Name: transcatheter pulmonary valve replacement from autologous pericardium with a self-expandable nitinol stent in an adult sheep model
Uploaded: 2022-06-08T13:20:00
Description: Watch this Scientific Journal Video about Transcatheter Pulmonary Valve Replacement from Autologous Pericardium with a Self-Expandable Nitinol Stent in an Adult Sheep Model at JoVE.com

We extend our heartfelt appreciation to all who contributed to this work, both past and present members. This work was supported by grants from the German Federal Ministry for Economic Affairs and Energy, EXIST - Transfer of Research (03EFIBE103). Yimeng Hao is supported by the China Scholarship Council (CSC: 202008450028).

This preclinical study approved by the legal and ethical committee of the Regional Office for Health and Social Affairs, Berlin (LAGeSo). All animals&#160;(Ovis aries) received humane care in compliance with the guidelines of the European and German Laboratory Animal Science Societies (FELASA, GV-SOLAS). The procedure is illustrated by performing autologous pulmonary valve replacement in a 3-year-old, 47 kg, female sheep J.
1. Preoperative management
<ol>
	<li>House...

<ol>
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Cardiovascualar Interventions. 13 (7), 008963 (2020).</li><li>Plessis, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Edwards+SAPIEN+transcatheter+pulmonary+valve+implantation:+Results+from+a+French+registry.">Edwards SAPIEN transcatheter pulmonary valve implantation: Results from a French registry.</a> JACC. Cardiovascular Interventions. 11 (19), 1909-1916 (2018).</li><li>Bergersen, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Harmony+feasibility+trial:+Acute+and+short-term+outcomes+with+a+self-expanding+transcatheter+pulmonary+valve.">Harmony feasibility trial: Acute and short-term outcomes with a self-expanding transcatheter pulmonary valve.</a> JACC. Cardiovascular Interventions. 10 (17), 1763-1773 (2017).</li><li>Cabalka, A. 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This study represents an important step forward in developing a living pulmonary valve for TPVR. In an adult sheep model, the method was able to show that an APV derived from the sheep&#39;s own pericardium can be implanted with a self-expandable Nitinol stent via jugular vein catheterization. In&#160;sheep J, the stented autologous pulmonary valve was successfully implanted in the correct pulmonary position using a self-designed universal delivery system. After implantation, the heart valve of sheep J showed go...

Bonhoeffer et al.1 marked the beginning of transcatheter pulmonary valve replacement (TPVR) in 2000 as a rapid innovation with significant progress toward minimizing complications and providing an alternative therapeutic approach. Since then, the use of TPVR for treating the right ventricular outflow tract (RVOT) or bioprosthetic valve dysfunction has increased rapidly2,3. To date, the TPVR devices currently available on the market have provided satisfying long-term and short-term results for patients with RVOT dysfunction4,5,6. Furthermore, various types of TPVR valves including decellularized heart valves and stem cell-driven heart valves are being developed and evaluated, and their feasibility has been demonstrated in preclinical large animal models7,8. Aortic valve reconstruction using an autologous pericardium was first reported by Dr. Duran, for which three consecutive bulges of different sizes were used as templates to guide the shaping of the pericardium according to the dimensions of the aortic annulus, with the survival rate of 84.53% at the follow-up of 60 months9. The Ozaki procedure, which is considered a valve repair procedure rather than a valve replacement procedure, involves replacing aortic valve leaflets with the glutaraldehyde-treated autologous pericardium; however, when compared to Dr. Duran&#39;s procedure, it improved significantly in measuring the diseased valve with a template to cut fixed pericardium10 and satisfactory results were not only achieved from the adult cases but also pediatric cases11. Currently, only the Ross procedure can provide a living valve substitute for the patient who has a diseased aortic valve with obvious advantages in terms of avoiding long-term anticoagulation, growth potential, and low risk of endocarditis12. But re-interventions may be required for the pulmonary autograft and right ventricle to pulmonary artery conduit after such a complex surgical procedure.
The current bioprosthetic valves that are available for clinical use inevitably degrade over time due to graft-versus-host reactions to the xenogeneic porcine or bovine tissues13. Valve-related calcification, degradation, and insufficiency could necessitate repeated interventions after several years, especially in young patients who would need to undergo multiple pulmonary valve replacements in their lifetime due to the lack of growth of the valves, a property inherent to current bioprosthetic materials14. Furthermore, the currently available, essentially non-regenerative, TPVR valves have major limitations such as thromboembolic and bleeding complications, as well as limited durability due to adverse tissue remodeling which could lead to leaflet retraction and universal valvular dysfunction15,16.
It is hypothesized that developing a native-like autologous pulmonary valve (APV) mounted onto a self-expandable Nitinol stent for TPVR with the characteristics of self-repair, regeneration, and growth capacity would ensure physiological performance and long-term functionality. And the non-toxic crosslinker treated autologous pericardium can awake from the harvesting and manufacturing procedures. To this end, this preclinical trial was conducted to implant a stented autologous pulmonary valve in an adult sheep model with the aim of developing ideal interventional valvular substitutes and a low-risk procedural methodology to improve the transcatheter therapy of RVOT dysfunction. In this paper, sheep J was selected to illustrate the comprehensive TPVR procedure including pericardiectomy and trans jugular vein implantation of an autologous heart valve.

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			<td>10 % Magnesium</td>
			<td>Inresa Arzneimittel GmbH</td>
			<td>PZN: 00091126</td>
			<td>0.02 mol/ L, 10X10 ml</td>
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		<tr>
			<td>10 Fr Ultrasound catheter</td>
			<td>Siemens Healthcare GmbH</td>
			<td>SKU &#160;10043342RH</td>
			<td>ACUSON AcuNav&#8482; ultrasound catheter</td>
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		<tr>
			<td>3D Slicer</td>
			<td>Slicer</td>
			<td>Slicer 4.13.0-2021-08-13</td>
			<td>Software: 3D Slicer image computing platform</td>
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			<td>Adobe Illustrator</td>
			<td>Adobe</td>
			<td>Adobe Illustrator 2021</td>
			<td>Software</td>
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			<td>Amiodarone</td>
			<td>Sanofi-Aventis Deutschland GmbH</td>
			<td>PZN: 4599382</td>
			<td>3- 5 mg/ kg, 150 mg/ 3 ml</td>
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			<td>Amplatz ultra-stiff guidewire</td>
			<td>COOK MEDICAL LLC, USA</td>
			<td>Reference Part Number:THSF-35-145-AUS</td>
			<td>0.035 inch, 145 cm</td>
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			<td>Anesthetic device platform</td>
			<td>Dr&#228;gerwerk AG &#38; Co. KGaA</td>
			<td>8621500</td>
			<td>Dr&#228;ger Atlan A350</td>
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			<td>ARROW Berman Angiographic Balloon Catheter</td>
			<td>Teleflex Medical Europe Ltd</td>
			<td>LOT: 16F16M0070</td>
			<td>5Fr, 80cm (X)</td>
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			<td>Butorphanol</td>
			<td>Richter Pharma AG</td>
			<td>Vnr531943</td>
			<td>0.4mg/kg</td>
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			<td>C-Arm</td>
			<td>BV Pulsera, Philips Heathcare, Eindhoven, The Netherlands</td>
			<td>CAN/CSA-C22.2 NO.601.1-M90</td>
			<td>Medical electral wquipment</td>
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			<td>Crimping tool</td>
			<td>Edwards Lifesciences, Irvine, CA, USA</td>
			<td>9600CR</td>
			<td>Crimper</td>
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			<td>CT</td>
			<td>Siemens Healthcare GmbH</td>
			<td>&#8722;</td>
			<td>CT platform</td>
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			<td>Dilator</td>
			<td>Edwards Lifesciences, Irvine, CA, USA</td>
			<td>9100DKSA</td>
			<td>14- 22 Fr</td>
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			<td>Ethicon Suture</td>
			<td>Ethicon</td>
			<td>LOT:MKH259</td>
			<td>4- 0 smooth monophilic thread, non-resorbable</td>
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			<td>Ethicon Suture</td>
			<td>Ethicon</td>
			<td>LOT:DEE274</td>
			<td>3-0, 45 cm</td>
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			<td>Fast cath hemostasis introducer</td>
			<td>ST. JUDE MEDICAL Minnetonka MN</td>
			<td>LOT Number: 3458297</td>
			<td>11 Fr</td>
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			<td>Fentanyl</td>
			<td>Janssen-Cilag Pharma GmbH</td>
			<td>DE/H/1047/001-002</td>
			<td>0.01mg/kg</td>
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			<td>Fragmin</td>
			<td>Pfizer Pharma GmbH, Berlin, Germany</td>
			<td>PZN: 5746520</td>
			<td>Dalteparin 5000 IU/ d</td>
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			<td>Functional screen</td>
			<td>BV Pulsera, Philips Heathcare, Eindhoven, The Netherlands</td>
			<td>System ID: 44350921</td>
			<td>Medical electral wquipment</td>
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			<td>Glycopyrroniumbromid</td>
			<td>Accord Healthcare B.V</td>
			<td>PZN11649123</td>
			<td>0.011mg/kg</td>
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			<td>Guide Wire M</td>
			<td>TERUMO COPORATION JAPAN</td>
			<td>REF*GA35183M</td>
			<td>0.89 mm, 180 cm</td>
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			<td>Hemochron Celite ACT</td>
			<td>International Technidyne Corporation, Edison, USA</td>
			<td>NJ 08820-2419</td>
			<td>ACT</td>
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			<td>Heparin</td>
			<td>Merckle GmbH</td>
			<td>PZN: 3190573</td>
			<td>Heparin-Natrium 5.000&#160;I.E./0,2&#160;ml</td>
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			<td>Hydroxyethyl starch (Haes-steril 10 %)</td>
			<td>Fresenius Kabi Deutschland GmbH</td>
			<td>ATC Code: B05A</td>
			<td>500 ml, 30 ml/h</td>
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			<td>Imeron 400 MCT</td>
			<td>Bracco Imaging</td>
			<td>PZN00229978</td>
			<td>2.0&#8211;2.5 ml/kg, Contrast agent</td>
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			<td>Isoflurane</td>
			<td>CP-Pharma Handelsges. GmbH</td>
			<td>ATCvet Code: QN01AB06</td>
			<td>250 ml, MAC: 1 %</td>
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			<td>Jonosteril Infusionsl&#246;sung</td>
			<td>Fresenius Kabi Deutschland GmbH</td>
			<td>PZN: 541612</td>
			<td>1000 ml</td>
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			<td>Ketamine</td>
			<td>Actavis Group PTC EHF</td>
			<td>ART.-Nr. 799-762</td>
			<td>2&#8211;5 mg/kg/h</td>
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			<td>Meloxicam</td>
			<td>Boehringer Ingelheim Vetmedica GmbH</td>
			<td>M21020A-09</td>
			<td>20 mg/ mL, 50 ml</td>
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			<td>Midazolam</td>
			<td>Hameln pharma plus GMBH</td>
			<td>MIDAZ50100</td>
			<td>0.4mg/kg</td>
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			<td>MRI</td>
			<td>Philips Healthcare</td>
			<td>&#8722;</td>
			<td>Ingenia Elition X, 3.0T</td>
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			<td>Natriumchloride (NaCl)</td>
			<td>B. Braun Melsungen AG</td>
			<td>PZN /EAN:04499344 / 4030539077361</td>
			<td>0.9 %, 500 ml</td>
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		<tr>
			<td>Pigtail catheter</td>
			<td>Cordis, Miami Lakes, FL, USA</td>
			<td>REF: 533-534A</td>
			<td>5.2 Fr 145 &#176;, 110 cm</td>
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			<td>Propofol</td>
			<td>B. Braun Melsungen AG</td>
			<td>PZN 11164495</td>
			<td>20mg/ml, 1&#8211;2.5 mg/kg</td>
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			<td>Propofol</td>
			<td>B. Braun Melsungen AG</td>
			<td>PZN 11164443</td>
			<td>10mg/ml, 2.5&#8211;8.0 mg/kg/h</td>
		</tr>
		<tr>
			<td>Safety IV Catheter with Injection port</td>
			<td>B. Braun Melsungen AG</td>
			<td>LOT: 20D03G8346</td>
			<td>18 G Catheter with Injection port</td>
		</tr>
		<tr>
			<td>Sulbactam- ampicillin</td>
			<td>Pfizer Pharma GmbH, Berlin, Germany</td>
			<td>PZN: 4843132</td>
			<td>3 g, 2.000 mg/ 1.000 mg</td>
		</tr>
		<tr>
			<td>Sulbactam/ ampicillin</td>
			<td>Instituto Biochimico Italiano G Lorenzini S.p.A. &#8211; Via Fossignano 2, Aprilia (LT) &#8211; Italien</td>
			<td>ATC Code: J01CR01</td>
			<td>20 mg/kg, 2 g/1 g</td>
		</tr>
		<tr>
			<td>Surgical Blade</td>
			<td>Brinkmann Medical ein Unternehmen der Dr. Junghans Medical GmbH</td>
			<td>PZN: 354844</td>
			<td>15 #</td>
		</tr>
		<tr>
			<td>Surgical Blade</td>
			<td>Brinkmann Medical ein Unternehmen der Dr. Junghans Medical GmbH</td>
			<td>PZN: 354844</td>
			<td>11 #</td>
		</tr>
		<tr>
			<td>Suture</td>
			<td>Johnson &#38; Johnson</td>
			<td>Hersteller Artikel Nr. EH7284H</td>
			<td>5-0 polypropylene</td>
		</tr>
	</tbody>
</table>

transcatheter pulmonary valve replacement from autologous pericardium with a self-expandable nitinol stent in an adult sheep model

Transcatheter pulmonary valve replacement has been established as a viable alternative approach for patients suffering from right ventricular outflow tract or bioprosthetic valve dysfunction, with excellent early and late clinical outcomes. However, clinical challenges such as stented heart valve deterioration, coronary occlusion, endocarditis, and other complications must be addressed for lifetime application, particularly in pediatric patients. To facilitate the development of a lifelong solution for patients, transcatheter autologous pulmonary valve replacement was performed in an adult sheep model. The autologous pericardium was harvested from the sheep via left anterolateral minithoracotomy under general anesthesia with ventilation. The pericardium was placed on a 3D shaping heart valve model for non-toxic cross-linking for 2 days and 21 h. Intracardiac echocardiography (ICE) and angiography were performed to assess the position, morphology, function, and dimensions of the native pulmonary valve (NPV). After trimming, the crosslinked pericardium was sewn onto a self-expandable Nitinol stent and crimped into a self-designed delivery system. The autologous pulmonary valve (APV) was implanted at the NPV position via left jugular vein catheterization. ICE and angiography were repeated to evaluate the position, morphology, function, and dimensions of the APV. An APV was successfully implanted in&#160;sheep J. In this paper, sheep J was selected to obtain representative results. A 30 mm APV with a Nitinol stent was accurately implanted at the NPV position without any significant hemodynamic change. There was no paravalvular leak, no new pulmonary valve insufficiency, or stented pulmonary valve migration. This study demonstrated the feasibility and safety, in a long-time follow-up, of developing an APV for implantation at the NPV position with a self-expandable Nitinol stent via jugular vein catheterization in an adult sheep model.

In sheep J, the APV (30 mm in diameter) were successfully implanted in the &#34;landing zone&#34; of the RVOT.
In sheep J, the hemodynamics remained stable throughout the left anterolateral minithoracotomy under general anesthesia with ventilation, as well as in the follow-up MRI and ICE (Table 1, Table 2, and Table 3). Autologous pericardium measuring 9 cm x 9 cm was harvested and trimmed by removing extra tissue (Figure ...

Watch this Scientific Journal Video about Transcatheter Pulmonary Valve Replacement from Autologous Pericardium with a Self-Expandable Nitinol Stent in an Adult Sheep Model at JoVE.com

Transcatheter Pulmonary Valve Replacement from Autologous Pericardium with a Self-Expandable Nitinol Stent in an Adult Sheep Model

This study demonstrates the feasibility and safety of developing an autologous pulmonary valve for implantation at the native pulmonary valve position by using a self-expandable Nitinol stent in an adult sheep model. This is a step toward developing transcatheter pulmonary valve replacement for patients with right ventricular outflow tract dysfunction.

Transcatheter pulmonary valve replacement has been established as a viable alternative approach for patients suffering from right ventricular outflow ...

This protocol demonstrates an autologous pulmonary valve with specific characteristics, such as self-repair, regeneration, and growth capacity, to ensure physiological performance and long-term functionality in our patients requiring TPVR. The autologous pulmonary valve can prevent tissue rejection, enable regenerative potential due to living endogenous cells, and does not require any medication intake. This method will provide a longer life expectancy of the implanted heart valve in the treatment of younger patients with right ventricular outflow tract that is dysfunctional.The autologous heart valve can be modified for transcatheter aortic valve implantation, which can benefit millions of patients suffering from aortic valve disease. To test the autologous pulmonary valve before implantation, hold the stented valve with a surgical tweezer. Lift and leave the valve in 0.9%sodium chloride to test the commissures for sufficient opening and closing of the orifice.Next, evaluate the degree of native valvular regurgitation in the vena contracta by intra-cardiac echocardiography. Using fluoroscopy via a portable C-arm, perform angiography of the right ventricle and pulmonary artery to guide the implantation. Also, perform functional screen by measuring the diameters of the right ventricular outflow tract, native pulmonary valve annulus, pulmonary bulb, sino-tubular junction, and supervalvular pulmonary artery and identify the landing zone.Then, advance the loaded delivery system via the pre-shaped guide wire through the right ventricular inflow tract and the right ventricular outflow tract to the position of the native pulmonary valve. Retract the cover tube of the delivery system and deploy the autologous pulmonary valve slowly and directly over the native pulmonary valve in the landing zone at the end of the diastolic phase under fluoroscopic guidance After deployment, carefully retract the tip of the delivery system into the cover tube and retrieve it from the sheep. Repeat intra-cardiac echocardiography and post-implantation angiography for the right ventricle and pulmonary artery.Follow up post-implantation by performing cardiac-computed tomography to evaluate the stent position and the deformation of the right heart throughout the entire cardiac cycle. Also, assess the relationship between the pulmonary artery and left coronary artery from the final computed tomography. Autologous pulmonary valves were successfully implanted in adult sheep.Stable hemodynamics throughout the left antero-lateral mini-thoracotomy and after implantation indicated the well-being of the animals. Intra-cardiac echocardiography and angiography assessment immediately after valve deployment showed no signs of paravalvular leak, no pulmonary valve insufficiency, and no valve migration. Post-implantation cardiac-computed tomography showed that implanted stent was anchored in the targeted position without migration.Final CT analysis showed that blood flow in the left anterior descending artery and left circumflex artery was unaffected throughout the cardiac cycle. The implanted stented autologous pulmonary valve demonstrated favorable function and hemodynamics in the right cardiac system, with only a 5 to 10%regurgitation fraction in follow-up magnetic resonance flow measurements and intra-cardiac echocardiography. For this procedure, it's crucial to harvest the autologous tissue, manufacture a 3D-shaped autologous heart valve, and implant it to the native pulmonary position.This method will pave the way for the development of a regenerative autologous pulmonary valve replacement that provides a lifetime solution for children with a congenital heart defect.

Research

JoVE Journal

Medicine

Human Internal Mammary Artery (IMA) Transplantation and Stenting: A Human Model to Study the Development of In-Stent Restenosis

Human Internal Mammary Artery IMA Transplantation and Stenting: A Human Model to Study the Development of In-Stent Restenosis

Preclinical in vivo research models to investigate pathobiological and pathophysiological processes in the development of intimal hyperplasia after vessel ...

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Despite  the considerable progress made in the stent development in the last decades,  cardiovascular diseases remain the main cause of death in western ...

Transplantation of Pulmonary Valve Using a Mouse Model of Heterotopic Heart Transplantation

Tissue engineered heart valves, especially decellularized valves, are starting to gain momentum in clinical use of reconstructive surgery with mixed ...

An Improved Method for Rapid Intubation of the Trachea in Mice

Despite some anatomical and physiological differences, mouse models continue to be an essential tool for studying human lung disease. Bleomycin toxicity ...

Full-root Aortic Valve Replacement by Stentless Aortic Xenografts in Patients with Small Aortic Roots

In patients with small aortic roots who need an aortic valve replacement with biological valve substitutes, the implantation of the stented pericardial ...

Standardized Technique of Aortic Valve Re-implantation for Valve-sparing Aortic Root Replacement

Despite the obvious advantages of the preservation of a normal aortic valve during aortic root replacement, the complexity of valve sparing procedures ...

Improved Registration of 3D CT Angiography with X-ray Fluoroscopy for Image Fusion During Transcatheter Aortic Valve Implantation

The fusion of 3D anatomical models derived from high-fidelity pre-interventional computed tomography angiography (CTA), and x-ray (XR) fluoroscopy to ...

An Image Guided Transapical Mitral Valve Leaflet Puncture Model of Controlled Volume Overload from Mitral Regurgitation in the Rat

Mitral regurgitation (MR) is a widely prevalent heart valve lesion, which causes cardiac remodeling and leads to congestive heart failure. Though the ...

An Intact Pericardium Ischemic Rodent Model

This protocol has shown that the pericardium and its contents play an essential anti-fibrotic role in the ischemic rodent model (coronary ligation to ...