in graft wall thickness over time

Goals:

1. Better delineate EGAM from non-occlusive thrombus 2. Characterize any venous dilation or other potential structural changes

that may occur as compensation for luminal occupancy by the graft

Peter A. Schneider, M.D.University of California San Francisco