European Journal of Cardio-thoracic Surgery 31 (2007) 4—6
`
`www.elsevier.com/locate/ejcts
`
`Editorial
`
`Aortic valve surgery: time to be open-minded and to rethink
`
`Successful treatment strategies for cardiovascular diseases
`have often been initiated and driven by surgeons, which is true
`for both coronary artery and valvular heart diseases. Radical
`excision of diseased tissue, repair and replacement strategies
`lead to long-term successful treatment of the underlying
`diseases and clearly improved patient outcome. For many
`surgeons it was and may still be hard to understand that
`balloon dilation and stenting of severely diseased arterio-
`sclerotic coronary arteries could be competitive for bypass
`surgery. The impact of all interventional strategies was
`underestimated by the surgeons, which lead to the
`overwhelming development of a new discipline of inter-
`ventional cardiology. They further developed and steadily
`improved such strategies, heavily supported by medical
`industry, which lead to a steady growth of PCI, by far
`surpassing CABG surgery worldwide. Right now interven-
`tional cardiologists supported by some cardiac surgeons are
`on their way to transform some conventional open surgical
`procedures into catheter-based less invasive interventions,
`such as valve repair and replacement. Most of the surgeons
`react very conservatively and some get themselves involved
`to evaluate such techniques in order to have a fair
`comparison and control.
`Conventional aortic and mitral valve replacement is a
`routine procedure that has been performed safely for decades.
`The majority of patients present with severely calcifying aortic
`valve stenosis, accounting for approximately 10—30% of
`cardiac surgical workload. Resection of all calcified tissue
`with subsequent prosthetic heart valve implantation using a
`standard suturing technique has been the only definitive
`therapy. Excellent haemodynamic outcome and functional
`results are achieved, and good long-term performance of
`conventional prostheses has been proven by numerous studies.
`Can similar results ever be accomplished by balloon dilation
`and stent based valve implantation without complete resec-
`tion of the heavily calcified cusps? This is hard to believe for
`most surgeons since balloon dilation of aortic valve stenosis
`alone did not lead to any convincing data.
`Also, it is of interest to note that there obviously is a major
`cohort of patients with both severe aortic and mitral valve
`disease who are not being referred to surgery usually for the
`reason that the operative risks are considered to be too high.
`According to a recent survey of the European Society of
`Cardiology in 2003, only one-third of these patients under-
`went surgery.
`
`Providing lower risk strategies and interventions may open
`potential treatment options. Surgeons should be part of it.
`In parallel to excellent results with conventional aortic
`valve surgery, a steady increase in the individual patient risk
`profile becomes apparent. Moreover, aortic valve stenosis is a
`disease of the elderly people. Although healthy octogenarians
`can be treated safely with good outcomes, additional risk
`factors may account for increased perioperative morbidity and
`mortality. Amongst others these are cardiac related factors
`such as low ejection fraction, pulmonary hypertension,
`previous cardiac surgery or respiratory dysfunction, renal
`failure and previous neurological insults. Preoperative risk
`evaluation can be performed using scoring systems such as the
`EuroSCORE or the STS risk calculator. The statistical risk may be
`somewhat higher than the effective risk in experienced hands.
`In the end, individual and sometimes challenging decisions
`based on the surgeons’ experience are required. Good surgical
`outcome remains the primary endpoint.
`However, this is the time to rethink!
`Do we need to care about a 20-year outcome in very old
`patients? In octogenarians with patent bypass grafts, does a
`potentially second or third reoperation for AVR necessarily
`need to be done through full sternotomy when taking the
`multiplied risks into account?
`In view of increasing patient risk profiles, cardiac surgeons
`should eventually rethink their whole conventional strategy.
`This may include the evaluation and eventually adaption of
`new technical developments such as transcatheter valve
`implantation techniques into routine practice. Potential
`steps to minimize the risk of aortic valve surgery are obvious:
`(i) a minimally invasive access avoiding sternotomy, (ii) valve
`implantation on the beating heart avoiding cardiac arrest and
`(iii) off-pump valve implantation. There will be concerns with
`such ‘revolutionary’ approaches — definitely. ‘Conventional
`outcomes are so good — we have done this successfully for
`years — why do we need to change’?
`The answer is that time can neither be stopped nor turned
`backwards. Some foresight will be required for modern
`surgical practice in future.
`Insisting on conventional
`approaches may be sufficient at present but may imply
`regression in the future.
`Thus there is an ultimate need to be open-minded and
`move forward. The application of transcatheter techniques
`for aortic valve implantation may lead, at least theoretically,
`to a significant decrease in perioperative trauma and
`
`1010-7940/$ — see front matter # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
`doi:10.1016/j.ejcts.2006.11.001
`
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`Editorial / European Journal of Cardio-thoracic Surgery 31 (2007) 4—6
`
`5
`
`eventually to a decrease in perioperative risk. This will
`ultimately be advantageous for our patients. Cardiac surgery
`is a very technical field and the surgeon is used to applying
`latest technological developments in routine practice. This
`is in strong conflict with some almost inherent concern with
`the introduction of new operative techniques. The routine
`cardiac surgeon seems to be quite conservative. Time to
`rethink!
`Apparently new transcatheter aortic valve implantation
`techniques have been developed by different groups. The
`continuous efforts of the two cardiologists, Dr Cribier and Dr
`Bonhoeffer lead to the first successful percutaneous aortic
`and pulmonary valve implantation, which paved the way for
`further implants and studies during the past 4 years. Despite
`being at an early stage of development, several devices have
`already been introduced into clinical practice at selected
`centres. A number of different devices (maybe twenty or
`more) currently are under development. In parallel, several
`experimental studies on the in vivo function of new devices
`have been performed. Several of these studies deal with
`some technical aspects of transcatheter valve implantation
`with special focus on the surgical therapy using a transapical
`approach [1—4].
`Initial clinical studies on transfemoral and transapical
`aortic valve implantation are being performed at present.
`The manuscript on 6 months
`follow-up results after
`transapical aortic valve implantation published in this issue
`is from the group from Vancouver that is on the real forefront
`of clinical application. They performed the first successful
`human transapical aortic valve implantations using an
`oversizing technique, starting in November 2005 on a
`compassionate use basis in patients deemed as having an
`excessive operative risk. Recently their initial results in seven
`patients have been published [5], and now they present early
`(6 months) follow-up data in four survivors [6]. The present
`information on persistently good valve function after hospital
`discharge probably is the most important message from this
`publication. Good valve function had already been proven in
`patients receiving a 23 mm Cribier-EdwardsTM prosthesis via
`a transfemoral approach from 2002 onwards by Cribier [7].
`The stringent application of the oversizing concept of 2—
`3 mm by the Vancouver group, implanting a 26 mm prosthesis
`only, has led to more successful haemodynamic and clinical
`outcomes. Further clinical studies under ethical approval for
`operable but high-risk surgical patients are under way. Thus
`we can anticipate more and more scientific information in the
`exciting field of transcatheter aortic valve implantation in
`the near future. Time to rethink!
`Another paper in this issue focuses on a specific device for
`left ventricular apical closure when using such new minimally
`invasive transapical techniques [8]. This is an elegant study
`demonstrating the effectiveness of device closure after
`transapical access. The superior results when using a cuffed
`device are clear indicators of a further technical development
`in this field. Transapical access usually can be performed
`without problems when using Teflon reinforced purse-string
`sutures. Fragile tissue, however, may lead to technical
`difficulties, especially when closing larger holes while being
`off-pump in high-risk elderly patients. Under such circum-
`stances the newly developed closure device may be used for
`safe and efficient closure of the transapical access. One of the
`
`most important aspects of the transapical approach is the
`unlimited feasibility even in presence of large sheaths, up to 30
`French or more. With the help of standard purse-string sutures
`or a closure device, there is no real limitation in size. This will
`allow surgeons to implant the most advanced, possibly cuffed
`prostheses to achieve optimal results in comparison to the
`transfemoral approaches with potential size limitations.
`Surgeons always have been on the forefront of developing
`new and excellent therapeutic strategies in medical history.
`Vaccination by Jenner and cardiac catheterization by
`Forssmann are only two of those examples that have been
`persistently condemned by medical colleagues for years as
`recently pointed out in an excellent article by Lewis on the
`CTSNet [9]. With new techniques, immediate acceptance
`cannot be expected by everyone, but new techniques should
`be fairly evaluated on a scientific basis. Definitive judgement
`can only be performed after performing controlled, if
`possible, randomized clinical studies. As such, surgeons
`are the most experienced physicians offering definitive
`treatment for aortic valve disease — for decades. To further
`direct the development, as well as to aim at optimal results
`with transcatheter valve implantation for the ultimate sake
`of our patient’s, surgeons have to stay in the game. Surgeons
`have to actively take part in the developments designing
`future joint inclusion criteria and performing comparative
`and eventually randomized clinical
`trials.
`In parallel,
`retraining with the new catheter-based techniques will be
`required. Last but not the least ‘the transapical approach
`may be the first clear pathway for cardiac surgeons to acquire
`and use catheter-based and image-guidance skills, especially
`if the procedure starts to replace traditional surgical valve
`replacement in higher risk patients’ [10]. Transcatheter valve
`implantation is an exciting new field with a strong surgical
`interest where surgeons should also be open to learn about
`transfemoral valve implantation themselves. A surgical OR
`for the future should implement high quality X-ray imaging
`such as in the catheterization laboratory. Thus the concept of
`a hybrid OR needs to be further applied.
`The clinical introduction of new techniques will always be
`discussed by the medical societies. There will always be
`criticism. However, potentially excellent developments that
`will lead to a significant decrease in the invasiveness of a
`standard surgical procedure should be favourably judged
`with an open mind. With our yet limited experimental and
`clinical experience in transapical and transfemoral trans-
`catheter aortic valve implantation, we have to say that this is
`one of those very promising techniques, even though we were
`non-believers 4 years ago.
`It is one of the few extremely innovative techniques that
`may even revolutionize the whole cardiac surgical practice in
`some years. Patient selection criteria should remain at
`present for high-risk candidates though may be changed after
`future successful studies. In addition this is an emerging field
`for the further establishment of a true team approach:
`Surgeons and cardiologists are working together in a hybrid
`operation theatre. Eventually a new speciality of patient and
`disease oriented physicians, valve specialist in this example,
`may evolve. Time to rethink!
`Despite all excitement, there are still pitfalls in the new
`transcatheter techniques. Risk for paravalvular leakage
`probably is the biggest issue at present. Newer valves may
`
`ENDOHEART AG, EX. 2033 Page 2
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00299, U.S Patent No. 8,182,530
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`6
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`Editorial / European Journal of Cardio-thoracic Surgery 31 (2007) 4—6
`
`come up with additional cuffs that would lead to a better
`sealing around the prosthesis towards potentially severely
`calcified native aortic valve cusps and annulus. In addition, a
`cuff material with gradual dilatative properties or even
`active sticking properties towards the calcified annulus may be
`advantageous. Further technical developments will come in
`future, leading to better functional outcomes. Future use of
`nanotechnology may lead to a complete shift in dimensions
`towards significantly smaller devices. At present relatively
`large diameter sheaths will be required for the insertion of
`larger and eventually cuffed prostheses. With the safe
`transapical approach this can be accomplished in a standard
`fashion. Thus in order to further develop the new transcath-
`eter techniques we have to keep the final goal of perfect valve
`function without leak in mind.
`In summary, conventional surgery remains the golden
`standard for the definitive treatment of patients with
`significant aortic valve disease. Transcatheter valve implan-
`tation techniques have been successfully introduced into
`early clinical practices. Further developments will come, and
`surgeons with all their expertise in the treatment of valvular
`heart disease need to be part of it. Cardiac surgeons have to
`rethink conventional aortic valve surgery and adapt the
`exciting new approaches of transapical and also transfemoral
`transcatheter valve implantation techniques. Times are
`changing and surgeons should be prepared.
`
`References
`
`[1] Huber CH, Cohn LH, vonSegesser LK. Direct access valve replacement. A
`novel approach for off-pump valve implantation using valved stents. J Am
`Coll Cardiol 2005;46:366—70.
`[2] Zhou JQ, Corno AF, Huber CH, Tozzi P, von Segesser LK. Self-expandable
`valved stent of large size: off-bypass implantation in pulmonary position.
`Eur J Cardiothorac Surg 2003;24:212—6.
`
`[3] Huber SH, Tozzi P, Corno AF, Marty B, Ruchat P, Gersbach P, Nasratulla M,
`von Segesser LK. Do valved stents compromise coronary flow? Eur J
`Cardiothorac Surg 2004;25:754.
`[4] Huber CH, Nasratulla M, Augustburger M, von Segesser LK. Ultrasound
`navigation through the heart for off-pump aortic valved stent implanta-
`tion: new tools for new goals. J Endovasc Ther 2004;11:503—10.
`[5] Lichtenstein SV, Cheung A, Ye J, Thompson CR, Carere RG, Pasupati S,
`Webb JG. Transapical transcatheter aortic valve implantation in humans.
`Initial clinical experience. Circulation 2006;114:591—6.
`[6] Ye J, Cheung A, Lichtenstein SV, Pasupati S, Carere RG, Thompson CR,
`Sinhal A, Webb JG. Six month outcome of transapical transcatheter aortic
`valve implantation in the initial seven patients. Eur J Cardiothorac Surg
`2007;31:16—21.
`[7] Cribier A, Eltchaninoff H, Bash A, Borenstein N, Tron C, Bauer F, Der-
`umeaux G, Anselme F, Laborde F, Leon MB. Percutaneous transcatheter
`implantation of an aortic valve prosthesis for calcific aortic stenosis. First
`human case description. Circulation 2002;106:3006—8.
`[8] Tozzi P, Pawelec-Wojtalic M, Bukowska D, Argitis V, von Segesser LK.
`Endoscopic off-pump aortic valve replacement: does the pericardial
`cuff improve the sutureless closure of left ventricular access. Eur J
`Cardiothorac Surg 2007;31:22—5.
`[9] Lewis RJ. The perils of pioneering. August 10, 2006. Available online at
`http://www.ctsnet.org/sections/newsandviews/inmyopinion/articles/
`article-60.html.
`[10] Carroll JD. Editorial: The evolving treatment of aortic stenosis: do new
`procedures provide new treatment options for the highest risk patients?
`Circulation 2006;114:533—5.
`
`Thomas Walther, Friedrich W. Mohr*
`Universita¨t Leipzig, Herzzentrum,
`Klinik fu¨r Herzchirurgie, Stru¨mpellstr. 39, 04289 Leipzig,
`Germany
`
`*Corresponding author. Tel.: +49 341 865 1421;
`fax: +49 341 865 1452
`E-mail address: mohrf@medizin.uni-leipzig.de (F.W. Mohr)
`
`Available online 17 November 2006
`
`ENDOHEART AG, EX. 2033 Page 3
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00299, U.S Patent No. 8,182,530