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