Expert Review of Medical Devices
`
`ISSN: 1743-4440 (Print) 1745-2422 (Online) Journal homepage: http://www.tandfonline.com/loi/ierd20
`
`An up-to-date overview of the most recent
`transcatheter implantable aortic valve prostheses
`
`Esther M.A. Wiegerinck, Floortje Van Kesteren, Martijn S. Van Mourik, Marije
`M. Vis & Jan Baan Jr
`
`To cite this article: Esther M.A. Wiegerinck, Floortje Van Kesteren, Martijn S. Van Mourik,
`Marije M. Vis & Jan Baan Jr (2016) An up-to-date overview of the most recent transcatheter
`implantable aortic valve prostheses, Expert Review of Medical Devices, 13:1, 31-45, DOI:
`10.1586/17434440.2016.1120665
`To link to this article: http://dx.doi.org/10.1586/17434440.2016.1120665
`
`© 2016 The Author(s). Published by Informa
`UK Limited, trading as Taylor & Francis
`Group
`
`Accepted author version posted online: 15
`Nov 2015.
`Published online: 11 Jan 2016.
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`Date: 14 September 2017, At: 15:13
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`Edwards Lifesciences Corporation, et al., Exhibit 1053, p. 1 of 16
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`

`

`Esther M.
`A. Wiegerinck ,
`Floortje Van Kesteren,
`Martijn S. Van Mourik,
`Marije M. Vis and
`Jan Baan Jr*
`Heart Center, Academic Medical
`Center, University of Amsterdam,
`Amsterdam, the Netherlands
`*Author for correspondence:
`j.baan@amc.nl
`
`Review
`
`An up-to-date overview of
`the most recent transcatheter
`implantable aortic valve
`prostheses
`
`Expert Rev. Med. Devices 13(1), 31–45 (2016)
`
`Over the past decade transcatheter aortic valve implantation (TAVI) has evolved towards the
`routine therapy for high-risk patients with severe aortic valve stenosis. Technical refinements
`in TAVI are rapidly evolving with a simultaneous expansion of the number of available devices.
`This review will present an overview of the current status of development of TAVI-prostheses;
`describes the technical features and applicability of each device and the clinical data available.
`
`KEYWORDS: Transcatheter aortic valve implantation ● aortic stenosis ● devices ● transcatheter valves
`
`Background
`For patients with severe aortic valve stenosis
`(AoS), considered inoperable or high risk for sur-
`gery,
`transcatheter aortic valve implantation
`(TAVI) is a firmly established minimal invasive
`treatment option. In TAVI, the aortic valve is not
`excised; instead, a bioprosthetic valve is implanted
`over the native valve via a transcatheter procedure.
`The first TAVI was performed in Rouen by
`Cribier in 2002.[1,2] A transseptal antegrade
`approach was used for aortic valve insertion in
`the first cases,
`later followed by a retrograde
`approach, with a successful delivery in 90% of
`cases.[3,4] In 2005, gradual expansion of treat-
`ment with the two initial prostheses, the balloon-
`expandable Edwards SAPIEN and the self-
`expanding Medtronic CoreValve, followed.[5–8]
`The safety and efficacy of the Edwards SAPIEN
`and the Medtronic CoreValve were established
`through well-designed randomized control trials
`(RCTs). The Placement of Aortic Transcatheter
`Valves (PARTNER) trials showed noninferiority
`of TAVI compared to surgical aortic valve
`
`replacement in high-risk patients and superiority
`compared to conservative management, including
`balloon valvuloplasty.[9,10] Since these first
`TAVI trials, the technology has been embraced
`and the number of procedures has expanded
`rapidly. Since 2012, TAVI has been incorporated
`into the international guidelines for the treatment
`of severe symptomatic AoS [11] and has evolved
`toward the routine therapy for patients unsuitable
`for surgery or with high-operative risk and more
`than 200,000 procedures have been performed
`worldwide.[12] Various approaches for TAVI
`have emerged: the retrograde transcatheter route
`(mainly transfemoral, subclavian, axillary), the
`directly aortic approach, via a mini-sternotomy,
`and the antegrade transapical cardiac route, via a
`mini lateral thoracotomy. Preprocedural imaging
`of the transfemoral trajectory and cardiac anatomy
`with a CT scan has become key in the preoperative
`assessment for these minimally invasive proce-
`dures.[13] Currently, the retrograde transfemoral
`approach is the most frequently exploited and least
`invasive technique and can be performed under
`
`Esther M.A. Wiegerinck and Floortje van Kesteren are equally contributed to this paper.
`This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-
`NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial
`re-use,
`distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered,
`transformed, or built upon in any way.
`
`www.tandfonline.com 10.1586/17434440.2016.1120665
`
`© 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
`
`ISSN 1743-4440
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`Review Wiegerinck et al.
`
`local or general anesthesia.[14] However, not all patients have a
`suitable femoral access due to small diameters, calcifications or
`tortuosity of the femoral and iliac arteries. Over the years, femoral
`delivery systems decreased in sheath size; however, a minimal arterial
`lumen diameter of <5.5–6 mm, found at CT scan, remains the most
`important limitation for a transfemoral approach. Valid alternatives
`are the transapical approach, first described in 2006,[15] or the
`transaortic approach as described with the CoreValve,[16] or with
`the Edwards SAPIEN.[17]
`
`Outcomes
`The initial exploratory studies evaluated TAVI procedures, out-
`comes, complications and predictors of adverse outcomes, all in
`their own manner. After the first experience, postoperative
`complications, management and long-term outcomes became
`subject of debate. Although on all-cause mortality TAVI proved
`to be noninferior to surgical aortic valve replacement, it was
`traditionally associated with a higher incidence of vascular com-
`plications and echographically determined postprocedural para-
`valvular regurgitation as compared to conventional cardiac
`surgery.[2,18] Therefore, both complications have been intro-
`duced as the “Achilles heel” of TAVI procedures.
`A major breakthrough in the research field was the consensus
`document of the Valve Academic Research Consortium (VARC) in
`2011 [19] with a revision in 2012 (VARC 2).[20] The VARC
`comprises
`an independent
`collaboration between US and
`European Academic Research organizations and cardiology and
`cardiac surgery societies. Their consensus criteria were developed
`to improve comparability and interpretability of study results.
`Important complications were identified, partly based on what was
`known from conventional surgery. Furthermore, the first research
`end points were defined in the VARC consensus document. The
`VARC-2 criteria describe updated definitions of important end
`points including mortality, myocardial infarction, stroke, bleeding
`complications, acute kidney injury, vascular complications, conduc-
`tion disturbances and arrhythmias and prosthesis performance.[21]
`In addition, quality of life and echocardiographic criteria are pro-
`vided for the evaluation of prosthetic valve function including
`quality of life questionnaires, criteria for re-stenosis, paravalvular
`regurgitation and regular follow-up assessment.[21]
`
`Prostheses
`Various anatomic considerations are to be taken into account in
`developing transcatheter devices, such as the access to the dis-
`eased valve [22,23] adjacent structures, the coronary arteries, the
`pressure regimen that complicates anchorage of the device,[24]
`and, finally, considerations regarding underlying disease. Since
`the first TAVI procedure, multiple prostheses have been devel-
`oped and adapted. Prosthesis function and characteristics can
`have a crucial influence on indications as well as prognosis. In
`conventional valvular surgery, assessment of device function has
`always been of considerable interest. This has resulted in valu-
`able advancements
`in device development.
`In the rapidly
`expanding field of TAVI, evaluation of prostheses is, therefore,
`of uttermost importance.
`
`Currently, several new generation valves have been intro-
`duced in an attempt to refine the procedure and reduce com-
`mon TAVI complications. The authors will evaluate both the
`prostheses used with the initial TAVI experience and the most
`commonly used new-generation prostheses with a glance on
`possible future devices (Table 1).
`
`Initial prostheses
`SAPIEN/SAPIEN XT
`The first TAVI was performed in 2002 with the Cribier–
`Edwards valve (Edwards Lifesciences Inc., Irvine California,
`USA). After this initial experience, the Edwards Company
`developed the Edwards SAPIEN. The first RCT in TAVI
`(PARTNER I), as mentioned above, was conducted with this
`prosthesis.[9,10] The PARTNER randomized trial, cohort B of
`358 patients, confirmed the superiority of the transfemoral
`TAVI compared with standard medical therapy with regard to
`overall survival and cardiac functional status. Cohort A showed
`noninferiority of TAVI compared to surgical aortic valve repla-
`cement in 699 patients with high surgical risk. The Edwards
`SAPIEN received CE mark in 2007 and FDA approval in the
`US in October 2012. The Edwards SAPIEN prosthesis consists
`of three bovine pericardial leaflets, mounted on a stainless steel
`stent. Using a crimper, the prosthesis is crimped around the
`catheter and is expanded by inflation of a balloon during rapid
`pacing. Radial force ensures fixation to the aortic annulus. The
`prosthesis can be
`implanted by retrograde or antegrade
`approach. The Edwards SAPIEN-XT subsequently followed
`the SAPIEN valve. The stainless steel frame was replaced by
`cobalt chromium, making the frame thinner, stronger and com-
`pressible. The refinement of the stent frame has resulted in a
`lower prosthesis profile with a smaller diameter delivery system
`that depends on valve size.[25] Important progress in reducing
`vascular adverse events was made with the introduction of the
`subsequent SXT-THV, as demonstrated in the PARTNER IIB
`trial (Figure 1).
`Recently, the 5-year results of the PARTNER I trial were pub-
`lished as follow-up data of cohort A with 699 patients with high
`surgical risk, as well as of cohort B with 358 inoperable patients.
`In patients participating in cohort A, the risk of all-cause mortal-
`ity in the TAVI group was 67.8% compared with 62.4% in the
`patients treated by surgical aortic valve replacement. Moderate or
`severe aortic regurgitation was significantly more frequent in
`patients treated by TAVI (14% vs 1%) and was associated with an
`increased 5-year risk of mortality in the TAVI group.[26] In addi-
`tion, the durability of the prosthesis was reported; hemodynamic
`benefit after TAVI was proven by echocardiographical assessment.
`There was no evidence of structural valve deterioration, and the
`mean gradient over the prosthesis remained low (11 mmHg).[26] In
`the patients participating in cohort B, the risk of all-cause mortality
`at 5 years was 71.8% in the TAVI group versus 93.6% in the
`standard treatment group. Of the survivors in the TAVI group,
`86% had New York Heart Association (NYHA) class 1 or 2
`symptoms compared with 60% in the standard treatment
`group.[27]
`
`32
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`Overview of the most recent transcatheter implantable aortic valve prostheses Review
`
`Table 1. Overview of transcatheter aortic valve implantation prostheses.
`Prosthesis
`Indication Valve material
`Balloon-expandable/
`Approach
`self-expandable
`Porcine pericardium Self-expandable
`
`Transfemoral
`
`Transfemoral
`Transfemoral/ transapical/
`transaortic
`Transfemoral/ transapical/
`transaortic
`Transfemoral/ transapical/
`transaortic
`Transfemoral
`Transfemoral/transapical
`
`CE
`mark
`2007
`
`2013
`2007
`
`First in
`human
`2004
`
`2012
`2007
`
`2011
`
`2011
`
`2014
`
`2014
`
`2012
`2011
`
`2011
`2009
`
`AoS
`
`Medtronic
`CoreValve
`CoreValve Evolut R AoS
`Edwards SAPIEN
`AoS
`
`Edwards SAPIEN
`XT
`Edwards SAPIEN 3 AoS
`
`AoS
`
`Portico
`JenaValve
`
`JenaValve
`
`AoS
`AoS
`
`AoR
`
`Lotus Valve system AoS
`Acurate (Symetis)
`AoS
`
`Acurate (Symetis)
`
`AoS
`
`AoS
`
`AoS
`
`Medtronic
`Engager
`Direct Flow
`Medical
`Edwards CENTERA AoS
`Colibri Heart Valve AoS
`Heart leaflet
`AoS
`technology
`Vanguard valve
`Trinity valve
`Innovare valve
`AorTech valve
`UCL TAV
`Perc Valve
`
`AoS
`AoS
`AoS
`AoS
`AoS
`AoS
`
`Porcine pericardium Self-expandable
`Bovine pericardium Balloon-expandable
`
`Bovine pericardium Balloon-expandable
`
`Bovine pericardium Balloon-expandable
`
`Self-expandable
`
`Porcine pericardium Self-expandable
`Porcine native aortic
`Self-expandable
`valve leaflets
`Porcine native aortic
`valve leaflets
`Bovine pericardium Self-expandable
`Porcine native aortic
`Self-expandable
`valve leaflets
`Porcine native aortic
`valve leaflets
`Bovine pericardium Self-expandable
`
`Self-expandable
`
`Transfemoral/transapical
`
`2013
`
`2009
`
`Transfemoral
`Transapical
`
`Transfemoral
`
`2007
`2009
`
`2013
`2011
`
`2013
`
`Transapical
`
`2013
`
`2008
`
`Bovine pericardium Inflation of ring balloons
`
`Transfemoral
`
`2013
`
`2006
`
`Bovine pericardium Self-expandable
`Bovine pericardium Self-expandable
`Porcine pericardium Self-expandable
`
`Transarterially
`Transfemoral
`Transarterially
`
`Bovine pericardium Self-expandable
`Bovine pericardium Self-expandable
`Bovine pericardium Balloon-expandable
`Biological
`Polymeric leaflets
`Nano-synthesized
`e-nitinol
`
`Self-expandable
`Self-expandable
`
`Transapical
`Transfemoral/transapical
`Transfemoral/transapical
`Transarterially
`Transarterially
`Transapical
`
`2014
`2014
`Awaiting
`
`2011
`
`2009
`
`2012
`2014
`2014
`2015
`2008
`2014
`2006
`2015
`Awaiting Awaiting
`Awaiting Awaiting
`
`AoR: Aortic valve regurgitation.
`
`CoreValve
`The CoreValve (Medtronic Inc., Minneapolis, Minnesota,
`USA) prosthesis is one of the two pioneer prostheses in TAVI
`technology. It was the first transcatheter prosthesis that received
`a CE mark for transfemoral implantation in May 2007 [28] and
`received FDA approval in January 2014. The first-generation
`CoreValve system consisted of bovine pericardium. All more
`recent generations of the prosthesis consist of three porcine
`pericardial leaflets, mounted on a self-expanding nitinol stent.
`The stent is composed of shape memory alloy, acquiring its final
`shape once released. Three segments can be identified; an upper
`
`and lower segment with radial forces to provide stability and to
`anchor the stent, and a middle segment that contains the three
`leaflets and maintains alignment of the leaflets by circumferen-
`tial forces. The prosthesis is crimped by hand, compressed into a
`sheath and positioned by removal of the sheath, usually during
`rapid ventricular pacing. This valve can only be delivered by
`retrograde approach. The Pivotal Trial, conducted in the US,
`was the landmark trial for the CoreValve.[29] Patients with
`symptomatic severe aortic stenosis were classified in an extreme-
`or high-risk cohort. Primary end point was a combined end
`point of all-cause mortality at 1 year. The CoreValve high-risk
`
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`Review Wiegerinck et al.
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`Figure 1. From left upper corner to right: Edwards SAPIEN, Edwards SAPIEN XT, Edwards SAPIEN 3, Medtronic CoreValve,
`Medtronic Evolut-R, Boston Lotus, JenaValve, Medtronic Engager, Edwards CENTERA.
`Reproduced with permission from Edwards Lifesciences, Medtronic Inc. a subsidiary of Medtronic plc, Boston Scientific and
`JenaValve.
`
`trial is the only randomized trial of TAVI versus surgical aortic
`valve replacement to show superior survival of TAVI. This was
`achieved with a numerically lower rate of major stroke and
`statistically superior changes in aortic valve function from base-
`line to 1 year. A significantly reduced risk of 1-year mortality by
`TAVI with CoreValve was
`reported (14.2% vs. 19.1%;
`p = 0.04).[18] A permanent pacemaker was implanted in
`23.7% of patients.[18] The incidence of a new permanent
`pacemaker is high compared to other prosthesis. The origin of
`cardiac conduction disorders after TAVI is thought to be com-
`pression of the endocardium containing the conduction system
`by the prosthesis, the prosthesis–tissue interaction.[30] Both the
`course of the left bundle branch and the proximity of the right
`atrium and the atrioventricular node to the implanted prosthesis
`increase the risk for conduction disorders after TAVI.[31]
`The CoreValve remains the signature Medtronic prosthesis;
`alterations in prosthesis frame height and delivery system were
`realized under the same name. Recently, the all-cause mortality
`up to 5 years was reported with rates of 21% at 1 year, 29% at 2
`years and 55% at 5 years.[32] Prosthetic valve degeneration was
`1.4% at 5 years. At follow-up, 17% required implantation of a
`permanent pacemaker. The CoreValve is currently evaluated in
`
`the surgical replacement and transcatheter aortic valve implanta-
`tion (SURTAVI) trial, comparing TAVI to surgical aortic valve
`replacement in intermediate-risk patients with severe aortic
`stenosis (NCT01586910: full details available at www.clincial
`trials.gov; last verified June 2015).
`In 2013, CoreValve announced the first implants in the
`CoreValve Evolut R Clinical Study. The Evolut R is a recapture-
`enabled valve and delivery system providing the option to recap-
`ture and reposition the CoreValve Evolut R valve during deploy-
`ment.[33] Furthermore, the nitinol frame of the CoreValve Evolut
`R has been redesigned with consistent radial forces, potentially
`reducing stress on the left bundle branch. With this new delivery
`system, transfemoral TAVI can be safely performed in patients
`with iliofemoral diameters as small as 5.4 mm.[34]
`
`Self-expandable versus balloon-expandable devices
`Both the Medtronic CoreValve and the Edwards SAPIEN/
`SAPIEN-XT have been used widely since the first TAVI proce-
`dure in 2002; however, differences in hemodynamic perfor-
`mance as well as device success have been reported.[35–37]
`The three major experiences published thus far—the Milan
`experience, the Pragmatic study and the French TAVI registry
`
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`Overview of the most recent transcatheter implantable aortic valve prostheses Review
`
`—showed no significant differences in both cardiovascular mor-
`tality and all-cause mortality.[36,38,39] However, likewise there
`are studies with contradictory results describing that patients
`who underwent CoreValve implantation had both lower all-
`cause mortality (1.9% vs. 14.3%; p = 0.032) and cardiovascular
`mortality (0.0% vs. 14.3%; p = 0.006) at 30 days follow-up,
`[40] and in a randomized trial published in 2014, describing
`that device success was significantly more likely with the bal-
`loon-expandable rather than the self-expanding valve system
`(95.9% vs. 77.5%), with a lower risk on aortic regurgitation
`(4.1% vs. 18.3%). In this randomized trial, placement of a new
`permanent pacemaker was less frequent in the balloon-expand-
`able valve cohort.[41] At present, it should be concluded that
`the debate on balloon- versus self-expanding systems remains
`ongoing.
`
`Current trials and prostheses
`SAPIEN 3
`The Edwards SAPIEN 3 valve (Edwards Lifesciences Inc., Irvine
`California, USA) is a next-generation balloon-expandable valve
`with a design based on the SAPIEN/SAPIEN XT. The valve was
`first used in January 2012 and received CE mark in January
`2014 [42] with FDA approval in June 2015. The prosthesis can
`be used for transfemoral, transaortic and transapical access. It is
`currently available in four sizes: 20, 23, 26 and 29 mm and for
`the transfemoral access delivered in a low-profile access sheath of
`14 F (or 16 F (29 mm device)). The possibility to deliver
`prosthesis with a 14 F sheath may lower vascular complication
`rates. The design of the valve leaflets and material remained
`bovine pericardium with ThermaFix Tissue Treatment, which
`should reduce calcification of the prosthesis. The frame struts at
`the top of the valve are wide angled and composed of four rows
`and columns for radial strength. Compared to earlier generation
`Edwards prostheses, the enhanced frame geometry allows lower
`delivery profiles with concomitant higher radial strength. This
`serves to maintain the circularity after deployment. The height
`of the valve is increased compared to older Edwards valves. If a
`similar implantation technique is used, this increased height
`may lead to more stent extension in the left ventricular outflow
`tract, which is an important predictor of pacemaker implanta-
`tion.[43] The reported 30-day incidence of pacemaker implan-
`tation for the Edwards 3 is indeed at the high end of normal for
`Edwards valves with currently reported rates ranging from 4.0%
`to 17.2%.[42,44] This is relatively high compared to the results
`of a search among studies using the older generation Edwards
`SAPIEN, reporting a median pacemaker rate of 6% (IQR 5–7).
`[45] In older generation Edwards valves, the lower two-thirds of
`the frame was already covered with an internal polyethylene
`terephthalate (PET) skirt. An innovative aspect of this new
`Edwards prosthesis is the outer skirt of polyethylene terephtha-
`late, aimed to reduce paravalvular leakage.[46] Thus far, this
`adjustment seems to be effective with reported low rates of ≥
`mild postprocedural paravalvular regurgitation of 7% compared
`to 42% in the Edwards XT group [47] and compared with
`other studies with earlier generation valves.[48] Further studies
`
`are required to show the clinical impact of these hemodynamic
`improvements. Recently reported all-stroke rates are similar to
`incidences described for older valve types, varying from 1.1% to
`5.7%. However, the reported most meaningful
`incidence of
`disabling stroke is relatively low varying between 0% and 2%.
`[12,44,49,50]
`Currently, the PARTNER II S3 RCT enrolls intermediate-risk
`and high-risk patients to evaluate the safety and efficacy of the
`SAPIEN 3 system on short and long term. Patient data will be
`collected for 5 years after valve replacement (NCT01314313 full
`details available at www.clincialtrials.gov ; last verified April 2015).
`
`Portico
`Jude Medical, St. Paul,
`The
`self-expanding Portico (St.
`Minnesota, USA) THV has a radiopaque, nitinol stent.[51] CE
`marking was issued in 2012 for the 23 mm valve and in 2013 for
`the 25 mm valve. The stent design has wide-open struts at aortic
`level to limit the risk of coronary ostial occlusion. The stent can
`be resheathed up to 80% of deployment, making reposition of
`the valve after almost complete placement possible. The valve
`leaflets are made of bovine pericardium and are treated with the
`Linx anti-calcification technology (St. Jude Medical). The valve is
`made of porcine pericardium and is implanted and deployed at
`annular level and extents no more than 5 mm into the left
`ventricle. The valve is manually loaded on the catheter. The
`placement catheter has a diameter of 18 F at the valve-loading
`segment, whereas the catheter itself has a 12 F diameter.
`The initial experience showed the repositionability of the
`prosthesis, with a recapture and repositioning in four patients.
`Ten percent had moderate paravalvular regurgitation in this
`small series. No patient required pacemaker implantation.[52]
`Ventricular (rapid) pacing is not required during valve deploy-
`ment.[53] In September 2014, St. Jude temporarily halted the
`implementation of valves worldwide for safety issues and evalua-
`tion of reduced valve leaflet mobility reported on CT scans.
`However, the issue seemed not to occur specifically in the
`Portico; moreover, it was described as a class problem, including
`surgical prosthesis. As a result, in June 2015 the FDA cleared St.
`Jude Medical to resume its study of the Portico.
`
`JenaValve
`The self-expanding JenaValve (JenaValve Technology GmbH,
`Munich, Germany) received CE approval for TAVI in AoS in
`September 2011. It is the only prosthesis that received CE mark
`for aortic regurgitation (September 2013 [54]). The now certi-
`fied JenaValve is a transapical positioned prosthesis, composed
`of a nitinol self-expanding stent and three native porcine aortic
`valves. The device provides the option of repetitive repositioning
`before final release. Rapid pacing is not necessary for positioning
`of this prosthesis. The JenaValve contains a clipping system that
`fixates the stent to the diseased native valve leaflets, a feature
`that creates the opportunity to implant the valve in minimally
`calcified aortic valves.[55] This is in contrast to the aforemen-
`tioned Edwards SAPIEN and Medtronic CoreValve devices, in
`which radial
`forces exerted on the aortic annulus provide
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`Review Wiegerinck et al.
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`alignment and fixation. A transfemoral JenaValve is currently
`being evaluated. The largest series to date using the JenaValve
`involves 88 patients, 79 patients with severe aortic stenosis and
`9 with severe aortic regurgitation. This German experience
`reports a device success of 91% and 10% 30-day mortality.
`[56,57]
`A JenaValve prosthesis for transfemoral use (The JenaValve
`TAVI Plus system) has been successfully implanted in animal
`experiments and currently still a subject of research and will be
`available in three sizes—23, 25 and 27 mm—delivered with an
`18 F catheter consisting of a sleeve that houses the prosthesis
`and a shaft that releases initially the feelers and finally the
`prosthesis during valve deployment.[58]
`
`Lotus
`the Lotus Valve system
`The first-in-man implantation of
`(Boston Scientific Corporation, Marlborough, Massachusetts,
`USA) was in 2007.[59] The system is CE marked; however,
`in the US, it is still an investigational device. It consists of a
`valve prosthesis, preattached to the delivery catheter. The pros-
`thesis is composed of three bovine pericardium leaflets mounted
`in a braided nitinol frame. Currently, the only access route is
`transfemoral. The delivery and anchoring method is based on
`controlled mechanical expansion; by rotating the delivery handle
`manually,
`the prosthesis is unsheathed,
`the device radially
`expands and shortens to achieve the final dimensions. The
`prosthesis is repositionable and retrievable even after full expan-
`sion, and the frame is designed with a central radiopaque marker
`to enable precise positioning. To minimize leakage, the valve is
`covered with an adaptive seal. The prosthesis is designed to
`function early during deployment and rapid pacing is not
`required,
`resulting in minimization of
`the hemodynamic
`changes during the procedure.[60]
`Recently, the REPRISE II published 30-day outcomes in 120
`patients. Successful valve implantation was achieved in all
`patients with a significant improvement in functional NYHA
`classes.[61] The rate of paravalvular leakage was 1.0% of the
`patients, which is considerably lower than rates described in
`literature.[12,48,61] Opponents of repositioning during TAVI
`argue that extra manipulation during the procedure may induce
`strokes. However, this could not be directly deduced from the
`REPRISE II; 30-day incidence of disabling stroke was 1.7%
`compared with 3.2% major strokes in a weighted meta-analysis
`of
`studies using mainly SAPIEN and CoreValve.[12,61]
`Furthermore, stroke rates in the REPRISE II differed not sig-
`nificantly between patients with and without repositioning
`attempts. A major complication of the Lotus valve seems to be
`the high rate of permanent pacemaker implantations after a
`TAVI of 28.6%, which is similar to the rates reported after
`CoreValve implantation but considerably higher than the pace-
`maker implantation rates in trials with the Edwards SAPIEN
`valve.[12,45] The results have to be confirmed in larger trials
`and will be directly compared with other valve systems in the
`REPRISE III, starting as an RCT of the Lotus and CoreValve
`prostheses (NCT02202434 full details available at www.clincial
`
`trials.gov; last verified July 2015). Some interventionalists argue
`that the high rates of pacemaker implantation imply that the
`first clinical Lotus
`implantations
`should be performed in
`patients who already have a permanent pacemaker. This will
`allow the operator to adjust to the implantation technique
`without negative consequences for the patient.
`
`Acurate
`The Acurate (Symetis, Ecublens, Switzerland) is a self-expand-
`able supracoronary prosthesis. The delivery systems consist of a
`flexible shaft for the transapical approach equipped with two
`radio opaque markers and for transfemoral use with an 18 F
`sheath with radio opaque stent holder. The prostheses comprise
`three porcine leaflets, mounted on a nitinol stent with an inner
`and outer impermeable skirt, designed to prevent paravalvular
`regurgitation. The prostheses consist of stabilization arches, an
`upper and lower crown. Once deployed, resheathing, reposition-
`ing and retrieval are not possible.
`Initially, the valve was developed for the transapical access
`route and received the CE mark in 2011,[62–64] with now
`more than 1200 transapical implants. The prosthesis for trans-
`femoral access followed, with a CE mark in 2014. The first-in-
`man study for a transaortic system is expected to start in 2015.
`For the transapical device, clinical follow-up results of 40 patients
`showed a 30-day device success rate, as defined by VARC 1, of
`92.5%, with two valve-in-valve procedures and one moderate leak-
`age after implantation. At 6 months follow-up, 96.7% demon-
`strated either none/trivial or mild paravalvular regurgitation.[65] A
`multicenter registry on 250 patients reported a 30-day mortality rate
`of 6.8%. At least moderate paravalvular regurgitation was reported
`in 2.3% of patients.[65,66] A comparison between the transapical
`systems of Edwards SAPIEN and Acurate among 103 propensity
`matched pairs showed more redilatation after treatment with the
`Acurate device (40% vs. 9%).[67] The first-in-man trial for the
`transfemoral route reports procedural success of 95% in 20 patients,
`with two pacemaker implantations (10%).
`
`Medtronic Engager
`The Engager (Medtronic Inc., Minneapolis, Minnesota, USA) is
`a transapical implantable prosthesis consisting of three bovine
`pericardial leaflets mounted on a self-expandable nitinol frame.
`The prosthesis consists of a main frame and a support frame.
`The main frame in sewn to a polyester sleeve. The support
`frame contains three control arms to fixate and position the
`prosthesis. The prosthesis is available in 23 and 26 mm in size.
`[68] After a successful feasibility study,[69] a European pivotal
`trial was conducted with a total of 61 patients.[70] Overall
`device success, defined by modified VARC criteria, was achieved
`in 94.3%. All-cause mortality was 9.9% at 30 days. The CE
`mark was received in February 2013.
`
`Direct Flow
`The Direct Flow (Direct Flow Medical Inc., Santa Rosa,
`California, USA) has an entirely nonmetallic framework double
`ring design, with upper (aortic) and lower (ventricular) ring
`
`36
`
`Expert Rev. Med. Devices 13(1), (2016)
`
`Downloaded by [208.226.153.28] at 15:13 14 September 2017
`
`Edwards Lifesciences Corporation, et al., Exhibit 1053, p. 7 of 16
`
`

`

`Overview of the most recent transcatheter implantable aortic valve prostheses Review
`
`balloons of Dacron polyester. In between the inflatable rings is
`the bovine pericardial valve. The rings can be pressurized inde-
`pendently through position-fill lumens with saline and contrast
`solution, inducing immediate visibility when inflated. The pros-
`thesis is repositionable and retrievable before anchoring by
`deflation of the cuffs. Rapid pacing is not required for implan-
`tation since the valve leaflets are functional during expansion. A
`specific feature of the Direct Flow Medical is the ability to
`perform TAVI with minimal or no contrast; a feature especially
`favorable in patients with an impaired renal function. The
`Discover trial was the first multicenter nonrandomized study
`of the Direct Flow Medical.[71] The VARC-defined device
`success rate was 93%, and 30-day freedom from VARC-defined
`safety event rate was 91% with an all-cause mortality rate of
`1.0% (1 of 100) at 30 days. In January 2013, the Direct Flow
`Medical has received CE mark.
`
`Future valves at a glance
`CENTERA
`Irvine,
`The Edwards CENTERA (Edwards Lifesciences,
`California, USA) is a self-expandable prosthesis with a radio-
`paque nitinol frame prepack