Transapical Aortic Valve Implantation: An Animal
`Feasibility Study
`Todd M. Dewey, MD, Thomas Walther, MD, PhD, Mirko Doss, MD, David Brown, MD,
`William H. Ryan, MD, Lars Svensson, MD, PhD, Tomislav Mihaljevic, MD,
`Rainer Hambrecht, MD, Gerhard Schuler, MD, Gerhard Wimmer-Greinecker, MD,
`Friedrich W. Mohr, MD, PhD, and Michael J. Mack, MD
`Cardiopulmonary Research Science and Technology Institute, Dallas, Texas, Heart Center Leipzig, Leipzig, Germany, Department
`for Thoracic and Cardiovascular Surgery, JW-Goethe University, Frankfurt, Germany, and Cleveland Clinic Foundation,
`Cleveland, Ohio
`
`Background. Percutaneous aortic valve implantation
`has recently been performed in nonsurgical patients with
`severe aortic stenosis. Retrograde valve delivery has been
`problematic because of the size of the delivery system
`and concomitant peripheral vascular disease. We inves-
`tigated a minimally invasive approach through the left
`ventricular apex for antegrade placement of a device-
`deliverable valve.
`Methods. Transapical aortic valve implantation was
`performed using a 23-mm equine valve mounted on a
`stainless steel stent in 24 swine (weight range, 35 to 45
`kg). A limited or full sternotomy approach was used to
`access the apex of the heart. The crimped valve was
`introduced through a sheath in the left ventricular apex.
`Fluoroscopy and echocardiography were used for guid-
`ance. Deployments were performed on the beating heart
`either with ventricular unloading using femoral extracor-
`poreal circulation or rapid ventricular pacing.
`
`Results. All valves were successfully delivered at the
`selected target site with acceptable visualization of the
`noncalcified aortic annulus. Valve migration occurred
`during eight deployments (two distal and six retrograde)
`secondary to persistent cardiac output, unfavorable an-
`nular anatomy, and dislodgement by the delivery cathe-
`ter. Exact positioning of the nonmigrated valves at the
`aortic annulus was examined by necropsy of all animals
`at the end of the procedures. Paravalvular leak was noted
`in 14 of 18 (77.8%) valves remaining in situ.
`Conclusions. The transapical approach was used for the
`successful antegrade placement of a stented valve, obvi-
`ating the technical problems associated with a large
`delivery system transiting the peripheral vascular sys-
`tem. Stent design contributing to paravalvular leak re-
`mains problematic.
`
`(Ann Thorac Surg 2006;82:110 – 6)
`© 2006 by The Society of Thoracic Surgeons
`
`Aortic valve replacement using cardiopulmonary by-
`
`pass and cardioplegic arrest has been the standard
`approach for the treatment of severe aortic stenosis for
`decades. Increases in overall life expectancy combined
`with a rapidly growing elderly population have increased
`the numbers of patients presenting with calcific degen-
`erative aortic stenosis. Patients now routinely present
`with comorbid illnesses that increase their operative risk
`with standard valve surgery. Although most surgeons
`believe that the preponderance of patients with critical
`aortic stenosis are referred for surgery, there likely exists
`a sizable subset of patients with critical aortic stenosis
`that are never referred for surgical evaluation. Reasons
`identified for nonreferral include an apparent lack of
`patient symptoms, a wish to avoid major surgery on the
`part of the patient, or a perceived prohibitive operative
`risk by the referring cardiologist. Balloon valvuloplasty
`
`Accepted for publication Feb 13, 2006.
`Presented at the Basic Science Forum of the Fifty-second Annual Meeting
`of the Southern Thoracic Surgical Association, Orlando, FL, Nov 10–12,
`2005.
`
`Address correspondence to Dr Dewey, 7777 Forest Lane, Suite A323,
`Dallas, TX 75230; e-mail: tdewey@csant.com.
`
`has been used selectively in some patients considered
`nonoperative candidates. Valvuloplasty achieves an in-
`crease in aortic valve area by the fracturing of calcific
`deposits, separation of commissural fusion, and stretch-
`ing of the aortic root. Unfortunately, widespread adop-
`tion of this technique remains low because of a high
`return of symptoms and restenosis within months of the
`procedure [1–3].
`Recent advances in the field of aortic valve replacement
`have focused on avoiding a sternotomy and minimizing the
`incision size required to reach the valve. Comparative
`reports have demonstrated equivalent perioperative out-
`comes with corresponding reduced length of hospital stay
`using these minimally invasive techniques. Unfortunately,
`the greatest source of potential complications in a high-risk
`population, ie, the use of extracorporeal circulation with
`cardioplegic arrest, remains unchanged.
`Advances in the integration of bioprosthetic valve
`
`Drs Dewey, Doss, and Wimmer-Greinecker disclose
`that they have a financial relationship with Edwards
`Lifesciences.
`
`© 2006 by The Society of Thoracic Surgeons
`Published by Elsevier Inc
`
`0003-4975/06/$32.00
`doi:10.1016/j.athoracsur.2006.02.035
`
`CARDIOVASCULAR
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`ENDOHEART AG, EX. 2036 Page 1
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
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`

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`CARDIOVASCULAR
`
`Ann Thorac Surg
`2006;82:110–6
`
`DEWEY ET AL
`PERCUTANEOUS AORTIC VALVE IN ANIMALS
`
`111
`
`compliance with the NIH “Guide for the Care and Use of
`Laboratory Animals” (revised 1996). All components of
`the transapical animal work that were performed at the
`Edwards Lifesciences facility in Irvine were conducted in
`an American Association for Accreditation of Laboratory
`Animal Care–accredited facility and reviewed by the
`Edwards Institutional Animal Care and Use Committee.
`Experiments in Leipzig had been approved by the local
`government offices.
`Device preparation was completed just before implan-
`tation for an antegrade delivery through the left ventric-
`ular apex. The delivery catheter was first flushed and
`primed using a heparinized saline solution. The deploy-
`ment balloon was then inflated with a 4:1 mixture of
`saline and contrast and purged of air. The balloon was
`then reinflated and compared with a sizing ring to obtain
`the exact amount of saline and contrast to expand the
`balloon to 22 mm. The balloon was then deflated, and a
`partially crimped valve was placed over the balloon
`between two radiopaque markers. The valve is then fully
`crimped to just under 24F to permit passage through the
`delivery sheath (Fig 2). Confirmation of adequate crimp-
`ing was obtained by passing the catheter with the valve
`through a 24F sizing bushing. All valve deployments
`were performed using volumetric inflation of the balloon
`owing to the variability of balloon expansion with pres-
`sure inflation.
`
`Procedure
`The animals were anesthetized, intubated, and placed in
`the dorsal recumbent position. Anesthesia was main-
`tained with inhaled anesthetics and narcotic agents. An
`introducer sheath was placed in the right external jugular
`vein for volume and drug administration. A surgical
`cutdown was performed to cannulate the right internal
`carotid artery for placement of a calibrated pigtail cath-
`eter in preparation for preimplant and postimplant an-
`giography. Intracardiac or epicardial echocardiography
`was performed on all pigs to aid with annular sizing,
`implantation, and evaluation of valve performance after
`
`Fig 2. Fully crimped valve on delivery catheter.
`
`Fig 1. Cribier-Edwards Aortic Bioprosthesis Model 9000.
`
`technology and balloon-expandable stainless steel stents
`have made intervention of the nonoperative patient with
`severe aortic stenosis feasible [4]. Once successfully de-
`livered, the stent valves have demonstrated a significant
`reduction in transvalvular gradients [5]. Additionally,
`valve fixation in the annulus has been stable as evi-
`denced by no reports of migration or embolization of the
`devices. Unfortunately, actual delivery of the device to
`the aortic annulus has been extremely problematic. Ret-
`rograde delivery of this prosthesis has been difficult
`because of the obligatory size of the delivery system and
`anatomic factors such as the diameter of the patients’
`peripheral arterial tree and concomitant occlusive dis-
`ease. Thus, the majority of the procedures to date have
`been performed antegrade using a challenging transsep-
`tal approach to the aortic valve. Although possible, this
`approach places a premium on the individual practitio-
`ners’ experience and skill level with transseptal puncture
`and may not be widely applicable to the average
`operator.
`Previous reports have described the use of the left
`ventricular apex as a reproducible route for minimally
`invasively accessing the aortic annulus [6]. We per-
`formed a series of animal studies validating this ap-
`proach as a valuable technique for facilitating the place-
`ment of a catheter-deliverable aortic stent valve in the
`aortic annulus.
`
`Material and Methods
`Experimental Group and Protocol
`twenty-six
`Transapical aortic valve implantation of
`23-mm Cribier-Edwards Aortic Bioprosthesis (Edwards
`Lifesciences, Irvine, CA; Fig 1) equine valves mounted on
`a stainless steel stent was performed in twenty-four 35- to
`46-kg juvenile swine. Ten procedures were performed at
`the Edwards Lifesciences Biological Resource Center,
`(Irvine, CA), and 14 animals were operated on in the
`experimental animal
`laboratory at the Heart Center,
`Leipzig, Germany. All animals received humane care in
`
`ENDOHEART AG, EX. 2036 Page 2
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`DEWEY ET AL
`PERCUTANEOUS AORTIC VALVE IN ANIMALS
`
`Ann Thorac Surg
`2006;82:110–6
`
`cised and tacked to the chest wall. A double pursestring
`suture of 3-0 polypropylene was placed in the apex of the
`heart to provide hemostasis. The animals were then
`anticoagulated with 300 IU/kg of heparin. Activated clot-
`ting times were measured every 15 to 20 minutes to
`maintain adequate anticoagulation. Cineangiography of
`the aortic root with a calibrated catheter was then per-
`formed to size the aortic annulus. Confirmation of the
`measured annular size was achieved by echocardiogra-
`
`CARDIOVASCULAR
`
`Fig 3. (A) Illustration of guidewire crossing the left ventricular cav-
`ity and into the descending thoracic aorta. (B) Fluoroscopic image of
`guidewire crossing the left ventricular cavity and into the descending
`thoracic aorta.
`
`placement. Femoral cutdowns were performed to access
`the femoral vessels for cannulation in all 11 animals
`placed on cardiopulmonary bypass.
`The apex of the heart was exposed either through a
`ministernotomy that extended from the subxiphoid
`notch cranially for two rib spaces or a full sternotomy to
`facilitate epiaortic ultrasound. The pericardium was in-
`
`Fig 4. (A) Illustration of valve on the delivery catheter crossing the
`aortic annulus. (B) Fluoroscopic image of valve on the delivery cath-
`eter crossing the aortic annulus.
`
`ENDOHEART AG, EX. 2036 Page 3
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
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`
`

`
`CARDIOVASCULAR
`
`Ann Thorac Surg
`2006;82:110–6
`
`DEWEY ET AL
`PERCUTANEOUS AORTIC VALVE IN ANIMALS
`
`113
`
`Fig 5. Fluoroscopic image of valve during deployment.
`
`phy. The animals were selected by weight to provide an
`aortic annulus of between 15 and 21 mm in size. Land-
`marks from the cineangiogram were used to identify the
`noncalcified porcine annulus. Additionally, small puffs of
`contrast were given during implantation to locate the
`annulus for deployment.
`The left ventricle was accessed with an 18-gauge nee-
`dle through the pursestring sutures. A 5F introducer
`sheath was inserted over a small guide wire into the left
`ventricle and secured with snares. This introducer was
`then used to place a 0.035-inch superstiff guidewire
`across the aortic valve and down the descending thoracic
`aorta (Fig 3). Once the stiff wire was positioned, the small
`introducer sheath was then removed. A cruciate incision
`was then made in the apex, and the 24F introducer sheath
`was placed into the left ventricle below the aortic valve
`under fluoroscopic guidance (Fig 4). The crimped valve
`on the delivery catheter was then introduced through the
`delivery sheath and into the left ventricle. The catheter
`has two radiopaque markers to identify the margins of
`the deployment balloon. Cardiac output was then re-
`duced, either by initiating cardiopulmonary bypass or by
`instituting rapid ventricular pacing. Once transaortic
`valve flow had been reduced, as confirmed by loss of
`systolic pressure spike on arterial monitoring, the valve
`was positioned so that the annulus bisected the stent.
`Small boluses of contrast were given to aid in identifying
`the noncalcified porcine annulus and coronary ostia.
`Once positioned, the valve was deployed by inflating the
`delivery balloon with saline mixed with contrast to
`achieve full expansion of the stent (Fig 5). Once deployed,
`the balloon was deflated and rapid ventricular pacing
`discontinued. The stent-valve sits within the confines of
`the native porcine annulus and leaflets. The delivery
`catheter, sheath, and guidewire are then completely
`removed. Pigs on cardiopulmonary bypass are then
`weaned from extracorporeal support. A completion cine-
`angiogram was then performed to assess for paravalvular
`leak (Fig 6) and positioning. Additionally, echocardiog-
`
`Fig 6. Completion angiogram after valve deployment.
`
`raphy was used to evaluate valve function, leaflet motion,
`and regurgitation. The animals were then sacrificed, and
`an examination of the heart was performed to evaluate
`the positioning of the valve and to identify any damage to
`the annulus or adjacent structures.
`
`Results
`The average diameter of the aortic annulus in the juve-
`nile swine was 19.7 ⫾ 1.3 mm as measured using a
`calibrated catheter and cineangiography of the aortic root
`(Table 1). All valves were deployed successfully at the
`intended target site primarily using fluoroscopy. Intra-
`cardiac echocardiography was available for 10 animals
`but did not provide the necessary discrimination of the
`aortic annulus and the delivery catheter to be the pri-
`mary imaging modality for implantation. The first 2
`animals had the valves deployed without maneuvers to
`decrease cardiac output. Of the remaining valve deploy-
`ments, 11 were performed using cardiopulmonary by-
`pass, and 11 were done using rapid ventricular pacing to
`decrease cardiac output and forward flow across the
`aortic annulus. Three animals had ventricular fibrillation
`
`Table 1. Results of Animal Experimentsa
`
`Characteristics
`
`Mean weight (kg)
`Mean annular size (mm)
`None
`CPB
`RVP
`Distal embolization
`LV embolization
`Regurgitation (yes/no)
`Mean regurgitation Value
`
`a Twenty-six valves were deployed in 24 animals.
`CPB ⫽ cardiopulmonary bypass;
`LV ⫽ left ventricle;
`ventricular pacing.
`
`Results
`
`40.0 ⫾ 3.1
`19.7 ⫾ 1.3
`2/24 (8.3%)
`11/24 (45.8%)
`11/24 (45.8%)
`2/26 (7.7%)
`6/26 (23.1%)
`14/18 (77.8%)
`1.8 ⫾ 1.4
`
`RVP ⫽ rapid
`
`ENDOHEART AG, EX. 2036 Page 4
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`DEWEY ET AL
`PERCUTANEOUS AORTIC VALVE IN ANIMALS
`
`Ann Thorac Surg
`2006;82:110–6
`
`shortly after valve placement and completion aortogram,
`and before intended sacrifice, secondary to ostial coro-
`nary artery impingement. A third animal experienced
`fibrillation after the valve migrated proximally into the
`left ventricular cavity.
`Eight of 26 valves (31%) migrated (two distally into the
`ascending aorta, and six proximally into the left ventricle)
`after being deployed in the aortic annulus. The two distal
`migrations were in the first 2 experimental animals in
`which ventricular unloading either with rapid ventricular
`pacing or cardiopulmonary bypass was not used. One of
`the proximal migrations occurred as a result of the delivery
`balloon sticking to the stent and subsequently dragging the
`valve back into the left ventricle as the catheter was being
`removed. The remaining valves were pushed back into the
`left ventricle by systemic pressure once the animal was
`weaned from cardiopulmonary bypass or rapid ventricular
`pacing discontinued. A second valve was subsequently
`successfully deployed into the aortic annulus in 2 animals
`without removing the initial valve from the heart. These
`animals account for 26 valves being deployed into 24 swine.
`One animal experienced fibrillation when the valve mi-
`grated proximally into the left ventricle; the other migra-
`tions were not associated with any adverse hemodynamic
`consequences.
`Paravalvular leak or aortic regurgitation was noted in
`14 of the 18 (77.8%) valves that remained intraannular
`and did not migrate. The degree of regurgitation was
`visually estimated from the completion aortogram per-
`formed after implantation and retention of the valve in
`the annulus. A scale was derived in which mild regurgi-
`tation was denoted as 1⫹, moderate 2⫹, moderate to
`severe 3⫹, and wide open reflux of contrast into the
`ventricle as 4⫹. The mean degree of regurgitation was 1.8
`⫾ 1.4. Only two valves showed severe (4⫹) regurgitation
`secondary to nonfunction of one of the leaflets that
`became trapped by a fold of aorta at the sinotubular
`junction. This occurred in 2 animals with smaller than
`average ascending aortas. The remaining animals exhib-
`ited lesser degrees of paravalvular leak across the annu-
`lus into the left ventricle on completion angiogram. The
`leak primarily appeared to be caused by regurgitation of
`blood back through the stent interstices, thereby going
`around the leaflets in an area not covered by cloth.
`Central leak through the valve was not noted in the
`majority of animals.
`
`Comment
`Percutaneous implantation of a stent type aortic valve
`became a clinical reality with the first reported successful
`human case by Cribier and colleagues in 2002 [4]. Sub-
`sequently, intense interest has formed toward the devel-
`opment of a catheter-delivered valve for use in patients
`with critical aortic stenosis declined for surgery. These
`first-generation devices have now been implanted in
`selected patients worldwide. As with any new device,
`significant questions regarding patient selection, implan-
`tation technique, potential for valve migration, long-term
`affect of paravalvular regurgitation, valve durability, and
`
`what constitutes an acceptable result remain to be
`answered.
`This study was initiated to validate the transapical
`technique as a viable alternative to either an antegrade
`transseptal or a retrograde approach to the aortic valve.
`The majority of cases documented in the literature have
`been performed antegrade, in which the valve travels
`over a superstiff guidewire across the atrial septum,
`through the mitral valve, and ultimately across the aortic
`valve [7]. The wire by necessity forms a loop in the left
`ventricle so that the guidewire becomes coaxial with the
`ventricular outflow tract and the valve is not angulated
`across the annulus. Dramatic hemodynamic deteriora-
`tion has been documented when the loop of wire in the
`ventricle becomes too large and places traction on the
`anterior leaflet of the mitral valve, causing severe mitral
`regurgitation [7]. Another limitation of the transseptal
`technique is that the operator has reduced fine motor
`control over the valve as the intervening loop provides
`significant “play” in the system. Most of the described
`morbidity and mortality of the procedure can be traced to
`the technical difficulty of this challenging approach. Like-
`wise, the retrograde approach can be problematic be-
`cause of the obligatory size of the 24F delivery sheath.
`Many of these elderly patients have coexisting peripheral
`vascular disease that precludes passing large size sheaths
`or catheters from the groin, around the arch of the
`thoracic aorta, and across the aortic valve annulus. More-
`over, this technique also runs the risk of embolizing
`atherosclerotic material from the aorta into the distal
`circulation. However, in patients with adequate vessel
`size and without peripheral vascular disease, a retro-
`grade approach would be the easiest and most direct of
`the percutaneous routes. We believe that the transapical
`approach provides a reliable alternative to either of these
`techniques. The distance of the aortic valve from the left
`ventricular apex is straight and relatively short, which
`provides good control over the delivery catheter. Addi-
`tionally, in this animal series, control over the placement
`of the valve was believed to be optimal, and all valves
`were deployed at the intended target site.
`Valve migration after deployment was seen in eight
`valves for clearly identifiable reasons. The two distal
`embolizations were in animals in which no attempt was
`made to decrease cardiac output during deployment. It
`became quickly obvious that with maintained blood flow
`across the aortic valve, the deployment balloon acts like a
`sail and carries the valve distally into the ascending aorta.
`Once measures such as cardiopulmonary bypass or rapid
`ventricular pacing were instituted to decrease cardiac
`output during deployment, no further distal emboliza-
`tions were noted. Likewise, the six episodes in which the
`valve migrated into the ventricle could primarily be
`attributed to the animal model. On one occasion, early in
`the experience, a valve was crimped too tightly to the
`delivery catheter, so that on deployment the valve stuck
`to the balloon and was pulled back into the ventricle on
`removal of the catheter. The rest of the valve migrations
`were thought to be caused by the fact that the annular
`model was anatomically normal and not calcified. The
`
`CARDIOVASCULAR
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`ENDOHEART AG, EX. 2036 Page 5
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`

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`CARDIOVASCULAR
`
`Ann Thorac Surg
`2006;82:110–6
`
`DEWEY ET AL
`PERCUTANEOUS AORTIC VALVE IN ANIMALS
`
`115
`
`primary fixation of the valve within the annulus is pred-
`icated on the resistance of a calcified annulus opposing
`the radial expansion forces of the valve. Additionally,
`friction between the stent interstices and the irregular
`surface of a calcified aortic annulus helps to anchor the
`valve. The juvenile swine annulus is highly elastic in
`nature and has a tendency to “watermelon seed” the
`valve back into the ventricular cavity when afterload is
`applied to the valve. Several times during these experi-
`ments, well-placed valves dislodged back into the ven-
`tricular cavity once cardiopulmonary bypass or rapid
`ventricular pacing was discontinued and afterload in-
`creased. Currently, there are no reports in the literature
`of valves embolizing either distally into the ascending
`aorta or proximately back into the ventricle once accu-
`rately placed in the annulus.
`In the limited number of patients reported, particulate
`embolization leading to stroke has also not been noted to
`be a significant risk with this procedure; it does, however,
`remain a theoretical possibility. Assuming a stroke rate of
`1% to 4% as reported in the balloon valvuloplasty litera-
`ture [2, 8], the use of filters or other embolic protection
`devices may be a useful adjunct to the procedure.
`In most reported series, paravalvular regurgitation is
`noted in nearly all patients [9, 10]. The stainless steel
`skeleton of this stent expands radially to become a
`perfect sphere with little deformability. The radial
`strength is an asset to the device in that it provides
`tremendous strength to force and hold open tightly
`stenotic valves. Unfortunately, it also contributes to para-
`valvular leak in that it cannot conform to the irregular
`annulus formed by calcific aortic stenosis. Areas of poor
`coaptation between the stent and calcium nodules within
`the annulus provide points for blood to leak back across
`the annulus and into the ventricle. The long-term signif-
`icance of such leaks, provided they are not severe and do
`not lead to hemolysis, remains to be examined. Theoret-
`ically, exchanging critical aortic stenosis and obstructive
`physiology for mild to moderate regurgitation with min-
`imal transvalvular gradient could be well tolerated for
`many years, and may never be an issue as current
`percutaneous candidates have such severe comorbidities
`that overall life expectancy is severely reduced.
`Paravalvular leak was seen in 14 of the 18 valves that
`remained in situ after deployment in the aortic annulus.
`Again, the animal model was identified as the primary
`cause of
`the observed regurgitation. The Cribier-
`Edwards Aortic Bioprosthesis, as designed for the human
`aortic annulus, is 14 mm in height, and has a cloth
`covering the proximal 6 mm of the valve. The cloth-
`covered portion of the valve must sit within the aortic
`annulus to prevent blood from flowing back into the left
`ventricle by way of the stent interstices in an uncovered
`area. Swine have a short annulocoronary distance of
`approximately 5 to 7 mm, which obligates that the stents
`be placed relatively low to avoid coronary obstruction.
`Three episodes of coronary obstruction directly contrib-
`uted to the demise of the animals from myocardial
`ischemia shortly after valve deployment. Low placement
`resulted in the covered portion of the stent being below
`
`the annulus in the majority of animals, thereby resulting
`in frequent trans-stent regurgitation. Additionally, the
`sinotubular junction diameter in several animals was
`smaller than the aortic annulus. On two occasions in
`animals with narrow sinotubular junctions, the aortic
`wall invaginated over the edge of the stent and trapped
`one of the leaflets, resulting in severe central insuffi-
`ciency. In the animals in which the cloth-covered portion
`was within the annulus, no paravalvular or central leak
`was identified. Finally, coronary obstruction from the
`valve has not been shown to be a problem in the clinical
`cases reported in the literature.
`In vivo valve durability remains unknown. Accelerated
`wear testing in bench-top pulse duplicators demon-
`strates acceptable durability up to 200 million cycles (5
`years) [9]. What effect crimping the valve onto the deliv-
`ery catheter has on the leaflet tissues and the longevity of
`the valve remains to be seen. However, the fact that these
`first-generation devices are unlikely to have the same
`durability as current surgically implanted valves should
`be used in selecting appropriate candidates for the
`procedure.
`That being said, identifying appropriate patients for
`percutaneous valve implantation remains difficult. To
`date, patients having undergone percutaneous valve im-
`plantation have all been refused conventional aortic
`valve replacement because of either the presence of
`severe comorbidities or hemodynamic instability. Until
`this technology is scientifically validated by prospective
`trials, good-risk patients, as determined by surgeons,
`should undergo conventional valve replacement and not
`be offered percutaneous therapy. Patients turned down
`for standard valve replacement for contraindications to
`the procedure (eg, porcelain ascending aorta) or those
`believed to have an excessive operative risk, using an
`accepted risk-scoring algorithm, could be considered
`candidates for inclusion into early feasibility trials. The
`construction of larger pivotal studies remains challenging
`in the sense of what current therapy do you compare this
`technology with for safety and efficacy. Medical therapy
`and balloon valvuloplasty have notoriously poor long-term
`outcomes in patients with critical aortic stenosis. Further-
`more, is it ethical to randomize patients who might be
`considered candidates for conventional surgery to a device
`with an unproven track record of durability and high rates
`of postimplant paravalvular regurgitation? These and other
`questions remain to be answered as this technology nears
`the point of large multi-institutional studies.
`In summary, despite the limitations of the animal
`model, we believe that the transapical approach for
`implantation of a stented aortic valve provides a reliable
`method for prosthesis delivery. Furthermore, this ap-
`proach obviates the risk and complications associated
`with the extremely challenging transseptal technique,
`and provides an alternative to a retrograde delivery
`should patients have severe coexisting peripheral vascu-
`lar disease. Other approaches to the aortic annulus such
`as retrograde from the left subclavian artery may also
`offer advantages over peripheral techniques, and have
`been successfully reported in small animal series [11].
`
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`PERCUTANEOUS AORTIC VALVE IN ANIMALS
`
`Ann Thorac Surg
`2006;82:110–6
`
`Valve performance, in regards to proclivity for migration
`and propensity for paravalvular leak, is more reliably
`gauged by the reported clinical experience than in the
`noncalcified animal annulus.
`
`The authors wish to acknowledge the research support of
`Edwards Lifesciences, including providing research funding and
`supplying the tested valves. Additionally, Jane Olin, DVM, Petra
`Böske, DVM, Cris Ullmann, PhD, and Fabian Emrich also
`provided excellent technical support during the procedures.
`
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`
`CARDIOVASCULAR
`
`The Society of Thoracic Surgeons Policy Action Center
`
`The Society of Thoracic Surgeons (STS) is pleased to
`announce a new member benefit—the STS Policy Action
`Center, a website that allows STS members to participate
`in change in Washington, DC. This easy, interactive,
`hassle-free site allows members to:
`
`● Personally contact legislators with one’s input on key
`issues relevant to cardiothoracic surgery
`● Write and send an editorial opinion to one’s local media
`
`● E-mail senators and representatives about upcoming
`medical liability reform legislation
`● Track congressional campaigns in one’s district—and
`become involved
`● Research the proposed policies that help—or hurt—
`one’s practice
`● Take action on behalf of cardiothoracic surgery
`
`This website is now available at www.sts.org/takeaction.
`
`© 2006 by The Society of Thoracic Surgeons
`Published by Elsevier Inc
`
`Ann Thorac Surg 2006;82:116 • 0003-4975/06/$32.00
`
`ENDOHEART AG, EX. 2036 Page 7
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00299, U.S Patent No. 8,182,530