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Anatomic three-dimensional echocardiographic correlation of bicuspid aortic valve
Anatomic Three-dimensional Echocardiographic Correlation of Bicuspid Aortic Valve Nilda Espinola-Zavaleta, MD, PhD, Luis Mun ˜oz-Castellanos, MD, Fause Attie´, MD, Gunther Herna´ndez-Morales, MD, Carlos Zamora-Gonza´lez, MD, Roy Duen ˜ as-Carbajal, MD, Nuria Granados, MD, Candace Keirns, MD, and Jesu´s Vargas-Barro´n, MD, Mexico City, Mexico
This study was undertaken to verify the echocardiographic characteristics of bicuspid aortic valve (AV) using 3-dimensional transesophageal echocardiography by comparing the findings with anatomic examination of autopsy specimens from carriers of this condition. Three-dimensional reconstructions of transesophageal echocardiograms were performed on 14 patients with bicuspid AV, and 20 autopsy specimens of bicuspid AVs were analyzed. Echocardiographic images and autopsy material were correlated. Two variants of bicuspid aorta were identified. In group I the AV had 2 leaflets. This group included 9 (9/14) 3-dimensional echocardio-
B
icuspid aortic valve AV is one of the most common forms of congenital heart disease, with a prevalence of up to 3% of the general population.1 Bicuspid AV can be either congenital or acquired, in the latter case, secondary to inflammatory processes.2,3 A congenital bicuspid AV can have a vestigial raphe that partially subdivides one of the leaflets; in acquired bicuspid AV the raphe is more pronounced and fibrous, and reaches the free edge of the leaflet. The origin can always be determined by direct inspection, and histologic examination of the leaflets is only necessary in exceptional cases.1,2 Anatomopathological series have shown a broad spectrum of bicuspid AV anatomic variations, including anteroposterior or left-to-right orientation. Variants appear in similar proportions.1,2 The importance of studying bicuspid AV is the tendency of this malformation to lead to stenosis.4-7 There is a general consensus that approximately
From the Instituto Nacional de Cardiologı´a “Ignacio Cha´vez.” Reprint requests: Nilda Espinola-Zavaleta, MD, PhD, Department of Echocardiography, Instituto Nacional de Cardiologı´a “Ignacio Cha´vez,” Juan Badiano No. 1, Colonia Seccio´n XVI, 14080 Tlalpan, Mexico City, Mexico. Copyright 2003 by the American Society of Echocardiography. 0894-7317/2003/$30.00 ⫹ 0 doi:10.1067/mje.2003.30
46
graphic studies and 13 (13/20) necropsies. In group II 3 sigmoid leaflets had originally developed and 2 underwent dysplastic fusion, resulting in functionally bicuspid valves. Five (5/14) echocardiographic studies and 7 (7/20) anatomic specimens fell into this category. There was a clear correspondence between anatomic and echocardiographic findings, which leads to the conclusion that 3-dimensional echocardiography is a technique that reliably defines the morphological details of bicuspid AV with the precision of anatomopathologic examination. (J Am Soc Echocardiogr 2003;16:46-53.)
50% of adults between 60 and 75 years of age with aortic stenosis have bicuspid AV.4 In these patients the stenosis progresses more rapidly when the leaflets are unequal in size and their disposition is anteroposterior. As an isolated phenomenon, biscupid AV can cause severe aortic regurgitation (1.5%3%).8 Diagnosis of bicuspid AV is difficult for the clinician. Work by Brandenburg et al9 has established how echocardiography can be used to analyze the AV and demonstrate 2 leaflets and 2 commissures in the parasternal short-axis image. However, the morphology of a bicuspid AV cannot be determined with a transthoracic technique in 25% of the cases because of severe fibrosis or calcification of the leaflets. By contrast, transesophageal echocardiography with multiplane probe has high sensitivity and specificity (87% and 91%, respectively) for characterizing AV anatomy with precision.10 Three-dimensional (3D) echocardiography is a new diagnostic technique that makes it possible to obtain more anatomic details of bicuspid AV in vivo and, thus, predict the clinical course of the lesion. In addition, preoperative familiarity with the valvular lesion would be of great help in planning surgical strategy before thoracotomy. This study was undertaken to confirm the fidelity of 3D reconstruction of the transesophageal echocardiographic images of bicuspid AV by correlating them with autopsy specimens of this lesion.
Journal of the American Society of Echocardiography Volume 16 Number 1
Figure 1 A, Transverse section of aorta at level of valve. Note bicuspid structure with lateralized (left and right) commissures. Right-anterior semilunar (ASV) and posterior (PSV) leaflets have thickened edges (arrowheads) and calcifications on external aspect of anterior leaflet (arrow). B, Three-dimensional arterial view of aortic valve. Lateralized commissures and anteroposterior leaflets (ASV and PSV) with thickening (arrowheads) and calcifications (arrows) on external aspect of both leaflets can be seen. Left panel, in diastole; right panel, in systole.
MATERIALS AND METHODS Fourteen patients with suspected bicuspid AV were studied. Five were men and 9 women; average age was 29.9 years (range 18 to 47). Transesophageal echocardiography with 3D reconstruction was performed on all of the patients. Twenty anatomic specimens of this lesion were examined. 3D Echocardiographic Studies Examination procedure. All patients underwent transesophageal echocardiography using the Sonos 5500 system (Hewlett-Packard, Andover, Mass), which has the capability for acquisition of serial cross-sectional echocardiographic images by a multiplane probe. With patients under conscious sedation, the inserted probe was positioned at the level of the AV, and cross-sectional images with increments of 2 degrees were acquired with cardiac and respiratory cycle gating. The AV had to be visualized somewhere from 30 to 70 degrees and then again approximately from 120 to 150 degrees during 1 complete rotation of the transducer with the probe fixed. The stored serial cross-sectional data in the optical disk were transferred to a computer (Echo-Scan, version 3.1, TomTec Gmb H, Munich, Germany) for analysis of the 3D echocardiographic data set, as previously described.11 The analysis program of the 3D echocardio-
Espinola-Zavaleta et al 47
Figure 2 A, Arterial view of specimen shows lateralized commissures (asterisks), thickened edges (arrowheads), and areas of calcification on internal aspect (arrow). B, Threedimensional echocardiographic image shows lateralized commissures (asterisks) and semilunar leaflets in anteroposterior orientation. In image in systole, calcification on internal aspect of anterior leaflet (arrow) and thickening of edges of both leaflets (arrowheads) is evident. ASV, rightanterior semilunar leaflet; PSV, posterior leaflet; left panel, in diastole; right panel, in systole.
graphic system performed data processing offline. Cardiac cross-sections were formatted in their correct sequence according to their electrocardiogram phase in cubic data sets (256 ⫻ 256 pixels/each 8 bits). The postprocessing of the data set was performed offline with the reconstruction software. The image data were converted from polar to Cartesian coordinate format and interpolated to “fill the gaps” between sequential cross-sections. A reduction of spatial artifacts filter was used to reduce motion artifacts created by patients, probe movement, or respiration. Image display. The AV was imaged from a computergenerated short-axis view (aortotomy view) that allowed for identification of the number, size, and features of cusps; the fusion of the commissures; and the presence of thickenings and calcification. Volume-rendered display. Once an appropriate cut plane had been chosen, a threshold value was selected to differentiate cardiac structures from the blood pool and background. The gray-scale information of the structures
48 Espinola-Zavaleta et al
Figure 3 A, Arterial view of bicuspid aortic valve (AV). Lateral position of 2 commissures and anteroposterior orientation of semilunar leaflets (asterisks) can be observed. Both leaflets are thickened (arrowheads). B, Arterial view of bicuspid AV. Image on left (diastole) shows lateral position of commissures and anteroposterior orientation of semilunar leaflets with thickened edges (arrowheads). Right panel is in systole. ASV, right-anterior semilunar leaflet; PSV, posterior leaflet.
was rendered, and a gradient shading algorithm enhanced the views. Image analysis. Two experienced observers analyzed all the echocardiograms. Echocardiographic images were compared with anatomic specimens to determine similarity. The anatomic specimens were selected from the museum of pathology of the National Institute of Cardiology “Ignacio Cha´vez.”
RESULTS Two variants of bicuspid AV were found. In the first (group I) the AV had 2 well-defined leaflets. This was found in 9 echocardiographic studies and 13 anatomic specimens. The position of the 2 commissures in the anatomic specimens was left-to-right with the leaflets in anterior and posterior positions in 8 (Figures 1, A; 2, A; and 3, A). In 5, the commissures
Journal of the American Society of Echocardiography January 2003
Figure 4 A, Arterial view of bicuspid aortic valve (AV) with anteroposterior commissures (asterisks) and lateralized right (RSV) and left (LSV) leaflets with thickened edges (arrowheads) and calcified areas on external aspect (arrows). B, Three-dimensional view of bicuspid AV demonstrates position of comissures (asterisks), lateralized leaflets, thickening of edges (arrowheads) and calcifications on external aspect (arrows). Left panel, in diastole; right panel, in systole.
were oriented in an anteroposterior position with lateral leaflets (Figures 4, A; and 5, A). The leaflets were thickened with dysplastic nodulations on both their internal and external aspects (Figures 2, A; 3, A; and 4, A), and calcified areas (Figures 1, A; and 4, A). In one case in this group, bicuspid AV was associated with a fibrous subvalvular crest and thickening beneath the leaflets (Figure 6, A). Anatomoechocardiographic comparison shows the correspondence of anatomic findings and 3D reconstruction of the echocardiographic image. In the latter, the positions of the leaflets and commissures can be observed (Figures 1, B; 2, B; 3, B; 4, B; and 5, B), as can thickened edges (Figures 2, B; 3, B; 4, B; and 5, B) and areas of calcification (Figures 1, B, ventricular diastole; 2, B, internal aspect; and 4, B, external aspect). The images are shown in systole and diastole and from the arterial view. The study with a subvalvular membrane showed a clear correspondence with the features of the anatomic specimen (Figure 6, B). Group II included 5 3D echocardiographic reconstructions and 7 autopsies. In these specimens, 3 commissures were identified, one of which showed variable degrees of involution (Figures 7, A; and 9, A) with fusion of the adjacent leaflets (Figures 8, A; 9, A; and 10, A). A comparison of the specimens
Journal of the American Society of Echocardiography Volume 16 Number 1
Espinola-Zavaleta et al 49
with the echocardiographic images in ventricular diastole showed that the sinuses of Valsalva and number of commissures (3) that could be identified correlated (Figures 7, B; 8, B; 9, B; and 10, B). The images in systole revealed the bicuspid functional structure. Figure 8, B, demonstrates the integration of the 2 sinuses of Valsalva outlined by the 2 fused leaflets (Figure 8, B; and 10, B).
DISCUSSION
Figure 5 A, Arterial view of bicuspid aortic valve with commissures in anteroposterior orientation (asterisks) and lateralized left (LSV) and right (RSV) leaflets. Edges of both leaflets (arrowheads) and external aspect (arrows) are thickened. B, Three-dimensional arterial image shows anteroposterior position of commissures (asterisks), thickening of external aspect (arrows) and edges of both leaflets (arrowheads). Left panel, in diastole; right panel, in systole.
The semilunar valves arise from the embryonic truncus arteriosus at the top of the infundibular region from 6 thickenings of mesenchymal tissue; 3 appear over the pulmonary canal and 3 over the aortic canal during the process of truncoconal septation. The dorsal and ventral septal ridges proliferate (Figure 11, A). The dorsal proliferation originates the left-posterior semilunar aortic swelling and the posterior pulmonary swelling; the ventral swelling forms the anterior aortic and the right-anterior pulmonary leaflets (Figure 11, B). The intercalating swellings that insinuate themselves between the swellings of septal origin arise from the wall of each great vessel and form the left-anterior leaflet of the pulmonary valve and the right-posterior leaflet of the aorta (Figure 11, A and B). Each mesenchymal swelling develops a sinus that
Figure 6 A, Internal view of left ventricle (LV) and aortic valve (AV). AV is bicuspid with 2 commissures (1 and 2). In central part of valve, semilunar leaflet can be seen (black asterisk). Second leaflet was cut (linear asterisks). Subvalvular thickening is evident (arrowhead) and beneath it is fibrous membrane (arrow). B, Three-dimensional transesophageal image shows bicuspid AV (asterisks), subvalvular thickening (arrowhead), and subvalvular fibrous membrane (arrow). RV, right ventricle; LA, left atrium; Ao, aorta; MV, mitral valve.
50 Espinola-Zavaleta et al
Journal of the American Society of Echocardiography January 2003
Figure 7 A, View of aortic valve (AV) demonstrates 3 commissures (1, 2, and 3), one of which has undergone several degrees of involution (asterisk) with fusion of leaflets adjacent to commissure (arrow). B, Three-dimensional image of AV in diastole showing 3 commissures (1, 2, and 3) and 3 sinuses of Valsalva. In image in systole (right panel) bicuspid structure of valve can be observed in which fusion of leaflets causes confluence of sinuses 2 and 3. Edges of leaflets are thickened (arrowheads). Left panel, in diastole. Figure 9 A, Ventricular view of biscuspid aortic valve (AV) with fusion of adjacent leaflets (arrow). Three commissures (1, 2, and 3) can be seen; one has undergone involution (asterisk). B, Three-dimensional arterial view of bicuspid AV with fusion of leaflets 2 and 3 in diastole (left panel). In systole (right panel) it is clear that 1 of 2 leaflets is formed by fusion of 2 adjacent leaflets (arrow). Leaflet edges are thickened (arrowheads).
Figure 8 A, Ventricular view of aortic valve (AV) reveals fusion of leaflets 2 and 3, constituting bicuspid structure. Fusion raphe can be observed (arrow). B, Three-dimensional image of AV in diastole shows 3 sinuses of Valsalva (1, 2, and 3) with fusion of leaflets 2 and 3 (arrow). In systole (right panel) bicuspid structure caused by leaflet fusion is apparent (arrow). Edges of both leaflets are thickened (arrowheads). Left panel, in diastole.
separates a part of this mesodermal tissue from the arterial wall. The mesenchyme differentiates into fibroblasts and the wall becomes thin, forming the leaflet (Figure 12).12 On the basis of this developmental reasoning, the pathogenesis of bicuspid AV can be explained by 2 processes: absence of a swelling or fusion of 2 adjacent swellings. Depending on the position of the bicuspid leaflets and commissures, the following variants can be identified. In the first, the leaflets are oriented in anteroposterior position and the commissures are lateralized (Figure 11, C and D), whereas in the second the leaflets are lateral (left and right) and the commissures anteroposterior (Figure 11, E and F). Two morphogenetic mechanisms have been proposed to explain true and acquired bicuspid AV. In the former case, only 2 leaflets develop, either because the intercalating swelling fails to develop (Figure 11, C) or because of the fusion of mesenchymal swellings of septal truncal origin (Figure 11, E).
Journal of the American Society of Echocardiography Volume 16 Number 1
Figure 10 A, Ventricular view of bicuspid aortic valve (AV) with 3 commissures (1, 2, and 3) and fusion of 2 leaflets. Arrow points to raphe. B, Arterial view of AV in diastole (left panel). Three sinuses and 3 commissures (1, 2, and 3) are visible. In systole (right panel) fusion of leaflets 2 and 3 (arrow) can be seen.
Acquired bicuspid AV can be understood as a development of the 3 semilunar leaflets with subsequent fusion of 2 adjacent formed leaflets, resulting in a single raphe. This anomaly involves dysplastic processes (Figure 11, D and F). In 1923 Lewis and Grant13 defined the principal characteristics of congenital bicuspid AV and presented the histologic criteria for differentiating congenital bicuspid AV from dysplastic or inflammatory bicuspid AV. These authors found that fusion could occur not only between the right-posterior and -anterior leaflets, but also between the right-posterior and left-posterior leaflets. The raphe dividing 1 of the 2 leaflets was identified in approximately half of the cases. The 2 leaflets could be equal or unequal in size, but usually the leaflet that included the raphe was larger, although it was not more than double the size of the undivided leaflet.13 Staining of transverse histologic sections of the congenital raphe reveals that it is primarily made up of elastic fibers similar to those of the media of the aorta. In contrast, transverse sections of the fused leaflets at the level of the true commissure are composed of elastic fibers and fibrous valvular tissues. A true bicuspid AV is distinguished by 2 individual semilunar leaflets separated by 2 commissures and by the absence of a raphe. When a raphe is present, it indicates an original tricuspid structure that underwent fusion of adjacent leaflets. This may
Espinola-Zavaleta et al 51
Figure 11 Diagrams represent development of semilunar leaflets in normal heart (A, B) and in hearts with true bicuspid aortic valve (AV) (C, E) and acquired bicuspid AV (D, F). Shaded swellings represent expansions of mesenchymal tissue from dorsal ridge of trunk. Swellings with circles correspond to mesenchymal expansion from ventral ridge of trunk, and swellings in white constitute intercalating primordium.
occur before or after birth. In the first case the fused raphe is congenital and, in the second, acquired. Other authors have found these distinctions useful but unspecific because the raphe can be the first site of calcification, and these calcium deposits can destroy the existing elastic fibers. Although a bicuspid AV consists of 2 leaflets, there is a great variation in the sizes of these; the size and structure of the raphe; and such secondary characteristics as calcification, fibrosis, myxomatous degeneration, annular dilatation, and fusion of commissures. In a study by Sabet et al1 the 2 leaflets were of unequal size in 95% of the cases (524), and 95% of the valves were stenotic. The findings of this study differed from other reports by Davies14 (30%), and Bacon and Matthews15 (28%). However, the percentage of disparate leaflet size was similar to the echocardiographic observation of 85% reported by Brandenburg et al.9 The importance of examining morphological aspects of bicuspid AV derives from the fact that this malformation is the most common cause of aortic stenosis (59%) in patients between 60 and 75 years of age. In individuals less than 60 years old it is found
52 Espinola-Zavaleta et al
Journal of the American Society of Echocardiography January 2003
Figure 12 Diagrams of longitudinal sections of aorta at time of development of leaflet swellings. A, Mesenchymal bud. Arrows point to beginning of process of excavation that separates swelling from arterial wall. B, Chamber appears between semilunar swelling and arterial wall that gives rise to sinuses of Valsalva (arrows). C, Definitive structure of semilunar leaflets once mesenchymal tissue has differentiated into fibroblasts.
in 40% and in those more than 75 years old in 32%. Patients with aortic stenosis secondary to bicuspid AV require AV replacement an average of 5 years earlier than those with stenosis of a tricuspid AV.1,3 Between 10% and 30% of patients with bicuspid AV have infective endocarditis develop. It results in death in 55% of the patients less than 30 years old and in 13% of those more than 70 years old. This points to the importance of early and precise determination of the different types of bicuspid AV to avoid the fatal consequences that can occur.5 Echocardiography has high sensitivity and specificity in the diagnosis of bicuspid AV. However, up until now the study of this entity has been limited to 2-dimensional techniques, and the fine details of surgical or autopsy specimens could be discerned. Today, 3D echocardiographic reconstruction makes it possible to characterize the morphology of a bicuspid AV. In this series, comparison of 3D echocardiographic images of bicuspid AV with equivalent anatomopathological specimens from autopsy demonstrated that the diagnostic fidelity of the former method is clear and precise. The 3D transesophageal echocardiography allowed us to delineate, exactly, the size and features of cusps; the fusion of the commissures; and the presence of thickening and calcification of bicuspid AV, providing an excellent framework for the surgeon. It is the first study to establish the correspondence between autopsy specimens and transesophageal 3D reconstructions of bicuspid AVs. On the basis of these findings, we can conclude that 3D echocardiography is a unique technique that provides morphological detail of bicuspid AV in vivo of the quality of a pathologic examination.
REFERENCES
1. Sabet HYBA, Edwards W, Tazelaar H, Daly RC. Congenitally bicuspid aortic valves: a surgical pathology study of 542 cases (1991 through 1996) and a literature review of 2,715 additional cases. Mayo Clin Proc 1999;74: 14-26. 2. Waller BF, Carter JB, Williams HJ, Wang K, Edwards JE. Bicuspid aortic valve: comparison of congenital and acquired types. Circulation 1973;48:1140-51. 3. Ward C. Clinical significance of the bicuspid aortic valve. Heart 2000;83:81-5. 4. Pomerance A. Pathogenesis of aortic stenosis and its relation to age. Br Heart J 1972;34:569-74. 5. Grant RT, Wood JE, Jones TD. Heart valve irregularities in relation to sub-acute bacterial endocarditis. Heart 1928;14: 247-55. 6. Roberts WC. The structure of the aortic valve in clinically isolated aortic stenosis. Circulation 1970;42:91-7. 7. Subramanian R, Olson LJ, Edwards WD. Surgical pathology of pure aortic stenosis: a study of 374 cases. Mayo Clin Proc 1984;59:683-90. 8. Guiney TE, Davies MJ, Parker DJ, Leech GJ, Leatham A. The aetiology and course of isolated severe aortic regurgitation: a clinical, pathological, and echocardiographic study. Br Heart J 1987;58:358-68. 9. Brandenburg RO Jr, Tajik AJ, Edwards WD, Reeder GS, Shub C, Seward JB. Accuracy of 2-dimensional echocardiographic diagnosis of congenitally bicuspid valve: echocardiographic-anatomic correlation in 115 patients. Am J Cardiol 1983;83:1469-73. 10. Espinal M, Fuisz AR, Nanda NC, Aaluri SR, Mukhtar O, Sekar PC. Sensitivity and specificity of transesophageal echocardiography for determination of aortic valve morphology. Am Heart J 2000;139:1071-6. 11. Nanda NC, Pinheiro L, Sanyal R, Rosenthal S, Kirklin JK.
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Multiplane echocardiographic imaging and threedimensional reconstruction. Echocardiography 1992;9: 667-76. 12. Kramer TC. The partitioning of the truncus and conus and the formation of the membranous portion of the interventricular septum in the human heart. Am J Anat 1942;71:34370.
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13. Lewis T, Grant RT. Observations relating to subacute infective endocarditis. Heart 1923;10:21-99. 14. Davies MJ. Pathology of cardiac valves. London: Butterworths; 1980. p. 1-61. 15. Bacon APC, Matthews MB. Congenital bicuspid aortic valves and the aetiology of isolated aortic valvular stenosis. Q J Med 1959;28:545-60.
This study was undertaken to verify the echocardiographic characteristics of bicuspid aortic valve (AV) using 3-dimensional transesophageal echocardiography by comparing the findings with anatomic examination of autopsy specimens from carriers of this condition. Three-dimensional reconstructions of transesophageal echocardiograms were performed on 14 patients with bicuspid AV, and 20 autopsy specimens of bicuspid AVs were analyzed. Echocardiographic images and autopsy material were correlated. Two variants of bicuspid aorta were identified. In group I the AV had 2 leaflets. This group included 9 (9/14) 3-dimensional echocardio-
B
icuspid aortic valve AV is one of the most common forms of congenital heart disease, with a prevalence of up to 3% of the general population.1 Bicuspid AV can be either congenital or acquired, in the latter case, secondary to inflammatory processes.2,3 A congenital bicuspid AV can have a vestigial raphe that partially subdivides one of the leaflets; in acquired bicuspid AV the raphe is more pronounced and fibrous, and reaches the free edge of the leaflet. The origin can always be determined by direct inspection, and histologic examination of the leaflets is only necessary in exceptional cases.1,2 Anatomopathological series have shown a broad spectrum of bicuspid AV anatomic variations, including anteroposterior or left-to-right orientation. Variants appear in similar proportions.1,2 The importance of studying bicuspid AV is the tendency of this malformation to lead to stenosis.4-7 There is a general consensus that approximately
From the Instituto Nacional de Cardiologı´a “Ignacio Cha´vez.” Reprint requests: Nilda Espinola-Zavaleta, MD, PhD, Department of Echocardiography, Instituto Nacional de Cardiologı´a “Ignacio Cha´vez,” Juan Badiano No. 1, Colonia Seccio´n XVI, 14080 Tlalpan, Mexico City, Mexico. Copyright 2003 by the American Society of Echocardiography. 0894-7317/2003/$30.00 ⫹ 0 doi:10.1067/mje.2003.30
46
graphic studies and 13 (13/20) necropsies. In group II 3 sigmoid leaflets had originally developed and 2 underwent dysplastic fusion, resulting in functionally bicuspid valves. Five (5/14) echocardiographic studies and 7 (7/20) anatomic specimens fell into this category. There was a clear correspondence between anatomic and echocardiographic findings, which leads to the conclusion that 3-dimensional echocardiography is a technique that reliably defines the morphological details of bicuspid AV with the precision of anatomopathologic examination. (J Am Soc Echocardiogr 2003;16:46-53.)
50% of adults between 60 and 75 years of age with aortic stenosis have bicuspid AV.4 In these patients the stenosis progresses more rapidly when the leaflets are unequal in size and their disposition is anteroposterior. As an isolated phenomenon, biscupid AV can cause severe aortic regurgitation (1.5%3%).8 Diagnosis of bicuspid AV is difficult for the clinician. Work by Brandenburg et al9 has established how echocardiography can be used to analyze the AV and demonstrate 2 leaflets and 2 commissures in the parasternal short-axis image. However, the morphology of a bicuspid AV cannot be determined with a transthoracic technique in 25% of the cases because of severe fibrosis or calcification of the leaflets. By contrast, transesophageal echocardiography with multiplane probe has high sensitivity and specificity (87% and 91%, respectively) for characterizing AV anatomy with precision.10 Three-dimensional (3D) echocardiography is a new diagnostic technique that makes it possible to obtain more anatomic details of bicuspid AV in vivo and, thus, predict the clinical course of the lesion. In addition, preoperative familiarity with the valvular lesion would be of great help in planning surgical strategy before thoracotomy. This study was undertaken to confirm the fidelity of 3D reconstruction of the transesophageal echocardiographic images of bicuspid AV by correlating them with autopsy specimens of this lesion.
Journal of the American Society of Echocardiography Volume 16 Number 1
Figure 1 A, Transverse section of aorta at level of valve. Note bicuspid structure with lateralized (left and right) commissures. Right-anterior semilunar (ASV) and posterior (PSV) leaflets have thickened edges (arrowheads) and calcifications on external aspect of anterior leaflet (arrow). B, Three-dimensional arterial view of aortic valve. Lateralized commissures and anteroposterior leaflets (ASV and PSV) with thickening (arrowheads) and calcifications (arrows) on external aspect of both leaflets can be seen. Left panel, in diastole; right panel, in systole.
MATERIALS AND METHODS Fourteen patients with suspected bicuspid AV were studied. Five were men and 9 women; average age was 29.9 years (range 18 to 47). Transesophageal echocardiography with 3D reconstruction was performed on all of the patients. Twenty anatomic specimens of this lesion were examined. 3D Echocardiographic Studies Examination procedure. All patients underwent transesophageal echocardiography using the Sonos 5500 system (Hewlett-Packard, Andover, Mass), which has the capability for acquisition of serial cross-sectional echocardiographic images by a multiplane probe. With patients under conscious sedation, the inserted probe was positioned at the level of the AV, and cross-sectional images with increments of 2 degrees were acquired with cardiac and respiratory cycle gating. The AV had to be visualized somewhere from 30 to 70 degrees and then again approximately from 120 to 150 degrees during 1 complete rotation of the transducer with the probe fixed. The stored serial cross-sectional data in the optical disk were transferred to a computer (Echo-Scan, version 3.1, TomTec Gmb H, Munich, Germany) for analysis of the 3D echocardiographic data set, as previously described.11 The analysis program of the 3D echocardio-
Espinola-Zavaleta et al 47
Figure 2 A, Arterial view of specimen shows lateralized commissures (asterisks), thickened edges (arrowheads), and areas of calcification on internal aspect (arrow). B, Threedimensional echocardiographic image shows lateralized commissures (asterisks) and semilunar leaflets in anteroposterior orientation. In image in systole, calcification on internal aspect of anterior leaflet (arrow) and thickening of edges of both leaflets (arrowheads) is evident. ASV, rightanterior semilunar leaflet; PSV, posterior leaflet; left panel, in diastole; right panel, in systole.
graphic system performed data processing offline. Cardiac cross-sections were formatted in their correct sequence according to their electrocardiogram phase in cubic data sets (256 ⫻ 256 pixels/each 8 bits). The postprocessing of the data set was performed offline with the reconstruction software. The image data were converted from polar to Cartesian coordinate format and interpolated to “fill the gaps” between sequential cross-sections. A reduction of spatial artifacts filter was used to reduce motion artifacts created by patients, probe movement, or respiration. Image display. The AV was imaged from a computergenerated short-axis view (aortotomy view) that allowed for identification of the number, size, and features of cusps; the fusion of the commissures; and the presence of thickenings and calcification. Volume-rendered display. Once an appropriate cut plane had been chosen, a threshold value was selected to differentiate cardiac structures from the blood pool and background. The gray-scale information of the structures
48 Espinola-Zavaleta et al
Figure 3 A, Arterial view of bicuspid aortic valve (AV). Lateral position of 2 commissures and anteroposterior orientation of semilunar leaflets (asterisks) can be observed. Both leaflets are thickened (arrowheads). B, Arterial view of bicuspid AV. Image on left (diastole) shows lateral position of commissures and anteroposterior orientation of semilunar leaflets with thickened edges (arrowheads). Right panel is in systole. ASV, right-anterior semilunar leaflet; PSV, posterior leaflet.
was rendered, and a gradient shading algorithm enhanced the views. Image analysis. Two experienced observers analyzed all the echocardiograms. Echocardiographic images were compared with anatomic specimens to determine similarity. The anatomic specimens were selected from the museum of pathology of the National Institute of Cardiology “Ignacio Cha´vez.”
RESULTS Two variants of bicuspid AV were found. In the first (group I) the AV had 2 well-defined leaflets. This was found in 9 echocardiographic studies and 13 anatomic specimens. The position of the 2 commissures in the anatomic specimens was left-to-right with the leaflets in anterior and posterior positions in 8 (Figures 1, A; 2, A; and 3, A). In 5, the commissures
Journal of the American Society of Echocardiography January 2003
Figure 4 A, Arterial view of bicuspid aortic valve (AV) with anteroposterior commissures (asterisks) and lateralized right (RSV) and left (LSV) leaflets with thickened edges (arrowheads) and calcified areas on external aspect (arrows). B, Three-dimensional view of bicuspid AV demonstrates position of comissures (asterisks), lateralized leaflets, thickening of edges (arrowheads) and calcifications on external aspect (arrows). Left panel, in diastole; right panel, in systole.
were oriented in an anteroposterior position with lateral leaflets (Figures 4, A; and 5, A). The leaflets were thickened with dysplastic nodulations on both their internal and external aspects (Figures 2, A; 3, A; and 4, A), and calcified areas (Figures 1, A; and 4, A). In one case in this group, bicuspid AV was associated with a fibrous subvalvular crest and thickening beneath the leaflets (Figure 6, A). Anatomoechocardiographic comparison shows the correspondence of anatomic findings and 3D reconstruction of the echocardiographic image. In the latter, the positions of the leaflets and commissures can be observed (Figures 1, B; 2, B; 3, B; 4, B; and 5, B), as can thickened edges (Figures 2, B; 3, B; 4, B; and 5, B) and areas of calcification (Figures 1, B, ventricular diastole; 2, B, internal aspect; and 4, B, external aspect). The images are shown in systole and diastole and from the arterial view. The study with a subvalvular membrane showed a clear correspondence with the features of the anatomic specimen (Figure 6, B). Group II included 5 3D echocardiographic reconstructions and 7 autopsies. In these specimens, 3 commissures were identified, one of which showed variable degrees of involution (Figures 7, A; and 9, A) with fusion of the adjacent leaflets (Figures 8, A; 9, A; and 10, A). A comparison of the specimens
Journal of the American Society of Echocardiography Volume 16 Number 1
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with the echocardiographic images in ventricular diastole showed that the sinuses of Valsalva and number of commissures (3) that could be identified correlated (Figures 7, B; 8, B; 9, B; and 10, B). The images in systole revealed the bicuspid functional structure. Figure 8, B, demonstrates the integration of the 2 sinuses of Valsalva outlined by the 2 fused leaflets (Figure 8, B; and 10, B).
DISCUSSION
Figure 5 A, Arterial view of bicuspid aortic valve with commissures in anteroposterior orientation (asterisks) and lateralized left (LSV) and right (RSV) leaflets. Edges of both leaflets (arrowheads) and external aspect (arrows) are thickened. B, Three-dimensional arterial image shows anteroposterior position of commissures (asterisks), thickening of external aspect (arrows) and edges of both leaflets (arrowheads). Left panel, in diastole; right panel, in systole.
The semilunar valves arise from the embryonic truncus arteriosus at the top of the infundibular region from 6 thickenings of mesenchymal tissue; 3 appear over the pulmonary canal and 3 over the aortic canal during the process of truncoconal septation. The dorsal and ventral septal ridges proliferate (Figure 11, A). The dorsal proliferation originates the left-posterior semilunar aortic swelling and the posterior pulmonary swelling; the ventral swelling forms the anterior aortic and the right-anterior pulmonary leaflets (Figure 11, B). The intercalating swellings that insinuate themselves between the swellings of septal origin arise from the wall of each great vessel and form the left-anterior leaflet of the pulmonary valve and the right-posterior leaflet of the aorta (Figure 11, A and B). Each mesenchymal swelling develops a sinus that
Figure 6 A, Internal view of left ventricle (LV) and aortic valve (AV). AV is bicuspid with 2 commissures (1 and 2). In central part of valve, semilunar leaflet can be seen (black asterisk). Second leaflet was cut (linear asterisks). Subvalvular thickening is evident (arrowhead) and beneath it is fibrous membrane (arrow). B, Three-dimensional transesophageal image shows bicuspid AV (asterisks), subvalvular thickening (arrowhead), and subvalvular fibrous membrane (arrow). RV, right ventricle; LA, left atrium; Ao, aorta; MV, mitral valve.
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Figure 7 A, View of aortic valve (AV) demonstrates 3 commissures (1, 2, and 3), one of which has undergone several degrees of involution (asterisk) with fusion of leaflets adjacent to commissure (arrow). B, Three-dimensional image of AV in diastole showing 3 commissures (1, 2, and 3) and 3 sinuses of Valsalva. In image in systole (right panel) bicuspid structure of valve can be observed in which fusion of leaflets causes confluence of sinuses 2 and 3. Edges of leaflets are thickened (arrowheads). Left panel, in diastole. Figure 9 A, Ventricular view of biscuspid aortic valve (AV) with fusion of adjacent leaflets (arrow). Three commissures (1, 2, and 3) can be seen; one has undergone involution (asterisk). B, Three-dimensional arterial view of bicuspid AV with fusion of leaflets 2 and 3 in diastole (left panel). In systole (right panel) it is clear that 1 of 2 leaflets is formed by fusion of 2 adjacent leaflets (arrow). Leaflet edges are thickened (arrowheads).
Figure 8 A, Ventricular view of aortic valve (AV) reveals fusion of leaflets 2 and 3, constituting bicuspid structure. Fusion raphe can be observed (arrow). B, Three-dimensional image of AV in diastole shows 3 sinuses of Valsalva (1, 2, and 3) with fusion of leaflets 2 and 3 (arrow). In systole (right panel) bicuspid structure caused by leaflet fusion is apparent (arrow). Edges of both leaflets are thickened (arrowheads). Left panel, in diastole.
separates a part of this mesodermal tissue from the arterial wall. The mesenchyme differentiates into fibroblasts and the wall becomes thin, forming the leaflet (Figure 12).12 On the basis of this developmental reasoning, the pathogenesis of bicuspid AV can be explained by 2 processes: absence of a swelling or fusion of 2 adjacent swellings. Depending on the position of the bicuspid leaflets and commissures, the following variants can be identified. In the first, the leaflets are oriented in anteroposterior position and the commissures are lateralized (Figure 11, C and D), whereas in the second the leaflets are lateral (left and right) and the commissures anteroposterior (Figure 11, E and F). Two morphogenetic mechanisms have been proposed to explain true and acquired bicuspid AV. In the former case, only 2 leaflets develop, either because the intercalating swelling fails to develop (Figure 11, C) or because of the fusion of mesenchymal swellings of septal truncal origin (Figure 11, E).
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Figure 10 A, Ventricular view of bicuspid aortic valve (AV) with 3 commissures (1, 2, and 3) and fusion of 2 leaflets. Arrow points to raphe. B, Arterial view of AV in diastole (left panel). Three sinuses and 3 commissures (1, 2, and 3) are visible. In systole (right panel) fusion of leaflets 2 and 3 (arrow) can be seen.
Acquired bicuspid AV can be understood as a development of the 3 semilunar leaflets with subsequent fusion of 2 adjacent formed leaflets, resulting in a single raphe. This anomaly involves dysplastic processes (Figure 11, D and F). In 1923 Lewis and Grant13 defined the principal characteristics of congenital bicuspid AV and presented the histologic criteria for differentiating congenital bicuspid AV from dysplastic or inflammatory bicuspid AV. These authors found that fusion could occur not only between the right-posterior and -anterior leaflets, but also between the right-posterior and left-posterior leaflets. The raphe dividing 1 of the 2 leaflets was identified in approximately half of the cases. The 2 leaflets could be equal or unequal in size, but usually the leaflet that included the raphe was larger, although it was not more than double the size of the undivided leaflet.13 Staining of transverse histologic sections of the congenital raphe reveals that it is primarily made up of elastic fibers similar to those of the media of the aorta. In contrast, transverse sections of the fused leaflets at the level of the true commissure are composed of elastic fibers and fibrous valvular tissues. A true bicuspid AV is distinguished by 2 individual semilunar leaflets separated by 2 commissures and by the absence of a raphe. When a raphe is present, it indicates an original tricuspid structure that underwent fusion of adjacent leaflets. This may
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Figure 11 Diagrams represent development of semilunar leaflets in normal heart (A, B) and in hearts with true bicuspid aortic valve (AV) (C, E) and acquired bicuspid AV (D, F). Shaded swellings represent expansions of mesenchymal tissue from dorsal ridge of trunk. Swellings with circles correspond to mesenchymal expansion from ventral ridge of trunk, and swellings in white constitute intercalating primordium.
occur before or after birth. In the first case the fused raphe is congenital and, in the second, acquired. Other authors have found these distinctions useful but unspecific because the raphe can be the first site of calcification, and these calcium deposits can destroy the existing elastic fibers. Although a bicuspid AV consists of 2 leaflets, there is a great variation in the sizes of these; the size and structure of the raphe; and such secondary characteristics as calcification, fibrosis, myxomatous degeneration, annular dilatation, and fusion of commissures. In a study by Sabet et al1 the 2 leaflets were of unequal size in 95% of the cases (524), and 95% of the valves were stenotic. The findings of this study differed from other reports by Davies14 (30%), and Bacon and Matthews15 (28%). However, the percentage of disparate leaflet size was similar to the echocardiographic observation of 85% reported by Brandenburg et al.9 The importance of examining morphological aspects of bicuspid AV derives from the fact that this malformation is the most common cause of aortic stenosis (59%) in patients between 60 and 75 years of age. In individuals less than 60 years old it is found
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Figure 12 Diagrams of longitudinal sections of aorta at time of development of leaflet swellings. A, Mesenchymal bud. Arrows point to beginning of process of excavation that separates swelling from arterial wall. B, Chamber appears between semilunar swelling and arterial wall that gives rise to sinuses of Valsalva (arrows). C, Definitive structure of semilunar leaflets once mesenchymal tissue has differentiated into fibroblasts.
in 40% and in those more than 75 years old in 32%. Patients with aortic stenosis secondary to bicuspid AV require AV replacement an average of 5 years earlier than those with stenosis of a tricuspid AV.1,3 Between 10% and 30% of patients with bicuspid AV have infective endocarditis develop. It results in death in 55% of the patients less than 30 years old and in 13% of those more than 70 years old. This points to the importance of early and precise determination of the different types of bicuspid AV to avoid the fatal consequences that can occur.5 Echocardiography has high sensitivity and specificity in the diagnosis of bicuspid AV. However, up until now the study of this entity has been limited to 2-dimensional techniques, and the fine details of surgical or autopsy specimens could be discerned. Today, 3D echocardiographic reconstruction makes it possible to characterize the morphology of a bicuspid AV. In this series, comparison of 3D echocardiographic images of bicuspid AV with equivalent anatomopathological specimens from autopsy demonstrated that the diagnostic fidelity of the former method is clear and precise. The 3D transesophageal echocardiography allowed us to delineate, exactly, the size and features of cusps; the fusion of the commissures; and the presence of thickening and calcification of bicuspid AV, providing an excellent framework for the surgeon. It is the first study to establish the correspondence between autopsy specimens and transesophageal 3D reconstructions of bicuspid AVs. On the basis of these findings, we can conclude that 3D echocardiography is a unique technique that provides morphological detail of bicuspid AV in vivo of the quality of a pathologic examination.
REFERENCES
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Multiplane echocardiographic imaging and threedimensional reconstruction. Echocardiography 1992;9: 667-76. 12. Kramer TC. The partitioning of the truncus and conus and the formation of the membranous portion of the interventricular septum in the human heart. Am J Anat 1942;71:34370.
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13. Lewis T, Grant RT. Observations relating to subacute infective endocarditis. Heart 1923;10:21-99. 14. Davies MJ. Pathology of cardiac valves. London: Butterworths; 1980. p. 1-61. 15. Bacon APC, Matthews MB. Congenital bicuspid aortic valves and the aetiology of isolated aortic valvular stenosis. Q J Med 1959;28:545-60.