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Aortic atresia: Morphologic characteristics affecting survival and operative palliation
J
THoRAc CARDIOVASC SURG
88:620-626, 1984
Aortic atresia: Morphologic characteristics affecting survival and operative palliation A quantitative anatomic study of 54 cardiac specimens with aortic atresia is related to surgical treatment of patients with aortic atresia and hypoplastic left heart syndrome. Coarctation of the aorta was present in 80 % of patients with aortic atresia and should influence the extent of aortic arch recomtruction when present Other associated cardiac defects were uncommon but, when present, may be contraindicatiom to operative palliation became of added complexity of the operation. Anatomic abnormalities of the tricuspid or pulmonary valve were present in 7 % of cases and could be important in the outcome of palliative procedures. Natural survlval was related to thickness of the right ventricular wall so that selection of those infants with thicker and better functioning right ventricles may improve short-term and long-term operative results in aortic atresia.
John A. Hawkins, M.D., and Donald B. Doty, M.D., Salt Lake City, Utah
Aortic valve atresia represents the largest group of the various anomalies constituting the hypoplastic left heart syndrome. In addition to atresia of the left ventricular outflow tract, anatomic features include hypoplasia of the ascending aorta and transverse arch, hypoplasia or atresia of the mitral valve, and variable hypoplasia of the left ventricle.' Although long survival has beeureported,' over 95% of infants with aortic atresia die within the first month of life.' Medical therapy is largely supportive and does not appreciably alter the uniformly fatal outcome. Recent success with palliativer" and physiological, corrective operations? has offered new hope to some infants with aortic atresia. Despite some encouraging efforts, palliative operations have been minimally successful and physiological correction with a modified Fontan procedure has been reported in only two infants to date." This study was done to determine anatomic factors that affect natural survival and operative palliation. Analysis of 54 cardiac specimens with aortic atresia showed right ventricular thickness to be the most important factor affecting natural survival. This implies that operative palliation may be most successful in those infants with a more hypertrophied right ventricle and From the Division of Thoracic and Cardiovascular Surgery, Primary Children's Medical Center, Salt Lake City, Utah. Received for publication Oct. 6, 1983. Accepted for publication Dec. 14, 1983. Address for reprints: Donald B. Doty, M.D., 324 Tenth Avenue, #160, Salt Lake City, Utah 84103.
620
better right ventricular function. Surgical palliation of aortic atresia also should take into account the common occurrence of coarctation of the aorta and the less common additional intracardiac anomalies. Materials and methods Fifty-four cardiac specimens with aortic atresia and 24 normal hearts were examined from the University of Iowa Pediatric Cardiology Museum. All specimens were from infants who had situs solitus and levocardia. Only aortic atresia specimens with atrioventricular and ventriculoarterial concordance were included in the study. Each heart had been previously fixed in 10% formalin and opened in the inflow and outflow tracts. Age at death in aortic atresia ranged from 1 to 96 days (mean 6 days). Aortic atresia patients had a mean body surface area of 0.21 ± 0.02 m', which was similar to the surface area of infants with normal hearts (0.20 ± 0.02 rn') who had died of noncardiac causes. Cardiac anomalies were noted in each specimen with aortic atresia. Mitral valve hypoplasia was defined as a patent left atrioventricular connection with identifiable valve tissue, and mitral atresia was defined as complete absence of a left atrioventricular connection. Each specimen was evaluated for coarctation of the aorta, including position (juxtaductal versus preduetal) and severity (mild, moderate, or severe). Measurements were made of both normal and aortic atresia specimens according to the methods of Rowlatt, Rimoldi, and Lev.1O Right ventricular thickness was measured to the nearest 0.5 mm in three locations; 0.5
Volume 88 Number 4 October, 1984
Aortic atresia
1.0
Table I. Cardiac anomalies associated with aortic atresia Anomaly Patent ductus arteriosus Patent foramen ovale Coarctation of the aorta Mitral valve hypoplasia Mitral valve atresia Ventricular septal defect Bicuspid pulmonary valve Anomalous origin of left subclavian artery Cor triatriatum Cleft tricuspid valve Tricuspid and pulmonary valve dysplasia Ruptured sinus of Valsalva aneurysm Anomalous papillary muscle of tricuspid valve
No. 54
53 43 40 14 2 2 2 I I I I I
em below the tricuspid valve on the anterior free wall, excluding trabeculae; at the apex, excluding trabeculae; and 0.5 to 1.0 cm below the pulmonary valve, full thickness. Circumference of the ascending aorta was measured to the nearest 0.5 mm at a point 0.5 to 1.0 em distal to the coronary ostia. Valve circumference was measured to the nearest 1.0 mm at the tricuspid and mitral (when applicable) anuli and at the level of the pulmonary valve commissures. Quantitative measurements of the patent ductus arteriosus and foramen ovale were not made, since it is nearly impossible to ascertain the real in vivo size of such dynamic and pliable structures in the ex vivo formalin-fixed state. The age at death, sex, height, and weight were obtained for each infant from hospital records. Body surface area was calculated from the recorded height and weight by standard nomograms. Standard statistical methods were used to analyze the data. A standard t test was used to compare measurements of aortic atresia and normal heart specimens. One-way analysis of variance and Tukey's multiple comparison test were used to compare cardiac measurements of aortic atresia subgroups to normal specimens. The chi square test and Fisher's exact test were also used for analysis of expected frequencies, where applicable. Cox's" proportional hazard model was utilized in both a single factor and as a multifactorial analysis of natural survival. Eleven infants that had undergone previous surgical procedures': 12 were excluded from the survival analysis. Factors analyzed for effect on survival included sex, surface area, coarctation, mitral hypoplasia or atresia, thickness of the right ventricle in the tricuspid, pulmonic, and apical areas, and the circumference of the ascending aorta and tricuspid and pulmonary valves.
621
~
,80
'>
s
~ .60
(f)
z o i= .40 u
l.L
.20
10
20
30
40
50
DAYS
Fig. 1. Actuarial survival in aortic atresia. Over 80% of deaths occur in the first week of life, and nearly all patients are dead by 3 weeks. 9.0
E .5
8.0
(J) (J)
w
~ u
7.0 n = 44 Y =.0595X r =0.85 P < .001 •
I
~ 6.0
i3 C>'
5.0
+ 3.25
I-
~ 4.0 I-
§
3.0 ~ ..•
0::
2.0+--,-----,---,----.----,--,---r----.---,---. a 10 20 30 40 50 60 70 80 90 100 SURVIVAL (days)
Fig. 2. Survival as a function of right ventricular wall thickness in aortic atresia. Thicker right ventricle correlates with longer survival.
Results Aortic atresia occurred with a 2.4: 1 male/female ratio. Mitral atresia occurred in 14 hearts, and the remainder had a spectrum of mitral valve hypoplasia and stenosis. Ventricular septal defects occurred in only two hearts, which were in the latter group. All except two patients died within the first 3 weeks of life, with the longest survival time being 96 days. Actuarial analysis of the survival time is shown in Fig. 1. Over 80% of deaths occurred in the first week of life. Cardiac anomalies associated with aortic atresia are listed in Table I. The most common associated anomalies were those that are considered to be part of the aortic atresia complex; patent ductus arteriosus (100%), valve incompetence or patent foramen ovale (98%), and mitral valve hypoplasia (74%) or atresia (26%). Another
622
The Journal of Thoracic and Cardiovascular Surgery
Hawkins and Doty
Table II. Coarctation of the aorta in aortic atresia Coarctation Mild Mitral hypoplasia Mitral atresia Ventricular septal defect
II 3
I
Moderate
....Q
Severe
6 2
10 9
Q
-.1.
8 (18%)
14 (32%)
I
21 (50%)
Position
I
Total 27 14
-.1. 43
I
I Preductal
No. (%)
Juxtaductal
38 ( 71%) 14 (100%) -.1. (100%) 54 ( 80%)
26 13
I I
-.1.
Q
41
2
Table m. Measurement in hearts with aortic atresia-mitral hypoplasia (AA-MH). aortic atresia-mitral atresia (AA-MA). aortic atresia-ventricular septal defect (AA-VSD). and normal hearts
AA-M~
AA-VSD
2.4 3 6 5.5
4.7 ± 1.1 27 ± 4 45 ± 6
7.8 ± 2.5 23 32 ± 4 15.5 ± 2.1
3.6 ± 0.7 4.1 ± 1.1 1.4 ± 0.4
4.1 ± 1.7 4.5 ± 1.6 1.6 ± 0.4
3.3 ± 0.4 4.3 ± 0.4 1.8 ± 1.0
_ _ _ _ _ _ _ _.,..--_ _-'--__A_A_-_M_H__ Circumference (mean ± SD) Ascending aorta Pulmonary artery Tricuspid valve Mitral RV thickness (mean ± SD) Tricuspid area Pulmonic area Apical area
6.7 25 43 11.5
± ± ± ±
---y:-o-ta-l---,----N-or-m-a-l6.3 25 43 11.7
± ± ± ±
2.3 4 6 5.4
3.7 ± 1.1 4.3 ± 1.3 1.5 ± 0.4
16.7 20 33 29
± ± ± ±
1.7 2 4 3.5
2.9 ± 0.5 3.2 ± 0.6 1.2 ± 0.3
Legend: RV, Right ventricular. SD, Standard deviation.
common abnormality noted was coarctation of the aorta, which occurred in 80% of all cases and was usually in a juxtaductal position (Table 11). Coarctation of the aorta was more common and more severe in the mitral atresia subgroup than in the mitral hypoplasia subgroup (p < 0.05, Table II). Other associated anomalies occurred in 20% of the specimens, but no individual anomaly occurred in more than 4%, as listed in Table I. Quantitative data are listed in Table III. The pulmonary and tricuspid valves and right ventricular wall thickness in all three areas were greater than the same measurements in normal specimens (p < 0.001). The ascending aorta was much smaller in hearts with aortic atresia than in normal cardiac specimens (p < 0.0001). In addition, the ascending aorta in the mitral atresia subgroup was significantly smaller than in the mitral hypoplasia subgroup (p < 0.05). The relative importance of each single factor unadjusted for other factors is shown in Table IV. This indicates that right ventricular thickness in all three areas and pulmonary artery circumference were independently predictive of survival (p < 0.05), without taking into account the other variables. Multifactorial analysis was then performed. This examines the primary predictors of survival, while simultaneously accounting for the contribution of the other variables. This multifactorial analysis showed that right ventricular thickness
in the tricuspid area was the best predictor of survival (p < 0.0001), whereas the other variables were not predictive (p> 0.01). The following model was obtained through a stepwise regression procedure: log A (T)lAO (T = 0.8869T, where T was the thickness of the right ventricle in the tricuspid area (RV-T) and log A (T)/Ao (7') was the relative risk. The relationship between right ventricular thickness and survival is shown in Fig. 2. Discussion Most anatomic studies of aortic atresia have focused on the severely altered left heart morphology.":" This study has documented with a high degree of statistical significance that the left-sided heart structures are extremely small in aortic atresia compared to normal left heart anatomy. This study has also focused on the right heart anatomy in aortic atresia, since successful surgical management must rely entirely on the structure and function of the right ventricle. Anatomic factors important in natural survival have been analyzed with the reasoning that anatomy favorable to survival should also favorably affect surgical treatment. Previous studies and this report have documented the universally poor prognosis for infants with aortic atresia, with 95% of patients dying in the first month of life. Occasional survival past infancy has been reported.2 Anatomic and physiological characteristics of aortic atresia, which have been reported to be associated with a
Volume 88 Number 4 October. 1984
Aortic atresia
623
Fig. 3. Mild coarctation flange (arrows) developsopposite the patent ductus arteriosus (DA) in aortic atresia. Asc Ao, Ascending aorta. Desc Ao, Descending aorta. PA, Pulmonary artery.
longer natural survival, include a large 5,15 or restrietive"" interatrial communication, a relatively large ascending aorta," increased left atrial thickness," elevated pulmonary vascular resistance,I8 and a large patent ductus arteriosus." Although all these factors undoubtedly have an effect on survival, the right ventricular wall thickness was the single best predictor of natural survival in patients with aortic atresia in this study. This impliesthat the hypertrophied right ventricle in aortic atresia was better equipped to supply both systemic and pulmonary circulations than a less hypertrophied or normal right ventricle. This hypothesis is supoorted by the report of McGarry, Taylor, and Macartney" of a patient who survived to 6 years of age with aortic atresia, dextro-transposition of the great arteries, hypoplastic right (systemic) ventricle, and a normal left (pulmonary) ventricle." It is possible that other factors were responsiblefor longer life and that the right ventricle became thicker in response to time and load, so that there was an apparent correlation with prolongedsurvival.The short time period of less than 21 days until death in all except two patients, however, suggests that most compensatory hypertrophy of the heart likely would have occurred prior to birth. Similar quantitative studies of cardiac specimens with right ventricular overload have shown that hypertrophy of the right ventricle does not occur this rapidly in the first 3 months of life.20 , 21 In addition to good right ventricular performance, other factors that seem essential for natu-
Table IV. Single factor analysis of survival in aortic atresia Variable
p Value
RV thickness-tricuspid area RV thickness-pulmonic area RV thickness-apex Pulmonary artery circumference Sex Mitral valve atresia or hypoplasia Tricuspid valve circumference Presence of coarctation Body surface area Ascending aortic circumference
<0.0001 0.0026 0.0035 0.024 0.10 0.11 0.15 0.20 0.23 0.64
ral survival in aortic atresia include maintenance of the patency of the ductus arteriosus and some degree of physiological restriction of pulmonary blood flow by increased pulmonary vascular resistance.t" Since natural survival in aortic atresia is poor, operative intervention has been attempted to palliate the condition and prolong life." Planning for operation on infants with aortic atresia must take into account associated cardiac anomalies that might complicate operative palliation or repair. The most common associated cardiac abnormalities are those that are part of the aortic atresia complex:patent ductus arteriosus, coarctation of the aorta, mitral valve hypoplasia or atresia, and valve incompetence or patent foramen ovale (Table I). Other cardiac anomalies are uncommon but may
624
Hawkins and Doty
The Journal of Thoracic and Cardiovascular Surgery
Fig. 4. Severe coarctation segment of aorta (arrows) develops as a flange in juxtaductal position in aortic atresia. DA, Ductus arteriosus. Asc A o, Ascending aorta . Desc Ao, Descending aorta. PA, Pulmonary artery .
include a variety of complex defects , as shown in this study (Table I). Other investigators have also described total anomalous pulmonary venous connection, 14. 15 coronary sinus atresia," common pulmonary vein atresia," complete atrioventricular canal defect," quadricuspid pulmonary valve," double-orifice tricuspid valve," and interrupted aortic arch" in association with aortic atresia. Of these anomalies, anatomic abnormalities of the right heart, especially those involving the tricuspid or pulmonary valve, would seem to be unfavorable to successful palliative operations in aortic atresia. Dysfunction of an anatomically abnormal tricuspid or pulmonic valve would likely be poorly tolerated by infants having operations for aortic atresia and represent a relative contraindication to operative intervention. Functional integrity of these valves is so essential for good right ventricular performance that normal structure should be assured before operation. Other associated cardiac anomalies that could be considered contraindications to surgical intervention include total anomalous pulmonary venous connection, common pulmonary vein atresia, and ruptured sinus of Valsalva aneurysm, only because of the added complexity that correction of these anomalies would bring to any operation. Coarctation of the aorta is a commonly associated defect found in approximately 75% to 80% of all cases of aortic atresia, as reported by Von Reuden and assoelates" and in this series (Table II) . There is some
controversy as to actual occurrence, and other authors have reported the incidence of coarctation in aortic atresia to be relatively low.t" The reported occurrence of coarctation in aortic atresia might be affected by morphologic criteria, with mild or moderate degrees of narrowing being ignored in low incidence series and counted in other series. A mild degree of formation of a coarctation flange, which could easily be dismissed as insignificant, is shown in Fig. 3. A more severe juxtaductal flange, as shown in Fig. 4, would always be classified as coarctation. Hutchins" postulated that coarctation should be expected to occur frequently with aortic atresia as a result of development of a coarctation flange at a branch point of blood flow in the ductus arteriosus. Since there is marked diminution of blood flow from the left heart into the ascending aorta in aortic atresia, all of the aortic arch and descending aortic flow is derived from the ductus arteriosus." The coarctation flange develops and extends into the area of least flow and resistance at the point where ductal flow divides (Figs. 3 and 4). Hutchins" supported his theory by an extensive examination of both autopsy and surgical specimens. The severity of coarctation associated with aortic atresia appears to be variable (Table II). Evaluation of the degree of distal arch narrowing is essential in order to determine if arch reconstruction is necessary at the time of palliative operation. Even what appears to be "mild" coarctation may become hemodynamically significant when the ductus arteriosus is ligated or the
Volume 88 Number 4 October. 1984
infant grows. For these reasons, we4 • 26 have always recommended reconstruction of the aortic arch to a point distal to any possible coarctation in all cases. Complete arch reconstruction has apparently not been done in other successful surgical experiences.v? It is possible to perform direct anastomosis of the pulmonary artery to the aortic arch, even using an extended aortotomy in the transverse arch to a point distal to the juxtaductal coarctation. An anastomosis made in this manner should relieve any residual outflow tract obstruction, which would not be tolerated by the right ventricle in aortic atresia perioperatively or might later require revision of the arch. The essence of successful operative palliation in aortic atresia relates to the capacity of the single ventricle of right ventricular morphology to maintain adequate hemodynamics. Recent successful palliation and physiological repair of aortic atresia suggests that it is possible for a right ventricle to support the entire circulation.v 9 Experience with atrial repair of dextro-transposition of the great arteries, however, has shown that there is at least some doubt about the long-term ability of the right ventricle" and tricuspid valve" to function in the systemic position. Additional experience with the modified Fontan procedure has demonstrated that ventricular function is a major determinant of both operative and long-term survival of patients with only one effective ventricle." The long-term ability of the right ventricle to function as the systemic ventricle will be known only as surgical experience with aortic atresia increases. The present study has shown variation in right ventricular wall thickness in hearts with aortic atresia, which apparently relates to natural survival. Although ventricular thickness is not synonymous with ventricular function, it is to a certain extent a reflection of the work capacity of the right ventricle. Changes in ventricular thickness and mass reflect the adaptive process in utero which allows the right ventricle the function at more normal levels at greater work loads." It would be reasoned that better candidates for surgical intervention in aortic atresia might then be those infants with a thicker right ventricle at birth. Echocardiographic measurements of right ventricular wall thickness combined with estimates of ventricular function might allow better selection of those infants who will survive operation.
Aortic atresia
2
3
4
5
6
7
8
9
10
II 12 13
14 15
16
We wish to thank Tom O'Gorman, Ph.D., for the statistical analysis, Norman Hu for photographic assistance, and Linda Jarvis for typing the manuscript. REFERENCES Freedom RM: Hypoplastic left heart syndrome, Moss' Heart Disease in Infants, Children and Adolescents, FH
17
18
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Adams, GC Emmanouilides, eds., Baltimore, 1983, The Williams & Wilkins Company, pp 411-422 Moodie DS, Gallen WJ, Friedberg DZ: Congenital aortic atresia. Report of long survival and some speculations about surgical approaches. J THORAC CARDIOVASC SURG 63:726-731, 1972 Fyler DC, Rothman KJ, Bulkley LP, Cohn HE, Hellenbrand WE, Castaneda A: The determinants of five year survival of infants with critical congenital heart disease, Pediatric Cardiovascular Disease, Cardiovascular Clinics, MA Engle, ed., Philadelphia, 1981, F. A. Davis Company, pp 393-405 Doty DB, Marvin WJ, Schieken RM, Lauer RM: Hypoplastic left heart syndrome. Successful palliation with a new operation. J THORAC CARDIOVASC SURG 80:148-152, 1980 Levitsky S, Vander Horst RL, Hastreiter AR, Eckner FA, Bennett EJ: Surgical palliation in aortic atresia. J THORAC CARDIOVASC SURG 79:456-463, 1980 Mohri H, Horiuchi T, Haneda K, Sato S, Kahata 0, Ohmi M, Ishizawa E, Kagawa Y, Fukada M, Yoshida Y, Shima T: Surgical treatment for hypoplastic left heart syndrome. J THORAC CARDIOVASC SURG 78:223-228, 1979 Behrendt DM, Rocchini A: An operation for the hypoplastic left heart syndrome. Preliminary report. Ann Thorac Surg 32:284-288 1981 . Lang P, Norwood WI: Hemodynamic assessment after palliative surgery for hypoplastic left heart syndrome. Circulation 68:104-108, 1983 Norwood WI, Lang P, Hansen D: Physiologic repair of aortic atresia-hypoplastic left heart syndrome. N Engl J Med 308:23-26, 1983 Rowlatt UF, Rimoldi JHA, Lev M: The quantitative anatomy of the normal child's heart. Pediatr Clin North Am 10:499-591, 1963 Cox DR: Regression model and life tables. J R Stat Soc B34187-220, 1972 Doty DB, Knott HW: Hypoplastic left heart syndrome. J THORAC CARDIOVASC SURG 74:624-630, 1977 Roberts WC, Perry LW, Chandra RS, Myers GE, Shapiro SR, Scott LP: Aortic valve atresia. A new classification based on necropsy study of 73 cases. Am J Cardiol 37:753-756, 1976 Watson 00, Rowe RD: Aortic valve atresia. Report of 43 cases. JAMA 179: 112-116, 1962 Kanjuh VI, Eliot RS, Edwards JE: Coexistent mitral and aortic valvular atresia. A pathologic study of 14 cases. Am J Cardiol 15:611-621, 1965 Sinha SN, Rusnak SL, Sommers HM, Cole RB, Muster AJ, Paul MH: Hypoplastic left ventricle syndrome. Analysis of thirty autopsy cases in infants with surgical considerations. Am J Cardiol 21166-173, 1968 Hastreiter AR, Vander Horst RL, Dubrow IW, Eckner FO: Quantitative angiographic and morphologic aspects of aortic valve atresia. Am J CardioI51:1705-1708, 1983 Saied A, Folger GM: Hypoplastic left heart syndrome.
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20
21
22
23
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Clinicopathologic and hemodynamic correlation. Am J Cardiol 29: 190-198, 1972 McGarry KM, Taylor JFN, Macartney FJ: Aortic atresia occurring with transposition of the great arteries. Br Heart J 44:711-713, 1980 Lev M, Rimoldi HJA, Paira R, Arcilla RA: The quantitative anatomy of simple complete transposition. Am J Cardiol 23:409-416, 1969 Lev M, Rimoldi HJA, Rowlatt UF: The quantitative anatomy of cyanotic tetralogy of Fallot. Circulation 30:531-538, 1964 Rosenquist GC, Taylor JFN, Stark J: Aortopulmonary fenestration and aortic atresia. Report of an infant with ventricular septal defect, persistent ductus arteriosus, and interrupted aortic arch. Br Heart J 36:1146-1148,1974 Von Reuden TJ, Knight L, Moller JH, Edwards JE: Coarctation of the aorta associated with aortic valvular atresia. Circulation 52:951-954, 1975 Hutchins GM: Coarctation of the aorta explained as a branch point of the ductus arteriosus. Am J Pathol 63:203-214, 1971
The Journal of Thoracic and Cardiovascular Surgery
25 Rudolph AM, Heymann MA, Spitznas V: Hemodynamic considerations in the development of narrowing of the aorta. Am J Cardiol 30:514-525, 1972 26 Doty DB: Aortic atresia. J THORAC CARDIOVASC SURG 79:462-463, 1980 27 Graham TP, Atwood GJ, Boucek RJ, Boerth RS, Bender HW: Abnormalities of right ventricular function following Mustard's operation for transposition of the great arteries. Circulation 52:678-684, 1975 28 Tynan M, Aberdeen E, Stark J: Tricuspid incompetence after the Mustard operation for transposition of the great arteries. Circulation 45,46:Suppl 1:111-115, 1972 29 Rice MJ, Mair DD, Puga FJ, Danielson GK, Driscoll OJ, Edwards WD: Clinical hemodynamic and functional assessment of 180 patients undergoing the modified Fontan procedure (abstr), Circulation 66:Suppl 2:30, 1982 30 Perloff JK: Development and regression of increased ventricular mass. Am J Cardiol 50:605-611, 1982
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THoRAc CARDIOVASC SURG
88:620-626, 1984
Aortic atresia: Morphologic characteristics affecting survival and operative palliation A quantitative anatomic study of 54 cardiac specimens with aortic atresia is related to surgical treatment of patients with aortic atresia and hypoplastic left heart syndrome. Coarctation of the aorta was present in 80 % of patients with aortic atresia and should influence the extent of aortic arch recomtruction when present Other associated cardiac defects were uncommon but, when present, may be contraindicatiom to operative palliation became of added complexity of the operation. Anatomic abnormalities of the tricuspid or pulmonary valve were present in 7 % of cases and could be important in the outcome of palliative procedures. Natural survlval was related to thickness of the right ventricular wall so that selection of those infants with thicker and better functioning right ventricles may improve short-term and long-term operative results in aortic atresia.
John A. Hawkins, M.D., and Donald B. Doty, M.D., Salt Lake City, Utah
Aortic valve atresia represents the largest group of the various anomalies constituting the hypoplastic left heart syndrome. In addition to atresia of the left ventricular outflow tract, anatomic features include hypoplasia of the ascending aorta and transverse arch, hypoplasia or atresia of the mitral valve, and variable hypoplasia of the left ventricle.' Although long survival has beeureported,' over 95% of infants with aortic atresia die within the first month of life.' Medical therapy is largely supportive and does not appreciably alter the uniformly fatal outcome. Recent success with palliativer" and physiological, corrective operations? has offered new hope to some infants with aortic atresia. Despite some encouraging efforts, palliative operations have been minimally successful and physiological correction with a modified Fontan procedure has been reported in only two infants to date." This study was done to determine anatomic factors that affect natural survival and operative palliation. Analysis of 54 cardiac specimens with aortic atresia showed right ventricular thickness to be the most important factor affecting natural survival. This implies that operative palliation may be most successful in those infants with a more hypertrophied right ventricle and From the Division of Thoracic and Cardiovascular Surgery, Primary Children's Medical Center, Salt Lake City, Utah. Received for publication Oct. 6, 1983. Accepted for publication Dec. 14, 1983. Address for reprints: Donald B. Doty, M.D., 324 Tenth Avenue, #160, Salt Lake City, Utah 84103.
620
better right ventricular function. Surgical palliation of aortic atresia also should take into account the common occurrence of coarctation of the aorta and the less common additional intracardiac anomalies. Materials and methods Fifty-four cardiac specimens with aortic atresia and 24 normal hearts were examined from the University of Iowa Pediatric Cardiology Museum. All specimens were from infants who had situs solitus and levocardia. Only aortic atresia specimens with atrioventricular and ventriculoarterial concordance were included in the study. Each heart had been previously fixed in 10% formalin and opened in the inflow and outflow tracts. Age at death in aortic atresia ranged from 1 to 96 days (mean 6 days). Aortic atresia patients had a mean body surface area of 0.21 ± 0.02 m', which was similar to the surface area of infants with normal hearts (0.20 ± 0.02 rn') who had died of noncardiac causes. Cardiac anomalies were noted in each specimen with aortic atresia. Mitral valve hypoplasia was defined as a patent left atrioventricular connection with identifiable valve tissue, and mitral atresia was defined as complete absence of a left atrioventricular connection. Each specimen was evaluated for coarctation of the aorta, including position (juxtaductal versus preduetal) and severity (mild, moderate, or severe). Measurements were made of both normal and aortic atresia specimens according to the methods of Rowlatt, Rimoldi, and Lev.1O Right ventricular thickness was measured to the nearest 0.5 mm in three locations; 0.5
Volume 88 Number 4 October, 1984
Aortic atresia
1.0
Table I. Cardiac anomalies associated with aortic atresia Anomaly Patent ductus arteriosus Patent foramen ovale Coarctation of the aorta Mitral valve hypoplasia Mitral valve atresia Ventricular septal defect Bicuspid pulmonary valve Anomalous origin of left subclavian artery Cor triatriatum Cleft tricuspid valve Tricuspid and pulmonary valve dysplasia Ruptured sinus of Valsalva aneurysm Anomalous papillary muscle of tricuspid valve
No. 54
53 43 40 14 2 2 2 I I I I I
em below the tricuspid valve on the anterior free wall, excluding trabeculae; at the apex, excluding trabeculae; and 0.5 to 1.0 cm below the pulmonary valve, full thickness. Circumference of the ascending aorta was measured to the nearest 0.5 mm at a point 0.5 to 1.0 em distal to the coronary ostia. Valve circumference was measured to the nearest 1.0 mm at the tricuspid and mitral (when applicable) anuli and at the level of the pulmonary valve commissures. Quantitative measurements of the patent ductus arteriosus and foramen ovale were not made, since it is nearly impossible to ascertain the real in vivo size of such dynamic and pliable structures in the ex vivo formalin-fixed state. The age at death, sex, height, and weight were obtained for each infant from hospital records. Body surface area was calculated from the recorded height and weight by standard nomograms. Standard statistical methods were used to analyze the data. A standard t test was used to compare measurements of aortic atresia and normal heart specimens. One-way analysis of variance and Tukey's multiple comparison test were used to compare cardiac measurements of aortic atresia subgroups to normal specimens. The chi square test and Fisher's exact test were also used for analysis of expected frequencies, where applicable. Cox's" proportional hazard model was utilized in both a single factor and as a multifactorial analysis of natural survival. Eleven infants that had undergone previous surgical procedures': 12 were excluded from the survival analysis. Factors analyzed for effect on survival included sex, surface area, coarctation, mitral hypoplasia or atresia, thickness of the right ventricle in the tricuspid, pulmonic, and apical areas, and the circumference of the ascending aorta and tricuspid and pulmonary valves.
621
~
,80
'>
s
~ .60
(f)
z o i= .40 u
l.L
.20
10
20
30
40
50
DAYS
Fig. 1. Actuarial survival in aortic atresia. Over 80% of deaths occur in the first week of life, and nearly all patients are dead by 3 weeks. 9.0
E .5
8.0
(J) (J)
w
~ u
7.0 n = 44 Y =.0595X r =0.85 P < .001 •
I
~ 6.0
i3 C>'
5.0
+ 3.25
I-
~ 4.0 I-
§
3.0 ~ ..•
0::
2.0+--,-----,---,----.----,--,---r----.---,---. a 10 20 30 40 50 60 70 80 90 100 SURVIVAL (days)
Fig. 2. Survival as a function of right ventricular wall thickness in aortic atresia. Thicker right ventricle correlates with longer survival.
Results Aortic atresia occurred with a 2.4: 1 male/female ratio. Mitral atresia occurred in 14 hearts, and the remainder had a spectrum of mitral valve hypoplasia and stenosis. Ventricular septal defects occurred in only two hearts, which were in the latter group. All except two patients died within the first 3 weeks of life, with the longest survival time being 96 days. Actuarial analysis of the survival time is shown in Fig. 1. Over 80% of deaths occurred in the first week of life. Cardiac anomalies associated with aortic atresia are listed in Table I. The most common associated anomalies were those that are considered to be part of the aortic atresia complex; patent ductus arteriosus (100%), valve incompetence or patent foramen ovale (98%), and mitral valve hypoplasia (74%) or atresia (26%). Another
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Table II. Coarctation of the aorta in aortic atresia Coarctation Mild Mitral hypoplasia Mitral atresia Ventricular septal defect
II 3
I
Moderate
....Q
Severe
6 2
10 9
Q
-.1.
8 (18%)
14 (32%)
I
21 (50%)
Position
I
Total 27 14
-.1. 43
I
I Preductal
No. (%)
Juxtaductal
38 ( 71%) 14 (100%) -.1. (100%) 54 ( 80%)
26 13
I I
-.1.
Q
41
2
Table m. Measurement in hearts with aortic atresia-mitral hypoplasia (AA-MH). aortic atresia-mitral atresia (AA-MA). aortic atresia-ventricular septal defect (AA-VSD). and normal hearts
AA-M~
AA-VSD
2.4 3 6 5.5
4.7 ± 1.1 27 ± 4 45 ± 6
7.8 ± 2.5 23 32 ± 4 15.5 ± 2.1
3.6 ± 0.7 4.1 ± 1.1 1.4 ± 0.4
4.1 ± 1.7 4.5 ± 1.6 1.6 ± 0.4
3.3 ± 0.4 4.3 ± 0.4 1.8 ± 1.0
_ _ _ _ _ _ _ _.,..--_ _-'--__A_A_-_M_H__ Circumference (mean ± SD) Ascending aorta Pulmonary artery Tricuspid valve Mitral RV thickness (mean ± SD) Tricuspid area Pulmonic area Apical area
6.7 25 43 11.5
± ± ± ±
---y:-o-ta-l---,----N-or-m-a-l6.3 25 43 11.7
± ± ± ±
2.3 4 6 5.4
3.7 ± 1.1 4.3 ± 1.3 1.5 ± 0.4
16.7 20 33 29
± ± ± ±
1.7 2 4 3.5
2.9 ± 0.5 3.2 ± 0.6 1.2 ± 0.3
Legend: RV, Right ventricular. SD, Standard deviation.
common abnormality noted was coarctation of the aorta, which occurred in 80% of all cases and was usually in a juxtaductal position (Table 11). Coarctation of the aorta was more common and more severe in the mitral atresia subgroup than in the mitral hypoplasia subgroup (p < 0.05, Table II). Other associated anomalies occurred in 20% of the specimens, but no individual anomaly occurred in more than 4%, as listed in Table I. Quantitative data are listed in Table III. The pulmonary and tricuspid valves and right ventricular wall thickness in all three areas were greater than the same measurements in normal specimens (p < 0.001). The ascending aorta was much smaller in hearts with aortic atresia than in normal cardiac specimens (p < 0.0001). In addition, the ascending aorta in the mitral atresia subgroup was significantly smaller than in the mitral hypoplasia subgroup (p < 0.05). The relative importance of each single factor unadjusted for other factors is shown in Table IV. This indicates that right ventricular thickness in all three areas and pulmonary artery circumference were independently predictive of survival (p < 0.05), without taking into account the other variables. Multifactorial analysis was then performed. This examines the primary predictors of survival, while simultaneously accounting for the contribution of the other variables. This multifactorial analysis showed that right ventricular thickness
in the tricuspid area was the best predictor of survival (p < 0.0001), whereas the other variables were not predictive (p> 0.01). The following model was obtained through a stepwise regression procedure: log A (T)lAO (T = 0.8869T, where T was the thickness of the right ventricle in the tricuspid area (RV-T) and log A (T)/Ao (7') was the relative risk. The relationship between right ventricular thickness and survival is shown in Fig. 2. Discussion Most anatomic studies of aortic atresia have focused on the severely altered left heart morphology.":" This study has documented with a high degree of statistical significance that the left-sided heart structures are extremely small in aortic atresia compared to normal left heart anatomy. This study has also focused on the right heart anatomy in aortic atresia, since successful surgical management must rely entirely on the structure and function of the right ventricle. Anatomic factors important in natural survival have been analyzed with the reasoning that anatomy favorable to survival should also favorably affect surgical treatment. Previous studies and this report have documented the universally poor prognosis for infants with aortic atresia, with 95% of patients dying in the first month of life. Occasional survival past infancy has been reported.2 Anatomic and physiological characteristics of aortic atresia, which have been reported to be associated with a
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Aortic atresia
623
Fig. 3. Mild coarctation flange (arrows) developsopposite the patent ductus arteriosus (DA) in aortic atresia. Asc Ao, Ascending aorta. Desc Ao, Descending aorta. PA, Pulmonary artery.
longer natural survival, include a large 5,15 or restrietive"" interatrial communication, a relatively large ascending aorta," increased left atrial thickness," elevated pulmonary vascular resistance,I8 and a large patent ductus arteriosus." Although all these factors undoubtedly have an effect on survival, the right ventricular wall thickness was the single best predictor of natural survival in patients with aortic atresia in this study. This impliesthat the hypertrophied right ventricle in aortic atresia was better equipped to supply both systemic and pulmonary circulations than a less hypertrophied or normal right ventricle. This hypothesis is supoorted by the report of McGarry, Taylor, and Macartney" of a patient who survived to 6 years of age with aortic atresia, dextro-transposition of the great arteries, hypoplastic right (systemic) ventricle, and a normal left (pulmonary) ventricle." It is possible that other factors were responsiblefor longer life and that the right ventricle became thicker in response to time and load, so that there was an apparent correlation with prolongedsurvival.The short time period of less than 21 days until death in all except two patients, however, suggests that most compensatory hypertrophy of the heart likely would have occurred prior to birth. Similar quantitative studies of cardiac specimens with right ventricular overload have shown that hypertrophy of the right ventricle does not occur this rapidly in the first 3 months of life.20 , 21 In addition to good right ventricular performance, other factors that seem essential for natu-
Table IV. Single factor analysis of survival in aortic atresia Variable
p Value
RV thickness-tricuspid area RV thickness-pulmonic area RV thickness-apex Pulmonary artery circumference Sex Mitral valve atresia or hypoplasia Tricuspid valve circumference Presence of coarctation Body surface area Ascending aortic circumference
<0.0001 0.0026 0.0035 0.024 0.10 0.11 0.15 0.20 0.23 0.64
ral survival in aortic atresia include maintenance of the patency of the ductus arteriosus and some degree of physiological restriction of pulmonary blood flow by increased pulmonary vascular resistance.t" Since natural survival in aortic atresia is poor, operative intervention has been attempted to palliate the condition and prolong life." Planning for operation on infants with aortic atresia must take into account associated cardiac anomalies that might complicate operative palliation or repair. The most common associated cardiac abnormalities are those that are part of the aortic atresia complex:patent ductus arteriosus, coarctation of the aorta, mitral valve hypoplasia or atresia, and valve incompetence or patent foramen ovale (Table I). Other cardiac anomalies are uncommon but may
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Fig. 4. Severe coarctation segment of aorta (arrows) develops as a flange in juxtaductal position in aortic atresia. DA, Ductus arteriosus. Asc A o, Ascending aorta . Desc Ao, Descending aorta. PA, Pulmonary artery .
include a variety of complex defects , as shown in this study (Table I). Other investigators have also described total anomalous pulmonary venous connection, 14. 15 coronary sinus atresia," common pulmonary vein atresia," complete atrioventricular canal defect," quadricuspid pulmonary valve," double-orifice tricuspid valve," and interrupted aortic arch" in association with aortic atresia. Of these anomalies, anatomic abnormalities of the right heart, especially those involving the tricuspid or pulmonary valve, would seem to be unfavorable to successful palliative operations in aortic atresia. Dysfunction of an anatomically abnormal tricuspid or pulmonic valve would likely be poorly tolerated by infants having operations for aortic atresia and represent a relative contraindication to operative intervention. Functional integrity of these valves is so essential for good right ventricular performance that normal structure should be assured before operation. Other associated cardiac anomalies that could be considered contraindications to surgical intervention include total anomalous pulmonary venous connection, common pulmonary vein atresia, and ruptured sinus of Valsalva aneurysm, only because of the added complexity that correction of these anomalies would bring to any operation. Coarctation of the aorta is a commonly associated defect found in approximately 75% to 80% of all cases of aortic atresia, as reported by Von Reuden and assoelates" and in this series (Table II) . There is some
controversy as to actual occurrence, and other authors have reported the incidence of coarctation in aortic atresia to be relatively low.t" The reported occurrence of coarctation in aortic atresia might be affected by morphologic criteria, with mild or moderate degrees of narrowing being ignored in low incidence series and counted in other series. A mild degree of formation of a coarctation flange, which could easily be dismissed as insignificant, is shown in Fig. 3. A more severe juxtaductal flange, as shown in Fig. 4, would always be classified as coarctation. Hutchins" postulated that coarctation should be expected to occur frequently with aortic atresia as a result of development of a coarctation flange at a branch point of blood flow in the ductus arteriosus. Since there is marked diminution of blood flow from the left heart into the ascending aorta in aortic atresia, all of the aortic arch and descending aortic flow is derived from the ductus arteriosus." The coarctation flange develops and extends into the area of least flow and resistance at the point where ductal flow divides (Figs. 3 and 4). Hutchins" supported his theory by an extensive examination of both autopsy and surgical specimens. The severity of coarctation associated with aortic atresia appears to be variable (Table II). Evaluation of the degree of distal arch narrowing is essential in order to determine if arch reconstruction is necessary at the time of palliative operation. Even what appears to be "mild" coarctation may become hemodynamically significant when the ductus arteriosus is ligated or the
Volume 88 Number 4 October. 1984
infant grows. For these reasons, we4 • 26 have always recommended reconstruction of the aortic arch to a point distal to any possible coarctation in all cases. Complete arch reconstruction has apparently not been done in other successful surgical experiences.v? It is possible to perform direct anastomosis of the pulmonary artery to the aortic arch, even using an extended aortotomy in the transverse arch to a point distal to the juxtaductal coarctation. An anastomosis made in this manner should relieve any residual outflow tract obstruction, which would not be tolerated by the right ventricle in aortic atresia perioperatively or might later require revision of the arch. The essence of successful operative palliation in aortic atresia relates to the capacity of the single ventricle of right ventricular morphology to maintain adequate hemodynamics. Recent successful palliation and physiological repair of aortic atresia suggests that it is possible for a right ventricle to support the entire circulation.v 9 Experience with atrial repair of dextro-transposition of the great arteries, however, has shown that there is at least some doubt about the long-term ability of the right ventricle" and tricuspid valve" to function in the systemic position. Additional experience with the modified Fontan procedure has demonstrated that ventricular function is a major determinant of both operative and long-term survival of patients with only one effective ventricle." The long-term ability of the right ventricle to function as the systemic ventricle will be known only as surgical experience with aortic atresia increases. The present study has shown variation in right ventricular wall thickness in hearts with aortic atresia, which apparently relates to natural survival. Although ventricular thickness is not synonymous with ventricular function, it is to a certain extent a reflection of the work capacity of the right ventricle. Changes in ventricular thickness and mass reflect the adaptive process in utero which allows the right ventricle the function at more normal levels at greater work loads." It would be reasoned that better candidates for surgical intervention in aortic atresia might then be those infants with a thicker right ventricle at birth. Echocardiographic measurements of right ventricular wall thickness combined with estimates of ventricular function might allow better selection of those infants who will survive operation.
Aortic atresia
2
3
4
5
6
7
8
9
10
II 12 13
14 15
16
We wish to thank Tom O'Gorman, Ph.D., for the statistical analysis, Norman Hu for photographic assistance, and Linda Jarvis for typing the manuscript. REFERENCES Freedom RM: Hypoplastic left heart syndrome, Moss' Heart Disease in Infants, Children and Adolescents, FH
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Clinicopathologic and hemodynamic correlation. Am J Cardiol 29: 190-198, 1972 McGarry KM, Taylor JFN, Macartney FJ: Aortic atresia occurring with transposition of the great arteries. Br Heart J 44:711-713, 1980 Lev M, Rimoldi HJA, Paira R, Arcilla RA: The quantitative anatomy of simple complete transposition. Am J Cardiol 23:409-416, 1969 Lev M, Rimoldi HJA, Rowlatt UF: The quantitative anatomy of cyanotic tetralogy of Fallot. Circulation 30:531-538, 1964 Rosenquist GC, Taylor JFN, Stark J: Aortopulmonary fenestration and aortic atresia. Report of an infant with ventricular septal defect, persistent ductus arteriosus, and interrupted aortic arch. Br Heart J 36:1146-1148,1974 Von Reuden TJ, Knight L, Moller JH, Edwards JE: Coarctation of the aorta associated with aortic valvular atresia. Circulation 52:951-954, 1975 Hutchins GM: Coarctation of the aorta explained as a branch point of the ductus arteriosus. Am J Pathol 63:203-214, 1971
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25 Rudolph AM, Heymann MA, Spitznas V: Hemodynamic considerations in the development of narrowing of the aorta. Am J Cardiol 30:514-525, 1972 26 Doty DB: Aortic atresia. J THORAC CARDIOVASC SURG 79:462-463, 1980 27 Graham TP, Atwood GJ, Boucek RJ, Boerth RS, Bender HW: Abnormalities of right ventricular function following Mustard's operation for transposition of the great arteries. Circulation 52:678-684, 1975 28 Tynan M, Aberdeen E, Stark J: Tricuspid incompetence after the Mustard operation for transposition of the great arteries. Circulation 45,46:Suppl 1:111-115, 1972 29 Rice MJ, Mair DD, Puga FJ, Danielson GK, Driscoll OJ, Edwards WD: Clinical hemodynamic and functional assessment of 180 patients undergoing the modified Fontan procedure (abstr), Circulation 66:Suppl 2:30, 1982 30 Perloff JK: Development and regression of increased ventricular mass. Am J Cardiol 50:605-611, 1982
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