First human cases of self-expandable

percutaneous pulmonary valve implantation

using knitted nitinol-wire stent mounted with a

tri-leaflet porcine pericardial valve

Gi Beom Kim1, Mi Kyung Song1, Eun Jung Bae1, Chung Il Noh1, Jae Gun Kwak2, Woong Han Kim2, Jung Ryeol Lee2

Department of Pediatrics1, Thoracic and Cardiovascular Surgery2

Seoul National University Children’s Hospital

Disclosure

Valve development

A grant of the Korea Health 21 Research and

Development Project, Ministry for Health,

Welfare, Republic of Korea

(Project No. : A040004-006)

TaeWoong Medical Co., Ltd.: technical support

Hunan clinical trial

TaeWoong Medical Co., Ltd.: financial support

The effect of chronic PR on RV

(Hadhad F et al. 2008 Circulation)

Surgical PVR

J Am Coll Cardiol Intv. 2011;4(7):721-732

Porcine bioprosthetic valve

Bovine bioprosthetic valve

Stentless bioprosthetic valve

Limitation of balloon expandable valve

•Melody valve and Edwards valve

- fit for patients with a conduit or a bioprosthetic

valve in RVOT

- post-op patient with RVOT lesions: indicate only 15-20%

Most post-op TOF patients : Native RV Outflow Tract Valve!

Self-expandable pulmonic valved-stent

Harmony Valve Medtronic, USA

Venous P Valve Medtech, China

Valve diameter: 22 mm 25 Fr. delivery cable

Valve diameter: 16-32 mm 14-22 Fr. delivery cable

Pulsta Valve SNUCH, South Korea

Valve diameter: 18-28 mm 18 Fr. delivery cable

• Long and Bulky • Risk of stent fracture • Difficult to do re-do PVR • Need large delivery cable

Beginning of valved-stent in SNUCH

Xenotransplantation research center

- Since 2004.5

• Pancreas for DM treatment • Cornea • Heart valve

Various tissue treatment of porcine and bovine pericardium to decrease immunogenicity

1. Decellularization with 0.25% SDS (sodium dodecyl sulfate)

2. 0.1 units/mL alpha-galactosidase treatment

(for reduction of immunogenicity)

3. Space filler with PEG (polyethylene glycol)

4. 0.5 % GA fixation with solvent (75% ethanol + 5% octanol)

5. Detoxification with 0.1M glycine

Tissue preservation for porcine pericardium

J Heart Valve Dis. 2012;21:387-97.

Eur J Cardiothorac Surg. 2012;41:383-90.

Int J Cardiol. 2014;173: 74–79.

Self-expandable valved stent in SNUCH

Stent using Knitted Nitinol-wire backbone

self-expandable (with TaeWoong Medical)

Tri-leaflet valve using porcine pericardium

multiple steps for valve tissue preservation

Animal study of percutaneous PVR

Since 2011.8

About 6 Month-old

40- 50 kg

Endothelialization

Full endothelialization after 3 months

Int J Cardiol. 2014;173: 74–79.

Trans-catheter delivery system

Delivery catheter - Useable length: 110 cm 12Fr. shaft

18Fr. (5.9 mm)

Head Handle

Hook block

Valve loading

In Vitro valve motion test

In diseased valve model : 22 mm valve in 19 mm porcine Ao. valve

In normal valve model

Stent fatigue test - 400,000,000 times

Accelerated wear test - 200,000,000 times

Clinical trial Status in South Korea

Orphan device approval by Korean FDA: 2014. 12. 29

SNUCH IRB approval: 2015. 06. 01

Clinical trial approval by Korean FDA (> 19 years): 2015. 07. 24

Site Initiation Meeting: 2015. 08. 26

Indication extension (> 10 years, B. Wt. > 30kg): 2016. 07. 25

ClinicalTrials.gov Identifier: NCT02555319

* TPV: Transcatheter Pulmonary Valve

A feasibility study to evaluate the safety and short-term effectiveness of implantation of 'Transcatheter

Pulmonary Valve (TPV)' for the treatment of Congenital heart disease with Pulmonary valve disease

A feasibility study: 10 patients

Primary outcome

- Procedure success

- Procedural / Device related serious adverse events at 6month

- Hemodynamic functional improvement rate at 6month

A feasibility study

Study Procedure

Screening Procedure Follow-up

F/U

(Short-term) F/U

(Long-term)

Visit1 Visit2 Visit3 Visit4 Visit5 Visit 6 Visit 7~11

Baseline Day1 Discharge 1mon ±1week

3mon ±2week

6mon ±4week

Annually ±8week

OPD/Adm. Adm. Adm. OPD OPD OPD OPD

Consent √

Demographic data √

Vital sign √ √ √ √ √ √ √

physical exam. √ √ √ √ √ √

History/Allergy √

Blood test √ √ √ √ √ √ √

12-Lead ECG √ √ √ √ √ √

Cardiac MRI √ √

X-ray √ √ √ √ √ √ √

Echocardiography √ √ √ √ √ √

Cardiac catheterization with Angiography

√ √

TPV procedure √

Procedural success evaluation

√

Clinical evaluation

NYHA classification √ √ √ √ √ √

Concomitant med. √ √ √ √ √ √ √

Adverse event/SAE √ √ √ √ √ √

Pulsta Valve

Outer Diameter

(mm)

Total Length (mm)

Flare Diameter

(mm)

Expansion Force (gf)

Compression Force (gf)

TPV18 Ø 18 28 ± 1.4

Ø 22 628 1707

TPV20 Ø 20 Ø 24 630 1758

TPV22 Ø 22 31 ± 1.55

Ø 26 448 1468

TPV24 Ø 24 Ø 28 452 1540

TPV26 Ø 26 33 ± 1.65

Ø 30 473 1713

TPV28 Ø 28 Ø 32 453 1725

First patient – 2016.2.25.

Female/20 years with Tetralogy of Fallot

Two times of open heart surgery

2 months old: TOF total repair

14 years old: pulmonary valvuloplasty for severe

pulmonary regurgitation

NYHA: Ⅲ

Max VO2: 14.9 mL/kg/min

First patient – 2016.2.25.

Before procedure

Severe pulmonary regurgitation, PR fraction: 38.4%

Enlarged Rt. Ventricle: End-diastolic volume – 181.7 mL/m2

End-systolic volume – 89.9 mL/m2, EF- 50.5%

Deployment of Pulsta Valve

Full deployment Partial deployment and positioning

Hemodynamic study after PPVR

3D valve motion from TEE MPA angiogram

Chest PA change – 1st case, 20 yr-old female

6 month after CT ratio: 48.8%

Pre- procedure CT ratio: 54.3%

• NYHA: Ⅲ • Max VO2: 14.9 mL/kg/min

• NYHA: Ⅰ • Max VO2: 25.8 mL/kg/min

First patient – 6 Mo. F/U

RV End-diastolic volume: 181.7 mL/m2 126.7 mL/m2

Catheter Cardiovasc Interv. 2017 Feb 1.[Epub ahead of print]

SNUCH-TaeWoong valved-stent (Pulsta valve) in pulmonic position – A feasibility study

Age, year

B.Wt. kg

RVEDVi, pre

mL/m2

PRF, %

NYHA, pre

PA root, mm

Max. VO2, ml/kg/min

Valve D,

mm

Procedure time, min

Fluoro time, min

1 20 39.6 181.7 38.4 3 25 14.9 28 103 31.5

2 19 40.6 167.5 56 3 22.6 16.9 26 69 20.2

3 26 60 205.9 39 1-2 23.3 33.1 26 87 31.9

4 26 61.5 179 42.4 1-2 22.4 30.9 26 95 24.5

5 22 81 209.8 47 1-2 24 27.3 28 60 17.7

6 23 68.4 182.4 46.3 2 24 21 28 75 28.4

7 18 56 187.3 35.4 2 23.1 23.6 28 57 14.5

8 13 46 195 45 2 23.6 23.4 26 93 22.3

9 36 68 171.3 56 2 23 25.2 26 73 18.8

10 15 66 161 40.1 1 24.5 36.8 28 75 20.1

RVEDVi: indexed RV end-diastolic volume, PRF: PR fraction, PA: pulmonary artery, D: diameter

RV indexed end-diastolic volume Follow-up – 10 patients

167.5

112.6

205.9

159.5

179

103.2

182.4

125

209.8

124.9

195

124.3

187.3

122.6

161

128

171.3

141.6

100

125

150

175

200

225

Pre 6 Mo.

1st

2nd

3rd

4th

5th

6th

7th

8th

9th

10th

mL/m2

182

127

RV indexed end-diastolic volume Follow-up – 10 patients

167.5

112.6

205.9

159.5

179

103.2

182.4

125

209.8

124.9

195

124.3

187.3

122.6

100

125

150

175

200

225

Pre 6 Mo.

1st

2nd

3rd

4th

5th

6th

7th

8th

mL/m2

182

127

Mean: 184.1

Mean: 126.8

- 57.3 mL/m2

31.1% decrease

5

3

6 5

12

7

1 0

9

4

0

2

4

6

8

10

12

14

Pre 6 Mo.

1st

2nd

3rd

4th

5th

6th

7th

8th

9th

10th

mmHg

RV-PA peak pressure gradient Follow-up – 10 patients

11

2

12

Adverse Events

• Abdominal pain

• Anorexia

• Both inguinal bruise

• Bradycardia

• Chest discomfort

• Chest tightness

• Chilling

• Dizziness

• Dyspnea

• Fever

• General ache

• Headache

• Heartburn

• Hypotension

• Left chest pain

• Nausea

• A-line removal site pain

• Pharynx ulcer

• Premature Ventricular Contraction (PVC)

• Left arm cold sensation

• Right eye pain

• Sinus tachycardia

• Tingling sense in both legs

• Urticaria

• Ventricular tachycardia

• Vomiting

Total AEs: 50 times, 10 subjects

One Serious AE: admission due to duodenal ulcer in a 15 year-old boy

(aggravated by Plavix?), Not device-related

Merit of Pulsta Valve!

Multiple steps of specific tissue treatment

anticipate longer durability

Easy feasibility for stent implantation - Not bulky, Not long

Can be implanted in the patients with branch PA stenosis,

even in the triangular shape main PA

Low profile delivery catheter – 18 Fr. for 28 mm valve

Low risk of stent fracture due to knitted stent nature

Can be applied in the prosthetic valve after pre-stenting

Ideal shape to do re-do percutaneous PVR

Conclusions

New knitted Nitinol-based self-expandable valved

stent (Pulsta valve) for native RVOT lesions is on

the clinical trial in South Korea.

A feasibility study completed on April. 2017

Short-term result is good until now

No serious adverse event associated with Pulsta

valve occurred until now.

Multi-center study is on-going in South Korea