The Shockwave Lithoplasty Concept:

Finally the Solution for Calcified Lesions?

Andrew Holden, MBChB, FRANZCR

Disclosure

Speaker name:

Associate Professor Andrew Holden

I have the following potential conflicts of interest to report:

Consulting – Clinical Investigator for Shockwave

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s)

I do not have any potential conflict of interest

X

Arterial Calcification

• Most endovascular devices do not cope well with

vessel calcification

• Significant calcification is a common exclusion

criteria for many device trials

• Familiar Balloon-based endovascular technique

• “Front-line” balloon strategy (.014”compatible)

• Disrupts both deep & superficial calcium pre dilation

• Normalizes vessel wall compliance

• Ultra-low pressure

• Minimized effect on healthy tissue

Lithotripsy waves travel outside low pressure balloon,

Disrupt deep, superficial calcium pre-dilation

* Per

Manufacturer

LithoplastyTM

Lithotripsy disrupts calcium prior to low-pressure

dilation to reference vessel diameter

Inclusion Criteria

• Rutherford II-IV Intermittent Claudication (n= 35 Patients)

• ABI < 0.9

• Screen CT, MR, X-ray

• SFA/Popliteal Lesion > 70% stenosis, 3.3-7.0 mm, < 180 mm

• Angiographic Moderate/Severe Calcification

Procedure

• Lithoplasty 3.5 to 7.0 x 60 mm Multi-electrode Balloon

Endpoints

• Acute Angiographic Result-Core lab adjudicated

• Safety-30 day MAE-CEC Adjudicated

• Duplex Ultrasound 30 & 180 Days-Core lab adjudicated

• OCT Sub-study-Core lab adjudicated

DISRUPT PAD

Investigational Sites

Investigator Site Enrollment

Marianne Brodmann (PI)

Medizinische Universität Graz, Austria

23

Andrew Holden (co-PI)

Auckland City Hospital, New Zealand

7

Martin Werner Hanusch-Krankenhaus, Vienna, Austria

5

Total: 35

Core Labs

Angiography

• Alexandra Lansky, MD-Yale Cardiovascular Research Group

Duplex Ultrasound

• Michael Jaff, MD-Vascore (MGH)

Optical Coherence Tomography

• Case Western Reserve

Clinical Events Committee

Bill Gray MD (Chair)

• Columbia Presbyterian Medical Center- NY, NY

Nick Shammas MD

• Genesis Heart Center- Davenport, IA

Rob Lookstein MD

• Mt Sinai Medical Center- NY, NY

DISRUPT PAD

Clinical Baseline

Symptoms Total (N=35)

Rutherford Category, %(n/N)

0 0.0% ( 0/ 35)

1 0.0% ( 0/ 35)

2 40.0% ( 14/ 35)

3 57.1% ( 20/ 35)

4 2.9% ( 1/ 35)

5 0.0% ( 0/ 35)

6 0.0% ( 0/ 35)

ABI Resting (treated limb)

Mean ± SD (N) 0.7± 0.1 ( 31)

[95% Conf. Interval]¹ [ 0.7, 0.7]

Pain Scale

Mean ± SD (N) 3.6± 0.8 ( 35)

Median (Q1, Q3) 3.0 ( 3.0, 4.0)

Range (min, max) ( 2.0, 5.0)

[95% Conf. Interval]¹ [ 3.3, 3.9]

Pain Scale, %(n/N)

1 0.0% ( 0/ 35)

2 5.7% ( 2/ 35)

3 45.7% ( 16/ 35)

4 34.3% ( 12/ 35)

5 14.3% ( 5/ 35)

Lesion Characteristics (Core Lab) Angio Core Lab Baseline

N= 35 pts M=39 lesions

Morphology

Target Lesion Length (mm)

Mean ± SD (N) 61.5± 36.6 ( 39)

[95% Conf. Interval]¹ [ 49.6, 73.4]

Calcification, %(n/N)

None/Mild 0.0% ( 0/ 39)

Moderate 35.9% ( 14/ 39)

Severe 64.1% ( 25/ 39)

Total Length of Calcification (mm)

Mean ± SD (N) 80.3± 38.4 ( 39)

Median (Q1, Q3) 59.8 ( 55.7, 119.2)

Range (min, max) ( 28.6, 184.3)

[95% Conf. Interval]¹ [ 67.9, 92.7]

Thrombus Present

[95% Conf. Interval]² 0.0% ( 0/ 39) [ 0.0%, 9.0%]

Aneurysm Present

[95% Conf. Interval]² 7.7% ( 3/ 39)

[ 1.6%, 20.9%]

Distal Run-Off, %(n/N)

1 10.3% ( 4/ 39)

≥ 2 89.7% ( 35/ 39)

Primary Performance Endpoint < 50% residual stenosis

Lithoplasty with or without PTA Primary Performance Parameters

N=35 pts.

M= 39 lesions

Achieved < 50% DS

[95% Conf. Interval]²

100.0% ( 39/ 39)

[ 91.0%,100.0%]

Acute Gain (mm)

Mean ± SD (N)

Median (Q1, Q3)

Range (min, max)

[95% Conf. Interval]¹

2.9± 0.8 ( 39)

2.8 ( 2.4, 3.4)

( 1.4, 4.6)

[ 2.6, 3.1]

Percent Stenosis Reduction (%)

Mean ± SD (N)

Median (Q1, Q3)

Range (min, max)

[95% Conf. Interval]¹

68.7± 8.5 ( 39)

68.6 ( 62.0, 75.2)

( 48.2, 85.1)

[ 65.9, 71.4]

Adjunctive Angioplasty required in only 4 patients

DISRUPT PAD: Primary Performance Endpoint

Procedural Success: Residual diameter stenosis of <50% (with or without adjunctive PTA) of

moderate (36%) and severe (64%) calcified lesions assessed by quantitative angiography via

core lab evaluation.

Average Residual Stenosis 23%

Primary Endpoint

(<50%)

Exploratory Endpoint

(<30%)

Patency at 30 days

Follow up visit N <50% stenosis

30 days 38 100%

• Duplex Ultrasound at 30 days, core lab adjudicated results:

Patency – Matched Pairs • Duplex Ultrasound, core lab adjudicated

– Average PSVR at discharge: 1.40

– Average PSVR at 30 days: 1.21

*Core lab adjudicated

2

1,4

1,7

1,2 1,1

1,7

1,2 1,3

1

1,3

0,9

1,3

1,9

1,1 1,2

1,5

1,1

1,4 1,3 1,3

0,7

1,1

0,8

1,1

1,8

1,5

0,9

1,5

1,1

0,9

1,2 1,2

0,8 0,9

0,7

1,2 1,1 1,1 1,1

1,3

0,9

1,6

1,2 1,1

1,0

1,4

1,2

1,4

0

0,5

1

1,5

2

2,5

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Change in PSVR (Matched Pairs)

Discharge 30 Days

Is there continued remodeling of the vessel wall after Shockwave lithoplasty?

Subject AUC-007

Pre-procedure Post LB/ Final Lithoplasty Balloon Calcification

Subject AUC-007

Pre-procedure Pre-procedural OCT

Subject AUC-007

Post LB/ Final Post-procedural OCT

Subject AUC-007

Pre-procedure DUS

Subject AUC-007

Post-procedure DUS

ABI Scores - Change Summary by Visit for Matched Pairs

Visit N Baseline

Mean [95% CI]¹

Post-Proc Mean

[95% CI]¹

Δ from Baseline [95% CI]¹

P-value*

Discharge 31 0.7± 0.1 [ 0.7, 0.7]

1.0± 0.2 [ 0.9, 1.0]

0.3± 0.2 [ 0.2, 0.3]

< 0.0001

1 Month 31 0.7± 0.1 [ 0.7, 0.7]

1.0± 0.3 [ 0.9, 1.1]

0.3± 0.2 [ 0.2, 0.4]

< 0.0001

Heavily Calcified Superficial Femoral Artery Stenosis

Lithoplasty™

Active Lithoplasty™

Pre-procedure Post LB/ Final Lithoplasty Balloon Calcification

DS=100%

Lesion Length=76.5 mm Total Length of Ca=74.8 mm

Prox. RVD=5.50 mm

Dist. RVD=6.05 mm

Interpolated RVD=5.89 mm

MLD=4.59 MM

DS %=21.94%

27.5mm OL

Core Lab Residual: 22%

• 4 FIM cases treated at Auckland Hospital with 20mm long initial device – follow up > 2 years

• 2 cases treated with EU device pre-trial – follow up > 1 year

• No DUS evidence of restenosis

• No recurrent symptoms

• No re-interventions

Longer Term Follow Up

Post-Lithoplasty @ 0.5ATM Pre-treatment

Longer Term Follow Up

MRA Pre-treatment

Longer Term Follow Up

MRA @ 2 years

Conclusions • Lithoplasty is a novel balloon-based technology for treatment of

calcified vascular lesions

• The results of the DISRUPT PAD Trial demonstrate outstanding acute results for treatment of moderate and severe calcified SFA/Popliteal lesions

• The procedure was extremely well tolerated and had an excellent safety profile

• Patency determined by DUS at 30 days was 100 percent

• Clinical pain & walking scores at 30 days were excellent

• Peak velocity ratios suggest positive remodeling effects at 30 days that warrant further investigation

• Longer term vessel patency will be determined by DUS at 6 month follow-up

The Shockwave Lithoplasty Concept:

Finally the Solution for Calcified Lesions?

Andrew Holden, MBChB, FRANZCR