Catheterization and Cardiovascular Interventions 82:6~70 (2013)
`
`First-in-Man Transfemoral Transcatheter Aortic Valve
`Replacement With the 29 mm Edwards SAPIEN XT Valve
`
`MBBS, Josep Rodes-Cabau,2
`Melanie Freeman,1
`MD, Marina Urena,2 MD,
`Robert Delarochelliere/ MD, Eric Dumont,2 MD, Jean-Bernard Masson,3 MD,
`Alexander B. Willson, 1
`MBBS, MPH, Ronald K. Binder, 1 Mo, Stefan Toggweiler, 1
`MD,
`Jonathon Leipsic,1 MD, David A. Wood,1 MD, and John G. Webb,1
`'" MD
`
`Objectives: To demonstrate the feasibility of transfemoral transcatheter aortic valve
`replacement (TAVR) with the 29 mm Edwards SAPIEN XT valve and Novaflex™ +
`delivery system through a 20F expandable sheath (eSheath™, Edwards Lifesciences,
`USA). In addition, to describe the use of the Novaflex + delivery system and ex(cid:173)
`pandable sheath. Background: TAVR has undergone significant advances in device
`technology resulting in smaller profile sheaths and delivery systems, allowing transfe(cid:173)
`moral delivery of a 29 mm valve. Methods: Twelve patients underwent transfemoral
`TAVR with the 29 mm Edwards SAPIEN XT valve and Novaflex + delivery system
`through a 20F expandable sheath. Baseline clinical and procedural characteristics are
`evaluated. In-hospital and 30-day outcomes are reported according to Valve Academic
`Research Consortium criteria. Results: All patients were male with a mean aortic annu(cid:173)
`lus diameter of 25.0 :t 1.1 mm and 25.9 :t 1.2 mm, on transesophageal echocardiogra(cid:173)
`phy and multidetector computerized tomography, respectively. Mean iliofemoral mini(cid:173)
`mal luminal diameter (MLD) was 8.0 :t 0.8 mm. Successful deployment of the valve
`occurred in 11 out of 12 patients. Valve embolization occurred In one patient. Aortic
`valve area increased from 0.7 :t: 0.2 to 2.0 :t: 0.5 cm2 (P < 0.001). There were two major
`vascular complications; however, there were no in-hospital or 30-day neurological
`events, need for pacemaker insertion, or mortality. Conclusions: Transfemoral TAVR
`with the 29 mm Edwards SAPIEN XT valve and Novaflex + delivery system through a
`20F expandable sheath was feasible with acceptable short-term outcomes. c 2012 Wiley
`Periodicals, Inc.
`
`Key words: aortic valve stenosis; heart valve prosthesis; prosthesis design; heart valve
`prosthesis implantation; bioprosthesis
`
`BACKGROUND
`Transcatheter aortic valve replacement (T A VR) has
`emerged as a treatment option in patients with severe
`symptomatic aortic stenosis at high risk or not eligible
`for conventional aortic valve replacement [1,2].
`Since its advent, significant developments have been
`made in device technology, resulting in smaller profile
`sheaths and delivery systems [3]. This has led to a sig(cid:173)
`nificant reduction in vascular complications [4], and
`has expanded the number of patients eligible for the
`transfemoral approach who would otherwise have been
`excluded due lo small vessel diameter.
`Currently,
`the Edwards SAPIEN XT THV™
`(Edwards Lifesciences, USA) is manufactured in 20
`rnrn, 23 mm, 26 mm, and 29 mm external dian1cters.
`The 20 mm valve is compatible with the NovaFlex
`transarterial delivery system and has been utilized in
`Canada and Japan [5]. A 29 mm valve delivery system
`
`1Department of Cardiology, St. Paul's Hospital, University of
`British Columbia, Vancouver, Canada
`2Department of Cardiology, Quebec Heart and lung Institute,
`Laval University, Quebec, Canada
`3Department of Cardiology, Montreal University Hospital
`Center, Quebec, Canada
`
`Conflict of interest: Drs. Rodes-Cabau. Dumont. Binder. Wood and
`Webb are consultants for Edwards Lifesciences. Drs. Binder and
`Toggweiler received unrestricted research grants from the Swiss
`National Foundation.
`
`*Correspondence to: John G. Webb, MD. St. Paul's Hospital. 1081
`Burrard Street. Vancouver. BC, Canad;~ V6Z 1Y6.
`E-mail: john.webb@vch.ca
`
`Received 29 March 2012; Revision accepted 16 June 2012
`
`DOl !0.1002/ccd.24543
`Published online 28 June 2012
`(wiley onlinelibrary.com)
`
`in Wiley Online Library
`
`© 2012 Wiley Periodicals, Inc.
`
`Edwards Lifesciences Corporation, et al., Exhibit 1052, p. 1 of 7
`
`

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`666
`
`Freeman et al.
`
`TABLE I. Comparison of Sheath Sizes and SFAR Ratios
`
`Parameter
`
`16F cSheath
`
`I8F eSheath
`
`20F eSheath
`
`22F Rf3 sheath
`
`24F RF3 sheath
`
`Recommended valve
`
`SAPIEN XT
`
`Sheath ID
`Sheath 00
`
`SAPIEN
`Uncxpanded
`llncxpunded
`Exp:mded with valve
`Recommended minimum artery diameter
`Sheath 00/Vessel ID (SFAR)
`Unexpanded
`Expanded with valve
`
`20mm
`23 mm
`
`16F
`6.7
`8.9
`6
`1.12
`1.48
`
`26mm
`
`29mm
`
`18F
`7.2
`8.9
`6.5
`1.11
`1.37
`
`20F
`8
`9.9
`7
`1.14
`1.41
`
`23 mm
`22F
`8.4
`
`7
`1.2
`
`26 mm
`24f
`9.2
`
`8
`1.15
`
`SFAR: sheath to femoral artery ratio based on recommended minimum artery diameter. 10: Internal diametet. 00: Outer dinmeter.
`
`(Fig. 2). The sheath is introduced in its low profile
`configuration reducing the potential for arterial injury.
`The sheath transiently expands to allow passage of the
`valve. As the valve passes the sheath recoils to its
`lower profile diameter. The eShealh is available in
`16F. 18F, and 20F unexpanded internal diameters with
`6.7 mm. 7.2 mm, and 8.0 mm unexpanded outer diam(cid:173)
`eters respectively (Table I). The maximum temporary
`expanded internal diameter of the eSheath is 8.9 mm
`for sizes 16F and 18F and 9.9 mm for size 20F. All
`sheaths have a working length of 36 em.
`
`Edwards SAPIEN XT Valve
`The 29 mm SAPIEN XT valve consists of bovine
`pericardia! leaflets, a cobalt-chromium frame and a seal(cid:173)
`ing cuff on the inflow aspect of the stent to prevent par(cid:173)
`avalvular regurgitation. The current manufacturer's rec(cid:173)
`ommendations are to base device selection on two(cid:173)
`dimensional long axis TEE measurements of the aonic
`annulus. The 20 mm SAPIEN XT is recommended for
`use in patients with annulus diameters of 17-19 mm,
`the 23 nun SAPIEN XT valve is recommended for use
`in those with annulus diameters of 18-22 mm, while the
`26 mm SAPIEN XT is recommended in those with
`annulus diameters of 21- 25 mm. The 29 mm SAPfEN
`XT valve has been recommended for use in patients
`with annulus diameters of 24-27 mm. However many
`groups, including our own, are moving towards 3-
`dimensional annular sizing utilizing MDCT. Recommen(cid:173)
`dations for MDCT sizing are still in development [7,8].
`Once fully deployed, the valve heights are measured
`at 13.5 mm. 14.3 mm, 17.2 mm, and 19.1 mm for the
`20. 23. 26. and 29 mm valves, respectively (Fig. 3).
`
`Procedural Details
`The T A VR procedure has been described elsewhere
`in detail [9]. Briefly, all procedures were performed
`under general anesthesia with TEE guidance. The
`eSheath, with the introducer, is inserted over a guide(cid:173)
`wire into the common femoral anery, after femoral
`
`access is achieved. When introducing the sheath. the
`expansion seam is oriented toward the posterior wall of
`the artery being accessed and the sheath is inserted
`into the vessel in its unexpanded state. The introducer
`is then removed leaving the sheath in place. Following
`balloon aortic valvuloplasty, the 29 mm SAPIEN XT
`valve mounted on the Novaflex + delivery system is
`inserted into the sheath hub, protected by a loader
`which is retracted after the valve has passed through it.
`The Novafiex + delivery catheter is passed through the
`eSheath into the descending aorta, where adjustments
`are made to align the valve on the balloon catheter.
`The delivery catheter tip is then flexed to facilitate
`passage through the aortk arch and stenotic native
`valve. Once positioned, using TEE and angiographic
`guidance, the valve is deployed during rapid ventricu(cid:173)
`lar pacing. Once the delivery system is retrieved, the
`is closed utilizing J'reviously
`femoral access site
`inserted percutaneous sutures (ProGlide T. • Abbott
`Vascular. Abbott Park, IL) or by surgical closure.
`All patients underwent
`transthoracic echocardio(cid:173)
`graphy prior to discharge. In-hospital and 30-day out(cid:173)
`comes are reported according to Valve Academic
`Research Consortium criteria [10].
`
`Statistics
`Continuous variables are described as mean ± the
`standard deviation, while categorical variables are
`described with numbers and percentages. Means
`were compared using two tailed paired Students T test; P
`values of <0.05 were considered statistically significant.
`
`RESULTS
`Baseline Characteristics
`Baseline clinical characteristics are listed in Table Jl
`All patients were male with a mean height and weight
`of 1.7 ± 0.1 m and 77.8 ± 13.1 kg. The mean aortic
`annulus diameter on TEE was 25.0 ± 1.1 mm. All
`patients underwent preprocedural MDCT with contrast
`revealing a MDCf derived mean annular diameter of
`
`Catheterization and Cardiovascular Interventions DOl 10.1002/ccd.
`Published on behalf of The Society for Cardiovascular Angiography nnd Interventions (SCAI).
`
`Edwards Lifesciences Corporation, et al., Exhibit 1052, p. 3 of 7
`
`

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`

`

`TABLE IV. In-Hospital Outcomes and 30-Day Outcomes
`
`Transfemoral TAVR with the 29 mm Edwards Sapien XT Valve
`
`669
`
`TAVR [4]. The sheath to femoral artery ratio (SFAR),
`the ratio of the sheath outer diameter (mm) to the min(cid:173)
`imal femoral artery diameter (mm), has been proposed
`as a reference to avoid femoral vascular complications
`with TA VR l ll]. In those with moderately calcified
`arteries, a SFAR of > 1.05 has been associated with
`higher major vascular complications and 30-day mor(cid:173)
`tality, in
`those receiving CoreValve™ (Medtronic,
`USA) and earlier generation Edwards devices. The
`proposed SFAR cut-off in noncalcified vessels is 1.1,
`and 1.0 in heavily calcified vessels.
`Although the vascular complications associated with
`the eSheath have not been previously studied, it is pos(cid:173)
`sible that these complications may be minimized by
`the more transient increase in SFAR as compared with
`the older sheaths (Table I). Our initial data on the
`eSheath is encouraging with the occurrence of only
`one access site hematoma despite a mean unexpanded
`SFAR of 1.0 ± 0.1 and a mean expanded SFAR of
`1.3 ± 0.1.
`The other major vascular complication in this series
`occurred due to wire perforation of the left ventricle
`resulting in pericardia! tamponade. Ventricular wire
`perforation during T A VR has been reported in up to
`2.0% of patients [12,13] often resulting in procedural
`death. Early recognition with intraprocedural TEE and
`immediate insertion of a pericardia! drain with subse(cid:173)
`quent surgical repair of the apex resulted in a good
`outcome for our patient.
`The 29 mm SAPIEN XT transcathcter heart valve is
`recommended for use in patients with annulus diame(cid:173)
`ters of 24-27 mm, with device selection based on two(cid:173)
`dimensional long axis TEE measurements of the aortic
`annulus. It is generally proposed that the implanted
`prosthesis be slightly larger than the native aortic annu(cid:173)
`lus (14], however the degree of ovcrsizing has not
`been previously defined. In patients with borderline
`annulus dimensions between 24 and 25 nun. a 26 mm
`THY poses the risk of incomplete apposition, poten(cid:173)
`tially
`leading to paravalvular leak and prosthesis(cid:173)
`patient mismatch, which has been associated with less
`favorabl e valve hemodynamics and short-tenn out(cid:173)
`comes in TA VR [15]. Although the 29 mm THV
`would overcome this, the possibility of aortic rupture
`or aortic hematoma with a higher degree of oversizing
`is a major concern. We had one case of periaortic he(cid:173)
`matoma detecled on TEE following valve deployment.
`In this case there was some discrepancy between the
`annulus diameter measured on MDC f , and that meas(cid:173)
`ured on TEE, 23.5 mm and 26 mm, respectively. This
`was unusual since MDCf measurements have been
`shown to be consistently larger than TEE measure(cid:173)
`ments [7]. In this case, a 26 mm THY may have been
`chosen for implantation if sizing were based on MDCT
`Catheterization and Cardiovascular Interventions DOl lO. I~ccd.
`Published on behalf of The Society for Cardiovascular Angiography and Intervention~ (SCAI).
`
`Death
`Myocardial infarction
`Major stroke
`Minor stroke
`Major vascular complication
`Minor vascular complication
`Repeat procedure for valve related
`dysfunction
`Permanent pacemaker implantation
`Readmission 111 hospital
`
`In-hospital
`outcomes
`(11 = 12)
`0
`0
`0
`0
`2
`0
`0
`
`0
`NA
`
`30-Day
`outcomes
`(11 = 12)
`
`0
`0
`0
`0
`2
`0
`0
`
`0
`0
`
`ventricular perforation of the left ventricle and a femo(cid:173)
`ral hematoma requiring transfusion of four units of
`packed red blood cells. The hematoma occun·ed on the
`access side and became clinically evident 24 hr follow(cid:173)
`ing routine surgical closure. Since the presence of dis(cid:173)
`section or perforation was ruled out on cr, it was
`managed conservatively and the patient was discharged
`home safely without any major sequelae.
`In the 11 patients with successful transfemoral pro(cid:173)
`cedures, echocardiographic mean transaortic gradient
`was reduced from 47.9 ± 17.5 to 8.7 ± 1.6 mm Hg (P
`< 0.001) and aortic valve area increased from 0.7 ±
`0.2 to 2.0 ± 0.5 cm2 (P < 0.00 I). No patient had
`more than mild paravalvular or valvular aortic regurgi(cid:173)
`tation following T A YR.
`
`DISCUSSION
`
`The 29 mm SAPIEN XT transcatheter heart valve
`was successfully introduced into clinical use in Decem(cid:173)
`ber 2009 as part of the PREVAIL-TA trial [6] and
`received CE approval in February 2011 for transapicai
`T A YR. Promising results were seen in terms of valve
`functionality and short-term survival.
`The present study demonstrates the first-in-man ex(cid:173)
`perience and feasibility of transfemoral T A VR using
`the 29 mm SAPIEN XT and Novaflex + delivery sys(cid:173)
`tem through a 20F expandable sheath. The develop(cid:173)
`men£ of this system will enable a larger spectrum of
`patients to be treated who would olherwise have been
`excluded due to large annulus dimensions or small ilio(cid:173)
`femoral arterial systems. Other potential advantages
`include better hemodynamic results and a reduction in
`paravalvular leak, which has been associated with
`valve undersizing [8].
`Vascular complications, with reported rates between
`1.9 and 30.7%, have emerged as a major cause of mor(cid:173)
`bidity and mortality associated with
`transfemoral
`
`Edwards Lifesciences Corporation, et al., Exhibit 1052, p. 6 of 7
`
`

`

`670
`
`Freeman et al.
`
`alone. While fonnal recommendations for MDCT siz(cid:173)
`ing arc still in development, we believe an area-based
`sizing protocol with the intention to oversize the annu(cid:173)
`lus by approximately 10% may reduce technical errors
`related to sizing. Therefore, an area measurement of
`5.4--6.6 cm2 may be considered appropriate for a
`29 mm THV.
`
`CONCLUSION
`TA VR with the 29 mm Edwards SAPIEN XT valve
`delivered with the Novatlex + delivery system through
`the
`transfemoral
`a 20F eSheath was feasible via
`approach in those with aortic a1mulus diameters of 24-
`27 mm, and iliofemoral minimal luminal diameters of
`greater than 7 mm.
`
`REFERENCES
`
`I. Leon MB, Smith CR. Mack M, Miller DC, Moses JW, Svens(cid:173)
`son LG. Tuzcu EM. Webb JG, Fontana GP. Makkar RR. et al.
`Transcathcter aortic-valve implantation for aortic stenosis in
`patients who cannot undergo surgery. N Engl J Med 2010;363:
`1597-1607.
`2. Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svens(cid:173)
`son LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR. et al.
`Transcatheter versus surgical aortic-valve replacement in high(cid:173)
`risk patients. N Eng! J Med 201 1;364:2187-2198.
`3. Nietlispach F. Wijesinghe N. Wood D. Carere RG. Webb JG.
`Current balloon-expandable transcathetcr heart valve and deliv(cid:173)
`ery systems. Catheter Cardiov:ISc Jnterv 2010;75:295-300.
`4. Toggweiler S. Gurvitch R , Leipsic J. Wood DA. Willson AB,
`Binder RK. Cheung A, Ye J, Webb JG. Percutaneous aortic
`valve replacement vascular outcomes with a fully percutaneous
`procedure. 1 Am Coli Cardiol 2012;59:113-118.
`5. Rodes-Cabau J. Delarochelliere R, Dumont E. First-in-man
`transcatheter aortic valve implantation of a 20-mm edwards
`SAPIEN XT valve: One step f(lrward for the treatment of
`patients with severe aonic stenosis and small aortic annulus.
`Catheter C:u-diov:ISc lntcrv 2012;79:789-793.
`6. Walther T, Thielmann M, Kempfert J, Schroefel H, Wimmer(cid:173)
`Greinecker G, Treede H, Wahlers T, Wendler 0. Prevail Trans(cid:173)
`apical: Multicentre trial of transcatheter aortic valve implanta(cid:173)
`tion using the newly designed bioprosthesis (SAPIEN-XT) and
`
`delivery system (ASCENDRA-Il). Eur J Cardiothorac Surg
`201 2;42:278-283.
`7. Gurvitch R, Webb JG, Yuan R, Johnson M, Hague C, Willson
`AB, Toggweiler S, Wood DA, Yc J, Moss R, et al. Aortic annu(cid:173)
`lus diameter determination by multidetector computed tomogra(cid:173)
`phy: Reproducibility, applicability, and implications for trans(cid:173)
`cathe-ter aortic valve implantation. 1ACC Cardiovasc lnterv
`2011 ;4:1235-1245.
`8. Willson AB, Webb JG, Labounty TM. Achenbach S, Moss R.
`Wheeler M, Thompson C. Min JK, Gurvitch R. Norgaard BL.
`ct al. 3-Dimensional aortic annular assessment by multidctcctor
`computed tomography predicts moderate llr severe paravalvular
`regurgitation after rranscatheter aonic valve replacement: A
`multicenter retrospective analysis. 1 Am Coli Cardiol 2012:59:
`1287-294.
`9. Webb JG, Chandavimol M, Thompson CR. Ricci DR, Carere
`RG, Munt BI, Buller CE. Pasupati S, Lichtenstein S. Percutane(cid:173)
`ous aortic valve implantation retrograde from
`the femoral
`artery. Circulation 2006; 113:842-850.
`10. Leon MB. Piazza N, Nikolsky E. Blackstone EH. Cutlip DE.
`Kappetein AP, Krucoff MW. Mack M, Mehran R, Miller C, et
`al. Standardized endpoint definitions for Transcatheter Aortic
`Valve Implantation clinical trials: a consensus report from the
`Valve Academic Research Consortium. 1 Am Coli Cardiol
`20 II :57:253-269.
`II. Hayashida K, Lefevre T, Chevalier B. Hovasse T. Romano M.
`Garot P, Mylotte D, Uribe J, Farge A. Donzeau-Gouge P, et al.
`Transfemordl aortic valve implant.ation new criteria to predict
`vascular complications. JACC Cardiov:ISc lnterv 201 I :4:85 1-858.
`12. Himbert D. Descourures F. AI-Attar N, lung B. Ducrocq G,
`Detaint D, Brochet E, Mcssika-Zeitoun D. Francis F. Ibrahim
`H, et al. Results of transfcmoral or transapical aortic valve im(cid:173)
`plant.ation following a unifonn :ISSessment in hjgh-risk patients
`with aortic stenosis. J Am Coli Cardiol 2009:54:303-311.
`13. Grube E. Buellesfeld L, Mueller R, Sauren B. Zickrnann B,
`Nair D. Bcucher H, Felderhoff T. Iversen S, Gcrckens U.
`Progress and current status of percutaneous ao11ic valve
`replacement:
`results of
`three device generations of
`the
`CoreValve Rcvalving system. Circ Cardiova~c lntcrv 2008:1:
`167-175.
`14. Webb J, Cribier A. Percutaneous transarterial aortic valve im(cid:173)
`plantation: What do we know'? Eur Heart J 201 1 ;32: 140-147.
`15. Ewe SH, Muratori M. Delgadll V. Pepi M, Tamb(lrini G. Fusini
`L. Klautz RJ. Gripari P, Bax 11, Fusari M. ct al. Hemodynamic
`and clinical impact of prosthesis-patient mismatch after trans(cid:173)
`catheter aortic valve implantation. 1 Am Coil Cardiol 2011 ;58:
`1910-1918.
`
`Catheterization and Cardiovascular Interventions DOl 10.1002/ccd.
`Published on behalf of The Society for Cardiovascular Angiogr.tphy and lntcrventi<ms (SCAI).
`
`Edwards Lifesciences Corporation, et al., Exhibit 1052, p. 7 of 7
`
`