1. DCB - New Tool for managing Recurrent ISR in Full Metal Jackets

2. Peripheral Arterial Disease Critical limb ischemia admits (9)
64 year old woman with a history of PVD s/p attempted bypass grafting and multiple PVI (42 LE angiogram 32 PVI/stent placements) who presented from clinic with worsening claudication symptoms. Her ABI showed a significant decrease in L 0.8-->0.28. Her R side also trended down; > She had pain in both legs, but it is worse on the left side.
PAST MEDICAL HISTORY
Peripheral Arterial Disease
Critical limb ischemia admits (9)
Hypertension
Hypercholesterolemia
Blood clots
Breast CA
Rt Spigelian hernia
Completed tamoxifen 5 years of therapy april 2013
Completed chemotherapy for march 2008
Cough
Leg pain 00

3. Taking Colace 100 MG Capsule 1 capsule as needed BID
CURRENT MEDICATIONS
Taking Colace 100 MG Capsule 1 capsule as needed BID
Taking Pletal 100 MG Tablet 1 tablet 30 minutes before or 2
Taking Gabapentin 300 MG Capsule 1 capsule Twice a day
Taking ASA & Plavix 75 MG Tablet 1 tablet Once a day
Taking Lipitor 80 MG Tablet 1 tablet Once a day
Taking Librium 25mg 1 tablet twice daily
Taking Pantoprazole Sodium 20 MG Tablet
Taking Lisinopril 2.5 MG
Taking Metoprolol Tartrate 25 MG Tablet
Taking Oxycodone-Acetaminophen MG Tablet 1 tablet as 00

4. Diagnostic RLE peripheral angiogram 2008/06/12
PVI HISTORY
PTA/Stent Lt SFA 2008/08/18
Diagnostic RLE peripheral angiogram 2008/06/12
Thrombolysis/Thrombectomy Rt SFA 2008/06/11
TPA infusion Rt SFA 2008/04/03
PTA/Stent Rt SFA; PTA/Stent Rt distal SFA; Thrombectomy Rt
SFA/popliteal junction 2008/04/01
PTA/Stent Rt SFA; PTA/Stent Rt profunda femoral; PTA /Stent Rt popliteal artery; PTA/Stent Rt anterior tibia 2008/02/26
Bilateral AFRO 2008/02/01
PTA/tPA/Stent BM Lt SFA 2010/05/27
PTA/Stent Lt SFA; PTA Lt common femoral art; PTA Lt profunda
femoral art 2009/10/26
PTA Rt common femoral artery 2009/10/16
PTA/Arthrectomy Rt profunda femoral artery; PTA/Arthrectomy Rt common femoral artery 2009/08/05
PTA Lt SFA 2009/07/16
RLL angiogram 9/2011 00

5. PTA/Stent Lt SFA; PTA Lt common femoral art; PTA Lt profunda
PTA Rt common femoral artery 2009/10/16
PTA/Arthrectomy Rt profunda femoral artery 2011/08/05
PTA Lt SFA 9/2011
Last Intervention:
03/2015
- Successful PVI of the left external iliac artery.
TASC type A with a 20mmHg translesional gradient
POBA followed by self-expanding stent placement
- Successful PVI of the right SFA.
TASC type D
POBA - non-flow limiting dissection 00

8. Ann Vasc Surg. 2011 Jan;25(1):127-31. doi: 10.1016/j.avsg.2010.11.001.
Full metal jacket stenting of the superficial femoral artery: a retrospective review.
Shah PS1, Hingorani A, Ascher E, Shiferson A, Gopal K, Jung D, Marks N, Jacob T.
The technique of long segment stenting of the superficial femoral artery (SFA) has been associated with poorer short- and long-term results. The full metal jacket (FMJ) stenting is typically described as long segment continuous stenting of a vessel segment. Initially, this technique was described in percutaneous coronary interventions. However, until recently, FMJ of the SFA has not been studied. We examined our experience with FMJ of the SFA to evaluate the outcomes and the safety of this technique.

10. Left lower extremity:
- Left CIA has mild disease
- Left EIA has % (20 mm gradient with pull back
- EIA/CFA stent is totally occluded
- SFA stents occluded
- Pop stents occluded
- reconstitution BTK in the popliteal
- AT has 80 % ostial
- PT has severe ISR
- Peroneal is occluded in the prox and reconstitutes distally

11. Left lower extremity:
- Left CIA has mild disease
- Left EIA has % (20 mm gradient with pull back
- EIA/CFA stent is totally occluded
- SFA stents occluded
- Pop stents occluded
- reconstitution BTK in the popliteal
- AT has 80 % ostial
- PT has severe ISR
- Peroneal is occluded in the prox and reconstitutes distally

15. Right lower extremity: - Right CIA has mild disease
- Right EIA has severe (80 % stenosis)
- Right CFA has severe ISR
- SFA proximal has severe ISR 00

16. Right lower extremity: - Right CIA has mild disease
- Right EIA has severe (80 % stenosis)
- Right CFA has severe ISR
- SFA proximal has severe ISR (mid and distal angiography not done)
Left lower extremity:
- Left CIA has mild disease
- Left EIA has % (20 mm gradient with pull back
- EIA/CFA stent is totally occluded
- SFA stents occluded
- Pop stents occluded
- reconstitution BTK in the popliteal
- AT has 80 % ostial
- PT has severe ISR
- Peroneal is occluded in the prox and reconstitutes distally 00

17. Any Ideas Heavy Stent load Recurrent presentation
9 years of multiple procedures
Morbidity
Significant ISR

18. DRUG COATED BALLONS:

19. LIMITATIONS OF POBA,BMS & DES
Balloon angioplasty - elastic recoil and restenosis caused by cellular proliferation are major drawbacks of angioplasty.
Stenting, which could tackle dissections and eliminate elastic recoil, became the next model of intervention but was limited by stent thrombosis and increased neointimal hyperplasia, leading to in-stent restenosis.
Drug-eluting stents significantly attenuate the cellularity and reduce the need for repeat revascularization; however, late stent thrombosis, dependency on prolonged dual antiplatelet therapy, and continued restenosis led to a quest for new treatment modalities

20. Elastic recoil & negative remodeling

21. MEHANISMS OF RESTENOSIS
Recoiling and remodelling
Neointimal hyperplasia

22. ANGIOGRAPHIC RESTENOSIS & CLASSIFICATION
Diameter stenosis > 50%
Type I focal <10 mm in length
IA articulation or gap
IB margin
IC focal body
ID multifocal
Type 2 diffuse >10 mm intrastent
Type 3 proliferative >10 mm extending beyond stent margins
Type 4 total occlusion: restenotic lesions with TIMI flow grade of 0

23. MEHANISMS OF RESTENOSIS
Stent implantation causes arterial injury
Initiate inflammation
Platform material used is cobalt chromium
Lower nickel content than 316L stainless steel
Migration of smooth muscle cells
Activated smooth muscle cells to advance from G1 phase to S phase
Smooth muscle cell proliferation and extracellular matrix formation

24. Int J Cardiol. 2005 Oct 10;104(3): The impact of metallic allergy on stent implantation: metal allergy and recurrence of in-stent restenosis. Iijima R1, Ikari Y, Amiya E, Tanimoto S, Nakazawa G, Kyono H, Hatori M, Miyazawa A, Nakayama T, Aoki J, Nakajima H, Hara K.
Abstract
BACKGROUND:
Relation between metallic allergy and in-stent restenosis (ISR) has been inconclusive. We hypothesized that mechanism of restenosis is different between initial stent implantation and dilatation for ISR. Thus, we studied metallic allergy and restenosis in these two different situations separately.
METHODS AND RESULTS:
We performed follow-up angiography and patch test for metallic allergy in a total of 174 stented consecutive patients, 109 patients (63%) for restudy of initial stent implantation and 65 patients (37%) for restudy of treatment following ISR. The positive rate of patch test in initial stent implantation was not significantly different between with or without restenosis (10% vs. 9%; p=ns). Whereas, following dilatation of ISR, the incidence of positive patch test was significantly higher in patients with recurrence of restenosis than those without the recurrence (39% vs. 12%; p=0.02). Multivariate analysis revealed that the positive patch test (Odd Ratio 4.39, p=0.02) and diffuse typed ISR (Odd Ratio 3.68, p=0.03) were significant predictors of recurrent restenosis.
CONCLUSIONS:
Metal allergy does not have any correlation with the restenosis after initial stent implantation. However, metal allergy is frequently observed in patients with recurrence of ISR. Metal allergy may contribute to a mechanism in the repeat recurrence of ISR, but not to restenosis after initial stent implantation.

25. lesions in the superficial femoral artery & below knee
Rationale for the development of DEB derives mainly from the limitations of DES.
Nonstent-based local drug delivery using DEB maintains the antiproliferative properties of DES, but without the limitations of DES.
in torturous vessels
In treatment of ISR
in small vessels
lesions in the superficial femoral artery & below knee
In long diffuse calcified lesions (which can result in stent fracture)
in bifurcated lesions
when scaffolding obstructs major side branches

26. ISSUES WITH SFA/POP RESTENOSIS
PTA - High rate of restenosis (40 – 60%)
BMS - ISR – 30-50% (RESILIENT TRIAL)
DES - Same Issue (SIROCCO II TRIAL)
Long lesions, complex morphology, frequent multi level
Low flow rates
Calcification
Uneven delivery of local drug
Stent fracture
Polymer induced inflammation
Constant bio-mechanical pressure due to body movement

27. Paclitaxel with Spacer which was iopromide
History of DEB
INVENTORS
1979 – Professor Speck invented contrast agent Ultravist (iopromide)
2001 – Both Prof. Speck and Prof. Scheller introduced Ultravist / Paclitaxel Paccocath balloon
Paclitaxel with Spacer which was iopromide
Paccocath Balloon
B. Braun
Cotavance Balloon
MEDRAD

28. Paclitaxel
Paclitaxel was identified as the primary drug for DEB because of its rapid uptake and prolonged retention due to its strong lipophilic nature.
DEB technology demonstrated safety and efficacy in preclinical and in randomized clinical trials for patients with in-stent restenosis
Local Dose: 300 – 600 µg (100 – 200 µg in DES) which is 300 times less compare to systemic administration.
Immediate Release
Short acting exposure
No Polymers
Cytotoxic which inhibits G2 phase of Mitosis
Spacer / Excipient which facilitates local delivery

29. FIRST GENERATION BALLOON
Paccocath Technology Description
FIRST GENERATION BALLOON
Paclitaxel+Hydrophilic Spacer (iopromide)

30. 1.) After pre-dilatation of the stenosis, the DCB is centered across the entire treated area
2.) 30 second minimum inflation transfers therapeutic dose of the drug to the endoluminal surface
3.) Paclitaxel diffuses into the arterial wall from the endoluminal surface after drug delivery
4.) Therapeutic drug levels are sustained in the artery through 30 days post treatment
5.) Drug continues to inhibit restenosis in the arterial wall while allowing the lumen to restore and re-endothelialize
6.) Evidence of pharmacological effects peaks at 90 days

31. Current Drug Coated Balloons on the Market
Peripheral and coronary DCBs with CE Mark
Company
Device Name
Balloon Drug Load
Carrier
Lutonix
Moxy DCB
2 µg/mm²
Non- polymeric
Medrad-Possis
Coatavance
3 µg/mm²
iopromide
Medtronic/Invatec
In.Pact
3.5 µg/mm²
Urea
Biotronik
Pantera Lux, Passeo 18
BTHC
B. Braun
Sequent Please
Eurocor
DIOR II, Freeway
Shellac
Aachen Resonance
Elutax
Unknown
Blue Medical
Protege

32. First Generation Landmark trials
THUNDER TRIAL
FEMPAC TRIAL

33. Thunder & fempac trial 6 months results
No. of patients
FEMPAC TRIAL
THUNDER TRIAL
    Uncoated 42 54
    Coated 45 48
6-mo late lumen loss, mm
1.0±1.1
1.7±1.8
0.5±1.1
0.4±1.2
6-mo angiographic restenosis, % 47 44 19 17
6-mo % TLR 33 37 9 4
18–24 mo % TLR 52 20 15
6-mo major amputations 2

35. Follow up 18 and / or 24 Months
Fempac 2 year outcome
PAC Balloon Vs. Control
Follow up 18 and / or 24 Months

36. THUNDER FIVE YEAR OUTCOME
Freedom from TLR: Kaplan-Meier

37. Next generation trials
LEVANT I
PACIFIER
Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoro popliteal Restenosis Trial for Femoro popliteal Revascularization
Randomized Multicenter Trial Evaluating Prevention of Restenosis with Paclitaxel-Coated PTA Balloon Catheters in Stenosis or Occlusion of Femoro popliteal Arteries

38. LEVANT-I 6 months results

39. PACIFIER – 6 months Angiographic follow up
DEB
Control
P value
% Diameter Stenosis %
28.6%
40.4%
0.01
Min. Lumen Diameter mm
3.6 mm
3.0 mm
0.03
Binary Restenosis n/N (%)
4/40 (10%)
12/39 (31%)
Late Lumen Loss mm
-0.05 mm
0.61 mm
0.003

40. Metanalysis of deb randomized trials
Conclusion: Consistent with statistically significant lower rate of restenosis in DEB Trials.

41. DEB VS DES INPACT VS ZILVER PTX
Major Adverse Event
DEB
DES p
Adjusted p N
131 97
Any TLR
19.3% (21/109)
21.5% (21/79)
0.705
0.550
Clinical Driven TLR
15.6% (17/109)
19.0% (15/79)
0.543
0.572
Loss of Patency
23.9% (26/109)
30.4% (24/79)
0.319
0.372
DEB provisional Stent rate = 18.3%
Single Center
Retrospective with Propensity Score analysis
IN.PACT DEB vs Zilver PTX
228 Patients
Mean lesion length = 19 cm

42. DEB VS PTA INPACT TRIAL

43. SUMMARY Role of DEB in SFA/POP Intervention is promising.
DEB is superior to PTA in all clinical trials.
Results of DEB angioplasty are comparable or better than DES.
DEB are easier to use.
It is COST EFFECTIVE modality for De-Novo & restenosis lesions.
Compared to stents , NO anatomical Limitation.
DEB preserve future percutaneous and open surgical options.

44. LIMITATIONS OF DEB Acute recoil
Elimination of Late negative remodeling- not clear
Variability of pharmacokinetics and control of dosing of drug

45. Back to our patient - on her 42nd arrival to cath lab – treated with DEB
Successful PVI to right AT, Pop, SFA, CFA ISR using paclitaxel DCB and PVI to REIA with placement of nitninol SES.
- PVI to Left Pop ISR CTOusing 4.0 balloon followed by 4.0 DCB
- PVI to SFA ISR CTO (distal to prox) with 6 x 200 mm followed by 6.0 DCB
- PVI to CFA with 6.0 balloon followed by 6.0 DCB
- PVI to EIA using 7.0 DCB followed by placement of 8 x 60 SES.
Excellent final result with brisk flow all the way to the foot.
Contrast 20 c.c. and rest of angio was done using CO2 angiography.

46. - Excellent Results
Unbelievable ABI on 11/18/2015 was 1 on the left and 0.99 on the right
No Hospital admission for 9 months
- We have quite a few patients with FMJ in their LE vessels and have seen great results with use of DCB in these patients.

47. Thank You