Functionally bileaflet aortic valve

The functionally bileaflet, or “bicuspid,” aortic valve is found in almost nine-tenths of all congenitally malformed roots.^{Reference Sabet, Edwards, Tazelaar and Daly22,Reference Sillesen, Vøgg and Pihl23} Possessing 3 leaflets, sinuses, and interleaflet triangles, its presence reflects the fusion, during development, of 2 of the leaflets, with a resulting raphe. The corresponding interleaflet triangle is hypoplastic, no longer extending distally to reach the sinutubular junction. The “raphe” is the prominent tissue found at the site of fusion between the leaflets and can be variable in its extent. Fused variants have been described in its absence.^{Reference Michelena, Della Corte and Evangelista3} This could reflect ambiguity in the use of “raphe,” or indicate that the lesions are bisinuate rather than trisinuate. We have yet, in our collective experiences, to encounter a trisinuate root with 2 functional leaflets lacking a raphe. When a zone of fusion is present, our evidence suggests that a raphe will be present, even if minimally formed. Should ambiguity persist, attention should be turned toward long-axis echocardiographic imaging and cross-sectional interrogation of the hypoplastic interleaflet triangle, which would be present in the trisinuate but not the bisinuate variant (Supplemental Figures 1, 2).

Incomplete fusion of less than half of the zone of apposition is commonly considered a “partial,” or “forme fruste” bicuspid valve. We have found an inverse relationship between the length of the zone of fusion and the corresponding hypoplasia of the interleaflet triangle, with a spectrum from zero to complete (Figures 4A, 4B). This feature, along with asymmetry between the conjoined and third leaflets, dictates the plane of opening of the valvar orifice area relative to the long axis of the ascending aorta and to the plane of the sinutubular junction. Such asymmetry is pronounced compared with the normal aortic root.^{Reference Tretter, Spicer, Mori, Chikkabyrappa, Redington and Anderson6,Reference Sabet, Edwards, Tazelaar and Daly22} The degree of asymmetry is held to guide the type of surgical repair, as well as predicting its durability.

Figure 4. (A, B) Two different functionally bileaflet aortic valves. (A) Partial fusion between the right and noncoronary leaflets, with the zone of fusion (black double-headed arrow) representing <50% of the zone of apposition. (B) A functionally bileaflet aortic valve with greater fusion between the coronary leaflets and lower height of the corresponding interleaflet triangle (yellow caret). This reduces the aortic valvar opening area and tilts its plane at a greater angle relative to that of the sinutubular junction. (C) The bileaflet aortic valve with bisinuate aortic root. There are 2 leaflets, sinuses, and normal size interleaflet triangles, both with their apex reaching to the plane of the sinutubular junction (red dotted line). (D) A quadrileaflet and quadrisinuate aortic root, also without fusion between any of the leaflets, and therefore functioning as a quadrileaflet valve.

In the so-called symmetrical arrangement, with the 2 commissures positioned directly opposite each other at 160° to 180°, the surgical recommendation is usually an approach which maintains its “bicuspid” form. When the commissures are at 120° to 139° from each other, the arrangement is said to be “very asymmetric,” lending itself to “tricuspidization.” The intermediate position is deemed “asymmetric” (Figure 3, middle row). Depending on the strategy used for repair, and the commissural orientation, repositioning of the commissures has been demonstrated to improve valvar function and durability.^{Reference de Kerchove, Mastrobuoni and Froede24}

It is most usually the right and left coronary leaflets that are fused, followed by the right and noncoronary leaflets, and rarely, the left and noncoronary leaflets (Supplemental Figures 1A, 1B).^{Reference Sievers and Schmidtke1,Reference Sabet, Edwards, Tazelaar and Daly22} The rarity of the third variant may relate to the varied rotational position of the aortic root, and the corresponding variability in the underlying myocardial vs fibrous support.^{Reference Tretter, Mori and Saremi11,Reference Amofa, Mori and Toh12}

When preparing for surgical repair, note should be taken of the height of the interleaflet triangles, which can accurately be measured using 3-dimensional imaging with multiplanar reformatting.^{Reference Tretter, Izawa and Spicer4,Reference Hagendorff, Evangelista, Fehske and Schäfers25} The leaflets themselves can be thickened, calcified, or fenestrated, as well as being compromised by subcommissural fusion. Should any components of the root be hypoplastic, this should be described (Supplemental Table 3).^{Reference Tretter, Izawa and Spicer4}

Bileaflet and bisinuate aortic valve

A minority of malformed roots, less than one-tenth, are built on a bisinuate scaffold.^{Reference Sillesen, Vøgg and Pihl23} These phenotypes are more frequent in syndromes, particularly in Turner syndrome, which has the highest penetrance of bicuspid aortic valves, regardless of the valvar phenotype.^{Reference Klásková, Zapletalová and Kaprálová26} The root with 2 leaflets and 2 sinuses has only 2 interleaflet triangles, each of normal height, and hence equating to 2 normal commissures (Figure 4C). The normal height of the interleaflet triangles provides an orifice relatively parallel to the normal plane of the sinutubular junction.^{Reference Tretter, Spicer, Mori, Chikkabyrappa, Redington and Anderson6} This feature probably accounts for the lower propensity for ascending aortic dilation when compared with the functionally bileaflet variant. The paired leaflets and sinuses can be positioned anteroposteriorly or laterolaterally (Supplemental Figures 1C, 1D). The leaflets can be additionally malformed, be associated with subvalvar lesions impacting on leaflet motion, or the root itself can be hypoplastic.^{Reference Tretter, Izawa and Spicer4}

Functionally unileaflet aortic valve

The functionally unileaflet, or “unicuspid,” variant is built on a trisinuate scaffold. Considered rare in the adult populations,^{Reference Novaro, Mishra and Griffin27,Reference Roberts and Ko28} its true prevalence is likely underestimated due to misdiagnosis as a functionally bileaflet valve.^{Reference Roberts and Ko28,Reference Slostad, Witt and O’Leary29} In newborns, it is the commonest form of critical aortic stenosis.^{Reference Tretter, Spicer, Mori, Chikkabyrappa, Redington and Anderson6} Its leaflets show 2 zones of fusion, each with a corresponding raphe and hypoplasia of the corresponding interleaflet triangle. Most commonly, the solitary zone of apposition is between the noncoronary and left coronary leaflets, with the solitary commissure positioned above the aortic-mitral curtain (Figure 5; Supplemental Video 1).^{Reference Tretter, Spicer, Mori, Chikkabyrappa, Redington and Anderson6} The lines of attachment of the conjoined leaflets are much closer to being truly annular.^{Reference Tretter, Steffensen, Westover, Anderson and Spicer30} When found in neonates or infants, the leaflets tend to be severely thickened (Figures 5A, 5B), but in adolescents or adults, there tends to be less complete fusion between the leaflets, with a greater opening area, and a less annular line of leaflet attachment (Figures 5C, 5D; Supplemental Figure 3).^{Reference Tretter, Spicer, Mori, Chikkabyrappa, Redington and Anderson6} Either way, the 3-dimensional plane of the aortic valvar opening area is at a significantly increased angle relative to the long axis of the ascending aorta compared with the functionally bileaflet form (Supplemental Figure 3C; Supplemental Video 2).^{Reference Tretter, Izawa and Spicer4} This results in an increased perturbance of flow.^{Reference Entezari, Schnell and Mahadevia31}

Figure 5. Two functionally unileaflet and trisinuate aortic roots are shown with fusion between the right and left, and right and noncoronary leaflets (black dots mark the zones of fusion, and the yellow dot with the black border marks the normal commissure). (A, B) A greater degree of fusion is seen in this heart between both pairs of leaflets, with smaller interleaflet triangles. (C, D) The corresponding interleaflet triangles in this heart are larger. (A, B) Much thicker aortic valvar leaflets are additionally demonstrated. This combination results in a much smaller aortic valvar opening area. The difference in interleaflet triangle heights dictates the degree of inferior tilting of the aortic valvar opening area of the involved adjacent leaflets. (A, D) The red arrows mark the left coronary artery. The yellow dotted line represents the sinutubular junction.

In this light, it becomes intuitive that studies support early progression toward valvar dysfunction and dilation of the thoracic aorta in those with a functionally unileaflet aortic valve.^{Reference Mookadam, Thota and Garcia-Lopez32} These theories, however, require further investigation. Misdiagnosis may relate to the through-plane motion of 2-dimensional echocardiography, which can suggest that the zone of apposition has been interrogated in its entirety.^{Reference Ewen, Karliova and Weber33} To avoid this problem, it is advantageous also to use 3-dimensional echocardiography (Supplemental Video 3).^{Reference Hagendorff, Evangelista, Fehske and Schäfers25} If being considered for surgical repair, all features should all be interrogated by 3-dimensional imaging with multiplanar reformatting.^{Reference Tretter, Izawa and Spicer4,Reference Hagendorff, Evangelista, Fehske and Schäfers25} The leaflets themselves are usually abnormal, particularly when encountered in neonates, and are usually associated with hypoplasia of the aortic root.^{Reference Tretter, Izawa and Spicer4}

Additional congenital and acquired abnormalities

Attention should be directed in all variants toward the presence of thickening or nodularity, perforation,^{Reference Hill, Bansal, Razzouk, Liu, Bailey and Gundry36} fenestration,^{Reference Reade, Szeto and Bavaria37} elongation, retraction, bending,^{Reference Soga, Takaya, Mori, Nishii and Hirata38} prolapse, flail, or billowing of the leaflets. A leaflet may rarely be absent^{Reference Tretter, Steffensen, Westover, Anderson and Spicer30} or duplicated (Supplemental Table 3). If present, the location of the associated calcification should be described. Calcification along a zone of apposition can produce acquired fusion, thus mimicking congenital fusion.^{Reference Pawade, Sheth, Guzzetti, Dweck and Clavel39,Reference Jilaihawi, Makkar and Kashif40} Dilation can involve any part of the root or the ascending aorta. Abnormal function can reflect obstruction to flow, with stenosis within the left ventricular outflow tract or at the level of the leaflets or sinutubular junction, or incompetency of the valve.

Mention is required of the aortoventricular tunnel. This channel bypasses the attachment line of a leaflet, producing a passage from the valvar sinus into the left or right ventricle. This can be accompanied by bileaflet, dysplastic, or ectopic aortic valvar tissue.^{Reference McKay, Anderson and Cook41} Abnormal communications can also result from rupture of an acquired or congenital aneurysm of a sinus of Valsalva, infective endocarditis, aortic dissection, and traumatic or iatrogenic injury.

Normal aortic root dimensions

Accurate imaging requires an adequate terminology. The virtual basal ring extends between the nadirs of the semilunar leaflets. Long-axis 2-dimensional imaging will hover between an off-center plane joining the nadirs of the right and noncoronary leaflets and a nonspecific center plane.^{Reference Mori, Izawa, Shimoyama and Tretter42,Reference Mori, Anderson and Tahara43} It is difficult to be sure of the true plane of the virtual basal ring itself without the use of 3-dimensional imaging and multiplanar reformatting.^{Reference Tretter, Izawa and Spicer4} Long-axis imaging, in the absence of such 3-dimensional imaging, often cuts the virtual basal ring in oblique fashion, with an increasing value achieved when moving toward a nonspecific center plane (Figure 6).^{Reference Tretter and Mori44} These caveats underscore the limitations of the continuity equation in assessing the dimensions of the oval virtual basal ring.

Figure 6. The left-side image demonstrates a 3-dimensional reconstruction of a normal aortic root in diastole, with the virtual basal ring marked with the green oval. The blue and purple circles mark the nadirs of the assessed leaflets. The middle panels demonstrate short-axis 2-dimensional planes at the virtual basal ring and aortic root. (A-C) The right-side panels are framed in the color of the corresponding colored dashed lines in the left-side panels. Only the center bisecting plane (A), with accurate marking of the virtual basal ring plane using multiplanar reformatting, permits precise measurement of the effective height (EH), coaptation length (CL), geometric height (GH), commissural height (CH), and free margin length (FML). Long-axis imaging of the aortic root, as obtained by 2-dimensional echocardiography, hovers between lines B and C, leading to underestimation (superscript U) and overestimation (superscript O) of these various metrics. The brown line represents the plane of the sinutubular junction. (LCA, left coronary artery; RCA, right coronary artery.)

Two-dimensional assessment of the sinuses by long-axis imaging provides a maximal dimension when moving from the off-center plane joining the nadirs of the visualized leaflets toward a nonspecific center plane. An apparent decrease in the coaptation length will be noted centrally (compare Figure 2 and Figure 6). This provides a clue that the cut plane is approaching the central zone of coaptation.^{Reference Tretter, Izawa and Spicer4,Reference De Kerchove, Momeni and Aphram8,Reference Mori, Anderson and Tahara43}

Three separate methods have been proposed to measure the short axis of the root (Supplemental Figure 4). Of these measurements, 2 carry the name “cusp-to-cusp.” The original method is better described as “largest sinus-to-sinus” dimension. The more recent method provides a “center of sinus-to-center of sinus” measurement,^{Reference Tretter and Mori44} which correlates well with long-axis measurements.^{Reference Rodríguez-Palomares, Teixidó-Tura and Galuppo45} Only the “largest sinus-to-sinus” dimensions have normative values established in adults using magnetic resonance imaging.^{Reference Burman, Keegan and Kilner46} The “cusp-to-commissure” method, more accurately described as “center of sinus-to-opposite commissure,” does have normative adult values.^{Reference Tretter and Mori44} This method correlates strongly with 3-dimensional volumes.^{Reference Suzuki, Mori and Izawa7} No evidence currently supports the use of one method over the others, nor are we aware of any evidence to suggest the benefits of measuring “leading edge to leading edge” vs “inner edge to inner edge,” or using a specific time of the cardiac cycle. Institutional consistency is therefore paramount, with reporting provided of both the method used and the timing of the cardiac cycle.

Compared with the virtual basal ring, the sinutubular junction is relatively more circular. Its plane differs by approximately 5° to 10° relative to that of the virtual basal ring, with a lower tilt angle produced during ventricular systole.^{Reference Tretter, Spicer, Mori, Chikkabyrappa, Redington and Anderson6,Reference Izawa, Mori and Tretter17}

Dimensions of the congenitally malformed aortic root

Assessing dimensions becomes increasingly complex when the root is congenitally malformed. In the functionally unileaflet and bileaflet roots, there is frequent significant asymmetry between the aortic leaflets and sinuses, potentially making transthoracic echocardiography inaccurate in this setting.^{Reference Vis, Rodríguez-Palomares and Teixidó-Tura47} This technique should maintain its central role in the serial follow-up, but there should be a lower threshold also for obtaining cross-sectional imaging to provide the most accurate measurements. The cross-sectional methods established for the trisinuate root are inappropriate for measuring the bisinuate root. Instead, it may be more appropriate to measure from center of sinus-to-center of sinus, with subsequent measurement from commissure-to-commissure.^{Reference Tretter and Mori44} Similarly, trisinuate methods should not be applied to the quadrisinuate root. All said, there are no normative values for comparison to these patients without a trisinuate root. In the congenitally malformed aortic root with hypoplasia of 1 or more interleaflet triangles, furthermore, it becomes challenging to define the plane of the sinutubular junction. In these rare variants, suggested methods thus far are guided by opinion only. When monitoring these patients, given the complexity of measuring the congenitally malformed aortic root, it may be helpful to measure cross-sectional areas or three-dimensional volumes.^{Reference Suzuki, Mori and Izawa7}

Standardized assessment of aortic valvar dysfunction

Echocardiographic assessment of the degree of aortic valvar stenosis and regurgitation is well established, occasionally complimented by cardiac magnetic resonance imaging.^{Reference Baumgartner, Hung and Bermejo48} More recently, standard assessment of the aortic leaflets and their diastolic competency has been established using 3-dimensional imaging with multiplanar reformatting (Supplemental Table 1).^{Reference Tretter, Izawa and Spicer4,Reference Izawa, Mori and Tretter17,Reference Hagendorff, Evangelista, Fehske and Schäfers25} Such measurements have been used to guide a geometric approach toward surgical repair or preservation of the aortic valve.^{Reference Schäfers, Bierbach and Aicher49,Reference The50} They are commonly assessed in middiastole.^{Reference Izawa, Mori and Tretter17,Reference Hagendorff, Evangelista, Fehske and Schäfers25,Reference Mori, Izawa, Shimoyama and Tretter42} Accurate assessment, where a difference of a few millimeters becomes important, can only be achieved when using the center bisecting plane (Figure 6A, red dotted in the left-side panel), having accurately identified the plane of the virtual basal ring.^{Reference Izawa, Mori and Tretter17,Reference Mori, Izawa, Shimoyama and Tretter42}

The dimensions of the leaflets are based on their geometric height,^{Reference Mori, Izawa, Shimoyama and Tretter42,Reference Schäfers, Bierbach and Aicher49,Reference Schäfers, Schmied, Marom and Aicher51} a curvilinear measurement taken within the extent of the root along the midline of the leaflet from its nadir at the virtual basal ring to the center point of its free margin edge, along with the free margin length, a curvilinear measure of the distance between the commissures along the edge of the leaflet.^{Reference Mori, Izawa, Shimoyama and Tretter42} The commissural height is the distance from the virtual basal ring along the long axis of an interleaflet triangle to the sinutubular junction. Comparison of these measurements becomes increasingly important in the congenitally malformed aortic root with 1 or more zones of fusion between the leaflets and with hypoplasia of the corresponding interleaflet triangles.

The coaptation length represents the linear extent of the segment of apposition involved at the central point of coaptation. When moving laterally from the center bisecting plane, the visualized coaptation length increases relative to the normal increased coaptation surface area along the lateral aspects of the zone of apposition (compare Figure 2 with Figure 6).^{Reference Tretter, Izawa and Spicer4,Reference De Kerchove, Momeni and Aphram8} Standardized assessments, obtained from the central bisecting plane, are obtained at the central point of coaptation.^{Reference Tretter, Izawa and Spicer4} The effective height is the linear measurement from the center of the virtual basal ring to the cephalad edge of the central segment of coaptation of the leaflets. Normative values have now been reported intraoperatively,^{Reference De Kerchove, Momeni and Aphram8,Reference Schäfers, Schmied, Marom and Aicher51} and more recently for adults using computed tomography.^{Reference Tretter, Izawa and Spicer4}