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Surgical Anatomy and Pathology of Aortic Valve
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parts within the aortic sinuses become incorporated, functionally, into the aorta. Second, the
parts of the wall of the aortic sleeve that are in between adjacent leaflets, lie above the
anatomic ventriculo-arterial junction but become, haemodynamically, a part of the ventricle
when the valve is closed.
Functional Anatomy
Considering the aortic root as one functional unit, it is a three-dimensional structure
adjoining distally to the aorta and proximally to the ventricle, and all parts have to work in
harmony. When there is dysfunction it is unlikely to involve only a single element, apart
from, for example, isolated perforation of the leaflet.
In a series of fixed preparations of human aortic roots, the mean circumference was found
to be 65.8 mm at the sinutubular junction and 69.2 mm at the base of the root [19]; in another
series of cadaveric studies, the sinutubular junction was found to be narrower than the basal
part and the middle of the sinusal part was the widest [20].
The diameter at the sinutubular junction and at the nadirs of the leaflets change
continuously during the cardiac cycle in experimental studies [21]. During systole the
sinutubular junction increases initially as aortic pressure increases and decreases later as
aortic pressure drops, and the base decreases so the root adopts a cylindrical shape [22].
During diastole the sinutubular junction moves inwards and the base moves outwards
commissures, changing the cylindrical shape to a more conical shape.
The sinuses of Valsalva play an important role in the local hydrodynamic forces that
exert their effects on both cup motion and coronary flow; they generate a space behind the
open aortic leaflets, preventing closure of the coronary artery orifices. This space favors the
generation of “eddy currents” (first described by Leonardo da Vinci) behind the leaflets when
these are open. The “eddy currents” prevent the contact of the valve leaflets with the aortic
wall and promote smooth valve closure. The peripheral laminae of the flow in systole
encounter the “bottle neck” of the sinotubular junction that forces these laminae back down,
along the borders of the sinuses, distend the cusp borders at the end of systole, and finally
close the cusps during diastole.
The aortic root undergoes complex deformations during the cardiac cycle, which consists
in the strain of the aorto-ventricular base (putative annulus) and sinotubular junction, aortic
root elongation and compression, and shear and torsion deformities. During the first third of
systole, the aortic root gains its maximal expansion, approaching a cylindrical shape. Then its
volume decreases in mid-diastole, then it reapproaches a truncated cone shape in end-diastole.
The 39% increase of the ventriculoaortic junction ring area and the 63% expansion of the
apexes of the interleaflets triangles during systole reduce the opposition to ejection,
facilitating left ventricular unload.
The elastic properties of the root are crucial for the omeostatis of this complex structure.
The maximal stress on the leaflets is concentrated on their insertion at the sinotubular junction
and progressively decreases along the border of cusp insertion. During diastole, the stress on
the leaflets is almost four times higher than that on the sinuses. If the three sinuses do not
uniformly share the stress, the sinus wall would draw inward in diastole. Vice versa, the sinus
walls move outward, thus decreasing the stress and wear and tear on the aortic leaflets.
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Aortic Stenosis
Valve calcification is classified according to the extent and localization of the calcium
deposits [23]. In all imaging evaluations of the aortic root (echocardiography, CT scan, and
nuclear magnetic imaging), aortic valve calcification should be graded/classified as follows:
Grade 1: absence of calcification,
Grade 2: isolated small calcification spots,
Grade 3: bigger calcification spots interfering with cuspsmotion, and
Grade 4: extensive calcification of all cusps with restricted cusp motion.
For calcifications of ≤ grade 3, the localization of the calcium deposits should be
specified.
The early stages of aortic stenosis are in many ways similar to atherosclerosis. Indeed, the
2 conditions share many common risk factors, with large longitudinal studies consistently
demonstrating that the incidence of aortic stenosis is linked to factors such as smoking, age,
and hypertension [24]. As in atherosclerosis, endothelial damage due to increased mechanical
stress and reduced shear stress is believed to be the initiating injury, perhaps best illustrated
by bicuspid valve disease. In this congenital valve malformation, the characteristic 2-leaflet
structure of these valves results in less efficient dissipation of mechanical stress and
accelerated endothelial damage, so that patients almost universally develop aortic stenosis and
display more rapid disease progression [25].
Following endothelial damage, the same lipids implicated in atherosclerosis infiltrate the
valve, in particular, lipoprotein(a) and oxidized low-density lipoprotein (LDL) cholesterol.
Consequently, observational studies have identified cholesterol and its related lipoproteins as
independent risk factors for the development of aortic stenosis [26]. Progressive endothelial
injury and lipid oxidization then establishes an inflammatory response within the valve that is
characterized predominantly by infiltration of macrophages, but also involves T lymphocytes
and mast cells [27]. Features of fibrosis, calcification and activation of genes for osteoblastic
differentitation within the valve along with angiogenesis, lead to valve ossification in an
active, highly regulated pathological process [28].
Aortic Regurgitation
Aortic valve regurgitation may depend either on the valve or on the dysfunction of each
of the nonvalvular components of the aortic root. In a schematic way, the pathophysiology of
the aortic valve incompetence may result from failure of each of the six components of the
root, either variably combined or as isolated abnormali- ties of the sinotubular junction or
sinuses of Valsalva, or semilunar leaflets or three-coronet shaped ventriculoaor-tic junction.
Aortic regurgitation may be caused by age-related atherosclerosis and hypertension;
infective aortic disease (endocarditis); chronic inflammatory aortic valve disease such as
rheumatic disease; heritable connective tissue disease; congenital diseases such as true or
false bicuspid aortic valve (BAV); or acquired valve disease (aged aortic valve calcific
degeneration leading to mixed steno-insufficient valve). Whatever is the cause of valve
Surgical Anatomy and Pathology of Aortic Valve
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TYPE I
TYPE II
TYPE III
Ia: ascending aorta dilatation
Cusp Prolapse
Cusp retraction and thickening
Ib: Valsalva sinuses and STJ dilatation
Ic: FAA dilatation
Id: cusp perforation
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insufficiency, once established, all aortic root components enter a vicious circle with
corresponding damage and dysfunction, all contributing to worsening the regurgitation.
Morphofunctional Classification of Aortic Regurgitation
Based on above considerations, the mechanisms that may cause aortic regurgitation in the
presence of normal mor- phology of the aortic cusps are:
1. Dilatation of the aortic annulus, generally associated with dilation of the sinuses of
Valsalva (known as “annuloaortic ectasia”)
2. Isolated single sinus of Valsalva aneurysm affecting the function of a single leaflet
3. Loss of the sinotubular junction shape which assumes a rectilinear and enlarged
morphology
4. Isolated ascending aortic aneurysm (not involving the aortic root) that can stretch the
sinotubular junction, valve commissures, and interleaflets triangles.
El Khoury and co-workers [29] proposed a simplified functional anatomy classification
of the aortic root considering the two main components:
The functional aortic annulus (FAA) that includes the ventriculoaortic junction, the
sinuses of Valsalva, and the sinotubular junction
The three semilunar leaflets.
The two basic mechanisms of aortic regurgitation, i.e., FAA dilatation and pathology of
the leaflets are classified as follows:
Table 1. Functional classification of aortic regurgitation. STJ: Sino-Tubular Junction;
FAA: Functional Aortic Annulus
THE BICUSPID VALVE
Bicuspid aortic valve (BAV) disease has the characteristic of heredity with variable
genetic penetrance. And 0.5–2% of the population worldwide have the possibility to be
attacked by this disease, which 75% of them are male [30]. BAVs are known to prematurely
calcify leading to calcific aortic valve disease (CAVD), the second most common cause of
aortic valve stenosis. In addition, BAV predisposes affected individuals to aortic aneurysms
and infective endocarditis [31]. BAV has strong genetic components, as evidenced by reports
of familial clustering and calculated heritability [32].
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Morphology of BAV
The typical structure of the aortic valve had three semilunar leaflets in shape. Due to the
fusion of two cusps out of three, BAV usually included two unequal cusps and a central
raphe. From a surgical point of view, Sievers classification system was used widely [33].
Based on number of raphes, three categories of BAV are presented in patients including type
0 (no raphe in the valve), type 1 (only one raphe in the valve) and type 2 (two raphes in the
valve). And the most common type is type 1, which accounting for about 90% of the patients
[34]. On the basis of the raphe position with coronary sinuses, types 1 and 2 were classified as
left (L), right (R) and none (N) type. The right and left coronary leaflet (RL) were most
common accounted for about 80%, the right and non-coronary leaflet (RN) was about 17%
and left and non-coronary leaflet (LN) was 2%. Compared to Asians, type 0 BAV was more
frequently among Europeans, whereas the incidence of RN-BAV with a raphe was higher in
Asian [35].
Aortic stiffness was measured by pulse wave velocity (PWV) using velocity-encoded
magnetic resonance imaging (VENC-MRI) and patients with R-NC fusion were manifested as
greater PWV than patients with R-L fusion phenotype.
In order to show the relationship between BAV morphology type and valvulopathy or
aortopathy, the dichotomous classification method was introduced. The right and left
coronary leaflet cusp fusion was defined as the coronary cusp fusion (CCF) and all other
types were defined as the mixed cusp fusion (MCF). The MCF type of BAV was considered
as one of risk factors for the occurrence of aortic stenosis and associated aortopathy, which
resulted in significant hemodynamic changes [36]. Calcification of a bicuspid valve begins
first along the raphe and also on the aortic surface of the other leaflet.
Genetics of BAV
Although the initial potential genetic link for human BAV was mutations in the gene
KCNJ2 in the setting of Anderson syndrome, no mutations in this gene had been reported in
nonsyndromic BAV. The first genetic etiology of nonsyndromic BAV was identified through
the use of genome-wide linkage analysis by studying families with autosomal-dominant
disease. NOTCH1 is a transmembrane receptor known to function in highly conserved
signaling pathways that play important roles in cell fate and cardiovascular developmental
processes [37]. Since then, several mutations in NOTCH1 have been found to be associated
with aortic valve disease [38]. GATA5 belongs to the family of GATA transcription factors,
and several of these factors have been implicated in human disease. It was recently shown
that targeted deletion of GaTa5 in mice leads to a partially penetrant BAV phenotypes [39].
Mutations in SMAD6, a member of the Bmp signaling pathway, display functional deficits in
vitro and have been found in humans with BAV [40]. Consistent with this, cardiac cushion
abnormalities have also been observed in Smad6-null mice [41].
Aortic Stenosis in BAV
In adults, the development of aortic stenosis is often due to leaflet calcification, which
occurs in a similar fashion to that seen in patients with trileaflet leaflet calcification. This
Surgical Anatomy and Pathology of Aortic Valve
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process is felt to be an active process, perhaps initiated by endothelial dysfunction and
involving inflammation, lipoprotein deposition, calcification, and ossification of the aortic
side of the valve leaflets [42]. The folding and creasing of the valves and the turbulent flow
are felt to contribute to development of fibrosis and calcification [43]. The combination of
these processes results in an accelerated disease progression. Calcification is often present by
40 years of age. Although in some series a peculiar arrangement of valve morphology (raphe
location) was found to be associated with increased risk of valve calcification [44, 45], two
large studies in adults have not identified leaflet orientation as a risk factor for late adverse
events [46, 47]. This finding that valve orientation was not predictive of outcomes in adults
may reflect the modifying role of atherosclerosis risk factors and/or more advanced
degenerative process encountered in adults. A composite index of valve degeneration, which
incorporated valve thickening, calcification, and mobility, that was an independent predictor
of long-term cardiac events in a population of adults with no baseline valve dysfunction. The
predictive role of both morphology and function in adults with BAV parallels that observed in
series examining older adults with aortic stenosis mostly of acquired basis.
Aortic Regurgitation in BAV
Aortic incompetence can develop in the setting of redundant or prolapsing cusps,
endocarditis, or after balloon valvuloplasty. With age, aortic incom- petence may also
develop secondary to dilation of the ascending aorta. Although adults with BAV often have
some degree of aortic regurgitation, the actual prevalence of pure aortic incompetence has
varied, with some suggesting it is rare and others suggesting that it is common. In the
Olmstead county echocardio- graphic study of asymptomatic adults [46], 47% had some
degree of aortic incompetence at baseline; however, interventions for severe aortic
incompetence were relatively uncommon, occurring in only 3% of the cohort during followup. In the Toronto study [47], 21% of the population had moderate or severe aortic
incompetence at baseline; however, only 6% had an intervention for symptomatic aortic
incompetence or progressive left ventricular dysfunc- tion. Despite variations in prevalence,
moderate or severe aortic incompetence is clinically important and is an independent
predictor for late adverse cardiac events.
Aortopathy and Aortic Dissection in BAV
In BAV disease, the aortic annulus, sinus, and proximal ascending aorta are larger than
those found in adults with trileaflet valves [48, 49]. These differences persist even after
adjusting for blood pressure (systolic and diastolic), peak aortic velocities, and left ventricular
ejection time. Aortic root size is shown to be related to valve morphology and the presence of
significant valve disease (82, 84). Specifically, the increased stroke volume from aortic
incompetence is felt to result in stress on the diseased aorta and subsequent aortic dilation.
The most feared complication is aortic dissection, pri- marily due to the high associated
mortality rate; however, the actual incidence of this complication is debated. In the Toronto
series (7), the prevalence of dissection was 0.1% per patient-year of follow-up, and in the
Olmsted County study (6), there were no cases of dissection. Despite the low rates of
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dissection, the increased prevalence of BAV disease relative to Marfan syndrome make
dissections due to BAV equal to or more common than dissections due to Marfan syndrome
[50]. Dissection in BAV, when it occurs, typically involves the ascending aorta, but
involvement of the descending aorta has been reported in older patients. Risk factors for
dissection have included aortic size, aortic stiffness, male sex, family history, and the
presence of other lesions such as coarc- tation of the aorta or Turner syndrome.
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