Calcium: The Achilles Heel of Endovascular Procedures ... · Calcium: The Achilles Heel of...

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Calcium: The Achilles Heel of Endovascular Procedures?

Scaffold or remove before drug delivery

Konstantinos Stavroulakis MD

University of Münster and

St. Franziskus Hospital

Germany

Disclosure

K Stavroulakis

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

Factors associated with restenosis in peripheral interventions

• Lesion length1

• Diabetes2

• CTOs3

• Calcification4

1. Norgren et al. Eur J Vas Endovasc Surg 33, S1-S75: 2007. 2. DeRubertis et al. J Vasc Surg 2008;47:101-108. 3. Lida et al. Cath and Cardiovasc Interven 2011 Oct 1;78(4):611-7. 4. Cioppa et al. CV Revasc. Med. 2012 Jul-Aug:219-23.

Calcium still a challenge for ET

• Prevalence of vascular calcification in symptomatic PAD is unknown (~30-50% in asymptomatic patients)

• Vessel non-compliance leads to overstretch in non-diseased tissue causing dissection, recoil, excessive injury and poor outcomes

Fully Inflated BalloonElastic Recoil

(Residual High Grade Stenosis)

Impact of Calcium

Okuno et al JEVT, 2016. 23(5) 731–737

The current problems of POBA

Okuno et al JEVT, 2016. 23(5) 731–737

Scaffolds for calcified lesions

Rocha-Singh et al. Catheterization and Cardiovascular Interventions 89:1250–1256 (2017)

Bare Metal Stents

Garcia et al, Catheterization and Cardiovascular Interventions 89:1259–1267 (2017)

Interwoven Nitinol Stents

Scaffolds for severely calcified lesions

IN.PACT DCB and Calcium Registry Study (n=60) 12 month Results1

1. Fanelli F, et al. Cardiovasc Intervent Radiol, 37: 898-907 (2014).2. Tepe G, et al. J Endovasc Ther. 2015 Oct;22(5):727-33.

• Retrospective analysis of 91 patients2

• Analysed at 6M post DEB• Lesion calcification analysed by core labs

(PACSS score + angiographic calcium score)• Severity of lesion calcification is associated

with LLL after treatment with DCB. • Author conclusion: “One possible approach

to overcome this limitation might be plaque modification or removal prior to DEB usage.”

Drug coated balloons

DCB and Bailout stent rates

LUTONIX Global1ILLUMENATE

Global2

IN.PACT Global Full Clinical

Cohort3

IN.PACT Global Long Lesion4

IN.PACT Global CTO5

IN.PACT Global ISR6

Follow-up

691 subjectsComplete follow-up

Site-reported

InterimCore Lab-

adjudicated

Core Lab-adjudicated

Key Lesion Characteristics

Length (cm)CTO (%)Ca2+ (%)

10.12cm31.2%50.2%

7.2cm28.3%62%

12.1cm35.5%68.7%

26.4cm60.4%71.8%

22.9 cm100.0%71.2%

17.2cm34.0%59.1%

Primary Patency FF TLR/CD-TLR

85.4%94.1%

86.5%93.9%

-92.6%

91.1%94.0%

84.4%88.2%

88.7%92.9%

Bail-out Stent (%) 25.2% 15.0% 25.3% 40.4% 46.8% 14.5%

1. Presented by Benenati, JF. VIVA 2016 BARD Symposium2. Presented by Krishnan, P. NCVH 2016.3. Presented by Jaff M, VIVA Las Vegas 2016.

4. Presented by Scheinert D, PCR Paris 2015.5. Presented by Tepe G, CX London 2016.]6. Presented by Brodmann M, VIVA Las Vegas 2015.

Plaque Modification

Luminal Gain

Less Dissections

Increased Drug Uptake

Less permanent scaffolds

Improved patency

Why debulking?

Drug uptake after vessel prep

Tzafriri et al, J Control Release. 2017; 264: 203–210

Roberts, Catheterization and Cardiovascular Interventions 84:236–244 (2014)

Directional atherectomy

Minko et al, Cardiovasc Intervent Radiol (2014) 37:1165–1170

Directional atherectomy as standalone therapy

Directional atherectomy with anti-restenotic therapy (DAART)

Severe calcified lesions

Mean lesion length: 115 mm

CTOs: 13.3%

Bailout Stent: 6.7%

12 M PPR: 90%

12 M TLR: 10%

Amputation Rate: 0%

A. Cioppa et al. / Cardiovascular Revascularization Medicine 13 (2012) 219–223

DAART for popliteal disease

DCB DAART P Wert

Primary patency 65% 82% 0.021

Freedom from TLR 82% 94% 0.7

Stavroulakis et al JEVT. 2017;24(2):181-188

DEFINITIVE AR – Study design

Inclusion Criteria• RCC Score of 2, 3 or 4

• 70% stenosis, restenosis or occlusion in the SFA and/or popliteal artery

• Target lesion(s) length is 7-15 cm

• Target vessel diameter is 4 mm and ≤ 7 mm

Exclusion Criteria• In-stent restenosis

• Aneurysmal target vessel

• 2 or more lesions that require treatment in the target limb

Zeller et al, Circ Cardiovasc Interv. 2017;10:e004848.

DEFINITIVE AR – Baseline Demographics

* p-value for DA+DCB RCT and DCB groups

Baseline DemographicsDA+DCB(N=48)

DCB (N=54) p-Value*DA+DCB Severe

Ca++(N=19)

Lesion Length (cm) 11.2 9.7 0.05 11.9

Diameter Stenosis 82% 85% 0.35 88%

Reference vessel diameter (mm) 4.9 4.9 0.48 5.1

Minimum lumen diameter (mm) 1.0 0.8 0.34 0.7

Calcification 70.8% 74.1% 0.82 94.7%

Severe calcification 25.0% 18.5% 0.48 89.5%

DEFINITIVE AR – Peri-procedural Outcomes

Higher Technical Success and Lower Incidence of Flow-Limiting Dissection in DA+DCB RCT Arm

Technical success defined as achieving ≤30% residual stenosis following protocol-defined treatment and before adjunctive therapy (ie post-dilatation). No surgical interventions were required for any patient.

* p-value for DA+DCB RCT and DCB groups

OutcomesDA+DCB(N=48)

DCB (N=54) p-Value*DA+DCB Severe

Ca++(N=19)

Technical Success 89.6% 64.2% 0.004 84.2%

Distal Embolization 6% (3/48) 0% (0/54) 0.101 5.3% (1/19)

Bail-Out Stent 0% (0/48) 3.7% (2/54) 0.50 5.3% (1/19)

Dissection (flow limiting, Grade C/D)

2% (1/48) 19% (10/54) 0.01 0% (0/19)

Perforation 4% (2/48) 0% (0/54) 0.22 0% (0/19)

DEFINITIVE AR – 12 Month OutcomesAngiographic Patency

Results for all patients who returned for angiographic follow-up

Per Core Lab Assessment. “All Severe Ca++ “ group includes all patients treated with DA+DCB therapy including randomized and non-randomized patients with severe calcium.

The value of Luminal gain after DAART

After Atherectomy After DAARTLong-Severely Calcified Lesion

DAART for calcified lesion

Treatment Algorithm for severely calcified lesions

Scaffolds

• CKD patients

• Long CTOs

• CLI (?)

• Subintimal (?)

Vessel Prep + DCBs

• Younger patients

• Claudicants

• ‘No-stenting-zones’

• Benefit from the use of scaffolds

• DCB angioplasty is associated with increased LLL and

loss of patency

• Vessel Prep can improve the outcomes of ‘leave-

nothing-behind’

• Debulking:

- Less permanent scaffolds

- Increased Drug Uptake

- Improved patency