Photoablation and DCB in in-stent restenosis

Craig M. Walker, MD, FACC, FACP

Clinical Professor of Medicine

Tulane University School of Medicine

New Orleans, LA

Clinical Professor of Medicine

LSU School of Medicine

New Orleans, LA

Founder, President, and Medical Director

Cardiovascular Institute of the South

Houma, LA

Disclosure

Speaker name:

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

I have the following potential conflicts of interest to report:

Consulting

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s)

I do not have any potential conflict of interest

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• Single Center US Experience Registry in treating very long segment highly symptomatic chronic SFA total in-stent occlusions.

Inclusion Criteria

• Documented chronic total occlusion (≥2 mos) of SFA stents ≥ 18 cm

• Rutherford 3 or 4 classification (no mild claudicants or established tissue loss)

• At least one patent run-off vessel

• No type 3 or 4 stent fractures

• Lesions crossable

• TIMI 3 flow before DEB

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Background: fem-pop ISR

1. Osherov AB, Gotha L, Cheema AN, Qiang B, Strauss BH. Proteins mediating collagen biosynthesis and accumulation in arterial repair: novel targets for

anti-restenosis therapy. Cardiovasc Res. 2011 Jul 1;91(1):16-26

2. Inoue S, Koyama H, Miyata T, Shigematsu H. Pathogenetic heterogeneity of in-stent lesion formation in human peripheral arterial disease. J Vasc Surg.

2002 Apr;35(4):672-8

3. Brodmann M, Rief P, Froehlich H, Dorr A, Gary T, Eller P, Hafner F, Deutschmann H, Seinost G, Pilger E. Neointimal hyperplasia after silverhawk

atherectomy versus percutaneous transluminal angioplasty (PTA) in femoropopliteal stent reobstructions: a controlled, randomized pilot trial. Cardiovasc

Intervent Radiol. 2013 Feb;36(1):69-74

ISR vs. de-novo: different pattern, higher restenosis burden

Initial (de-novo)

lesion

ISR Dense rubbery cap of

smooth muscle cells

Hydrated collagen matrix (watery sponge; 60-80% of NIH volume)

Calcium: rare

Thrombus: can be present, but typically

a small part of the total volume

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LASER

Recanalization (Pilot Channel)

Plaque vaporization

Limited embolization

No moving blades

Only FDA approved Atherectomy for ISR

Recanalization, Debulking and Plaque Modification

Photochemical: Molecular bond break

Photothermal Thermal energy

Photomechanical Kinetic energy

√ √ √ √ √

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Laser in long fem-pop ISR

Laser + PTA vs. PTA @ 6-month:

71.1% vs. 56.4% (p=0.004)

Primary Patency

EXCITE ISR RCT Laser + PTA vs. PTA in fem-pop ISR • 250 Patients (169 ELA+PTA vs. 81 PTA)

• Occlusive ISR: 30.5% vs.36.8%

• Mean ISR length: 19 cm

Laser + PTA better than PTA, proportionally better in longer lesions

• Dippel EJ, Makam P, Kovach R, George JC, Patlola R, Metzger DC, Mena-Hurtado C, Beasley R, Soukas P, Colon-Hernandez PJ, Stark MA, Walker C; EXCITE ISR

Investigators. Randomized controlled study of excimer laser atherectomy for treatment of femoropopliteal in-stent restenosis: initial results from the EXCITE ISR trial

(EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis). JACC Cardiovasc Interv. 2015 Jan;8(1 Pt A):92-101

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Laser + DCB pre-Clinical Insights

R.Virmani VIVA 2015

DC

B a

lon

e

Reduced % stenosis and intimal thickness with Laser+DCB vs. DCB alone at 28 days in pre-clinical ISR model

Rabbit model of (carotid) CTO ISR treated by Laser + DCB vs. DCB alone

Lase

r +

DC

B

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Laser + DCB in ISR: Clinical Insights

• SFA-ISR case series (N=14) 13 cm, treated with Laser+DCB

• Time to first TLR (after PTA) = 8 months

Reduced TLR rate and time-to-TLR vs. initial PTA treatment

1 TLR (7%) at 3 years

• Van Den Berg JC, Pedrotti M, Canevascini R, Chimchila Chevili S, Giovannacci L, Rosso R. Endovascular treatment of in-stent restenosis using excimer laser

angioplasty and drug eluting balloons. J Cardiovasc Surg (Torino). 2012 Apr;53(2):215-22

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Laser+DCB vs. DCB in long, occlusive ISR: RCT

12-month Primary Patency

ELA + DCB vs. DCB:

66.7% vs. 37.5% (p=0.01)

Significant reduction of TLR and

MAE and improved wound healing

with Laser + DCB vs. DCB alone at

12 months

• Gandini R, Del Giudice C, Merolla S, Morosetti D, Pampana E, Simonetti G. Treatment of chronic SFA in-stent occlusion with combined laser atherectomy and drug-

eluting balloon angioplasty in patients with critical limb ischemia: a single-center, prospective, randomized study. J Endovasc Ther. 2013 Dec;20(6):805-14

• Single center randomized trial (Laser+DCB vs. DCB)

• N=48; CLI: 100%; Diabetes: 100% • Occlusive ISR (Tosaka III): 100% • mean ISR treated length: 22.4±9.4

(Laser + DCB) vs. 25.9±8.7 cm (DCB)

Planned Follow-up Evaluation

• Pre procedural ABI, Duplex, Rutherford

• 1 month clinical evaluation

• 6 month clinical evaluation, ABI, Art Duplex

• 1 yr clinical evaluation, ABI, Art Duplex

• Yearly clinical evaluation, ABI, Art Duplex

Treatment Protocol

• All SFA treatment via contralateral approach to avoid prolonged compression of treated artery.

• Following angiography lesion crossed and treated with Turbo-Elite laser catheter (2 passes at 1mm/sec advancement rate).

• Repeat angiography.

• PTA with non-compliant balloon to reference vessel size for 2 minutes).

• Repeat Angio.

• Drug-Eluting PTA of entire treated segment avoiding treatment miss (Two minute inflations).

• Angiography.

24 patients treated between Feb 2015 – June 2015

• 22 Rutherford 3

• 2 Rutherford 4 (Both had severe Profunda disease).

• Lesion length 18cm – 43cm (mean 28cm)

• Pt age 48 - 78

• 19 males 5 females

• Reference vessel diameter

– 4mm 2 pts

– 5mm 19 pts

– 6mm 3 pts

Baseline hemodynamis

• ABI 0.3 – 0.76 (Mean .52)

• Duplex – Totally occluded segment

Acute Treatment Outcomes

• All lesions were crossed (in 3 cases laser step by step approach was required)

• Following laser atherectomy angiography disclosed a patent channel with TIMI 3 flow in 23/24. One pt had TIMI 2 flow treated successfully with local 2B/3A administration

• Following intial PTA 22/24 widely patent with TIMI 3 flow. 2 had TIMI 1 flow treated successfully with local 2B/3A

• Following DEB all 24 had excellent angiographic result with TIMI 3 flow.

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Follow-up

• 24 patients treated within time period to assess 6 month outcomes

• 2 patients did not return for visits or follow-up but were reached by phone (Patients stated they were a symptomatic)

• 1 patient could not be reached

• 21 patients returned to office for full evaluation

Clinical findings in 21 patients at 6 mos

• 18 pts Rutherford 0

• 2 pts Rutherford 2

• 1 pt Rutherford 3

Objective findings at 6 mos

• ABI .52 – 1.3 (Average .92)

• Art Duplex

– 19 patients, no significant stenosis PSVR <2

– 1 patient, total SFA occlusion (had stopped anti-platelet drugs)

– 1 patient, had several high grade lesions

Major Adverse Events at 6 mos

• 1 pt had clinically driven TLR → Laser + DEB with good initial result

• No deaths or CVA

• No major bleeding requiring transfusion

Conclusion

• The treatment of long-segment SFA in-stent occlusions is challenging and has been historically associated with poor patency. Laser de-bulking followed by DEB is feasible. These initial outcomes are encouraging but longer-term evaluation is needed.

Photoablation and DCB in in-stent restenosis

Craig M. Walker, MD, FACC, FACP

Clinical Professor of Medicine

Tulane University School of Medicine

New Orleans, LA

Clinical Professor of Medicine

LSU School of Medicine

New Orleans, LA

Founder, President, and Medical Director

Cardiovascular Institute of the South

Houma, LA