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Ann Thorac Surg 2002;73:1346-1354
© 2002 The Society of Thoracic Surgeons

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Review

Cause of degenerative disease of the trileaflet aortic valve: review of subject and presentation of a new theory

^a Department of Thoracic and Cardiovascular Surgery and the Heineman Research Laboratory, Carolinas Medical Center, Charlotte, North Carolina, USA

* Address reprint requests to Dr Robicsek, Carolinas Heart Institute, Carolinas Medical Center, 1000 Blythe Blvd, Charlotte, NC 28203 USA
e-mail: tjohn{at}sanger-clinic.com

	Abstract

Top Abstract Introduction Risk factors of degenerative... Characteristics of degenerative... Function of the aortic... Stress and the aortic... Age-related loss of aortic... Effects of decreased aortic... Effects of surgical procedures Conclusions Acknowledgments References

 
Risk factors for both atherosclerotic aortic wall disease and degenerative disease of the trileaflet aortic valve are very similar if not identical. This correlation grows even stronger as the person advances in years. Because of this, it is the prevailing view that sclerosis of the trileaflet aortic valve, unless previously affected by septic or rheumatic endocarditis, is a disease similar in origin to sclerosis of the aortic wall, ie, degenerative aortic valve disease is arteriosclerosis of the aortic valve. Our studies challenge these views. The aortic valve is a functional assembly composed of the three cusps, corresponding sinuses, and the sino-tubular junction, characterized not only by morphologic features but also by its functional properties, which together create an environment that is optimal for distribution of diastolic pressure load and assures proper and timely valve opening and closure. Our more recent experiments also demonstrate that loss of aortic wall compliance at the level of the sinuses leads to significant stress-overload on the aortic leaflets and it is likely to start a chain of events, which begins with minor changes in their microstructure, then continues in more evident sclerosis, and finally ends in gross distortion or calcification of the cusps. The loss of the "pull-and-release" process may also play a part in disintegration of bioprosthetic valves and in degeneration of native aortic valves encased in noncompliant prostheses.

	Introduction

Top Abstract Introduction Risk factors of degenerative... Characteristics of degenerative... Function of the aortic... Stress and the aortic... Age-related loss of aortic... Effects of decreased aortic... Effects of surgical procedures Conclusions Acknowledgments References

 

Discovery means seeing something everybody has seen and thinking something nobody has ever thought.

Albert Szent-Györgi, 1946 [1]

We must be respectful of the aortic root.

Carlos M. G. Duran, 2000 [2]

Aortic valve disease, particularly aortic stenosis, is a known clinical entity since 1672 when Rayger [3] recorded the demise of a patient whose aortic cusps at autopsy showed "osseous fusion." In the next two and a half centuries many references were made to different aspects of clinically manifest aortic valve disease; the early stage of this condition, however, received first attention only in 1904, when Moenckeberg [4] studied incipient pathologic changes of the aortic valve and noted that "if they are present in an extreme degree, they would produce aortic stenosis."

Even after its morphology had been studied extensively, the cause of aortic valve disease remained—and to a great degree still remains—elusive. It was known early that septic endocarditis may damage the aortic valve. The concept that the overwhelming majority of aortic stenosis is caused by rheumatic heart disease, however, was not seriously challenged until the mid-20th century. In 1970, Roberts’s classic article [5] finally settled the issue that rheumatic damage to the aortic valve may occur indeed, but with a much lower frequency than initially suspected.

According to contemporary views, patients with chronic aortic valve disease fall into three principal groups: (1) inflammatory, which includes both septic and rheumatic lesions, (2) congenital, and (3) degenerative, a category now the center of our discussion.

During the past 30 years among industrialized nations the number of patients operated on for aortic valve disease is holding steady; the share of those caused by rheumatism, however, has dropped dramatically. In the surgical series of Soler-Soler and Galve [6], encompassing the time period of 1980 to 1985, the number of patients with bicuspid valves varied only slightly by time, 37% to 33%, postinflammatory disease decreased from 30% to 18%, and the proportion of patients with degenerative trileaflet aortic disease grew from 30% to 46% (Fig 1).

View larger version (17K): [in this window] [in a new window]   Fig 1. Among patients undergoing operation for isolated aortic stenosis (637 cases total), the relative number of cases attributed to various causes changed from 1965 to 1990. (Reprinted from Dare AJ, et al, Human Pathol; 1993;24:1330–8 [7], with permission.)

Early studies on the cause of this condition emphasized what the disease was not, rather than speculating what it really was. Finally, at the beginning of this century it was concluded that the basic feature of aortic sclerosis is fibrosis, which may be the precursor to secondary calcification and eventually aortic stenosis [8]. More recently, it has also been suggested that degenerative aortic valve disease is an atherosclerotic process with calcification [9]. This conclusion was based on the histologic picture and the fact that risk factors of arteriosclerosis and degenerative aortic valve disease are virtually identical.

	Risk factors of degenerative disease of the trileaflet aortic valve

Top Abstract Introduction Risk factors of degenerative... Characteristics of degenerative... Function of the aortic... Stress and the aortic... Age-related loss of aortic... Effects of decreased aortic... Effects of surgical procedures Conclusions Acknowledgments References

 
Among risk factors associated with both symptomatic and clinically silent degenerative aortic valve disease, Stewart and colleagues [10] identified age (two-fold increase for every 10 years), male sex (two-fold excess risk), and history of hypertension (20% increase in risk). Another significant risk factor is hyperlipidemia (both high-density lipoproteins and low-density lipoproteins as well as cholesterol) [10, 11]. Mohler and associates [12] also established a relationship between smoking and degenerative aortic valve disease.

Among the above risk factors of degenerative aortic valve disease, age appears to be the most prevalent. As a matter of fact, age seems to be a precondition rather than just a risk factor. Degenerative disease of the trileaflet aortic valve is rare in younger patients, but thickening, fibrosis, and spotty calcification affect as many as 21% to 26% of those older than 65 years and 48% of individuals older than 85 years of age [10, 13, 14]. Most of the time these changes remain clinically and hemodynamically silent; however, in an appreciable number, they advance into clinically manifest symptomatic aortic valve disease: stenosis, regurgitation, or both [15]. Because such a progression is in a linear relation to age, one may speculate that in an extended lifetime, most, if not all, patients with cusp sclerosis would end up with clinically manifest aortic valve disease.

Stewart and colleagues [10], using echocardiography in a cohort of 5,201 subjects older than 65 years of age, detected aortic valve sclerosis in 26%, and aortic valve stenosis in 2%. In patients older than 75 years, these numbers increased to 37% and 2.6%, respectively.

	Characteristics of degenerative aortic valve disease

Top Abstract Introduction Risk factors of degenerative... Characteristics of degenerative... Function of the aortic... Stress and the aortic... Age-related loss of aortic... Effects of decreased aortic... Effects of surgical procedures Conclusions Acknowledgments References

 
To the naked eye degenerative aortic disease is characterized by increased leaflet thickness, stiffening, and calcification but usually without commissural fusion [10].

The histologic picture at the early stage reveals subendothelial thickening, usually on the aortic aspect of the cusps, deposition of intracellular and extracellular neutral lipids and protein, fine striped mineralization, disruption of the basement membrane overlying the lesions, and thickened areas of fibrosis adjacent to the lesions, as well as infiltration by macrophages and T cells [13]. This shows many similarities between aortic valve sclerosis and arteriosclerosis. There are, however, differences, too, such as the notable absence of smooth muscle cells and the larger amounts of protein that one may expect in the early stages of arteriosclerosis [16].

The most characteristic feature of degenerative aortic valve disease is calcification, which at the early stage of the disease is usually spotty and finely distributed. For this reason, Roberts [17] regarded degenerative aortic valve disease as part of the "senile cardiac calcification syndrome." In the study of 221 surgical specimens we have identified two distinctive patterns of calcification: one along the line of cusp-coaptation, the other in a radial arrangement from the leaflet attachment to the center of the leaflet [18]. The concept that these changes eventually progress to severe calcific valve disease has been substantiated by a plethora of clinical and histopathologic data [12, 16, 19, 20]. In these advanced cases, the mass of calcium is either uniformly distributed or is in large nodular deposits, which may impede cusp mobility but is usually without commissural fusion [21]. Although adequate opening during systole is hindered, the cusps may still coapt during diastole enough to either prevent regurgitation or to keep it minimal.

	Function of the aortic valve

Top Abstract Introduction Risk factors of degenerative... Characteristics of degenerative... Function of the aortic... Stress and the aortic... Age-related loss of aortic... Effects of decreased aortic... Effects of surgical procedures Conclusions Acknowledgments References

 
To understand the working of the diseased aortic valve, one must appreciate how the normal valve opens and closes.

The three leaflets of the normal valve function as interconnected units with attachments to the aortic wall in the lateral direction and inferiorly to the aortic root (Fig 2). The length of the free edges exceeds that of the intercommissural distances, an arrangement that allows wrinkle-free coaptation during ventricular diastole. This excess in the free margin also assures cusp mobility and full opening during systole [23].

View larger version (24K): [in this window] [in a new window]   Fig 2. Schematic drawing of the aortic root with various dimensions of the valve. (a-d = (alpha) leaflet angle; cc = coaptation height; da = aortic diameter [other dimensions are reported with respect to da as 1]; dsm = maximum sinus diameter; ds = area averaged sinus diameter; dv = flow inlet diameter; f = free edge; h = height from valve base to top of commissure; 1c = width of the leaflet; 1s = length of the sinus; 0 = free edge angle.) (Reprinted from Swanson WM, Circ Res; 1974;35:871–82 [22], with permission.)

These sinuses, named after the 17th-century Italian anatomist, Antonio Valsalva, are pouchlike bulges on the aortic root corresponding to the three leaflets. Their significance in aortic leaflet function was earlier and most precisely described by Leonardo da Vinci, who besides his many attributes as artist, architect, anatomist, and military engineer, was also a leading hydrodynamic expert of his time. He was puzzled by the presence of these seemingly useless bulges, which at the first glance created nothing but turbulence in blood flow. To shed light on this paradox, Leonardo performed an ingenious physiologic experiment: he poured wax into a heart of an oxen, then used the mold to recreate the left ventricular outflow tract and the ascending aorta out of glass. After transferring the aortic valve of a pig into the appropriate position, Leonardo pumped water through the model and sprinkled fine grass seed into the stream to outline the pattern of flow, thus creating not only the first "pulse-duplicator," but also the first biologic valve.

Using this model, Leonardo was able to demonstrate that whereas the lion’s share of fluid ejected from the "left ventricle" was streaming in a linear fashion through the "ascending aorta," a fraction of the fluid reversed its direction, recoiled, and formed eddy currents between the leaflets and their respective sinuses. Leonardo concluded that these currents contributed to the leaflet’s smooth and timely closure. In his notes, which by the way were made almost a century before Harvey shed light on the circulation of the blood, Leonardo also mentions that the structure of the aortic valve excels not only in its perfection, but also in its simplicity, which man could recreate. Then, in an almost casual fashion, Leonardo provides a sketch of what is undoubtedly the first design for an artificial heart valve [25].

Leonardo’s postulate on the significance of the sinuses [26] were confirmed by modern data obtained in vitro [26–28] and in vivo experiments [29].

From our computer simulation, we concluded that besides the eddy currents, the aortic sinuses modulate valve function several other ways [30]. First of all, we have established that the compliant aortic root undergoes complex dimensional changes during various phases of the cardiac cycle; including aortoventricular and sino-tubular junction diameter changes, elongation, and transverse expansion as well as torsional deformation [31]. These changes significantly moderate leaflet stresses by creating optimal cusp loading and minimizing transvalvular turbulence.

This stress-decreasing modulation occurs the following way: during diastole, the tension (according to the law of LaPlace, tension = transmural pressure x radius) on the coapted leaflets is transmitted to the commissures and pulls them inward. When ventricular pressure rises during systole, the inward pull of the commissures is released. This, as well as the increase in both left ventricular and intraaortic pressures, leads to an outward movement of the commissures, which in turn creates a tangential tension on the leaflets, pulling them open to produce a stellate orifice (Fig 3). In our experiments, using radiopaque markers, we found this increase of the systolic diameter to be 11% to 12% [31]. Others, such as Greenfield and Patel [33] in patients undergoing open heart operation, found an average 0.14% increase in the radius of the ascending aorta per millimeter of mercury pressure and an 11% increment in the cross-sectional area during systole. In the most recent studies in the sheep model, Pang and coworkers [2] revealed the total root volume to enlarge by as much as 22% to 40%. We have also observed that as the aortic perimeter increases by 9%, an initial small opening of the valve occurs without detectable rise in either pressure or flow through the aortic root [31]. Vesely [34], using cinefluoroscopy and sonometry, also confirmed a 5% to 7% aortic root expansion, which occurs at the initial stage of ventricular systole even before valve opening, induced by ventricular pressure rise and by release of the inward pull on the commissures. Similar results were reported by Pang and coworkers [2]. An interesting recent discovery is that of Wassenaar and associates [35] and Chester and colleagues [36], who detected contractile properties in the aortic cusps. It is, however, unclear how contraction of the cusps may contribute to valve function under either physiologic or pathologic circumstances.

View larger version (19K): [in this window] [in a new window]   Fig 3. Actual data points showing the dynamic motion of the leaflets and commissures in three cardiac cycles. (SEC = seconds.) (Reprinted from Thubrikar M, Am J Cardiol; 1977;40:563–8 [32], with permission from Excerpta Medica, Inc.).

This "Noble phenomenon" raises the number of these relatively unknown aortic valve paradoxes to four: (1) The cusps begin to open even before flow occurs across the valve (initiated by rise in intraventricular pressure, acting on the ventricular aspect of the valve). (2) Flow through the aortic valve continues in late systole even when the aortic pressure exceeds that in the left ventricle. (3) Because of the eddy currents of Leonardo, aortic valve closure begins even while the blood is still streaming through the aortic orifice. (4) The leaflets themselves may have some ability to contract.

It is evident that if the aortic wall is not compliant at the commissural level, some of these mechanisms could not exist.

	Stress and the aortic valve

Top Abstract Introduction Risk factors of degenerative... Characteristics of degenerative... Function of the aortic... Stress and the aortic... Age-related loss of aortic... Effects of decreased aortic... Effects of surgical procedures Conclusions Acknowledgments References

 
In the search for the cause of degenerative aortic valve disease, we find it most likely that the culprit is increased mechanical stress on the leaflets by loss of elasticity of the aortic wall.

Elasticity is that property of materials by which they store energy by deformation. Elastic modulus is the ratio of the force relative to the amount of deformation produced [38].

The degree of stiffness of an artery is measured in term of the elastic modulus, ie, the less the artery dilates, the stiffer (less elastic) the wall is. The increase in diameter involves the transfer of the circumferential wall stress from the elastin fibers stretched to the maximum to the relatively inextensible collagen fibers.

Aortic wall compliance (C) has been defined as

where Ep is the pressure-strain modulus of the aortic wall, D is the lumen diameter at perfusion pressure, and D is the increase in diameter of the lumen produced by an increment P in pressure [39]. The stress load the aortic cusp may bear is considerable. At a diastolic pressure of 100 mm Hg, Vesely [34] estimated the vertical force of 12.8 N or about 1.3 kg, and the horizontal component to be about 7.4 N or about 2.5 N/commissure.

Elasticity of the aorta is a significant physiologic variable, which partakes in the regulation of many vital functions, such as blood flow, blood pressure, and perfusion of individual organs. So far, however, no one has implied that aortic wall stiffness may induce degenerative aortic valve disease.

Aortic compliance depends mainly on the elements that compose its wall, ie, elastin and collagen as well as smooth muscle cells, contained in a matrix of nonfibrous tissue. These constituents of the tunica media exist in various proportions, depending on their distance from the heart. In the human, the elastin component is highest in early life and then gradually decreases in the last decades [40].

Aortic behavior is defined primarily by the proportion of its elastin and collagen. It is also stipulated that forces at high pressures are born by collagen fibers, whereas the elastin lamellae and fibers are responsible for their uniform distribution [41].

Other causes for aortic wall stiffening are dilatation and thickening features, which also correspond with advanced age [42]. Evidently, an aorta that is already pathologically dilated even in diastole will be unlikely to expand significantly in systole. Also, because of the increased blood volume contained, there is a rise in inertial forces acting on the valve cusps and against ventricular ejection at end diastole [43]. This may affect myocardial performance as well as the stress load on the cusps. Because it is known that the walls of a tubular structure become thinner as the tube dilates, one may expect that when the aorta dilates with age, its wall becomes thinner. Wellman and Edwards [44], however, proved in 335 autopsies that this is not the case. They found that owing to fibrosis, the thickness of the media increases from an average of 1.22 mm in the group from birth to 9 years to 1.67 mm in the fifth decade, then remains almost constant from 50 to 69 years.

Dilatation of the aortic root may also directly interfere with aortic valve function by preventing appropriate cusp coaptation and thus induce aortic regurgitation [45].

In an average human lifetime the aortic valve may open and close 3 x 10⁹ times [3]. In each cycle, the cusps are exposed to physiologic stresses of bending and to the mechanical trauma of coaptation. The most significant stresses the valve cusp has to endure are tension during diastole and flexion during valve opening and closing. Relationships between aortic sclerosis and tensile stresses are implied by the site of focal changes of sclerosis on the aortic side of the leaflets [31].

The scope of research on the cause and effects of abnormally high leaflet stresses is narrow. Finite-element modeling is one of the methods, which may yield important data about stress patterns in the valve cusps [46, 47]. In the past, such studies, however, were aimed primarily at design improvements of bioprosthetic valves and only a few [47] have taken the actual layered structure of the native leaflet into consideration. With some notable exceptions [48], these studies also assumed an identical and homogeneous valve composition [47], and all but a handful included the entire aortic root [30, 48]. Most of the investigations were also limited to efforts to make bioprosthetic valves more durable. None of them investigated as to how the native aortic valve may become dysfunctional.

In our own experiments, finite-element models of the aortic root were constructed either with or without sinuses. In the models with sinuses, each sinus-leaflet unit formed cylindrical geometry and was loaded with an internal pressure of 80 mm Hg (0.01 N/mm²) and the stresses determined (Fig 4). We found the stress at the leaflet-belly to be 0.26 N/mm² and not affected by the geometry or the stiffness of the root. In the model without sinuses, however, the stress along the leaflet attachment line increased to 0.65 N/mm², although it was lower (0.3 N/mm²) if the sinus root was present [30]. Furthermore, the stress increased if the sinus was not flexible. To the earlier postulates we add the following:

View larger version (49K): [in this window] [in a new window]   Fig 4. Stress contours in the aortic root when the flexible sinuses are present versus when the sinuses are absent (tubular graft). Colors correspond to stress values in newtons per square millimeter. (Reprinted from Beck A, et al, J Heart Valve Dis; 2001;10:1–11 [30], with permission.).

For this reason, we have recently designed a new aortic root prosthesis, which includes compliant sinuses of Valsalva, for valve-sparing operations (Fig 5).

View larger version (137K): [in this window] [in a new window]   Fig 5. Newly designed aortic root prosthesis having the compliant sinuses is shown in position after the aortic valve-sparing operation is completed. (Reprinted from Thubrikar MJ and Robicsek F, United States Patent Office, 2000 [50] with permission.)

	Age-related loss of aortic wall elasticity

Top Abstract Introduction Risk factors of degenerative... Characteristics of degenerative... Function of the aortic... Stress and the aortic... Age-related loss of aortic... Effects of decreased aortic... Effects of surgical procedures Conclusions Acknowledgments References

Patients with coronary artery disease have decreased aortic distensibility [51]. The studies of Bouthier and associates [52] and Honda and colleagues [53] revealed that decreased arterial compliance is also a classic feature of essential hypertension. Abnormalities of lipid metabolism, especially if associated with elevated blood pressure, are also found to increase the stiffness of the aortic wall [11]. Because of this, it has been suggested that aortic valve stiffening is part of the generalized atherosclerotic process.

Since the first report of Bromwell and Hill in 1922 [54], the decreased elasticity of the aorta, especially the thoracic aorta, with age is well known (Fig 6). As one gets older, there is a gradual increase of collagen as well as calcium deposits [56]. In the older person, the aorta and major arteries become gradually less distensible, and the ability to absorb pulsation from the ejecting ventricle is reduced [54]. This loss of distensibility is attributed to cumulative changes in the composition of the medial matrix—an aging phenomenon—as well as to intimal thickening caused by arteriosclerosis [57]. The degree of stiffening may be enhanced by associated diseases, such as hypertension [57] or diabetes [58]. In this loss of elasticity, elastin apparently plays a pivotal part because there is a marked drop in the concentration of elastin of the arterial wall as the subject ages [38].

View larger version (16K): [in this window] [in a new window]   Fig 6. Aortic distensibility decreases markedly as the ages grow older even though their atherosclerotic changes are very slight. (P = pressure; R = radius; t = wall thickness.) (Reprinted from Nakashima T and Tanikawa J, Angiology 1971;22:477–90 [55], with permission.).

	Effects of decreased aortic wall compliance on aortic valve function

Top Abstract Introduction Risk factors of degenerative... Characteristics of degenerative... Function of the aortic... Stress and the aortic... Age-related loss of aortic... Effects of decreased aortic... Effects of surgical procedures Conclusions Acknowledgments References

Our findings were as follows:

1. In the left heart simulator set on the variables noted, the fluid dynamics in both the freshly harvested and the cryopreserved and thawed aortic roots revealed no appreciable pressure gradient. Aortic valve function, as documented by high-speed cinematography, was characterized by smooth and regular leaflet dynamics, as well as by synchronous opening and closure in all specimens.
   
2. After the roots were stiffened by the external application of the plastic adhesive, the pressure-flow measurements remained unchanged; however, the morphologic function of the valve leaflets altered dramatically. The previously smooth leaflet opening and closure became irregular and asynchronous, and the leaflet motion showed whipping and curling. This change from smooth and coordinated leaflet function in the naturally compliant aortic root to irregular leaflet function in the stiffened root occurred in every specimen and was caused by the loss of compliance and slight reduction in valve dimension. The leaflet surface developed multiple wrinkles and creases once the root compliance was lost (Fig 7).
   
3. The diameter of the intact aortic roots mounted in the simulator increased at the commissural level by an average of 9% in each cardiac cycle as the pressure increased from 80 to 120 mm Hg. After stiffening, however, this expansion was eliminated. Furthermore, stiffening of the root at 40 mm Hg froze the diameter of the root, which was 12% less than the same at 80 mm Hg pressure. Thus, it appears that after stiffening the root, both the reduction in the diameter and the loss of compliance of the root are responsible for changes in the leaflet dynamics [49].
   

View larger version (67K): [in this window] [in a new window]   Fig 7. Five hundred frames/sec cinematography showing the leaflet surface during valve opening. In the natural, compliant aortic root, the leaflet free edges look sharp, and the leaflet surface is smooth and without wrinkles. In the stiffened aortic root, the leaflet free edges look blurry, and there are many wrinkles present in the leaflet surface. (Reprinted from Robicsek F and Thubrikar MJ, Am J Cardiol 1999;84:944-6 [49], with permission from Excerpta Medica Inc.).

	Effects of surgical procedures

Top Abstract Introduction Risk factors of degenerative... Characteristics of degenerative... Function of the aortic... Stress and the aortic... Age-related loss of aortic... Effects of decreased aortic... Effects of surgical procedures Conclusions Acknowledgments References

Flexible stents may lower the stress on bioprosthetic valves (as compared with rigid stents) but only if some other specific conditions are met [47].^.Even with flexible stents, however, leaflet stresses remain abnormally high [30, 47]. In the porcine valve, the leaflet-size relationship is: left more than right more than noncoronary, whereas in the human it is noncoronary more than right more than left [48]. This makes sinus-leaflet matching impossible. Even cylinder inclusion, free-hand, or root-replacement unstented grafts fail to provide a physiologic environment because of glutaraldehyde-fixed tissue and the influence on aortic root distensibility of the constraining sutures [63].

The concept of saving the aortic valve was introduced by Sarsam and Yacoub in 1983 into cardiac surgery [64]. The Yacoub procedure and its modification by David and coworkers [65] indeed preserve the patient’s own aortic valve, but because of a lack of compliant sinuses of matched dimensions, it leaves it exposed to abnormally high stresses [66].

As an alternative to the Yacoub procedure, we had proposed an anatomically more appropriate sinus prosthesis with bulging sinuses of Valsalva [67]. Later we developed a prosthesis [50], in which we modified our original design and added compliance to the sinuses. This prosthesis is of tubular woven Dacron with the usual transverse grooves to which three scalloped and convex "neosinuses" are attached (Fig 5). These are tailored to match the patient’s preserved cusps and made expandable by having the grooves in an axial instead of a transverse position. At present, altogether eight such protheses have been used in a native valve-preserving mode [68] with good short-term results. Postinsertion intraoperative echocardiography showed a normally appearing root anatomy trace with no regurgitation. A more extended period of observation is needed to judge the benefits of the prosthesis, especially the persistence of its compliance.

The idea of substituting the failed aortic valve with the patient’s pulmonary valve was developed by Ross in 1967 [69]. Different anatomic and functional aspects of this procedure withstood extensive clinical and experimental scrutiny. From a stress-loading angle, however, the Ross operation has the shortcoming that the autograft pulmonary root expands to its near-maximal diameter even under diastolic pressure, thus loses most of its systolic-diastolic expansion. The studies of Vesely and associates [70] confirmed that pulmonary roots may indeed withstand the forces imposed by aortic pressure, but have also shown that they distend by 30% more than the native aortic root. This leaves only 3% ± 1.6% systolic-diastolic diameter variation for the transferred pulmonary root subjected to physiologic aortic pressures. Because the pulmonary autograft placed in a subcoronary position does not affect aortic root compliance, subcoronary implantation appears to have definite advantages over root replacement. Even the subcoronary Ross procedure, however, fails to provide perfect matching of the leaflets with the sinuses.

As the situation stands today among methods, aortic leaflet, and aortic root replacements, only fresh or cryopreserved aortic homografts offer optimal stress loading on the cusps. In the long run, however, some of this advantage of homografts may be lost because of fibrosis or calcification [71].

	Conclusions

Top Abstract Introduction Risk factors of degenerative... Characteristics of degenerative... Function of the aortic... Stress and the aortic... Age-related loss of aortic... Effects of decreased aortic... Effects of surgical procedures Conclusions Acknowledgments References

 
Stiffening of the aortic wall at the level of the sinuses leads to loss of the physiologic pull-and-release function of the aortic root, stress overload on the aortic leaflets, eventually cusp fibrosis and calcification, and in some cases hemodynamically significant aortic valve disease.[7]

	Acknowledgments

Top Abstract Introduction Risk factors of degenerative... Characteristics of degenerative... Function of the aortic... Stress and the aortic... Age-related loss of aortic... Effects of decreased aortic... Effects of surgical procedures Conclusions Acknowledgments References

 
Supported by grants From the Minna-James Heineman Foundation. The authors gratefully acknowledge the assistance of Cryolife Incorporated for providing Cryo-preserved samples of aortic roots.

	References

Top Abstract Introduction Risk factors of degenerative... Characteristics of degenerative... Function of the aortic... Stress and the aortic... Age-related loss of aortic... Effects of decreased aortic... Effects of surgical procedures Conclusions Acknowledgments References

 

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