Min Invas Ther 81 Allied Technol 2000: 9(3f4) 287—292
`
`Aortic and venous valve for
`percutaneous insertion
`
`D. Pavcnik, B.T. Uchida. H. Timmermans, C.L. Corless, ES. Keller and J. Resch
`
`Dotter tnterventr’onat institute. Oregon Hearth Sciences University; Portland. OR, USA
`
`Summary
`
`The purpose of this paper is to present in vitro and in vivo experimental evaluation of a new. artificial,
`bicuspid, aortic and venous valve. Valves were constructed from square stents with barbs covered by
`porcine small intestine submucosa (SIS). A valve 15 mm in diameter was tested in a flow model [2.5
`I/min) with pressure measurement. A 100-ml rubber bag attached to a side arm of the flow model
`simulated heart ejection fraction. In acute (n:6} and short—term (n=3) experiments conducted in four swine and
`four dogs. valves ranging from 16 — 28mm in diameter were placed into the ascending aorta through 10 F
`sheaths; three were placed subcoronary and six in a supracoronary position. Function and stability of the valves
`were studied with pressure measurements and aortograms. Three short—term animals were sacrificed for gross
`and histologic evaluation at one. two and four weeks respectively. In an acute experiment. venous valves with
`four barbs were placed into the IVC through an 8 F guiding catheter in three dogs. For longer—term testing.
`valves were placed into the IVCs and iliac veins of three young swine. The animals were followed up after two
`weeks with venograrns. then were sacrificed for gross and histologic evaluation.
`
`Keywords
`
`aortic valve. venous valve. stents and prostheses. interventional procedures. experimental. biomaterial
`
`Introduction
`
`Expandable stents have been widely used for more
`then 10 years in the treatment of obstructions in
`vascular and nonvascular systems. Expandable stents
`also have a great potential as carriers of per-
`cutaneoust—placed intravascular devices. They have
`been explored as carriers for an interior vena cava filter
`
`[1 —6]. a vascular occluder {r}. a prosthetic venous valve
`[8], a Monodisk for closure of cardiac septal defects [9]
`and a prosthetic aortic valve [1 0—1 2]. Self—expandable
`Gianturco Z— stents served as carriers for most of these
`
`devices. We present a report on a new stent. a self-
`expandable square stent. and its potential as a carrier
`for a venous and aortic valve.
`
`Square stent
`The square stent was constructed in our research
`laboratory from stainless steel wire ODDS—0.02"
`
`diameter. Selection of the wire diameter depends on
`the desired size and degree of expansile force of the
`square stent. The selected wire was hand—bent. on a
`wooden template with fixed metal pegs enabling
`bending the wire into an exact square. Stent sizes
`ranging from 5 mm to 50 mm can be made. The
`corners of the square stent were coil-bent. to reduce
`stress and fatigue of the stent. When barbs are
`needed for better fixation of the square stent. one or
`both wire ends were extended 1—2 mm over the stent
`
`frame to form a barb(s) on one or both sides of the
`stent. One. two or more anchoring barbs can be
`attached to the other side of the square stent with
`metal cannullae. Square stents can be made as a
`
`single stent (Figure 1 a. b. c). or connected by an
`elongated barb into combination of two or more
`stents. These combinations can be made of stents of
`
`Correspondence: D. Pavcnik MD. Cotter interventionai institute, Oregon Heafth Sciences University L342. 3181 SW Sam Jackson Park
`Road. Portland, OR 97201.USA.
`
`© 2000 Isis Medical Media Ltd
`
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`D. Pavcnik et al.
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`various sizes and lengths, and with different degrees
`of expansile force.
`
`Venous and aortic valve
`
`The square stent becomes a valve when the stent
`with barbs on all four corners is covered with low
`
`made. The square stent has four barbs and its
`diagonal axis is constrained to the length of arr.
`forming a diamond (rhombus or two equal triangles) in
`order to fit in the vein or aortic circumference of 2 Ttl'.
`
`For veins 15 mm in diameter. a diagonal axis of 20
`mm square stent is constrained to 22 mm and for a
`30 mm aorta diagonal axis of 40 mm square stent is
`constrained to 46 mm.
`
`Two separate triangular pieces of SIS were sutured
`to the square frame with 710 Prolene monotilament.
`
`running sutures allowing for the gap between the
`diagonal axes. The valve was front—loaded into a
`guiding catheter; the 15 mm venous valve was loaded
`into an 8 F guiding catheter. the 40 mm aortic valve
`into a 10 F guiding catheter. For deployment a special
`
`porous material, such as small intestine submucosa
`(SIS) or polytetrafluoroethylene (PTFE) (Figure 2 a. b.
`c). SIS provides an acellular framework that becomes
`remodeled by host tissue, while being degraded and
`reabsorbed over time [13]. This makes SIS a unique
`covering for intravascular devices.
`Venous
`and aortic
`valve
`
`have
`
`the
`
`same
`
`construction and differ only by the sizes of the square
`stent and diameter of the wire from which they are
`
`
`
`
`Figure 1. The square stent. (a) Single square stent 28 mm in length with four barbs for self-attachment to the vessel wall
`(arrows). (b) Square stent retained by wire pusher connected to one barb. {c} Square stent deployed into a tube 20 mm in
`diameter.
`
`Figure 2. Valve design. {a} Non—restricted valve 20 mm in length with four barbs. {b} Deployed valve in a plastic tube, open
`position. (0] Deployed valve in a plastic tube, closed position.
`
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`Aortic and venous valve for percutaneous insertion
`
`It
`pusher, with a small hook at its end was used.
`assured valve placement
`in proper position and
`prevented its dislodgement by blood flow before its
`barbs engage into the vessel wall. The valve was self—
`expanding so that the valve automatically assumed its
`operational form upon insertion. When the valve was
`deployed. two valvular sinuses were created between
`the venous or aortic wall and SIS or PTFE—mounted
`
`leaflets on the square stent. The valve was open in
`systole to permit fluid flow. In diastole. the valve was
`closed as its two triangular leaflets sealed against
`each other to prevent fluid flow.
`
`In vitro testing
`SIS—covered 20 mm square—stent valves, with four
`barbs, were repeatedly tested in a flow model,
`15 mm in diameter, for competency. Pressure was
`measured proximal and distal to the valve during
`prograde flow. The valves were exposed to retro-
`grade hydrostatic pressure of 60 mmHg, provided by
`a water column in a plastic tube. For venous testing,
`continuous forward flow was approximately 250 mL
`min“. For aortic testing, continuous forward flow
`was 2.5 L min“. Valves were also tested with
`
`additional pulsatile flow. A 100 mL rubber bag,
`attached by a side arm at the lower end of the flow
`model, provided pulsatile flow. Manual compression
`of the bag was used to simulate the calf muscle
`pump and heart ejection fraction. To simulate the calf
`pump, a mild-force bag compression was applied for
`2—3 s; to simulate the heart ejection fraction, a fast,
`< 1 3 bag compression was used. The flow model
`was in a vertical position during testing.
`At rest, without flow, the valve was closed, with a
`hydrostatic pressure of 61 mmHg below and 60 mm
`above the valve. With initiation of continuous non—
`
`pulsatile fonivard flow. the valve opened practically
`immediately with low venous or high arterial flow. The
`valve stayed in an open position during the whole
`duration of continuous flow. With pulsating flow. and
`either mild or strong force compression of the bag,
`the valve stayed open but closed immediately after
`the injection.
`With the imitation of venous testing, pressures
`below the valve tell to 6-16 mmHg (median 1 1 mmHg)
`and returned to the original 60 mmHg after 24—32 5
`continuous flow. When pressure increased to 45 mm
`Hg, the valve opened partially and stayed open to the
`next pulsatile injection. The valve pressure was
`unchanged.
`The aortic valve was tested at hydrostatic
`pressures of 100 mmHg. At rest without flow. the
`valve was closed by a hydrostatic pressure of 101
`mmHg below and 100 mmHg above the valve.
`In
`
`fast bag
`a
`after
`immediately
`flcw,
`pulsatile
`compression pressure above, it increased to 110 (
`:l:
`5) mm Hg and below it decreased to 79 (
`:l: ?}
`mmHg.
`
`Pilot animal study
`Aortic valve
`
`In acute (n = 6) and short—term experiments {n = 3)
`conducted in four swine and four dogs. valves ranging
`from 16—28 mm in diameter were placed into the
`ascending aorta through 10 F sheaths; three were
`placed in the subcoronary and six in the supra—
`coronary position (Figure 3 a. b). Function and stability
`of valves was studied with pressure measurements
`
`and aortograms. Three animals were sacrificed for
`short-term gross and histologic evaluation at 1. 2 and
`4 weeks, respectively.
`All the animals survived the initial post—implant
`period. The animals tolerated the procedure well and
`no arrhythmias or aortic pressure changes were
`observed. Valve movements were regular and there
`was no gradient across the valve. In two short-term
`animals with valves placed in the sub coronary
`position, one of the cusps of the native valve was
`trapped between the square stent and the aortic
`wall. This created considerable regurgitation and an
`appropriate model for evaluating SIS—valve efficacy.
`Both animals maintained systemic pressures of
`92/74 ( a: 9} mmHg and 110/80 ( j: 11} mmHg. None
`of the square stent valves caused stenoses and
`only small contrast regurgitation was seen in two
`animals. Left ventricular end-diastolic pressures were
`unchanged after
`stent-valve implantation in
`all
`animals.
`
`All nine prosthetic valves were undamaged by the
`implantation procedure. Aortic rupture was seen in
`one of the nine animals after 1 week. Aortograms
`revealed minimal regurgitation and no interference
`with coronary blood flow in all animals. Postmortem
`examination revealed the valves to be securely
`anchored. Histologic evaluation at 2 and 4 weeks
`revealed early remodeling of SIS with librocytes.
`fibroblasts and endothelial cells.
`
`Venous valve
`
`Venous valves were tested in an acute experiment
`on three dogs using a preloaded 20 mm square
`stent valve. The valve was placed into the 15 mm
`inferior vena cava (IVC)
`through an 8 F guiding
`catheter from the transjugular approach. Function
`of the valves and their stabflity was studied in the
`supine and upright positions, with injection of
`contrast medium and pressure measurement
`below and above the valve (Figure 4 a, b). For
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`D. Pavcnik et at.
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`longer—term testing, valves were placed into the weeks by venograms and pressure measurement.
`IVC and iliac veins of three young swine via the
`and were then sacrificed for gross and histologic
`transjugular approach. Animals were followed for 6
`evaluation.
`
`Figure 3. Aortic valve aortogram showing competency of the supra coronary placed presthetic aortic valve. (a) Diastole.
`{b} Systole.
`
`
`
`
`Figure 4. Venous valve cavogram in upright position with injection of contrast agent from the right femoral vein.
`(3} Early phase of injection shows valve patency with flow to upper IVC. (b) Late phase of contrast injection
`shows valve closure.
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`Aortic and venous valve for percutaneous insertion
`
`Good valve function was observed in all animals.
`
`There was no pressure gradient through the valve in the
`supine position. A pressure gradient of 12—15 mmHg
`developed immediately in upright position. with less
`pressure below the valves. All veins remained patent
`at 6 weeks and smooth incorporation of the SIS
`valves into the vein wall was observed. Valves
`
`mimicked natural vein valves. Histologic evaluation
`demonstrated host tissue replacement and collagen
`tissue stroma remodeling. with variable fibrocytes,
`fibroblasts and some inflammatory cells. Vascular
`endothelial cells covered valve leaflets.
`
`Discussion
`
`The catheter balloon—valve principle was suggested in
`1980. The concept was balloon periodical closure of
`the insufficient aortic valve orifice. using a system
`attached to an aortic balloon—pump control unit [14].
`A completely revolutionary concept, a catheter—based
`aortic valve. was
`introduced in 1992 with a
`
`percutaneously introduced ball-valve [1 0]. Whereas in
`the previous systems the inserted valve remained
`connected to the introducing catheter. the deployed
`ball valve stayed in the aorta without any support of
`the catheter. The ball valve consisted of a modified Z—
`
`stent. serving as a valve cage. and a detachable
`balloon as valve. The cage was deployed first.
`followed by introduction of the detachable balloon.
`Animal experiments showed good potential for this
`ball—valve [10]. The ‘stent valve” bioprosthesis was
`introduced in 1992 [11]. It consisted of an explanted
`porcine valve, fixed on a wire stent—skeleton. The
`whole system was compressed and mounted on a
`modified balloon catheter for valvuloplasty. it was then
`
`placed into the aortic position using a sheath with an
`outer diameter of 13.6 mm. Balloon inflation was used
`
`to press the wire skeleton against the aortic wall.
`Testing was performed both for the supracoronary
`and infracoronary positions [11]. A similar model. with
`a valve made from the porcine pericardium mounted
`on a stent base. was tested successfully in animals.
`This model required a 24 F catheter for introduction
`[12]. The size of the delivery catheter for the disc valve
`(10 F sheath) is similar to that for delivery of the ball-
`vaive and much smaller then the size of the stent-
`
`valve bioprostheses delivery catheters (24—41 F). A
`percutaneoust—introd uced disc valve was described
`in 1999 [15]. As with the ball—valve and stent-valve
`bioprostheses. the disc valve was delivered with a
`catheter. but stayed in place on its own.
`The square stent was designed to be an
`intravascular implant—device carrier [16]. In order to
`squeeze a device through a delivery catheter small
`enough for percutaneous delivery, the stent structure
`
`must have a low profile and the covering material must
`be thin. Devices placed within the aorta must also have
`adequate strength and durability to withstand the
`aortic presswe of the blood flow. The main effort of the
`engineering involved was to construct the optimal stent
`framework with the lowest profile and enough
`
`expandable force to distend the covering material and
`secure hemostatic apposition of the occluder or valve
`to the artery. aorta or vein. We have shown that. with
`the square stent as a carrier. it is possible to introduce
`an aortic or venous valve covered with SIS per—
`
`cutaneously through a 6—1 0 F guiding catheter.
`In a pilot study. only square stents covered with
`SIS were tested as venous or aortic valves. Square
`stents can also be covered with other materials. such
`as PTFE or Dacron.
`
`Square stents and square-stent—based devices are
`radiopaque and easy to place. Once the device is
`anchored against the vessel wall.
`it is released and
`the pusher catheter with the retention wire is
`removed. After deployment. the square stent self-
`centres. self- adapts and self—attaches with four barbs
`to the wall of tubular structure.
`
`The square stent is a new device with the potential
`to improve minimally-invasive treatment as a venous
`and aortic valve. The valve design is bicuspid and
`mimics natural valve anatomy. Initial studies showed
`
`that percutaneoust-placed SIS square—stent valves
`are promising one-way valves. capable of sustaining
`aortic and venous back—pressure. while allowing
`forward-flow with minimal resistance.
`
`Whether square-stent advantages in design. as a
`carrier for aortic and venous valves. will translate into
`
`intravascular devices
`long-term clinically—useful
`remains to be determined. More experimental studies
`are necessary to evaluate their long-term potential for
`possible future clinical use.
`
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