- Email: [email protected]
Frequency of aortic root dilation in children with a bicuspid aortic valve
enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study. Circulation 2003;108:1299 –1301. 12. Poulsen SH, Andersen NH, Ivarsen PI, Mogensen CE, Egeblad H. Doppler tissue imaging reveals systolic dysfunction in patients with hypertension and apparent “isolated” diastolic dysfunction. J Am Soc Echocardiogr 2003;16:724 –731. 13. Dutka DP, Donnelly JE, Palka P, Lange A, Nunez DJR, Nihoyannopoulos P. Echocardiographic characterization of cardiomyopathy in Freiderich’s ataxia
with tissue Doppler echocardiographically derived myocardial velocity gradients. Circulation 2000;102:1276 –1282. 14. Lane A, Fleming AD, Donnelly JE, Dutka DP, Starkey IR, Shaw TRD, Sutherland GR, Fox KAA. Differences in myocardial velocity gradient measured throughout the cardiac cycle in patients with hypertrophic cardiomyopathy, athletes and patients with left ventricular hypertrophy due to hypertension. J Am Coll Cardiol 1997;30:760 –768.
Frequency of Aortic Root Dilation in Children With a Bicuspid Aortic Valve Michelle Gurvitz,
MD,
Ruey-Kang Chang, MD, MPH, Stacey Drant, Vivekanand Allada, MD
Bicuspid aortic valve (BAV) is associated with aortic root dilation and dissection in adults, but the age and conditions when dilation begins are unknown. Using echocardiographic data, we compared the aortic root dimensions and valve hemodynamics of 76 children with BAV with valves derived from 41 normal children. The children with BAV had significantly larger aortic roots (p <0.001) regardless of the presence of aortic stenosis or regurgitation. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;94:1337–1340)
n normal children, the aortic root grows with the child and has been shown to correlate well with Iheight and body surface area, independent of gender.1–3 Few studies have addressed the presence of a bicuspid aortic valve (BAV) in children or the characterization of the aortic root in these children except in small case studies or in association with Turner’s or Marfan’s syndrome.4 –10 Whether progressive dilation of the root can be modified or prevented if initially detected in children with BAV is an important but unanswered question. The goal of this cross-sectional study was to determine if children with isolated BAV have dilated aortic roots and whether root dilation has any relation to the functional hemodynamic state of the valve. •••
This study was approved by the institutional review boards at 2 large academic medical centers in the Los Angeles area. All patients aged ⬍21 years with isolated BAV on echocardiography from January 1994 to August 2002 were reviewed retrospectively, and the most recent available study for each was used for evaluation. IncluFrom the Division of Cardiology, Department of Pediatrics, Mattel Children’s Hospital at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, California. Dr. Chang received research funding (1 R03 HS13217-01) from the Agency for Healthcare Research and Quality, Rockville, Maryland, the American Heart Association (0365041Y), Burlingame, California and the National Center for Research Resources (1 K23 RR17041– 01), National Institutes of Health, Bethesda, Maryland. Dr. Gurvitz’s address is: B2– 427 MDCC, UCLA Medical Center, 10833 Le Conte Avenue, Los Angeles, California 90095-1743. E-mail: [email protected]. Manuscript received February 6, 2004; revised manuscript received and accepted July 15, 2004. ©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 November 15, 2004
MD,
and
sion in the study group required a technically adequate echocardiogram (described in the following). Patients with other cardiac anomalies, diagnosis of Turner’s or Marfan’s syndrome, or a surgical or catheter-based aortic valve intervention before echocardiography were excluded. Age, height, weight, body surface area, and cardiovascular medications were recorded for all patients. Echocardiograms and aforementioned clinical information of 41 normal children from the echocardiogram database were also reviewed to establish normal aortic root dimensions. Echocardiographic measurements in the standard parasternal and apical views were obtained using Acuson 128XP or Sequoia (Mountain View, California) systems. Technically adequate echocardiograms consisted of clear 2-dimensional views of the aortic valve, aortic root and left ventricle, and complete spectral and color Doppler interrogation of the aortic valve. All echocardiograms were examined by an independent reviewer (MG) who was blinded to the original report of the echocardiogram and to any information about the study subjects. The morphology of the BAV was determined by the presence of 2 distinct functional cusps in the parasternal short-axis view.11 Aortic root dimensions at the annulus, sinus of Valsalva, sinotubular junction, and proximal ascending aorta were assessed in the parasternal long-axis view in systole using the leading edge technique.2 Results recorded for each patient were an average of 3 measurements at each level. Left ventricular ejection fraction was assessed by 2-dimensional volume measurements from the apical views, when available, or by visual estimation of the reviewer. The hemodynamic state of the aortic valve was evaluated using color flow and spectral Doppler. Stenosis assessment, an average of 3 measurements for each subject, involved the following guidelines of mean gradients: mild or less, ⬍17 mm Hg; moderate, ⬎17 or ⬍27 mm Hg; and severe, ⬎27 mm Hg.12 When mean gradients could not be determined, a peak gradient of ⬎25 mm Hg was considered hemodynamically significant (greater than mild) stenosis. The degree of regurgitation was measured using several established criteria, including the pressure half-time technique, width of aortic regurgitation (AR) jet relative to the diameter of the left ventricular outflow 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.07.130
1337
TABLE 1 Demographic and Clinical Characteristics of Patients in the Study Group (n ⫽ 76) and in Normal Children (n ⫽ 41)*
Males Age (yrs) Height (cm) Body surface area (m2) Stenosis Regurgitation Both AS ⫹ MR Neither AS or MR
Study Group (n ⫽ 76)
Normal Children (n ⫽ 41)
p Value
62 (81%) 8.54 ⫾ 4.87 (0.01–19) 129 ⫾ 33 (50–180) 1.07 ⫾ 0.48 (0.22–2.07) 22 (29%) 5 (7%) 4 (5%) 45 (59%)
19 (46%) 9.38 ⫾ 5.67 (0.01–18) 133 ⫾ 36 (48–185) 1.16 ⫾ 0.54 (0.25–2.27) 0 0 0 41 (100%)
⬍0.01 0.42 0.48 0.36
*Results for gender, medications, and hemodynamics are listed as percentages. Age, height, and body surface area are listed as mean ⫾ SD, (range).
FIGURE 1. Measurements in the normal children (n ⴝ 41) of the diameters (in millimeters) of the aortic valve annulus (Annulus), sinus of Valsalva (Sinus), sinotubular junction (STJ), and ascending aorta (AAO) plotted against height (in centimeters). Graphs show mean regression line and 95% prediction intervals.
tract, and/or the presence of flow reversal in the descending aorta. AR was categorized as mild or less, moderate, and severe.12,13 1338 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 94
The aortic root dimensions of normal children were used to establish normal values in relation to height, age, and body surface area by linear regression analNOVEMBER 15, 2004
ysis for all 4 levels of the aortic root. With use of these equations to predict a normal value for height, the measurement of each level of the aortic root of each of the patients with BAV was converted to a z score. The Kolmogorov-Smirnov test was used for normality of distribution. For data analysis, patients with BAV were first considered as a single group and then divided into 4 subgroups by hemodynamic status: (1) aortic stenosis (AS; moderate or severe), (2) AR (moderate or severe regurgitation), (3) both AS ⫹ AR (moderate or severe stenosis and regurgitation), and (4) neither AS nor AR (mild or less stenosis and regurgitation). The z scores of the patients with BAV were tested against the mean z score of normal subjects (zero). Two hemodynamic subgroups of patients with BAV—AS (AS) and hemodynamically normal (neither AS nor AR)—were compared separately with normal children and were then compared with each other. All comparisons were performed using t tests. The subgroups with regurgitation (AR, AR ⫹ AS) were not included for comparisons because those groups contained only 5 and 4 subjects, respectively. Multiple linear regression analyses were performed to determine if gender, presence of BAV, stenosis, or regurgitation were significant predictors of aortic root dilation. The variables of age and body surface area were not included because they closely correlated with height. A p value ⬍0.05 was considered statistically significant. Statistical analyses were done using SPSS 10.1 for Windows (SPSS Inc., Chicago, Illinois). Eighty-one children with isolated BAVs were identified. Five were excluded because of technically inadequate echocardiograms. The demographic and clinical data of patients with BAVs and normal children are listed in Table 1. The 2 groups were similar in age, height, and body surface area but differed in gender distribution. The proportion of males and females, however, was similar to the gender ratio of BAV in previous population studies.14,15 All patients with BAVs and normal children had a left ventricular ejection fraction within normal limits. Only 5 of 71 children with BAV were taking cardiovascular medication; each was taking an angiotensin-converting enzyme inhibitor. In normal subjects, root dimensions correlated well with height (Figure 1) and body surface area (r ⫽ 0.89 to 0.93 for both) better than with age (r ⫽ 0.86 to 0.91). As described previously, z scores of the levels of the aortic root were determined in relation to height for each of the patients with BAV. Mean z scores of BAV patients were ⬎0 at the annulus (2 ⫾ 1.9, p ⬍0.001), sinus (1.6 ⫾ 1.9, p ⬍0.001), sinotubular junction (1.2 ⫾ 1.9, p ⬍0.001), and proximal ascending aorta (3.3 ⫾ 2.4, p ⬍0.001) (Figure 2). In considering a z score of ⱖ2 (95th percentile) as severely dilated, 55 patients (68%) had severe dilation at the ascending aorta (p ⬍0.05), 23 patients (29%) at the sinotubular junction, 28 patients (35%) at the sinus, and 41 patients (50%) at the annulus. Two patient subgroups with BAV—stenosis (AS, n ⫽ 22) and hemodynamically normal (neither AS nor
FIGURE 2. The z score measurements of the aortic valve annulus (ANN), sinotubular junction (STJ), sinus of valsava (SINUS), and ascending aorta (AAO). Horizontal lines inside boxes denote medians. Lower and upper limits in boxes denote 25th and 75th percentiles, respectively. Lower and upper limits of vertical bars denote 10th and 90th percentiles, respectively. Dots below and above the plots are 5th and 95th percentiles, respectively. Horizontal line of z score ⴝ 0 is plotted to indicate the average z score of the measurements obtained from the normal children.
FIGURE 3. The z score measurements of the ascending aorta (AAO) in the 2 patient subgroups—BAV with AS (BAV-AS) and BAV with normal hemodynamics (BAV-no AS/AR) compared with the normal children (Normal). Horizontal lines inside boxes denote medians. Lower and upper limits of boxes denote 25th and 75th percentiles, respectively. Lower and upper limits of vertical bars denote 10th and 90th percentiles, respectively (p >0.05).
AR, n ⫽ 45)—were compared with normal children and then with each other as described previously. At every level of the root, the z scores of the 2 subgroups were significantly greater than normal (all p values ⬍0.05). This was most apparent in the ascending aorta (Figure 3). At every level, however, the 2 subgroups were not significantly different from each other (all p values ⬎0.2). Using multiple regression analyses, dilation at all levels of the aortic root was significantly associated with the presence of a BAV. Dilation at the level of the ascending aorta was also associated with the presence of AR despite the small number of patients with BRIEF REPORTS
1339
TABLE 2 Multiple Linear Regression Results Comparing the Presence of a Bicuspid Aortic Valve, Gender, Aortic Stenosis, and Regurgitation at the Four Levels of the Aortic Root for All Subjects Studied Ascending Aorta
 BAV Gender AR AS
2.7 0.56 1.87 0.92
Sinotubular Junction
Standardized  p Value 0.48 0.09 0.18 0.13

⬍0.01 1.03 0.257 0.16 0.02 ⫺0.5 0.11 0.48
Sinus of Valsalva
Standardized  p Value 0.26 0.04 ⫺0.7 0.1
0.02 0.70 0.48 0.33
AR (n ⫽ 9). Root dimensions at any level by heightdetermined z score were not significantly associated with gender or the presence of valve stenosis (Table 2). •••
We found that pediatric patients with an isolated BAV have aortic roots that are larger than normal at all of the measured anatomic levels. This dilation occurred at all heights and was present irrespective of the functional state of the valve. The dilation was most pronounced in the tubular portion of the ascending aorta. It has been demonstrated that dilation and rupture of the ascending aorta in patients with BAV is associated with an abnormality and weakness of the aortic media. Histologically, this abnormality is characterized by cystic medial necrosis, loss of smooth muscle, fragmentation of elastic fibers, and accumulation of mucopolysaccharides.4,16 –19 These changes have been documented in the ascending aortas of patients with BAV and dissection or severe dilation requiring surgery.15,16,18,20 Dilation in the aortic roots of children with BAV documented in our study supports the theory of a tissue abnormality, but histologic confirmation was not available. 1. Sheil ML, Jenkins O, Sholler GF. Echocardiographic assessment of aortic root
dimensions in normal children based on measurement of a new ratio of aortic size independent of growth. Am J Cardiol 1995;75:711–715. 2. Roman MJ, Devereux RB, Kramer-Fox R, O’Loughlin J. Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol 1989;64:507–512. 3. Rozendaal L, Groenink M, Naeff MS, Hennekam RC, Hart AA, van der Wall EE, Mulder BJ. Marfan syndrome in children and adolescents: an adjusted nomogram for screening aortic root dilatation. Heart 1998;79:69 –72.
1340 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 94
 1.6 0.24 ⫺1.4 0.06
Aortic Annulus
Standardized  p Value 0.42 0.06 ⫺0.19 0.01

⬍0.01 1.84 0.55 0.36 0.03 ⫺0.03 0.89 ⫺0.09
Standardized  p Value 0.43 0.08 ⫺0.01 0.02
⬍0.01 0.38 0.96 0.84
4. Burks JM, Illes RW, Keating EC, Lubbe WJ. Ascending aortic aneurysm and dissection in young adults with bicuspid aortic valve: implications for echocardiographic surveillance. Clin Cardiol 1998;21:439 – 443. 5. Basso C, Frescura C, Corrado D, Muriago M, Angelini A, Daliento L, Thiene G. Congenital heart disease and sudden death in the young. Hum Pathol 1995; 26:1065–1072. 6. Fikar CR, Koch S. Etiologic factors of acute aortic dissection in children and young adults. Clin Pediatr 2000;39:71– 80. 7. Lin AE, Lippe B, Rosenfeld RG. Further delineation of aortic dilation, dissection, and rupture in patients with Turner syndrome. Pediatrics 1998; 102:e12. 8. Miller MJ, Geffner ME, Lippe BM, Itami RM, Kaplan SA, DiSessa TG, Isabel-Jones JB, Friedman WF. Echocardiography reveals a high incidence of bicuspid aortic valve in Turner syndrome. J Pediatr 1983;102:47–50. 9. Pyeritz RE. Propranolol retards aortic root dilatation in the Marfan Syndrome. Circulation 1983;68:III-365. 10. Shores J, Berger KR, Murphy EA, Pyeritz RE. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan’s syndrome. N Engl J Med 1994;330:1335–1341. 11. Brandenburg RO Jr, Tajik AJ, Edwards WD, Reeder GS, Shub C, Seward JB. Accuracy of two-dimensional echocardiographic diagnosis of congenitally bicuspid aortic valve: echocardiographic and anatomic correlation in 115 patients. Am J Cardiol 1983;51:1469 –1473. 12. Snider AR, Serwer GA, Ritter SB. Echocardiography in Pediatric Heart Disease. 2nd Ed. St. Louis, MO: Mosby, 1997:427, 440. 13. Oh JK, Seward JB, Tajik AJ. The Echo Manual. New York, NY: Little, Brown, 1994:88, 104. 14. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002;39:1890 –1900. 15. Roberts WC. The congenitally bicuspid aortic valve. A study of 85 autopsy cases. Am J Cardiol 1970;26:72– 83. 16. Niwa K, Perloff JK, Bhuta SM, Laks H, Drinkwater DC, Child JS, Miner PD. Structural abnormalities of great arterial walls in congenital heart disease: light and electron microscopic analyses. Circulation 2001;103:393– 400. 17. Bonderman D, Gharehbaghi-Schnell E, Wollenek G, Maurer G, Baumgartner H, Lang IM. Mechanisms underlying aortic dilatation in congenital aortic valve malformation. Circulation 1999;99:2138 –2143. 18. McKusick VA. Association of congenital bicuspid aortic valve and Erdheim’s cystic medial necrosis. Lancet 1972;1:1026 –1027. 19. de Sa M, Moshkovitz Y, Butany J, David TE. Histologic abnormalities of the ascending aorta and pulmonary trunk in patients with bicuspid aortic valve disease: clinical relevance to the ross procedure. J Thorac Cardiovasc Surg 1999;118:588 –594. 20. Klima T, Spjut HJ, Coelho A, Gray AG, Wukasch DC, Reul GJ Jr, Cooley DA. The morphology of ascending aortic aneurysms. Hum Pathol 1983;14: 810 – 817.
NOVEMBER 15, 2004
with tissue Doppler echocardiographically derived myocardial velocity gradients. Circulation 2000;102:1276 –1282. 14. Lane A, Fleming AD, Donnelly JE, Dutka DP, Starkey IR, Shaw TRD, Sutherland GR, Fox KAA. Differences in myocardial velocity gradient measured throughout the cardiac cycle in patients with hypertrophic cardiomyopathy, athletes and patients with left ventricular hypertrophy due to hypertension. J Am Coll Cardiol 1997;30:760 –768.
Frequency of Aortic Root Dilation in Children With a Bicuspid Aortic Valve Michelle Gurvitz,
MD,
Ruey-Kang Chang, MD, MPH, Stacey Drant, Vivekanand Allada, MD
Bicuspid aortic valve (BAV) is associated with aortic root dilation and dissection in adults, but the age and conditions when dilation begins are unknown. Using echocardiographic data, we compared the aortic root dimensions and valve hemodynamics of 76 children with BAV with valves derived from 41 normal children. The children with BAV had significantly larger aortic roots (p <0.001) regardless of the presence of aortic stenosis or regurgitation. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;94:1337–1340)
n normal children, the aortic root grows with the child and has been shown to correlate well with Iheight and body surface area, independent of gender.1–3 Few studies have addressed the presence of a bicuspid aortic valve (BAV) in children or the characterization of the aortic root in these children except in small case studies or in association with Turner’s or Marfan’s syndrome.4 –10 Whether progressive dilation of the root can be modified or prevented if initially detected in children with BAV is an important but unanswered question. The goal of this cross-sectional study was to determine if children with isolated BAV have dilated aortic roots and whether root dilation has any relation to the functional hemodynamic state of the valve. •••
This study was approved by the institutional review boards at 2 large academic medical centers in the Los Angeles area. All patients aged ⬍21 years with isolated BAV on echocardiography from January 1994 to August 2002 were reviewed retrospectively, and the most recent available study for each was used for evaluation. IncluFrom the Division of Cardiology, Department of Pediatrics, Mattel Children’s Hospital at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, California. Dr. Chang received research funding (1 R03 HS13217-01) from the Agency for Healthcare Research and Quality, Rockville, Maryland, the American Heart Association (0365041Y), Burlingame, California and the National Center for Research Resources (1 K23 RR17041– 01), National Institutes of Health, Bethesda, Maryland. Dr. Gurvitz’s address is: B2– 427 MDCC, UCLA Medical Center, 10833 Le Conte Avenue, Los Angeles, California 90095-1743. E-mail: [email protected]. Manuscript received February 6, 2004; revised manuscript received and accepted July 15, 2004. ©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 November 15, 2004
MD,
and
sion in the study group required a technically adequate echocardiogram (described in the following). Patients with other cardiac anomalies, diagnosis of Turner’s or Marfan’s syndrome, or a surgical or catheter-based aortic valve intervention before echocardiography were excluded. Age, height, weight, body surface area, and cardiovascular medications were recorded for all patients. Echocardiograms and aforementioned clinical information of 41 normal children from the echocardiogram database were also reviewed to establish normal aortic root dimensions. Echocardiographic measurements in the standard parasternal and apical views were obtained using Acuson 128XP or Sequoia (Mountain View, California) systems. Technically adequate echocardiograms consisted of clear 2-dimensional views of the aortic valve, aortic root and left ventricle, and complete spectral and color Doppler interrogation of the aortic valve. All echocardiograms were examined by an independent reviewer (MG) who was blinded to the original report of the echocardiogram and to any information about the study subjects. The morphology of the BAV was determined by the presence of 2 distinct functional cusps in the parasternal short-axis view.11 Aortic root dimensions at the annulus, sinus of Valsalva, sinotubular junction, and proximal ascending aorta were assessed in the parasternal long-axis view in systole using the leading edge technique.2 Results recorded for each patient were an average of 3 measurements at each level. Left ventricular ejection fraction was assessed by 2-dimensional volume measurements from the apical views, when available, or by visual estimation of the reviewer. The hemodynamic state of the aortic valve was evaluated using color flow and spectral Doppler. Stenosis assessment, an average of 3 measurements for each subject, involved the following guidelines of mean gradients: mild or less, ⬍17 mm Hg; moderate, ⬎17 or ⬍27 mm Hg; and severe, ⬎27 mm Hg.12 When mean gradients could not be determined, a peak gradient of ⬎25 mm Hg was considered hemodynamically significant (greater than mild) stenosis. The degree of regurgitation was measured using several established criteria, including the pressure half-time technique, width of aortic regurgitation (AR) jet relative to the diameter of the left ventricular outflow 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.07.130
1337
TABLE 1 Demographic and Clinical Characteristics of Patients in the Study Group (n ⫽ 76) and in Normal Children (n ⫽ 41)*
Males Age (yrs) Height (cm) Body surface area (m2) Stenosis Regurgitation Both AS ⫹ MR Neither AS or MR
Study Group (n ⫽ 76)
Normal Children (n ⫽ 41)
p Value
62 (81%) 8.54 ⫾ 4.87 (0.01–19) 129 ⫾ 33 (50–180) 1.07 ⫾ 0.48 (0.22–2.07) 22 (29%) 5 (7%) 4 (5%) 45 (59%)
19 (46%) 9.38 ⫾ 5.67 (0.01–18) 133 ⫾ 36 (48–185) 1.16 ⫾ 0.54 (0.25–2.27) 0 0 0 41 (100%)
⬍0.01 0.42 0.48 0.36
*Results for gender, medications, and hemodynamics are listed as percentages. Age, height, and body surface area are listed as mean ⫾ SD, (range).
FIGURE 1. Measurements in the normal children (n ⴝ 41) of the diameters (in millimeters) of the aortic valve annulus (Annulus), sinus of Valsalva (Sinus), sinotubular junction (STJ), and ascending aorta (AAO) plotted against height (in centimeters). Graphs show mean regression line and 95% prediction intervals.
tract, and/or the presence of flow reversal in the descending aorta. AR was categorized as mild or less, moderate, and severe.12,13 1338 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 94
The aortic root dimensions of normal children were used to establish normal values in relation to height, age, and body surface area by linear regression analNOVEMBER 15, 2004
ysis for all 4 levels of the aortic root. With use of these equations to predict a normal value for height, the measurement of each level of the aortic root of each of the patients with BAV was converted to a z score. The Kolmogorov-Smirnov test was used for normality of distribution. For data analysis, patients with BAV were first considered as a single group and then divided into 4 subgroups by hemodynamic status: (1) aortic stenosis (AS; moderate or severe), (2) AR (moderate or severe regurgitation), (3) both AS ⫹ AR (moderate or severe stenosis and regurgitation), and (4) neither AS nor AR (mild or less stenosis and regurgitation). The z scores of the patients with BAV were tested against the mean z score of normal subjects (zero). Two hemodynamic subgroups of patients with BAV—AS (AS) and hemodynamically normal (neither AS nor AR)—were compared separately with normal children and were then compared with each other. All comparisons were performed using t tests. The subgroups with regurgitation (AR, AR ⫹ AS) were not included for comparisons because those groups contained only 5 and 4 subjects, respectively. Multiple linear regression analyses were performed to determine if gender, presence of BAV, stenosis, or regurgitation were significant predictors of aortic root dilation. The variables of age and body surface area were not included because they closely correlated with height. A p value ⬍0.05 was considered statistically significant. Statistical analyses were done using SPSS 10.1 for Windows (SPSS Inc., Chicago, Illinois). Eighty-one children with isolated BAVs were identified. Five were excluded because of technically inadequate echocardiograms. The demographic and clinical data of patients with BAVs and normal children are listed in Table 1. The 2 groups were similar in age, height, and body surface area but differed in gender distribution. The proportion of males and females, however, was similar to the gender ratio of BAV in previous population studies.14,15 All patients with BAVs and normal children had a left ventricular ejection fraction within normal limits. Only 5 of 71 children with BAV were taking cardiovascular medication; each was taking an angiotensin-converting enzyme inhibitor. In normal subjects, root dimensions correlated well with height (Figure 1) and body surface area (r ⫽ 0.89 to 0.93 for both) better than with age (r ⫽ 0.86 to 0.91). As described previously, z scores of the levels of the aortic root were determined in relation to height for each of the patients with BAV. Mean z scores of BAV patients were ⬎0 at the annulus (2 ⫾ 1.9, p ⬍0.001), sinus (1.6 ⫾ 1.9, p ⬍0.001), sinotubular junction (1.2 ⫾ 1.9, p ⬍0.001), and proximal ascending aorta (3.3 ⫾ 2.4, p ⬍0.001) (Figure 2). In considering a z score of ⱖ2 (95th percentile) as severely dilated, 55 patients (68%) had severe dilation at the ascending aorta (p ⬍0.05), 23 patients (29%) at the sinotubular junction, 28 patients (35%) at the sinus, and 41 patients (50%) at the annulus. Two patient subgroups with BAV—stenosis (AS, n ⫽ 22) and hemodynamically normal (neither AS nor
FIGURE 2. The z score measurements of the aortic valve annulus (ANN), sinotubular junction (STJ), sinus of valsava (SINUS), and ascending aorta (AAO). Horizontal lines inside boxes denote medians. Lower and upper limits in boxes denote 25th and 75th percentiles, respectively. Lower and upper limits of vertical bars denote 10th and 90th percentiles, respectively. Dots below and above the plots are 5th and 95th percentiles, respectively. Horizontal line of z score ⴝ 0 is plotted to indicate the average z score of the measurements obtained from the normal children.
FIGURE 3. The z score measurements of the ascending aorta (AAO) in the 2 patient subgroups—BAV with AS (BAV-AS) and BAV with normal hemodynamics (BAV-no AS/AR) compared with the normal children (Normal). Horizontal lines inside boxes denote medians. Lower and upper limits of boxes denote 25th and 75th percentiles, respectively. Lower and upper limits of vertical bars denote 10th and 90th percentiles, respectively (p >0.05).
AR, n ⫽ 45)—were compared with normal children and then with each other as described previously. At every level of the root, the z scores of the 2 subgroups were significantly greater than normal (all p values ⬍0.05). This was most apparent in the ascending aorta (Figure 3). At every level, however, the 2 subgroups were not significantly different from each other (all p values ⬎0.2). Using multiple regression analyses, dilation at all levels of the aortic root was significantly associated with the presence of a BAV. Dilation at the level of the ascending aorta was also associated with the presence of AR despite the small number of patients with BRIEF REPORTS
1339
TABLE 2 Multiple Linear Regression Results Comparing the Presence of a Bicuspid Aortic Valve, Gender, Aortic Stenosis, and Regurgitation at the Four Levels of the Aortic Root for All Subjects Studied Ascending Aorta
 BAV Gender AR AS
2.7 0.56 1.87 0.92
Sinotubular Junction
Standardized  p Value 0.48 0.09 0.18 0.13

⬍0.01 1.03 0.257 0.16 0.02 ⫺0.5 0.11 0.48
Sinus of Valsalva
Standardized  p Value 0.26 0.04 ⫺0.7 0.1
0.02 0.70 0.48 0.33
AR (n ⫽ 9). Root dimensions at any level by heightdetermined z score were not significantly associated with gender or the presence of valve stenosis (Table 2). •••
We found that pediatric patients with an isolated BAV have aortic roots that are larger than normal at all of the measured anatomic levels. This dilation occurred at all heights and was present irrespective of the functional state of the valve. The dilation was most pronounced in the tubular portion of the ascending aorta. It has been demonstrated that dilation and rupture of the ascending aorta in patients with BAV is associated with an abnormality and weakness of the aortic media. Histologically, this abnormality is characterized by cystic medial necrosis, loss of smooth muscle, fragmentation of elastic fibers, and accumulation of mucopolysaccharides.4,16 –19 These changes have been documented in the ascending aortas of patients with BAV and dissection or severe dilation requiring surgery.15,16,18,20 Dilation in the aortic roots of children with BAV documented in our study supports the theory of a tissue abnormality, but histologic confirmation was not available. 1. Sheil ML, Jenkins O, Sholler GF. Echocardiographic assessment of aortic root
dimensions in normal children based on measurement of a new ratio of aortic size independent of growth. Am J Cardiol 1995;75:711–715. 2. Roman MJ, Devereux RB, Kramer-Fox R, O’Loughlin J. Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol 1989;64:507–512. 3. Rozendaal L, Groenink M, Naeff MS, Hennekam RC, Hart AA, van der Wall EE, Mulder BJ. Marfan syndrome in children and adolescents: an adjusted nomogram for screening aortic root dilatation. Heart 1998;79:69 –72.
1340 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 94
 1.6 0.24 ⫺1.4 0.06
Aortic Annulus
Standardized  p Value 0.42 0.06 ⫺0.19 0.01

⬍0.01 1.84 0.55 0.36 0.03 ⫺0.03 0.89 ⫺0.09
Standardized  p Value 0.43 0.08 ⫺0.01 0.02
⬍0.01 0.38 0.96 0.84
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