PERCUTANEOUS AORTIC VALVE REPLACEMENT
`This proposal for a project
`to develop a
`percutaneous aortic valve replacement is divided into
`seven sections. The section on anatomy describes the
`native aortic valve and its function. The following
`section on the valve's dynamics and physics discusses the
`implications of the anatomy for the valve’s successful
`function. The sections on aortic stenosis and
`regurgitation describes valve dysfunction and the section
`on surgical therapy discusses current surgical
`replacement therapy and its problems. The final two
`sections outline the study objectives and stages. The
`purpose of the study is to develop a percutaneous
`placement
`technique and prosthetic valve that would mimic
`the function of the native valve and avoid problems
`associated with current methods for surgical replacement.
`
`I. Aortic Valve Anatomy
`The aortic valve directs the flow of blood from the
`left ventricle into the systemic circulation through the
`aortic artery.
`It accomplishes this function by opening
`during the contraction of the left ventricle and closing
`when the left ventricle relaxes.
`three leaflet-
`In a normally functioning valve,
`shaped cusps open widely to allow the unimpeded
`transference of blood, and then close tightly, not
`allowing any blood back into the left ventricle.
`Significant restriction to blood flow is called stenosis,
`and blood leakage back into the left ventricle is called
`regurgitation.
`
`NORRED EXHIBIT 2045 - Page 1
`Medtronic, Inc., Medtronic Vascular, Inc.,
`& Medtronic Corevalve, LLC
`
`v. Troy R. Norred, MD.
`Case |PR2014-00110
`
`
`This proposal for a project
`to develop a
`percutaneous aortic valve replacement is divided into
`seven sections. The section on anatomy describes the
`native aortic valve and its function. The following
`section on the valve's dynamics and physics discusses the
`implications of the anatomy for the valve’s successful
`function. The sections on aortic stenosis and
`regurgitation describes valve dysfunction and the section
`on surgical therapy discusses current surgical
`replacement therapy and its problems. The final two
`sections outline the study objectives and stages. The
`purpose of the study is to develop a percutaneous
`placement
`technique and prosthetic valve that would mimic
`the function of the native valve and avoid problems
`associated with current methods for surgical replacement.
`
`I. Aortic Valve Anatomy
`The aortic valve directs the flow of blood from the
`left ventricle into the systemic circulation through the
`aortic artery.
`It accomplishes this function by opening
`during the contraction of the left ventricle and closing
`when the left ventricle relaxes.
`three leaflet-
`In a normally functioning valve,
`shaped cusps open widely to allow the unimpeded
`transference of blood, and then close tightly, not
`allowing any blood back into the left ventricle.
`Significant restriction to blood flow is called stenosis,
`and blood leakage back into the left ventricle is called
`regurgitation.
`
`NORRED EXHIBIT 2045 - Page 1
`Medtronic, Inc., Medtronic Vascular, Inc.,
`& Medtronic Corevalve, LLC
`
`v. Troy R. Norred, MD.
`Case |PR2014-00110
`
`
`
`% A a
`
`
`
`Figure 1
`
`The aortic valve is a tricuspid structure. Each cusp
`folds up toward the aorta during the contraction phase
`and then folds back against the others in the relaxation
`phase.
`[Figure 1] However, it is important to understand
`that the structure of the aortic valve is complex, with
`integral relationships beyond its three-leaflet valve
`structure.
`For instance, each leaflet sits directly
`opposite an out pouching of the proximal aorta. This
`dilated segment, called the sinus of valsalva,
`is part of
`an anatomic relationship that assists the repetitive
`opening and closing of the valve while minimizing the
`stress on any point within this valvular apparatus.
`Further,
`the proximal portion of the aortic valve is
`highly elastic, which allows it to dilate during the
`contraction phase of the left ventricle.
`Moreover,
`these valvular structures are integrally
`related to the coronary arteries, which supply blood to
`the heart.
`These arteries, as represented in Figure 2,
`are located within 2 of the three sinuses. Thus, each
`component plays a vital role in the function and
`durability of the valve.
`The first components of the aortic valve I would
`like to discuss are the leaflets.
`As stated,
`the number of leaflets within a normal
`aortic valve is three. Any congenital variation in the
`
`NORRED EXHIBIT 2045 - Page 2
`
`
`
`number of leaflets causes significant problems with
`function. When there are less than three valves,
`the
`valve undergoes rapid stenosis and restriction. An
`individual with a unicusped valve rarely survives beyond
`the first year of life. Among individuals with congenital
`alterations in the valve number,
`the most frequently
`encountered is a bicuspid aortic valve.
`Individuals with
`this variation in valve number can survive into
`adulthood. However,
`this valve combination becomes more
`and more stenotic and regurgitant by the 4th and 5th
`decade, which usually results in the need for surgical
`replacement.
`(See figures 3 and 4). Rarely, an individual
`with a quadricusped valve will survive into adulthood.
`This alteration in design also results in marked
`stenosis.
`The anatomy of a normal aortic valve (three cusps,
`sinuses, aortic arteries) permits the dispersion of
`pressure over a larger surface area in the structure.
`
`30
`
`3O
`
`20
`
`Figure 4.1
`
`This dispersion resists the exhaustion of any one
`component of the valve. Moreover,
`the curvature of the
`
`NORRED EXHIBIT 2045 - Page 3
`
`
`
`cusp structure allows the leaflet to reverse curvature,
`an ability needed in order to fold and allow the maximum
`opening diameter during contraction. Finally,
`a curved
`design allows a redundancy in the coaptation area of the
`leaflets.
`The area of coaptation is the valve edge that
`must meet and close in order to prevent regurgitation.
`Hence, both the number of leaflets and their overall
`shape is important
`in the function and durability of the
`valve.
`
`the valve leaflets have a
`As mentioned earlier,
`direct relationship to the sinuses of valsalva.
`The
`sinus diameter is almost
`twice that of the aorta.
`
`/
`
`(A)
`
`(B)
`
`Figure4.2
`
`This cavity plays an important role in the mechanism of
`valve closure.
`
`An oblique section through
`[referenced Mano Thubrikar]
`the leaflet~sinus assembly shows this remarkable
`relationship (see Figure 4). This section reveals that
`the sinus and leaflet form a circle when the valve is in
`a closed position.
`Furthermore, it is angulated to a
`degree as to allow pressure
`transduction along the
`entire surface of this unit. All this suggests that the
`shape of the leaflet sinus assembly is important
`in
`determining how stresses are developed within the valve.
`
`this
`without straining the aortic valve. Finally,
`relationship of the sinuses and valve allows for the
`efficient flow of blood in the coronary ostia.
`
`NORRED EXHIBIT 2045 - Page 4
`
`
`
`the aortic root, has been
`Another structure,
`The
`observed to expand during ventricular contraction.
`dilatation of this structure reduces tension, which in
`turn reduces resistance to flow, as predicted by
`Poisselles‘ law, which describes the relationship of
`resistance to vessel diameter,
`length of tube and fluid
`viscosity. This phenomenon also allows for complete
`opening of the aortic valve.
`Interestingly, when the
`cusps open, a circular dimension is maintained that is at
`least the same diameter as before contraction(Medical
`Engineering & Physics 19(8): 696—710,l997). This
`behavior reduces circumferential stress on the valve and
`generates a reduced Reynolds shear stress number
`(the
`number used to evaluate the amount of stress in a
`confined fluid system).
`In a similar manner,
`the inner
`lining of the cusp of the valve,
`the lamina
`ventricularis, extends into the ventricular myocardium
`when the valve is in an open position.
`A confluence of
`fibers at the base, called the fibrous coronet,
`is a
`distinct structure separating the elastic fibers above
`and the myocardium below. However,
`this structure is not
`static.
`It is a very dynamic structure, which bends and
`molds to the forces exerted from the ventricular
`myocardium (Cardiovascular Research, 22,7,1988)(Journal
`of Biomechanics33 (6): 653~658, 2000 June).
`In a fashion
`similar to the aortic root,
`this structure allows the
`valvular apparatus to open with the least amount of
`strain.
`The coronary arteries arise within or above the
`sinuses of valsalva.
`The blood flow to the heart occurs
`during ventricular diastole. At this time,
`the cusps of
`the aortic valve are closed, and as mentioned,
`the
`diastolic forces of the blood against the valve are
`dispersed along the valve and adjacent sinus.
`The
`opening, or ostia, of the coronary arteries, when located
`near the apex and middle of the sinuses, allows for least
`turbulent, most
`laminar flow characteristics.
`
`NORRED EXHIBIT 2045 - Page 5
`
`
`
`
`
`Sinutubuiar junctio'n
`
`Left coronary
`sinus
`
`Right .coronary
`Sim-IS
`
`Non—coronary
`sinus
`
`Figure 1-6. Coronary Artery Orifice—Variations. Diagram showing the location oi the coro—
`nary orifices ln a series of 23 normal heart specimens. The luminal aspect of the aorta is
`displayed. The markers represent tenths of the horizontal and vertical measurements in the
`sinuses. (Adapted from ref. 3.)
`
`Figure 5
`
`(This optimal location will be important to keep in mind
`when designing a replacement valve because this
`relationship promotes the greatest amount of flow with
`the least amount of resistance.)
`In disease states where
`these relationships are lost, it has been proposed that
`this loss could increase stress at the coronary ostia.
`
`[The Aortic Valve CRC press].
`These integral relationships are not only seen in
`the gross anatomy of the valvular apparatus. The
`microanatomy shows the integral nature of these
`structures as well.
`The amount of elastin shown by
`staining methods is in a higher concentration here than
`anywhere else in the body( American Journal of Pathology
`445 (7): 1931). This concentration allows a greater
`amount of dilatation of the structures in this area.
`
`
`
`Figure 6
`
`NORRED EXHIBIT 2045 - Page 6
`
`
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