Controversies
`in Technology
`
`Optimal EVAR Fixation:
`Suprarenal Fixation Is Safe,
`Effective, and Necessary
`
`BY ROY K. GREENBERG, MD
`
`R ecent large, prospective, randomized trials have
`
`provided evidence justifying the treatment of
`aneurysms >5.5 cm in patients fit for open
`repair.1,2 Although questions remain with
`respect to the long-term durability of endovascular
`aneurysm repair and its application to higher-risk patient
`populations,3,4 it is blatantly clear that the opinion
`expressed by Collin and Murie in the British Journal of
`Surgery in 2001,5 “Endovascular treatment of abdominal
`aortic aneurysms: a failed experiment,” was incorrect.
`
`Despite widely spread enthusiasm for less-invasive
`repairs, endoprostheses represent a disruptive technolo-
`gy, and therefore must be subject to continuous scrutiny
`and criticism to encourage the evolution required to
`improve the devices, the technical aspects of the proce-
`dure, and physician judgment. Today, we are in an envi-
`able situation: we have learned that endovascular
`aneurysm repair is a reasonably good choice for most
`patients with acceptable anatomy; however, do we know
`which device to use? Are all implants equal? Will the
`
`Figure 1. This graph depicts the change in creatinine clearance for each patient that developed a creatinine rise >30% (Two
`patients, one from the endovascular group and one from the open surgical group, who required hemodialysis were excluded
`from this analysis). It is the universal improvement in creatinine clearance between 12 and 24 months that reassures us that
`suprarenal stenting is very unlikely to be associated with adverse renal function.The more likely culprits are atheroemboli and
`repeated contrast administration.
`
`66 I ENDOVASCULAR TODAY I AUGUST 2005
`
`Page 1
`
`IPR2014-00100 Pat. Owner Ex. 2026
`Medtronic v. Marital Deduction Trust
`
`

`

`COVER STORY
`Optimal EVAR Fixation
`
`results of a specific physician with a given prosthesis
`imply the ability to obtain equivalent results by other
`physicians? Ultimately, there exists too much art rather
`than science in device selection, implantation techniques,
`and follow-up paradigms. We do our patients a disservice
`by not carefully reviewing the data at hand, and applying
`this information to everyday practice. The specific ques-
`tion entertained by myself and my opponent is whether
`endografts should utilize the suprarenal aorta for fixation
`purposes with an uncovered suprarenal stent.The issue
`can be reduced to two fundamental questions: is
`suprarenal stenting necessary (implying there is likely a
`problem with infrarenal fixation systems), and, if so, is it
`harmful (to the renal arteries)?
`
`“It is entirely possible that
`migration will be the ultimate
`failure mode for most endovascular
`repairs—if these devices are placed
`into patients who live long enough.”
`
`THE NECESSITY OF SUPRARENAL STENTING
`Migration is a problem. It is a major issue in long-term
`follow-up studies and has been noted to occur with near-
`ly all endoprostheses. It is entirely possible that migration
`will be the ultimate failure mode for most endovascular
`repairs—if these devices are placed into patients who live
`long enough (ie, patients fit for open surgical repair). I feel
`the need to reiterate history to avoid reliving it. The first
`report on device migration was published by the Malmo
`group in 1997,6 subsequent studies noted early grafts to
`have a migration incidence of >40% using an infrarenal
`device.7 In many cases, the device was placed a significant
`distance below the renal arteries. These studies concluded
`that devices should utilize active fixation systems and be
`placed in close proximity to the renal arteries.
`The Malmo analyses prompted the development of
`devices utilizing active fixation (hooks and barbs) as well as
`stenting into suprarenal aorta, which was first reported in
`1997.8 Analyses of other devices (with only infrarenal fixa-
`tion), subsequent to the Malmo paper and as late as 2003,
`touted very high device migration rates, approaching or
`even exceeding 40% in the setting of only intermediate
`term follow-up.9-11 Some of the devices used in the afore-
`mentioned reports are still being implanted today. Why
`are these migrations occurring? Is it the physicians, the
`devices, or the patients who were selected for treatment
`that are causing this problem? The answer to all of these
`questions is yes.
`
`Have we grossly underestimated the displacement
`forces required to be borne by an endoprosthesis to
`maintain its position? We physicians did not know, 3 to
`5 years ago, how drastically we had erred in our
`assumptions regarding displacement forces enjoyed by
`an aortic device. We did not know the gravity of treat-
`ing short or conical necks with devices designed for
`achieving fixation and seal within an infrarenal neck.
`Numerous physicians did not understand the impor-
`tance of placing the fabric of a graft immediately below
`the renal arteries. Finally, many physicians did not
`understand the critical importance of proximal fixation.
`Are we any better off today?
`To a certain extent, things have improved from the
`days of early devices. Failures akin to those observed with
`the Stentor (formerly MinTec, the Bahamas) and
`Vanguard (Boston Scientific Corporation, Natick, MA)
`devices,12 such as component separation or fabric tears,
`have become rare, although failures still exist in the form
`of device migration and unanticipated progression of the
`aneurysmal disease. How many surgeons have operated
`on patients with aneurysms proximal to a previously
`repaired AAA? Why does this occur? Was the initial sur-
`geon so incompetent that he or she sutured the proximal
`anastomosis to obviously aneurysmal aorta? Unlikely.
`A more probable scenario is that the extent of the
`aneurysmal disease was not appreciated until later,
`when the patient re-presented with degeneration of the
`historical proximal infrarenal neck. Will this same effect
`occur after endovascular repairs? Absolutely, and the
`potential for late disasters is frightening. There are well-
`documented studies noting a considerable incidence of
`proximal neck dilation.13-15 Unlike the sutured anasto-
`mosis of an open surgical repair, an endograft, relying
`solely on infrarenal fixation, will be swimming upstream
`in a torrential current. What will hold it in place? These
`concerns must be paramount to aortic interventionists
`if they expect their patients to survive more than a few
`years after the procedure. It was commonplace for sur-
`geons to criticize our radiology colleagues when a beau-
`tiful completion angiogram was presented. Our retort
`was that nice pictures did not equate to durable results.
`Now, many of us are guilty of the same crime.
`The large number of patients subjected to cavalier
`placement of endovascular grafts into unsuitable
`anatomies, who were then touted as clinical successes
`and relegated to the purgatory of an undefined follow-
`up paradigm, is disappointing. I believe that many
`physicians don’t have the means or endurance to per-
`form meticulous migration or aneurysm growth analy-
`ses for each follow-up visit. It is in the latter situation
`that we may be worse than 7 years ago, when all
`
`AUGUST 2005 I ENDOVASCULAR TODAY I 67
`
`Page 2
`
`IPR2014-00100 Pat. Owner Ex. 2026
`Medtronic v. Marital Deduction Trust
`
`

`

`COVER STORY
`Optimal EVAR Fixation
`
`patients were enrolled into clinical trials requiring
`adherence to specific anatomic inclusion criteria and
`subject to scrutinized follow-up. Today, when devices
`are frequently used outside of the prescribed instruc-
`tions for use, in anatomy that is more challenging, the
`outcomes will be even less durable than clinical trials
`and preclinical analyses have led us to expect. It pains
`me to hear physicians who believe that suprarenal fixa-
`tion will be the answer for complex anatomy, but who
`argue that it is not necessary for more straightforward
`anatomy. Do they disbelieve the studies on device
`migration? Is there not clear evidence that the infrarenal
`proximal neck will ultimately fail in a substantial per-
`centage of patients? Why would we want excellent fixa-
`tion in the setting of challenging anatomy, and only
`marginal stability in another situation?
`
`“It remains clear that the presence
`or absence of suprarenal
`fixation does not affect the risk of
`renal deterioration.”
`
`The suprarenal aorta is more disease-resistant than
`the infrarenal aorta. This is clearly shown by the paucity
`of aneurysmal or occlusive disease that affects this aor-
`tic region. Why is this? Most explanations center upon
`the more stable biochemical composition of the aorta
`in regions of branches. This has the effect of limiting
`dilation to aortic segments, which is readily apparent in
`a patient manifesting aortic disease. Infrarenal
`aneurysms are most common, followed by thoracic
`aneurysms, whereas thoracoabdominal aneurysms are
`least frequently encountered. So, given the multitude of
`migration reports, and clear evidence that the proximal
`neck may not be as stable as we once assumed, where
`should an endovascular graft designed to treat AAAs be
`anchored? The resounding answer is the suprarenal vis-
`ceral aortic segment, if such a practice is safe.
`
`THE SAFETY OF SUPRARENAL STENTING
`Several reports published during the past 5+ years
`attest to the safety of crossing the renal arteries with a
`bare stent. Computational fluid dynamic models
`demonstrated minimal velocity disturbances and negli-
`gible effects on renal perfusion.16 Animal testing also
`failed to produce concerns with bare stents across the
`renal arteries. In fact, I am not aware of any preclinical
`testing that has shown what would be considered a
`detrimental effect of suprarenal stents on the kidneys
`or the aorta. The proof of this is in the fact that almost
`
`every major company in the interventional AAA arena
`has a device with a suprarenal stent (Zenith [Cook
`Incorporated, Indianapolis, IN], Talent [Medtronic AVE,
`Inc., Santa Rosa, CA], Fortron [Cordis Corporation, a
`Johnson & Johnson Company, Miami, FL], Powerweb
`[Endologix, Inc., Irvine, CA], to name a few). Would
`these companies have introduced devices into clinical
`trials or for commercial use if there were serious con-
`cern regarding the safety of suprarenal stenting? Likely
`not.
`There are many clinical series that also support the
`safety of suprarenal stenting. The largest series published
`involves a comparison of the Zenith graft with open
`infrarenal aneurysm repair (primarily with infrarenal
`clamping).17 Not only were the two methods of repair
`identical with respect to adverse renal events based on a
`careful analysis of calculated creatinine clearance but the
`renal infarction rate was remarkably low in both groups
`with only 3 of 199 patients in the endovascular group. A
`subset of patients in each group had renal dysfunction
`but it should be noted that each patient with evidence
`of worsening renal function within the first 12 months
`of follow-up had improved renal dysfunction by the 24-
`month follow-up visit (Figure 1). It is critical to under-
`stand, as demonstrated in figure 1, that every patient
`with initially declining renal function showed dramatic
`improvement between 12 and 24 months. This implies
`a lack of continued insult from the placement of
`suprarenal stenting, and one would hypothesize the ini-
`tial dysfunction relates to the procedure, or serial CT
`scanning rather than any aspect of transrenal fixation.
`The likely culprits include atheroemboli, ischemia, con-
`trast nephropathy, or the inadvertent placement of fab-
`ric across the renal ostia. The latter is the result of care-
`less deployment techniques, which I doubt will be the
`subject of future prospective evaluations. In fact, there
`was only a 1% incidence of renal artery occlusion in the
`endovascular arm, compared with a 1.4% incidence of
`renal artery occlusion in the open surgical arm. Each
`renal artery occlusion in the endovascular arm was
`noted to have graft material (the actual fabric) covering
`the renal orifice.
`We do not plan on studying this phenomenon fur-
`ther, but we have heard of numerous reports indicating
`that one should not cover the renal artery with pros-
`thetic graft material unless he wants the renal artery to
`occlude. There have been a number of underpowered
`studies that have demonstrated equivalence of
`suprarenal and infrarenal fixation systems with respect
`to renal adverse events.18-20 It is unlikely that any clinical
`trial will ever be designed to compare the two means of
`device stabilization. It remains clear that the presence or
`
`68 I ENDOVASCULAR TODAY I AUGUST 2005
`
`Page 3
`
`IPR2014-00100 Pat. Owner Ex. 2026
`Medtronic v. Marital Deduction Trust
`
`

`

`COVER STORY
`Optimal EVAR Fixation
`
`absence of suprarenal fixation does not affect the risk of
`renal deterioration.
`
`MORE SUBTLE SUPRARENAL ISSUES
`The use of a suprarenal stent to provide added fixa-
`tion is attractive but some more subtle advantages exist
`from a device design and deployment perspective.
`Uncovered proximal stents generally allow for more
`accurate fabric deployment in the region of the renal
`arteries. This can be accomplished without the need to
`drag a device across the renal ostia or estimate where
`the fabric will land. Durable and strong proximal fixa-
`tion can allow the body of the device to have limited
`columnar support, creating a device that will accommo-
`date aortic tortuosity as well as future morphologic
`changes. The composite device, consisting of secure
`proximal fixation within a stable region of the aorta,
`flexible body, and accurate deployment, is desirable for
`the treatment of aortic aneurysms.
`
`THE ABSOLUTE NECESSITY OF SUPRARENAL
`STENTING
`At the 2005 EndoVascular Course in Marseille, France,
`Jaap Buth, MD, presented an analysis of device migra-
`tion from the Eurostar database. The absence of a
`suprarenal stent was a very significant risk factor
`(P<.0001) for device migration. A word of caution must
`accompany all of the aforementioned analyses.
`Although we are singling out suprarenal stenting as the
`subject of this debate, it is the performance of the
`entire prosthesis rather than simply the suprarenal com-
`ponent that must be considered. For example, when
`separate analyses of the infrarenal devices in Professor
`Buth’s study were conducted, not all of them were asso-
`ciated with an increased risk for device migration. It was
`only the AneuRx (Medtronic) graft (which was noted to
`have an incidence of 8.6%) that bore the brunt of fixa-
`tion failures, whereas the incidence of migration with
`the Excluder (W. L. Gore & Associates, Flagstaff, AZ)
`graft was less but still higher than the Zenith device.
`Similarly, the devices that incorporate suprarenal
`stents fixate within the suprarenal aorta differently.
`Some use barbs and radial force, and some use radial
`force only. There are different alloys of stents, differing
`stent lengths, periods, and amplitudes. The uncovered
`proximal stents have varying flexibility, and each stent,
`much like the rest of the endoprosthesis, can fracture or
`fail. Thus, the device as a whole must be considered.
`It is clear that methods of establishing device fixation
`are are additive. Radial force in the infrarenal aorta may
`be good, but infrarenal radial force coupled with
`suprarenal tissue ingrowth and barbs is better. This is
`
`analogous to the belt and suspenders philosophy; how-
`ever, the belt has already been proven to have a very
`real and significant incidence of failure.
`At the end of the day, when we consider which device
`to use in a given patient, we must rely on clinical
`reports, preclinical analyses, an understanding of the
`fundamentals of aneurysmal disease of the aorta, and
`basic common sense to conclude that suprarenal stent-
`ing is both necessary and safe, not in some patients, but
`in almost all patients with infrarenal aneurysms. ■
`
`Roy K. Greenberg, MD, is Director of Endovascular Research,
`The Cleveland Clinic Foundation, Cleveland, Ohio. He has dis-
`closed that he receives research funding from Cook, Sulzer-
`Vascutek, and W. L. Gore & Associates; he is a paid consultant
`for Cook and receives royalties for patents licensed to Cook. Dr.
`Greenberg may be reached at (216) 445-5306; greenbr@ccf.org.
`
`1. Greenhalgh RM, Brown LC, Kwong GP, et al. Endovascular aneurysm repair versus open repair in
`patients with abdominal aortic aneurysm (EVAR trial 1): randomized controlled trial. Lancet.
`2005;365:2179-2186.
`2. Blankensteijn J, de Jong S, Prinssen M, et al. Two-year outcomes after conventional or endovascular
`repair of abdominal aortic aneurysms. N Engl J Med. 2005;352: 2398-2405.
`3. Endovascular aneurysm repair and outcome in patients unfit for open repair of abdominal aortic
`aneurysm (EVAR trial 2): randomized controlled trial. Lancet. 2005;365:2187-2192.
`4. Collin J, Murie J. Endovascular treatment of abdominal aortic aneurysm: a failed experiment. Br J
`Surg. 2001; 88:1281-1282.
`5. Collin J, Murie JA. Endovascular treatment of abdominal aortic aneurysm: a failed experiment. Br J
`Surg. 2001;88:1281-1282.
`6. Ivancev K, Malina M, Lindblad B, et al. Abdominal aortic aneurysms: experience with the Ivancev-
`Malmo endovascular system for aortomonoiliac stent-grafts. J Endovasc Surg. 1997;4:242-251.
`7. Resch T, Ivancev K, Brunkwall J, et al. Distal migration of stent-grafts after endovascular repair of
`abdominal aortic aneurysms. J Vasc Interv Radiol. 1999;10:257-264.
`8. Malina M, Brunkwall J, Ivancev K, et al. Renal arteries covered by aortic stents: clinical experience
`from endovascular grafting of aortic aneurysms. Europ J Vasc Endovasc Surg. 1997;14:109-113.
`9. Connors MI, Sternberg WI, Carter G, et al. Endograft migration one to four years after endovascular
`abdominal aortic aneurysm repair with the AneuRx device: a cautionary note. J Vasc Surg. 2002;36:476-
`484.
`10. Cao P, Verzini F, Zannetti S, et al. Device migration after endoluminal abdominal aortic aneurysm
`repair: analysis of 113 cases with a minimum follow-up of 2 years. J Vasc Surg. 2002;35:229-235.
`11. Lee J, Lee J, Aziz I, et al. Stent-graft migration following endovascular repair of aneurysms with large
`proximal necks: anatomical risk factors and long-term sequelae. J Endovasc Ther. 2002;9:652-654.
`12. Beebe HG. Lessons learned from aortic aneurysm stent graft failure; observations from several per-
`spectives. Semin Vasc Surg. 2003;16:129-138.
`13. Illig K, Green R, Ouriel K, et al. Fate of the proximal aortic cuff: implications for endovascular
`aneurysm repair. J Vasc Surg. 1997;26:492-499.
`14. Sonesson B, Malina M, Ivancev K, et al. Dilatation of the infrarenal aneurysm neck after endovascular
`exclusion of abdominal aortic aneurysm. J Endovasc Surg. 1998;5:195-200.
`15. Matsumura J, Chaikof E. Continued expansion of aortic necks after endovascular repair of abdomi-
`nal aortic aneurysms. EVT Investigators. Endovascular Technologies Inc. J Vasc Surg. 1998;28:422-430.
`16. Liffman K, Lawrence-Brown MM, Semmens JB, et al. Suprarenal fixation: effect on blood flow of an
`endoluminal stent wire across an arterial orifice. J Endovasc Ther. 2003;10:260-274.
`17. Greenberg RK, Chuter TA, Lawrence-Brown M, et al. Analysis of renal function after aneurysm repair
`with a device using suprarenal fixation (Zenith AAA Endovascular Graft) in contrast to open surgical
`repair. J Vasc Surg. 2004;39:1219-1228.
`18. Alsac JM, Zarins CK, Heikkinen MA, et al. The impact of aortic endografts on renal function. J Vasc
`Surg. 2005;41:926-930.
`19. Alric P, Hinchliffe RJ, Picot MC, et al. Long-term renal function following endovascular
`aneurysm repair with infrarenal and suprarenal aortic stent-grafts. J Endovasc Ther.
`2003;10:397-405.
`20. Parmer SS, Carpenter JP. Endovascular aneurysm repair with suprarenal versus infrarenal
`fixation: a controlled study of renal effects. Vascular Meeting Chicago, IL.Jun 18; 2005.
`
`AUGUST 2005 I ENDOVASCULAR TODAY I 69
`
`Page 4
`
`IPR2014-00100 Pat. Owner Ex. 2026
`Medtronic v. Marital Deduction Trust
`
`