A Heart Valve Tutorial
A Heart Valve Tutorial
The normal human heart can be considered a two stage pump, each containing two valves. The right side of the heart (with the blue arrows) receives blood from the veins and pumps it through the lungs to collect oxygen, while the more powerful left side(red arrows) ejects the oxygenated blood into the aorta. If a heart valve is congenitally defective or degenerates later in life, the heart cannot pump blood as efficiently. It must work harder to maintain the same cardiac output, enlarges and eventually fails. This degenerative process may take years and the quality of life for the patient diminishes severely. If the valve cannot be surgically repaired, the only alternative is replacement of the defective valve with an artificial or prosthetic valve. When implanting a prosthetic heart valve, the surgeon must choose from many commercially available designs. These can be divided into two groups: mechanical valves and bioprosthetic valves.
Mechanical Valves
One option for valve replacement is a
mechanical valve, made entirely of artificial
components. This is a tilting disc valve made
of pyrolitic carbon, stainless steel and
Dacron.
Early mechanical valves were of the ball-in-cage design. Later, the caged disc, the tilting disc and the bileaflet disc valves were introduced. Each step in the evolution of mechanical valves improved durability and hemodynamics, and reduced hemolysis. Although the mechanical valves are very durable, their main disadvantage is the risk of blood clots forming on valve components. Such thrombus formations can cause valve occlusion, or the thrombi can be liberated and lead to strokes or myocardial infarctions. Consequently, all patients receiving mechanical valves must be chronically anticoagulated and their treatment regimen closely monitored. Inadequate anticoagulation leads to blood clotting, while excess therapy can cause dangerous internal bleeding orblood loss from minor injury.
Currently the best-selling type of mechanical valve, the bileaflet design has demonstrated excellent durability and low thromboembolic event rates.
Mechanical valves can also fail suddenly and catastrophically. One example is the Bjork-Shiley tilting disk valve in which critical welds have broken enabling the disk to escape and lodge in the aorta with disastrous results.
The bioprosthetic valves in contrast are not usually thrombogenic and thus have a significant advantage over the mechanical valves since patients do not require long-term anticoagulant therapy. The degeneration and failure of the tissue valves, when it occurs, is also very gradual enabling elective valve replacement surgery. The bioprosthetic valves have been constructed from tanned calf pericardium, pig aortic valves or from glycerol treated human dura mater.
Pig aortic valves are used in the construction of bioprostheses because they are readily available fresh from slaughter in a wide range of sizes, and are anatomically very similar to the human aortic valve.
The porcine bioprosthesis provides good durability compared to other tissue valves and eliminates the need for anticoagulant therapy that is required with mechanical valves.
Biological valve materials are usually mounted on a metallic or polymer frame or stent for support. The frame gives the valve stability during implantation so that proper valve geometry is maintained. Additionally, a sewing ring is placed around the base of the stent for ease of installation.
Allografts
The allograft, a human aortic valve harvested
at autopsy, was the first device used for
replacement of diseased heart valves.
Durability is good, but with the recent
increase in heart transplantations,
availability has become a significant
problem. Recently, the allograft has regained
popularity since it can be stored frozen for
several months, and offers good clinical
results.
At present, glutaraldehyde is used exclusively in the tanning of the biological valves because the covalent bonds produced in the cross-linking process are both chemically and physically very strong. All foreign animal tissue must be treated with aldehydes prior to implantation to reduce their antigenicity and prevent the host foreign body reaction that would otherwise occur. Although the specific action of glutaraldehyde is still unclear, it is believed that it stabilizes the collagen fibers against proteolytic degradation thus ensuring survival of the implant.
The Natural Aortic Valve
From
their inception, the bioprosthetic valves
were designed to mimic the function of the
aortic valve. It is therefore necessary to
appreciate the unique and highly specialized
structure of the natural aortic valve. The
valve contains three leaflets, or flaps of
connective tissue that passively move apart
or mate together in response to the forces
imposed by the flow of blood.
The aortic valve cusps are mostly (90%)
water, but contain other components which
give it unique mechanical properties. The
connective tissue proteins collagen and
elastin are the main structural components,
while the role of GAG's (Glycosaminoglycans -
long chain sugars) and a small population of
cells is poorly understood. The cusp consists
of three layers of morphologically distinct
tissue:
The internal collagen framework of the
leaflets is arranged in three layers, the
fibrosa, spongiosa and ventricularis.
Towards the aortic surface is the fibrosa,
consisting mainly of collagen. The collagen
fibre bundles in the fibrosa are primarily
arranged in a circumferential direction, that
is, running from commissure to commissure.
Starting at one commissure, these fibre
bundles spread out into a somewhat isotropic
mesh near the belly of the cusp, and combine
again into clearly visible bundles towards
the opposite commissure. These
circumferentially oriented, large diameter
fibers, are arranged in a corrugated manner
that enables the leaflets to expand radially,
typically to 50% strain. During valve
loading, the radial expansion enables the
three leaflets to mate together and seal off
the orifice.
The ventricularis consists mainly of sheet
elastin and provides the tensile recoil
necessary to retain the folded shape of the
fibrosa. This relationship between the
fibrosa and the ventricularis requires the
fibrosa to remain preloaded in compression
(to retain its corrugated state) and the
ventricularis to remain in tension (to hold
the fibrosa in compression). Elastin is
believed to be primarily responsible for
generating the preload in the ventricularis,
and for maintaining the collagen fibre
architecture in its neutral state.
Between the fibrosa and ventricularis is a
very loosely organized spongiosa, consisting
of collagen, elastin, proteoglycans and
mucopolysaccharides. These long, multi-chain
proteins bind water readily and give the
spongiosa a gelatinous, watery consistency.
The specific function of the spongiosa at
this time is not well understood, but is
likely a buffer zone that enables the
localized movement and shearing between the
fibrosa and the ventricularis during loading
and unloading.
Overall, the valve leaflets themselves are a
fiber reinforced composite material. They
consist mainly of strong collagen fiber
bundles that run through the valve cusps and
attach to the walls of the aorta. These cords
behave like the lines of a parachute or the
cables of a suspension bridge and during
diastole, the filling phase of the heart
cycle, they transmit the forces imposed on
the leaflets to the aortic wall.
When these valves are treated in fixatives,
such as glutaraldehyde, their mechanical
properties become altered by the fixation
process such that they are unable to function
in the manner outlined above. Over time,
these valves become perforated, torn and
calcified and eventually degenerate and fail.
Consequently, much research has been done to
improve the fixation techniques of these
biomaterials and create a valve with improved
long-term performance.
Bioprosthetic Valves
Early Xenografts:
In an effort to reduce the clinically
significant transvalvular pressure gradient
of porcine xenograft valves, an alternate
design concept was developed in the mid
nineteen-seventies. This was the tri-leaflet
bovine pericardial valve. The use of flat
sheets of aldehyde-treated calf pericardium
enabled the engineers to "design" a new valve
without being constrained by the
predetermined configuration of the pig valve.
The result was a valve with a nearly circular
orifice producing better flow patterns and a
reduced transvalvular pressure gradient. The
early pericardial valves, however, have
demonstrated a significantly worse long-term
clinical performance when compared to the pig
xenografts. The poor durability of these
valves unfortunately has taken over a decade
to manifest itself and many have been
discontinued from the market. A new
generation of pericardial valves, however,
has been in use for several years, and
medium-term performance is encouraging.
The "Flexible" Stent Post
Like mechanical valves, the porcine
xenografts have also changed over the years.
Perhaps the most frequently redesigned
structure of these bioprostheses has been the
mounting frame or stent. The stent is
incorporated into the xenograft to provide
structural support for the leaflets and to
enable the use of a convenient sewing ring to
attach the valve to the aortic root. The
stent is made from stainless steel wire,
polypropylene or other polymers to enable the
stent posts to flex inward during leaflet
loading. Intuitively, if the stent posts are
flexible, then some of the load carried by
the outermost fibers at the free edge of the
leaflet can be transferred to the inner
fibers. Since the leaflets often tear at the
free edge near the commissures it was
hypothesized that this technique would reduce
leaflet tearing associated with high
commissural stresses. This "redesign" of the
valve, however, has never been shown to be
beneficial experimentally or clinically. In
fact, some have observed valves with flexible
stent posts in a pulse tank and measured post
deflections in the order of 0 to 0.2 mm. They
concluded that such minor movements could not
significantly alter stresses at the free edge
or within the body of the leaflet. Others
have simulated the forces imposed on the
leaflets of the closed valves using finite
element analysis and predicted a reduction of
stresses in the body of the leaflet but none
at the commissures; results contradictory to
the design goals. Finally, sometimes it is
observed that often the old style
bioprostheses with rigid stents outlived the
newer ones with flexible stents. Thus
whatever the effects of flexible stent posts
may be, it is doubtful that they represent a
dramatically beneficial feature of the
design.
The Low Profile Stent
A further design change was the reduction in
stent post height to make the valve more
compact. Although this made the valve
anatomically more suitable for the mitral
position, this "redesign" may have
detrimental consequences. Finite element
analysis technique showed that lowering the
stent height increased stresses near the
commissures. Low profile valves may therefore
be more susceptible to leaflet tearing and
may fail sooner than the original designs.
The Rigid Annulus
Besides having stiffer, less extensible
leaflets, the porcine xenografts have
departed from the behavior of the natural
aortic valves in one other major aspect. This
is the use of a mounting
frame which has a rigid,
non-expanding annulus. During valve opening,
the leaflets are constrained by the stent and
forced to bend in patterns quite different
from those of the natural aortic valve. The
natural aortic valve operates in an expansile
annulus which tends to pull the leaflets
tight between the commissures during systolic
ventricular contraction. This prevents the
sharp reversals of leaflet curvature normally
observed in xenograft valves.
The
sharp, reverse bending of the xenograft
leaflets has been implicated as the possible
cause of flexural fatigue leading to cuspal
tearing. Gross examination of valves with
torn leaflets indicated that tears develop at
the sites of maximal leaflet curvatures, both
at the free edge and near the attachment of
the leaflets to the stent. Histologic
assessment and Scanning Electron Microscopy
has further shown that severe compressive
buckling and fiber layer separation occur at
sites of sharp localized bending. Such
buckling could potentially be eliminated by
implanting the xenograft without a stent or
by developing a truly expansile stent.
The free-hand implantation of unstented
aortic valves, although technically very
difficult, is currently a favored alternative
to the use of stented xenografts. To date, it
has been attempted only on transplanted
aortic and pulmonary allografts.
Additionally, the medical centers with
experience in free-hand allograft
implantation report valve survival rates
significantly better than those for other
bioprosthetic valve. It may well be that the
better survival rates of allograft valves is
related to their ability to function more
like the natural aortic valve.
Tissue Properties
The success of free-hand allografts is likely
due to two factors; (i) proper systolic
behavior since a stent is not used, and (ii)
lower collagen disruption and calcification
because of greater leaflet pliability. Since
a host foreign body response is minimal, the
allograft valves do not have to be treated
with aldehydes and therefore retain much of
their natural pliability. Since allografts
also calcify substantially less than
xenografts, collagen fiber disruption is
likely also lower. Collagen fiber fragments
are also potential nuclei for calcium
deposits and thus the lower calcification
rates of allografts would suggest reduced
collagen disruption.
The analysis of stress/strain curves from
uniaxial tensile tests is a valuable aid in
understanding aortic leaflet mechanics. The
Poisson effects however are very significant
in such a highly extensible material and
biaxial tensile testing is therefore a more
appropriate technique. Tensile testing of the
material, however, does not explain the
propensity of the leaflets to tear at flexure
points. Furthermore, the ultimate tensile
strength of the material is about a order of
magnitude greater than the stresses the
leaflets normally endure in-vivo. Flexural
testing of valve leaflets, however, is
technically very difficult and has been
attempted only recently by us. Such an
assessment of pliability or bending stiffness
can help to evaluate potential materials for
bioprosthetic valves, or alternative tissue
fixatives. It is always desirable to
construct valves from materials that have
both tensile stress/strain and bending
properties as similar as possible to those of
the natural aortic valve leaflets.
These bending studies have recently shown
that although the tensile stress/strain
behavior of modern xenografts is very similar
to the natural valves, the xenografts have a
greater bending stiffness. This increased
bending stiffness of the glutaraldehyde-treated
tissue results largely from an increase in
compressive and shear moduli. Natural aortic
valve leaflets are both strong in tension and
highly compressible. The collagen fibers can
resist tensile forces yet when pushed upon,
they coil and move laterally. During the
bending of such a material, the neutral axis
exists near the outer surface of the
material. The tensile forces are therefore
resisted by a very thin section of tissue
near the outer surface, while compressive
forces are distributed over a much greater
cross-sectional area. When the material is
cross-linked with glutaraldehyde in the
preparation of a bioprosthetic valve, the
compressive modulus increases even though the
tensile modulus may remain the same. The
neutral axis is observed to shift inward.
Shear analysis of the material has shown that
during bending, the collagen layers within
the fibrosa can slide across one another
distributing tensile and compressive forces
over a greater portion of tissue. This in
turn reduces local tensile and compressive
stresses. Cross-linking with aldehydes has
been shown to significantly reduce shearing
capacity and thus it likely increases
internal stresses. Bending tests on the
material from unfixed allograft valves
indicate that it is significantly more
flexible than the leaflets of glutaraldehyde-treated
porcine xenografts. The greater pliability of
the allograft valves may well be responsible
for their better survivability.
Future Trends
The deficiencies in the long-term performance
of biological valves likely results from
- the use of materials that do not adequately mimic the mechanical properties of natural aortic valve leaflets and
- modifications to the original structure that promote abnormal leaflet stressing.
A possible solution to the
first problem may be a radical departure from
the glutaraldehyde-fixation technique which
has now become the industry standard.
Admittedly, glutaraldehyde is presently the
best fixative available, but it is not good
enough. Future research may therefore focus
on alternative treatment processes that
eliminate the antigenicity of foreign tissues
without compromising their mechanical
behavior.
A solution to the second problem of valve
dynamics will only arise from substantial
basic research into understanding how the
natural aortic valve functions. In-vivo
invasive studies and new imaging techniques
will play an important role in this field.
The numerical analysis and simulation of
aortic leaflets has made some headway into
understanding true valve behavior. The
availability of the supercomputer combined
with true biaxial, flexural, shear and micro
tensile testing of valve constituents will
enable better modeling of valve function.
An important issue that has not yet been
discussed is the problem of valve
calcification. Many consider calcification to
be the prime factor responsible for the
degeneration and ultimate failure of
bioprosthetic valves. Indeed, calcification
is very severe in patients younger than
twenty, probably because of their increased
calcium metabolism. The severity of
calcification can be correlated with both the
concentration of fixative used to process the
valve, and with the degree of mechanical
disruption of the collagen fibers. The
location of calcific deposits has also been
shown to correlate well with sites that are
likely to experience high tensile and
flexural stresses. The resultant stiffening
of the leaflets from calcification likely
increases stressing of the material and
accelerates the mechanical damage further.
Leaflet calcification and mechanical
disruption therefore appear to be
interrelated,although in some cases, both
calcification and tearing can occur without
the presence of the other. The development
and implementation of anti calcific
strategies such as diphosphonate loading of
cuspal material, and others will surely
increase. Since subdermal implants of cuspal
tissue calcify faster than whole valves in
situ, results from animal modeling cannot be
easily extrapolated to the clinical scenario.
The effectiveness of such anticalcification
schemes can, unfortunately, only be shown
over the course of time.
The designer of a bioprosthetic valve is
faced with a difficult challenge. How does
one know whether a new concept will result in
a better functioning valve when it takes
years, if not decades, to establish the
product's degree of success? Accelerated
cyclic testing of the valves in pulse-tanks
obviously did not forecast the early failure
of the pericardial valves. In developing new
devices that are to replace their defective
biological counterparts, one must bear in
mind that each biological structure has
evolved to fulfill its own specific purpose.
If it is to be replaced with a prosthesis, it
must be one which is mechanically and
biologically very similar to the structure it
replaces. Clearly, the success of future
bioprostheses will depend on the depth of
understanding of the functional mechanisms of
the natural valve. We must therefore
understand the specific purposes and
functions of the collagen, elastin and
mucopolysaccharide components of the valve
material, and the reasons for having a
fibrosa, spongiosa and a ventricularis.
Likewise, we must understand the mechanisms
of calcification of the natural as well as
the prosthetic valves. Can it be prevented at
all or only delayed? We must also become
aware of the biomechanical alterations that
storage, glutaraldehyde fixation and
cryopreservation produce in the collagen
architecture, the mucopolysaccharide matrix
and the overall antigenicity of the valve.
Once this understanding exists, then the way
to create a prosthetic valve will not be to
"design" it, but rather to copy the original
valve as precisely as possible.
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