1. Aimee K. Armstrong, MD, FACC, FSCAI
Novel Transcatheter Technologies for Congenital Heart Disease: What's on the Horizon?
Aimee K. Armstrong, MD, FACC, FSCAI
Director, Cardiac Catheterization & Interventional Therapies
Nationwide Children’s Hospital
Associate Professor of Pediatrics, The Ohio State University
There are a lot of novel transcatheter technologies for CHD on the horizon, so I’m going to jump right in.

2. Disclosure Statement of Financial Interest
Proctor/Consultant:
Abbott
  B. Braun Interventional Systems Inc.
Edwards Lifesciences
Research Support:
Medtronic Inc.
pfm medical, Inc.

3. GORE CARDIOFORM® ASD Occluder
Platinum-filled Nitinol frame with ePTFE membrane
5 sizes designed to treat secundum ASDs mm
Waist adaptable to anatomy
Pivotal phase of ASSURED trial
125 patients in up to 22 US sites
We currently only have one FDA approved device to close large secundum ASDs, but Gore now has the Cardioform ASD occluder, which made of a platinum-filled Nitinol frame and an ePTFE membrane. It comes in 5 sizes to treat defects 8-35 mm in diameter and has a waist that adapts to the ASD anatomy as you see in the center picture. The pivotal phase of the ASSURED trial to study the safety and efficacy of the device is starting to enroll patients later this month. 125 patients will be enrolled at up to 22 US sites.
The occluder portion of the GORE® CARDIOFORM ASD Occluder device consists of a six petal or eight petal platinum-filled nickel-titanium (Nitinol) wire frame covered
with an expandable polytetrafluoroethylene (ePTFE) membrane (Figure 1). The platinum-filled Nitinol wire is a drawn, filled tube of Nitinol with a platinum core (10% of cross-sectional surface area) for enhanced visibility under fluoroscopy. The ePTFE leaflet bag includes a hydrophilic surface treatment to facilitate echocardiographic imaging of the occluder and cardiac structures behind the implant during implantation. When fully deployed, the occluder assumes a right atrial disc and a left atrial disc configuration to prevent shunting of blood
between the right and left atria. The available occluder configurations are capable of treating defects from 8 to 35mm in diameter. The specific configurations of the occluders vary in terms of their maximum intra-disc waist diameter, as well as the intended defect range that they will treat F delivery catheter.
BioStar was made by NMT. So when Gore acquired rights to NMT IP, they got the Biostar. This project has been tabled indefinitely, according to multiple Gore reps. 
There are numerous devices in preclinical from China. Chinese Lantern and PDO Occluder to name two.
CAUTION: Investigational Device. Limited by Federal (or United States) Law to Investigational Use

4. Carag Bioresorbable Septal Occluder
World’s first septal occluder with a bioresorbable framework
PLGA framework with polyester patches
Treats 4-25 mm ASDs and PFOs with self-centering design
Fully retrievable and redeployable
CE mark is pending
We’d really love to have a bioresorbable device that does not have the complications of a metal frame and that allows easy transseptal puncture to the left atrium later in life. The Carag Bioresporbable Septal Occluder is the world’s first septal occluder with a bioresorbable framework, which is made of PLGA. The patches are made of polyester. It can treat Asds and PFOs 4-25 mm in diameter with its self-centering design. It is fully retrievable and redeployable. The first-in-human single center trial was completed in Germany, and CE mark is pending.
World’s first septal occluder which incorporates a bioresorbable framework.
Self-centering device with two foldable polyester covers.
The occluders are locked to each other by a locking mechanism
Framework is made of biodegradable filaments made of PLGA
Can treat up to 25 mm ASDs. Balloon sizing is performed. Peel away introducer. 12F sheath over 0.035” wire.
CBSO is delivered over a 0.018” guidewire. Sheath is pulled back to release it. Discs are locked to each other by a locking mechanism. The placement is checked by push-pull. To release, rotate the controls. Guidewire is kept in position. It can be reattached and repositioned. Guidewire is then removed.
Endothelialization within a few weeks.
Resorption occurs over 20 months (starts at 5 months).
Currently under clinical investigation (May 2014-June 2018). 15 patients with ASD or PFO. Prospective single center pilot clinical study to evaluate the safety and effectiveness of an intracardiac septal closure device with bioresorbable framework in patients with clinically significant ASD or PFO. Primary outcome measure effective closure at 6 months. Study is ongoing but not recruiting. Horst Sievert in Frankfurt, Germany.
May 14, 2014—Carag AG announced the first-in-human use of the Carag bioresorbable septal occluder (CBSO), which was implanted in a clinical investigation led by Prof. Horst Sievert, MD, and Björn Söderberg, MD, at the Cardiovascular Center Frankfurt in Frankfurt am Main, Germany. Two patients with patent foramen ovale underwent the CBSO procedure. The company expects confirmation of the clinical success of the CBSO by fall From a Swiss engineering company.

5. Bioresorbable ASD Device
P(LA/CL)
12 months after implantation in sheep model:
Toshi Shinoka at Nationwide Children’s Hospital has a completely bioresorbable ASD device in preclinical study. The retention discs are made of PLA and PCL, and the occlusive patches made from PGA. Twelve months after implantation in a sheep model, half of the material was still remaining, as it takes 1-2 years to resorb. He is currently developing a transcatheter delivery system that will be in pre-clinical testing this spring.
PLA has degradation period of 1-2 years, so half of the material is still remaining. This device was put through a PFO. They used on-pump beating heart condition. The steel screw will not resorb. It is patented but not published. Still improving the delivery system.
PGA
Device
Courtesy of Toshi Shinoka, MD

6. Histotripsy for ASD Creation
Proof of concept established in animal models
Can create ASDs and VSDs
In final pre-clinical testing before IDE application submitted for HLHS with IAS this year
Sometimes we need to create ASDs instead of closing them, and Gabe Owens and Zhen Xu at the University of Michigan are using histotripsy, which is therapeutic ultrasound, for non-invasive ASD creation. The proof of concept has been established in animal models, and both ASD and VSDs have been created. This is their new integrated imaging and therapeutic system and custom shaped transducer optimized for babies. They are in final pre-clinical testing before their IDE application is submitted for treatment of HLHS and IAS within the next year.
Courtesy of Gabe Owens, MD

7. Perimembranous VSD Device
Nit-Occlud Lê VSD Occluder
Flexible nitinol shaped into a double coil layer
5 distal loop sizes: 8-16 mm (2 mm increments)
Sizing: Coil at least twice the minimal diameter of the VSD
Premounted and delivered from the RV through a 6-7 F sheath
Intended for both muscular and perimembranous VSDs
CE mark in 8/2010
~10,000 devices shipped 8/ /2016
No mortality or complete AV block reported
What’s on the horizon for perimembranous VSD devices? The pfm Nit-Occlud Le (Lay) VSD Occluder is made of flexible nitinol, shaped into a double coil layer, and you can see how it forms on the right, with polyester fibers for rapid occlusion. There are 5 distal loop sizes from 8-16 mm in 2 mm increments. The distal loop must be at least twice the VSD diameter on the RV side. It is premounted and delivered prograde from the RV through a 6-7 F sheath. It is intended for both muscular and perimembranous VSDs. It received CE mark in About 10,000 devices were shipped from , and no mortality or complete AV block has been reported.
 I would respond with stating that the Nit-Occlud VSD is still CE Marked and available worldwide outside of the US & They will be the first to know when more details arise concerning the potential US market-so please stay tuned! As for a defined difference between the PDA and VSD devices, outside of the polyester, the nitinol coil itself is the same with the VSD being a bit stiffer than the PDA.  The reason being, the VSD has a double coil layer at its proximal portion, one inside the other.  The coil itself, compared to other technologies such as the double-umbrella, has been proven to be more gentle to the cardiac anatomy. 

8. PDA Device for Premature Infants
AMPLATZER® Duct Occluder II AS
9 sizes
3, 4, 5 mm waists
4, 5.25, 6.5 mm discs
2, 4, 6 mm lengths
Treats PDAs ≤ 4 mm
4F TorqVue™ sheath
Clinical Trial in US
Up to 10 sites, 50 pts
Pediatric interventionalists would all love to have a great device for closing PDAs in premature infants. There is one, the Amplatzer Duct Occluder II AS, which is available outside the US. It is really the best device available for closing PDAs in premature infants, which are typically type C. It comes in 9 sizes with 3, 4, 5 mm waists and retention discs that are slightly larger. It is much shorter than the AVPII which we are currently using for these PDAs (2mm versus 6mm), so it is less likely to protrude into the aorta or LPA. It treats PDAs ≤ 4 mm in diameter and ≥3 mm in length. It is delivered through a 4F sheath with a flexible delivery cable.
Abbott (formally St. Jude Medical) is initiating a clinical trial to evaluate the safety and effectiveness of the ADO II AS device. The ADO II AS IDE trial will enroll a maximum of 50 patients at up to 10 sites nationwide. Patients in the trial will fall within two study groups:
A minimum of 15 patients ≤2 kg
A minimum of 25 patients >2 kg
Enrollment into the trial is expected to begin very soon.”
Caution: Investigational device. Limited by Federal (or U.S.) law to investigational use. Not available for sale in the U.S.

9. Transcatheter Pulmonary Valves
Anomalies of the RVOT
Tetralogy of Fallot
Truncus Arteriosus
D-TGA, VSD, PS
Others
Pulmonary Stenosis
Pulmonary Atresia
Patched or Native RVOTs
RV–PA Conduit
Virtually all patients will require future procedure(s) to replace the conduit and/or pulmonary valve
~23% of RVOT patients
~77% of RVOT patients
~22% of all CHD patients
~8,800 US births/year
About 22% of all CHD patients have an anomaly of the RVOT. 23% of these require a repair using a RV-PA conduit, and the remainder have a patched RVOT or native RVOT. We have both the Melody transcatheter pulmonary valve and the Sapien XT approved for use in RV-PA conduits and the S3 is being studied in conduits currently in the COMPASSION S3 trial, but we do not have a device approved for use in patched or native RVOTs.

10. TPVs for Patched or Native RVOTs
Harmony™ TPV
Porcine pericardial tissue valve on a self-expanding nitinol frame with polyester cloth covering
22 mm ID
Single device size at this time
Loading funnel collapses valve into 25F coil loading delivery system
The Medtronic Harmony transcatheter pulmonary valve is a porcine pericardial tissue valve on a self-expanding nitinol frame with polyester cloth covering and has a 22 mm internal diameter. There is a single size of the device at this time. A loading funnel collapses the valve into a 25F coil loading delivery system.
Courtesy of John Cheatham, MD

11. TPVs for Patched or Native RVOTs
Harmony™ TPV – EFS Results
20 implants
Severe PR
95% pre-implant decreased to 0% at 12 mo
No more than trivial paravalvular leak at 12 mo
Mean RVOT gradient 15.4 ± 5.6 mmHg at 6 mo and stable at 12 mo
2 re-operations
Pivotal IDE study enrolling now in the US
20 patients underwent implantation in the early feasibility study. 95% of patients had severe PR pre-implant, and no patient had severe PR 12 mo post-implant. There was no more than trivial paravalvular leak at 12 months. And the mean RVOT gradient was 15.4 mmHg at 6 months. 2 patients required reoperation. The pivotal IDE study is enrolling now in the US.
2 reoperation (one for stent fracture with stenosis and one for migration with PVL and “erosion.”)
Courtesy of John Cheatham, MD

12. TPVs for Patched or Native RVOTs
Beijing Med-Zenith PT Valve
Porcine pericardial tissue valve on nitinol, self-expanding frame lined with porcine pericardium
Valve diameters: 20, 23, & 26 mm
5 frame dimensions with variable widths & lengths
21 F controlled release delivery system
Completed 6-month pre-clinical testing at Nationwide Children’s Hospital
John Cheatham and Beijing Med-Zenith have worked together to develop the PT valve, which is a porcine pericardial tissue valve on a nitinol, self-expanding frame lined with porcine pericardium. The valve sizes are 20, 23, & 26 mm with 5 frame dimensions with variable widths & lengths. It is delivered on a 21 F controlled release delivery system and has completed 6-month pre-clinical testing at Nationwide Children’s Hospital. A clinical trial in China is expected this year.
6 lambs implanted Nov 2015 – Feb 2016
Modifying delivery system
Evaluating design of frame
Clinical trial in China in 2017 after CFDA approval
Courtesy of John Cheatham, MD

13. TPVs for Patched or Native RVOTs
Venus-P Valve　
Porcine pericardial tissue valve on nitinol, self-expanding frame covered with porcine pericardium
Valve diameters: mm in 2 mm increments
20-35 mm straight section lengths
20-22F controlled release delivery system
Being studied in Asia and Europe (~100 implants world-wide)
CE study enrolling
The Venus P-valve is being studied in China. This is a porcine pericardial tissue valve on a nitinol, self-expanding frame covered with porcine pericardium, except for the distal cells. The valve diameters are mm in 2 mm increments with each diameter available in 20 and 30 mm straight section lengths. It is delivered on a 20-22F controlled release delivery system, depending on the size of the valve.
The proximal and distal flare diameters are 10 mm larger than the middle segment. 20–22 Fr capsule and a 16 Fr 100-cm-long shaft. The selected valve diameter was 2–4mm
larger than the balloon inflation diameter at its waist, whereas the selected mid-body length was equivalent to the distance from the right ventricular outflow tract to pulmonary artery bifurcation.
Maximal RVOT sizing of mm by balloon sizing with no coronary compression. There have been 47 patients enrolled in the Chinese study as of April 2016, and data are being analyzed. 46 patients have been implanted outside of China between were successful. 1 was aborted prior to implant and 2 experienced valve migration.
11 centers in 6 countries (Thailand, UK, India, etc). CE study was recently started.
Courtesy of Ziyad Hijazi, MD

14. Tissue Engineered Valves For Fetuses
What about transcatheter pulmonary valves for fetuses? Simon Hoerstrup in Zurich and Chris Breuer at Nationwide Children’s Hospital are working on tissue engineering pulmonary valves to be implanted into fetuses percutaneously through a RV apical approach. This is all in the very early stages but we are hoping to see this in humans in the next 5 years.
Weber et al. Placenta 32, 2011, S
Courtesy of Christopher Breuer, MD and Simon Hoerstrup, MD

15. Thank You!