Transcript SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial)

DCB - New Tool for managing
Recurrent ISR in Full Metal
Jackets
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; 0.41-->0.31.
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
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 5-325 MG Tablet 1 tablet as
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
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 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
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.
Left lower extremity:
- Left CIA has mild
disease
- Left EIA has 60 -70
% (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
Left lower extremity:
- Left CIA has mild
disease
- Left EIA has 60 -70
% (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
Right lower extremity:
- Right CIA has mild
disease
- Right EIA has severe
(80 % stenosis)
- Right CFA has severe
ISR
- SFA proximal has
severe ISR
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 60 -70 % (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
Any Ideas
• Heavy Stent load
• Recurrent presentation
• 9 years of multiple
procedures
• Morbidity
• Significant ISR
DRUG COATED BALLONS:
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
Elastic recoil & negative remodeling
MEHANISMS OF RESTENOSIS
• Recoiling
and
remodelling
• Neointimal
hyperplasia
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
MEHANISMS OF RESTENOSIS
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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
Int J Cardiol. 2005 Oct 10;104(3):319-25.
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.
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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.
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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
lesions in the
superficial
femoral artery
& below knee
in bifurcated
lesions
in small vessels
In long diffuse
calcified
lesions (which
can result in
stent fracture)
when
scaffolding
obstructs major
side branches
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
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
Paclitaxel
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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
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Spacer / Excipient which facilitates local delivery
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Paccocath Technology
Description FIRST GENERATION
BALLOON
• Paclitaxel+
Hydrophilic
Spacer
(iopromide)
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 reendothelialize
6.) Evidence of pharmacological
effects peaks at 90 days
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
3 µg/mm²
BTHC
B. Braun
Sequent Please
3 µg/mm²
iopromide
Eurocor
DIOR II, Freeway
3 µg/mm²
Shellac
Aachen Resonance Elutax
3 µg/mm²
Unknown
Blue Medical
3 µg/mm²
Unknown
Protege
First Generation Landmark trials
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THUNDER TRIAL
FEMPAC TRIAL
Thunder & fempac trial
6 months results
No. of patients
FEMPAC TRIAL
THUNDER TRIAL
Uncoated
42
54
Coated
45
48
Uncoated
1.0±1.1
1.7±1.8
Coated
0.5±1.1
0.4±1.2
Uncoated
47
44
Coated
19
17
Uncoated
33
37
Coated
9
4
Uncoated
48
52
Coated
20
15
Uncoated
2
0
Coated
0
2
6-mo late lumen loss, mm
6-mo angiographic restenosis, %
6-mo % TLR
18–24 mo % TLR
6-mo major amputations
Fempac 2 year outcome
• PAC Balloon Vs. Control
• Follow up 18 and / or 24 Months
THUNDER FIVE YEAR
OUTCOME
• Freedom from TLR: Kaplan-Meier
Next generation trials
LEVANT I
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Lutonix Paclitaxel-Coated Balloon
for the Prevention of Femoro
popliteal Restenosis Trial for
Femoro popliteal Revascularization
PACIFIER
Randomized Multicenter Trial
Evaluating Prevention of Restenosis
with Paclitaxel-Coated PTA Balloon
Catheters in Stenosis or Occlusion of
Femoro popliteal Arteries
LEVANT-I 6 months results
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%)
0.03
Late Lumen Loss mm
-0.05 mm
0.61 mm
0.003
Metanalysis of deb randomized trials
Conclusion: Consistent with statistically significant lower
rate of restenosis in DEB Trials.
DEB VS DES
INPACT VS ZILVER PTX
Major Adverse
Event
p
Adjusted p
21.5% (21/79)
0.705
0.550
15.6% (17/109)
19.0% (15/79)
0.543
0.572
23.9% (26/109)
30.4% (24/79)
0.319
0.372
DEB
DES
131
97
Any TLR
19.3% (21/109)
Clinical Driven TLR
Loss of Patency
N
DEB provisional Stent rate = 18.3%
1. Single Center
2. Retrospective with
Propensity Score
analysis
3. IN.PACT DEB vs Zilver
PTX
4. 228 Patients
5. Mean lesion length = 19
cm
DEB VS PTA
INPACT TRIAL
SUMMARY
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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.
LIMITATIONS OF DEB
• Acute recoil
• Elimination of Late
negative remodeling- not
clear
• Variability of
pharmacokinetics and
control of dosing of drug
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.
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•- 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.
- 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.
Thank You