**2. Histological structure**

Function of normal heart valves is based on their properties of ensuring unidirectional blood flow without regurgitation. They open and close 40 million times a year and 3 billion times over a lifetime. This property depends on the mobility, pliability, and structural integrity of their leaflets. The competency of the aortic valvular complex depends on the stretching and molding of its 3 cusps to fill the orifice during the closed phase of the cardiac cycle. [9]

[13] and the possibility that VECs may interact with VICs to maintain the integrity of valve tissues. [14] Evidence indicates that different transcriptional profiles are expressed by VECs on the opposite faces of a normal adult pig aortic valve and these may contribute to localiza‐ tion of early pathological aortic valve calcification [15]. Abnormal hemodynamic forces can cause tissue remodeling and inflammation which may lead to aortic valve diseases. [11]

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An understanding of valve architecture and cellular changes that occur in cardiac valves during fetal development, maturation, and aging would provide mechanistic insights into the pathogenesis of congenital and acquired valve abnormalities and aid assessment of ther‐ apeutic strategies for valve disease. A study which performed quantitative histological as‐ sessment of 91 human semilunar valves obtained from second and third trimester fetus,

Valves must accommodate to substantial hemodynamic changes throughout lifetime. Large populations of VICs undergo phenotypic modulation to become activated myofibroblasts and return to quiescent fibroblasts during adaptive remodeling in response to changing en‐ vironmental conditions. [17-19] VICs and VECs functions likely influence ECM synthesis and remodeling. Fetal valves possess a dynamic/adaptive structure and contain cells with an activated/immature phenotype. During postnatal life, activated cells gradually become qui‐ escent, whereas collagen matures through increased fiber thickness and alignment. Fetal sec‐ ond-trimester semilunar (aortic and pulmonary) valves lack distinguishable layers, are composed primarily of proteoglycans, have no detectable elastin, small amounts of disor‐ ganized collagen, and are histologically identical. [20] Fetal valves structure differs, even late in gestation, from that of adult valves, which have a trilayered architecture with a high‐ ly specialized and functionally adapted ECM. The study demonstrated that fetal valves have much higher cellular densities than adult valves, associated with an increased cell prolifera‐ tion-to-apoptosis ratio. VICs density was highest in the second trimester and decreased pro‐ gressively throughout gestation and postnatally. Fetal VICs proliferation indices were likewise greater than those of adult valves. Valvular cell turnover is high during fetal devel‐

They also demonstrated physiological activation of endothelial cells that consistently ex‐ pressed high levels of SMemb, MMP-1, MMP-13, ICAM-1, and VCAM-1 in fetal and chil‐ dren's valves in contrast to adult valves. Valvular cells that are activated in utero undergo phenotypic changes at birth and gradually become quiescent, whereas collagen matures through increased fiber thickness and alignment. This suggests a progressive adaptation to

The aortic valve is the cardiac centerpiece and forms the bridge between the left ventricle and the ascending aorta. Its components are the sinuses of Valsalva, the fibrous interleaflet

neonates, children and normal adults found very interesting results. [16]

opment and continues at a low rate postnatally. [16]

the prevailing hemodynamic environment. [16]

**3. Structure and anatomy of the aortic root**

triangles, and the valvular leaflets themselves. [1]

**2.2. Normal aortic valve development**

#### **2.1. Dynamic relations between the aortic valvular complex and its histological structure**

The substantial changes in size and shape of the valve cusps and leaflets that occur during the cardiac cycle are facilitated by a highly complex internal microarchitecture. The layered struc‐ ture of the aortic valve is formed by: a dense collagenous layer close to the outflow surface, which provides the primary strength component, a central core of loose connective tissue, and an elastin layer below the inflow surface. The essential functional components of the heart valves comprises the valvular endothelial cells (VECs), the valvular interstitial cells (VICs), and extracellular matrix (ECM), including collagen, elastin and glycosaminoglycans. [9]

The major component of valve cusps is collagen, 43% to 55% (predominantly type I but also some type III) [10] and 11% elastin. The quantity, quality, and architecture of the valvular ECM, particularly collagen, elastin, and glycosaminoglycans, are the major determinants of not only the cyclical functional mechanics over the second-to-second periodicity of the car‐ diac cycle, but also the lifetime durability of a valve. The cells of the heart valves through complex cell-ECM interactions, transduce forces into molecular changes that mediate nor‐ mal valve function and pathobiology. Through such mechanisms, healthy heart valves are able to maintain homeostasis, adapt to an altered stress state, and repair injury via connec‐ tive tissue remodeling mediated by the synthesis, repair, and remodeling of the several ECM components. [9]

The most abundant cell type in the aortic valve are VICs. They are distributed throughout all of its layers, are crucial for valvular function [11] and synthesize the ECM. VICs mediate matrix remodeling and continuously repair functional damage to collagen and the other ECM compo‐ nents. As a response to injury VICs may translate from one phenotypic state to another during valvular homeostasis. The 5 distinct VIC phenotypes include embryonic progenitor endothe‐ lial/mesenchymal cells (eVICs), quiescent VICs (qVICs), activated VICs (aVICs), postdevelop‐ mental/adult progenitor VICs (pVICs), and osteoblastic VICs (ob-VICs). [12] Adult heart valve VICs have characteristics of resting fibroblasts, are quiescent, without synthetic or destructive activity for extracellular matrix. They are activated by abrupt changes in the mechanical stress during intrauterine maturation.Once activated VICs can differentiate into a variety of other cell types, including myofibroblasts and osteoblasts. [11]

The blood-contacting surfaces of the aortic valve are lined by endothelial cells. VECs resem‐ ble to endothelial cells but evidence is increasing that VECs are phenotypically different from vascular endothelial cells elsewhere in the circulation, which is consistent with the in‐ creasing recognition of more widespread endothelial heterogeneity across circulatory sites, [13] and the possibility that VECs may interact with VICs to maintain the integrity of valve tissues. [14] Evidence indicates that different transcriptional profiles are expressed by VECs on the opposite faces of a normal adult pig aortic valve and these may contribute to localiza‐ tion of early pathological aortic valve calcification [15]. Abnormal hemodynamic forces can cause tissue remodeling and inflammation which may lead to aortic valve diseases. [11]

#### **2.2. Normal aortic valve development**

**2. Histological structure**

34 Calcific Aortic Valve Disease

ECM components. [9]

types, including myofibroblasts and osteoblasts. [11]

Function of normal heart valves is based on their properties of ensuring unidirectional blood flow without regurgitation. They open and close 40 million times a year and 3 billion times over a lifetime. This property depends on the mobility, pliability, and structural integrity of their leaflets. The competency of the aortic valvular complex depends on the stretching and molding

**2.1. Dynamic relations between the aortic valvular complex and its histological structure**

The substantial changes in size and shape of the valve cusps and leaflets that occur during the cardiac cycle are facilitated by a highly complex internal microarchitecture. The layered struc‐ ture of the aortic valve is formed by: a dense collagenous layer close to the outflow surface, which provides the primary strength component, a central core of loose connective tissue, and an elastin layer below the inflow surface. The essential functional components of the heart valves comprises the valvular endothelial cells (VECs), the valvular interstitial cells (VICs), and

The major component of valve cusps is collagen, 43% to 55% (predominantly type I but also some type III) [10] and 11% elastin. The quantity, quality, and architecture of the valvular ECM, particularly collagen, elastin, and glycosaminoglycans, are the major determinants of not only the cyclical functional mechanics over the second-to-second periodicity of the car‐ diac cycle, but also the lifetime durability of a valve. The cells of the heart valves through complex cell-ECM interactions, transduce forces into molecular changes that mediate nor‐ mal valve function and pathobiology. Through such mechanisms, healthy heart valves are able to maintain homeostasis, adapt to an altered stress state, and repair injury via connec‐ tive tissue remodeling mediated by the synthesis, repair, and remodeling of the several

The most abundant cell type in the aortic valve are VICs. They are distributed throughout all of its layers, are crucial for valvular function [11] and synthesize the ECM. VICs mediate matrix remodeling and continuously repair functional damage to collagen and the other ECM compo‐ nents. As a response to injury VICs may translate from one phenotypic state to another during valvular homeostasis. The 5 distinct VIC phenotypes include embryonic progenitor endothe‐ lial/mesenchymal cells (eVICs), quiescent VICs (qVICs), activated VICs (aVICs), postdevelop‐ mental/adult progenitor VICs (pVICs), and osteoblastic VICs (ob-VICs). [12] Adult heart valve VICs have characteristics of resting fibroblasts, are quiescent, without synthetic or destructive activity for extracellular matrix. They are activated by abrupt changes in the mechanical stress during intrauterine maturation.Once activated VICs can differentiate into a variety of other cell

The blood-contacting surfaces of the aortic valve are lined by endothelial cells. VECs resem‐ ble to endothelial cells but evidence is increasing that VECs are phenotypically different from vascular endothelial cells elsewhere in the circulation, which is consistent with the in‐ creasing recognition of more widespread endothelial heterogeneity across circulatory sites,

extracellular matrix (ECM), including collagen, elastin and glycosaminoglycans. [9]

of its 3 cusps to fill the orifice during the closed phase of the cardiac cycle. [9]

An understanding of valve architecture and cellular changes that occur in cardiac valves during fetal development, maturation, and aging would provide mechanistic insights into the pathogenesis of congenital and acquired valve abnormalities and aid assessment of ther‐ apeutic strategies for valve disease. A study which performed quantitative histological as‐ sessment of 91 human semilunar valves obtained from second and third trimester fetus, neonates, children and normal adults found very interesting results. [16]

Valves must accommodate to substantial hemodynamic changes throughout lifetime. Large populations of VICs undergo phenotypic modulation to become activated myofibroblasts and return to quiescent fibroblasts during adaptive remodeling in response to changing en‐ vironmental conditions. [17-19] VICs and VECs functions likely influence ECM synthesis and remodeling. Fetal valves possess a dynamic/adaptive structure and contain cells with an activated/immature phenotype. During postnatal life, activated cells gradually become qui‐ escent, whereas collagen matures through increased fiber thickness and alignment. Fetal sec‐ ond-trimester semilunar (aortic and pulmonary) valves lack distinguishable layers, are composed primarily of proteoglycans, have no detectable elastin, small amounts of disor‐ ganized collagen, and are histologically identical. [20] Fetal valves structure differs, even late in gestation, from that of adult valves, which have a trilayered architecture with a high‐ ly specialized and functionally adapted ECM. The study demonstrated that fetal valves have much higher cellular densities than adult valves, associated with an increased cell prolifera‐ tion-to-apoptosis ratio. VICs density was highest in the second trimester and decreased pro‐ gressively throughout gestation and postnatally. Fetal VICs proliferation indices were likewise greater than those of adult valves. Valvular cell turnover is high during fetal devel‐ opment and continues at a low rate postnatally. [16]

They also demonstrated physiological activation of endothelial cells that consistently ex‐ pressed high levels of SMemb, MMP-1, MMP-13, ICAM-1, and VCAM-1 in fetal and chil‐ dren's valves in contrast to adult valves. Valvular cells that are activated in utero undergo phenotypic changes at birth and gradually become quiescent, whereas collagen matures through increased fiber thickness and alignment. This suggests a progressive adaptation to the prevailing hemodynamic environment. [16]

#### **3. Structure and anatomy of the aortic root**

The aortic valve is the cardiac centerpiece and forms the bridge between the left ventricle and the ascending aorta. Its components are the sinuses of Valsalva, the fibrous interleaflet triangles, and the valvular leaflets themselves. [1]

**Figure 3.** The "rings" of the aortic root [1]

finally the left coronary sinus. [23]

Bottom of the Valsalva's sinus

both sexes (adapted from [24])

**3.2. Anatomic versus hemodynamic ventriculo-arterial junction**

the most basal portions within the sinus of Valsalva. [1]

As we have shown in figure 3, there is a marked discrepancy between the circular anatomic junction and the semilunar hemodynamic junction. [22] The hemodynamic junction sepa‐ rates the root into those compartments exposed to aortic as opposed to left ventricular pres‐ sures. By virtue of the semilunar attachments of the leaflets, portions of the fibrous aortic root are exposed to ventricular pressures, these being the superior portions of the interleaflet triangles, whereas portions of the left ventricle are exposed to aortic pressures, these being

The spaces between the luminal surface of the three bulges on the aortic root and their re‐ spective valvular leaflets are known as the aortic sinuses of Valsalva. [5] The sinuses are named according to the arteries arising from within them (right, left, and noncoronary). The right sinus structures have the greatest dimensions followed by the non coronary sinus, and

**Male Female**

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**3.3. Aortic sinuses, location of the coronary arteries and sinotubular junction**

**Distance between the ostium and Valsalva's sinus Sex**

Left commissure left coronary 9.7 9.3

Right commissure left coronary 10.9 10.8

**Table 1.** Mean values of the distances of the ostium and its relation to the corresponding Valsalva's sinus (in mm) in

right coronary 11.2 10.7

right coronary 11.3 9.9

left coronary 13.4 13.0 right coronary 15.0 13.8

#### **3.1. The "Annulus" controversy**

When defined literally "annulus" refers to a little ring. The aortic root contains at least 3 cir‐ cular rings and 1 crown-like ring. [21] The valvular leaflets are attached throughout the length of the root. Therefore, seen in 3 dimensions, the leaflets take the form of a 3-pronged coronet, with the hinges from the supporting ventricular structures forming the crown-like ring (Figure 1). The base of the crown is a virtual ring, commonly known as "annulus". This plane represents the inlet from the left ventricular outflow tract into the aortic root and is the diameter that is typically analysed by the echocardiographer when providing measure‐ ments of the diameter of the annulus.

The controversy arises from the fact that on one hand there are multiple rings described and on the other hand, the term "annulus" appears to describe a circle, a fibrous ring on which the leaflets are inserted, but such a structure does not exist in the anatomy of the aortic valve. No consensus has been found yet.

**Figure 3.** The "rings" of the aortic root [1]

**Figure 2.** View of a dissected heart (the atrial chambers and the arterial trunks are removed). The heart is photograph‐

When defined literally "annulus" refers to a little ring. The aortic root contains at least 3 cir‐ cular rings and 1 crown-like ring. [21] The valvular leaflets are attached throughout the length of the root. Therefore, seen in 3 dimensions, the leaflets take the form of a 3-pronged coronet, with the hinges from the supporting ventricular structures forming the crown-like ring (Figure 1). The base of the crown is a virtual ring, commonly known as "annulus". This plane represents the inlet from the left ventricular outflow tract into the aortic root and is the diameter that is typically analysed by the echocardiographer when providing measure‐

The controversy arises from the fact that on one hand there are multiple rings described and on the other hand, the term "annulus" appears to describe a circle, a fibrous ring on which the leaflets are inserted, but such a structure does not exist in the anatomy of the aortic

ed from above. [4]

36 Calcific Aortic Valve Disease

**3.1. The "Annulus" controversy**

ments of the diameter of the annulus.

valve. No consensus has been found yet.

#### **3.2. Anatomic versus hemodynamic ventriculo-arterial junction**

As we have shown in figure 3, there is a marked discrepancy between the circular anatomic junction and the semilunar hemodynamic junction. [22] The hemodynamic junction sepa‐ rates the root into those compartments exposed to aortic as opposed to left ventricular pres‐ sures. By virtue of the semilunar attachments of the leaflets, portions of the fibrous aortic root are exposed to ventricular pressures, these being the superior portions of the interleaflet triangles, whereas portions of the left ventricle are exposed to aortic pressures, these being the most basal portions within the sinus of Valsalva. [1]

#### **3.3. Aortic sinuses, location of the coronary arteries and sinotubular junction**

The spaces between the luminal surface of the three bulges on the aortic root and their re‐ spective valvular leaflets are known as the aortic sinuses of Valsalva. [5] The sinuses are named according to the arteries arising from within them (right, left, and noncoronary). The right sinus structures have the greatest dimensions followed by the non coronary sinus, and finally the left coronary sinus. [23]


**Table 1.** Mean values of the distances of the ostium and its relation to the corresponding Valsalva's sinus (in mm) in both sexes (adapted from [24])

In the majority of cases, the orifices of the coronary arteries arise within the 2 anterior si‐ nuses of Valsalva, usually positioned just below the sinotubular junction, but are rarely cen‐ trally located. It is not unusual, however, for the arteries to be positioned superior relative to the sinotubular junction. Accessory coronary arterial orifices are found in the majority of the anterior aortic sinuses. [25]

lar junction, forming the commissures. The body of the leaflets are pliable and thin in the young, although its thickness is not uniform. With age, the leaflets become thicker and stiffer.

Each leaflet has a somewhat crimped surface facing the aorta and a smoother surface facing the ventricle. The leaflet is slightly thicker towards its free margin. On its ventricular surface is the zone of apposition, known as the lunulae, occupying the full width along the free mar‐ gin and spanning approximately one-third of the depth of the leaflet. This is where the leaf‐ let meets the adjacent leaflets during valvular closure. At the midportion of the lunulae, the ventricular surface is thickened to form the nodule of Arantius that extends along 60% of the inferior margin of the lunulae. When the valve is in closed position, the inferior margin of the lunulaes meet together, separating blood in the left ventricular cavity from blood in the aorta. Fenestrations in the lunulaes are common, especially in the elderly, but the valve re‐

The leaflets have a core of fibrous tissue, with endothelial linings on their arterial and ven‐ tricular aspects. Their origin from the supporting left ventricular structures, where the ven‐ tricular components give rise to the fibroelastic walls of the aortic valvular sinuses, marks the anatomic ventriculo-arterial junction. Significantly, in those areas where the leaflets arise from the ventricular myocardium, their basal attachments are well below the level of the

**Male Female**

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**Leaflet Measure Sex**

Left coronary Leaflet height 15.2 14.9

Right coronary Leaflet height 15.2 14.5

Noncoronary Leaflet height 15.0 14.6

**Table 2.** Mean values of the height of the leaflets and size of the lunulae (width and length) and internal

intercommissural distances in mm in both sexes (adapted from [24])

Lunulae width 4.6 4.3 Lunulae length 30.7 29.3 External intercommissural distance 25.4 23.5 Internal Intercommissural distance 20.0 18.5

Lunulae width 4.4 4.2 Lunulae length 30.4 27.9 External intercommissural distance 24.5 23.8 Internal Intercommissural distance 19.2 18.7

Lunulae width 4.3 4.2 Lunulae length 30.3 28.2 External intercommissural distance 24.4 22.1 Internal Intercommissural distance 20.1 19.1

mains competent because they are above the closure line. [5]

anatomic ventriculo-arterial junction. [1]

Several studies emphasize on the importance of large variations of coronary ostia origins. Also, there are significant differences between in vivo and ex vivo measurements regarding the right coronary ostium. [26,27]

The superior border of the sinuses is the sinotubular junction (also known as the supra-aort‐ ic ridge). On the outside, the sinotubular junction is where the tubular portion of the aorta joins onto the sinusal portion. Inside, there is usually a slightly raised ridge of thickened aortic wall. But the sinotubular junction is not perfectly circular. It takes on the contour of the three sinuses, giving it a mildly trefoil or scalloped outline. [5]

A comparison between the circumferences measured at the level of the sinotubular junction and at the level of the aortic root base shows that the circumference of the sinotubular junc‐ tion is 95% of the circumference measured at the aortic root base. [23]

#### **3.4. Aortic valvular leaflets**

The normal aortic valve has three leaflets. Each of the three leaflets has a free margin and a mar‐ gin where it is attached in semilunar fashion to the aortic root. The maximal height of each leaf‐ let is considerably less than that of its sinus on account of its scoop-shaped free margin. When the valve opens, the leaflets fall back into their sinuses without the potential of occluding any coronary orifice. The semilunar hingelines of adjacent leaflets meet at the level of the sinotubu‐ lar junction, forming the commissures. The body of the leaflets are pliable and thin in the young, although its thickness is not uniform. With age, the leaflets become thicker and stiffer.

In the majority of cases, the orifices of the coronary arteries arise within the 2 anterior si‐ nuses of Valsalva, usually positioned just below the sinotubular junction, but are rarely cen‐ trally located. It is not unusual, however, for the arteries to be positioned superior relative to the sinotubular junction. Accessory coronary arterial orifices are found in the majority of the

Several studies emphasize on the importance of large variations of coronary ostia origins. Also, there are significant differences between in vivo and ex vivo measurements regarding

**Figure 4.** Left (L) and right (R) aortic sinuses that give origin to the main coronary arteries and the non-coronary (N)

The superior border of the sinuses is the sinotubular junction (also known as the supra-aort‐ ic ridge). On the outside, the sinotubular junction is where the tubular portion of the aorta joins onto the sinusal portion. Inside, there is usually a slightly raised ridge of thickened aortic wall. But the sinotubular junction is not perfectly circular. It takes on the contour of

A comparison between the circumferences measured at the level of the sinotubular junction and at the level of the aortic root base shows that the circumference of the sinotubular junc‐

The normal aortic valve has three leaflets. Each of the three leaflets has a free margin and a mar‐ gin where it is attached in semilunar fashion to the aortic root. The maximal height of each leaf‐ let is considerably less than that of its sinus on account of its scoop-shaped free margin. When the valve opens, the leaflets fall back into their sinuses without the potential of occluding any coronary orifice. The semilunar hingelines of adjacent leaflets meet at the level of the sinotubu‐

the three sinuses, giving it a mildly trefoil or scalloped outline. [5]

tion is 95% of the circumference measured at the aortic root base. [23]

anterior aortic sinuses. [25]

38 Calcific Aortic Valve Disease

sinus. [5]

**3.4. Aortic valvular leaflets**

the right coronary ostium. [26,27]

Each leaflet has a somewhat crimped surface facing the aorta and a smoother surface facing the ventricle. The leaflet is slightly thicker towards its free margin. On its ventricular surface is the zone of apposition, known as the lunulae, occupying the full width along the free mar‐ gin and spanning approximately one-third of the depth of the leaflet. This is where the leaf‐ let meets the adjacent leaflets during valvular closure. At the midportion of the lunulae, the ventricular surface is thickened to form the nodule of Arantius that extends along 60% of the inferior margin of the lunulae. When the valve is in closed position, the inferior margin of the lunulaes meet together, separating blood in the left ventricular cavity from blood in the aorta. Fenestrations in the lunulaes are common, especially in the elderly, but the valve re‐ mains competent because they are above the closure line. [5]

The leaflets have a core of fibrous tissue, with endothelial linings on their arterial and ven‐ tricular aspects. Their origin from the supporting left ventricular structures, where the ven‐ tricular components give rise to the fibroelastic walls of the aortic valvular sinuses, marks the anatomic ventriculo-arterial junction. Significantly, in those areas where the leaflets arise from the ventricular myocardium, their basal attachments are well below the level of the anatomic ventriculo-arterial junction. [1]


**Table 2.** Mean values of the height of the leaflets and size of the lunulae (width and length) and internal intercommissural distances in mm in both sexes (adapted from [24])

Variations exist among individuals in the dimensions of the root, but in the same indi‐ vidual, there can be marked variations in all aspects of the dimensions of the individual leaflets, including the height, width, surface area and volume of each of the supporting sinuses of Valsalva. [28, 29, 30] A study of 200 normal hearts revealed that the average width, measured between the peripheral zones of attachment along the sinus ridge, for the right, the noncoronary, and the left coronary leaflets was 25.9, 25.5, and 25.0 mm, re‐ spectively. [28]

#### **3.5. Interleaflet fibrous triangles**

As a result of the semilunar attachment of the aortic valvular leaflets, there are 3 trian‐ gular extensions of the left ventricular outflow tract that reach to the level of the sino‐ tubular junction. [31] These triangles, however, are formed not of ventricular myocardium but of the thinned fibrous walls of the aorta between the expanded sinuses of Valsalva. Their most apical regions represent areas of potential communication with the pericardial space or, in the case of the triangle between the right and left coronary aortic leaflets, with the plane of tissue interposed between the aorta and anteriorly locat‐ ed sleeve-like subpulmonary infundibulum. [1]

The triangles are thinner and less collagenous than the hingelines or the sinusal walls. These areas are potential sites of aneurysmal formation. [32]

**Figure 5.** A dissected atrioventricular junction viewed from above showing how the aortic valve wedges itself be‐

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Guarding the left ventricular outflow tract, the aortic root also has an intimate relationship with the ventricular septum and the mitral valve. In attitudinal orientation, it is apparent that the aortic root leans rightward slightly, over the ventricular septum, to overly the right ventricle. In the elderly, the relationship between septal crest and aortic root changes to give

Relative to the aorta, the mitral valve is located posterior and to the left, the tricuspid valve

The ends of the area of fibrous continuity are thickened to form the left and right fibrous trigones. The interleaflet triangle between the noncoronary and left coronary leaflet is part of the area of fibrous continuity because the aortic-mitral curtain seen from within the left ventricular outflow tract represents the equivalent of the anterior mitral valvular annulus. The interleaflet triangle located between the right coronary and noncoronary aortic leaflets is confluent with the membranous septum. Together, the membranous septum and the right fibrous trigone form the central fibrous body of the heart. This is the area within the heart where the membranous septum, the atrioventricular valves and the aortic valve join in fi‐

The atrioventricular node, located in the wall of the right atrium at the apex of the triangle of Koch, is relatively distant from the root. As the conduction axis, penetrates to the left, through the central fibrous body, however, it is positioned at the base of the interleaflet tri‐

*3.6.2. Interleaflet triangles and their relationship to the mitral valve and membranous septum*

tween the mitral and tricuspid valves (reproduced from http://www.rjmatthewsmd.com)

*3.6.3. Relationship between the aortic valve and the conduction system*

a sigmoid-shaped ventricular septum. [4]

is located inferiorly and to the right.

brous continuity. [1]

#### **3.6. The relationships of the aortic root**

The aortic root is positioned to the right and posterior relative to the subpulmonary infun‐ dibulum. The leaflets of the aortic valve are attached only in part to the muscular walls of the left ventricle, since so as to fit the orifices of both aortic and mitral valves within the cir‐ cular profile of the left ventricle, there is no muscle between them in the ventricular roof. The aortic root, furthermore, is wedged between the orifices of the two atrioventricular valves. The root is related to all four cardiac chambers. [4]

The plane of the aortic valve tilts inferiorly at an angle to the pulmonary valve. The nadirs of the aortic sinuses lie in a plane at an angle of 30º from the horizontal. [32] Thus, the arterial surface of the closed leaflets of the aortic valve is directed not only upwards but also right‐ ward at an angle of at least 45º to the median plane. [33]

#### *3.6.1. Relationship between the left ventricular outflow tract and the aortic root*

The left ventricular outflow tract is composed of a muscular component and a more exten‐ sive fibrous component. The orientation of the outflow tract is known to change with aging. In individuals aged under 20 years, the angle varies between 135 and 180 degrees and the left ventricular outflow tract represents a more direct and straight extension into the aortic root. In hearts from individuals aged over 60 years, the angle varies between 90 and 120 de‐ grees and the left ventricular outflow tract may not extend in straight fashion into the aortic root but rather in a rightward "dog leg". [1]

Variations exist among individuals in the dimensions of the root, but in the same indi‐ vidual, there can be marked variations in all aspects of the dimensions of the individual leaflets, including the height, width, surface area and volume of each of the supporting sinuses of Valsalva. [28, 29, 30] A study of 200 normal hearts revealed that the average width, measured between the peripheral zones of attachment along the sinus ridge, for the right, the noncoronary, and the left coronary leaflets was 25.9, 25.5, and 25.0 mm, re‐

As a result of the semilunar attachment of the aortic valvular leaflets, there are 3 trian‐ gular extensions of the left ventricular outflow tract that reach to the level of the sino‐ tubular junction. [31] These triangles, however, are formed not of ventricular myocardium but of the thinned fibrous walls of the aorta between the expanded sinuses of Valsalva. Their most apical regions represent areas of potential communication with the pericardial space or, in the case of the triangle between the right and left coronary aortic leaflets, with the plane of tissue interposed between the aorta and anteriorly locat‐

The triangles are thinner and less collagenous than the hingelines or the sinusal walls. These

The aortic root is positioned to the right and posterior relative to the subpulmonary infun‐ dibulum. The leaflets of the aortic valve are attached only in part to the muscular walls of the left ventricle, since so as to fit the orifices of both aortic and mitral valves within the cir‐ cular profile of the left ventricle, there is no muscle between them in the ventricular roof. The aortic root, furthermore, is wedged between the orifices of the two atrioventricular

The plane of the aortic valve tilts inferiorly at an angle to the pulmonary valve. The nadirs of the aortic sinuses lie in a plane at an angle of 30º from the horizontal. [32] Thus, the arterial surface of the closed leaflets of the aortic valve is directed not only upwards but also right‐

The left ventricular outflow tract is composed of a muscular component and a more exten‐ sive fibrous component. The orientation of the outflow tract is known to change with aging. In individuals aged under 20 years, the angle varies between 135 and 180 degrees and the left ventricular outflow tract represents a more direct and straight extension into the aortic root. In hearts from individuals aged over 60 years, the angle varies between 90 and 120 de‐ grees and the left ventricular outflow tract may not extend in straight fashion into the aortic

spectively. [28]

40 Calcific Aortic Valve Disease

**3.5. Interleaflet fibrous triangles**

ed sleeve-like subpulmonary infundibulum. [1]

**3.6. The relationships of the aortic root**

areas are potential sites of aneurysmal formation. [32]

valves. The root is related to all four cardiac chambers. [4]

ward at an angle of at least 45º to the median plane. [33]

root but rather in a rightward "dog leg". [1]

*3.6.1. Relationship between the left ventricular outflow tract and the aortic root*

**Figure 5.** A dissected atrioventricular junction viewed from above showing how the aortic valve wedges itself be‐ tween the mitral and tricuspid valves (reproduced from http://www.rjmatthewsmd.com)

#### *3.6.2. Interleaflet triangles and their relationship to the mitral valve and membranous septum*

Guarding the left ventricular outflow tract, the aortic root also has an intimate relationship with the ventricular septum and the mitral valve. In attitudinal orientation, it is apparent that the aortic root leans rightward slightly, over the ventricular septum, to overly the right ventricle. In the elderly, the relationship between septal crest and aortic root changes to give a sigmoid-shaped ventricular septum. [4]

Relative to the aorta, the mitral valve is located posterior and to the left, the tricuspid valve is located inferiorly and to the right.

The ends of the area of fibrous continuity are thickened to form the left and right fibrous trigones. The interleaflet triangle between the noncoronary and left coronary leaflet is part of the area of fibrous continuity because the aortic-mitral curtain seen from within the left ventricular outflow tract represents the equivalent of the anterior mitral valvular annulus. The interleaflet triangle located between the right coronary and noncoronary aortic leaflets is confluent with the membranous septum. Together, the membranous septum and the right fibrous trigone form the central fibrous body of the heart. This is the area within the heart where the membranous septum, the atrioventricular valves and the aortic valve join in fi‐ brous continuity. [1]

#### *3.6.3. Relationship between the aortic valve and the conduction system*

The atrioventricular node, located in the wall of the right atrium at the apex of the triangle of Koch, is relatively distant from the root. As the conduction axis, penetrates to the left, through the central fibrous body, however, it is positioned at the base of the interleaflet tri‐ angle between the non- and right coronary aortic sinuses. Having penetrated through the fi‐ brous plane providing atrioventricular insulation, the bundle then branches on the crest of the muscular ventricular septum, the left bundle branch fanning out on the smooth left ven‐ tricular side, while the cord-like right bundle branch penetrates back through the muscular septum, emerging on the septal surface in the environment of the medial papillary muscle (figure 6). [4]

tween the non-coronary and the right-coronary aortic sinus is incorporated within the mem‐ branous part of the septum and is also made of fibrous tissue. In contrast, the triangle between the right-coronary and left-coronary sinus in the area of the subpulmonary infun‐

Anatomy and Function of Normal Aortic Valvular Complex

http://dx.doi.org/10.5772/53403

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The sinuses are arranged with very different components, but the largest part of all the three sinuses is composed in a similar manner to the three layers of the aortic wall: tunica intima, tunica media and tunica externa (adventitia). The inner layer of the intima is composed of endothelial cells arranged in the direction of the vessel. The subendothelial connective tissue is arranged in the same manner as the endothelial cells. This layer is divided from the intima by the membrana elastica interna. The media is composed of circular arranged structures: smooth muscle cells, elastic fibres, collagen fibres type II and III and proteoglycans. The ad‐ ventitia is the external layer. It is separated from the intima by the membrana elastica exter‐ na. Similar to the intima, the elements of the adventitia are arranged in a longitudinal fashion and composed of collagen fibres of type I. The sinotubular junction shows the same principal arrangement of tissue elements compared with the sinuses and the ascending aor‐

dibulum is supported by muscular tissue and only fibrous at its apex.

ta, but the diameter of the wall is thicker. [34]

**Figure 7.** Histology of the aortic valvular complex [1]

**Figure 6.** Aortic sinuses, coronary arteries and the the location of the atrioventricular conduction axis, as seen by look‐ ing down through the aortic root (schematic from [4])
