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Cardiovascular Disease in Down Syndrome
Symposium on Pediatric Cardiology
Cardiovascular Disease in Down Syndrome Robert L. Spicer, M.D. *
The association of cardiovascular disease in patients with Down syndrome has been recognized for nearly 100 years. A wide variety of cardiovascular malformations have been identified in these patients, 13. 16,24, 26, 37 and the majority of malformations are acutely or chronically life-threatening. Prior to the development of advanced cardiac surgery techniques, severe defects led invariably to death. Recent advances in the surgical management of patients with severe cardiac malformations have resulted in improved survival of these patients. In addition, new techniques of ultrasonography and angiography have aided in the diagnosis, therapy, and follow-up of these patients. Perhaps even more relevant is the recent change in social attitudes toward patients with physical and mental abnormalities. This social awareness has found its way into courts of law, where two cases that have made national headlines have involved children with Down syndrome. 34, 35, 39 This article will discuss the cardiovascular diseases associated with Down syndrome. The highlights of clinical evaluation of these children will be presented. Recent advances in diagnosis and management will be discussed, and the medical or surgical approach to the patient with severe cardiovascular malformations will be presented. In view of the social concerns regarding these patients, the present discussion will provide assistance in caring for these children. INCIDENCE Down syndrome occurs in approximately 1 in 800 live births; it is the most common chromosomal abnormality. The incidence of cardiovascular malformations in Down syndrome is about 40 per cent. 26 Of patients with Down syndrome who were hospitalized, the incidence of congenital heart disease is much greater (62 per cent),13 The cardiac malformations associated with Down syndrome are predominantly endocardial cushion defect Clinical Assistant Professor of Pediatrics, University of Michigan, Ann Arbor, Michigan, Director of Pediatric Cardiology, William Beaumont Hospital, Royal Oak, Michigan
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and ventricular septal defect. In the prospective study reported by Rowe in 1961, endocardial cushion defects made up approximately 36 per cent of the patients with Down syndrome who were found to have congenital heart disease. 26 Ventricular septal defect was present in 33 per cent of this population. In studies performed reviewing cardiac disease in patients with Down syndrome followed by cardiology centers, endocardial cushion defect was found to be the most common cardiac malformation (43 to 49 per cent). 13, 24 In these studies, isolated ventricular septal defects were present in 28 to 32 per cent of patients with Down syndrome. Autopsy studies suggest a higher incidence of endocardial cushion defect (60 per cent) as opposed to isolated ventricular septal defects (30 per cent).37 Other cardiovascular malformations occur much less often. Atrial septal defects of the secundum type, tetralogy of Fallot, and patent ductus arteriosus are found in less than 10 per cent of patients. It is important to note that approximately 30 per cent of patients with Down syndrome and congenital heart malformation have multiple cardiac defects. 24 The most commonly associated defects are patent ductus arteriosus (5 to 15 per cent) and pulmonic stenosis (9 per cent). Without treatment, there is very high mortality and morbidity in the form of congestive failure, pulmonary hypertension, and pulmonary vascular obstructive disease. 13, 20, 24, 26 Of all patients seen at Children's Hospital in Boston between 1962 and 1973 who had Down syndrome and congenital heart disease, 33 per cent had died over that period of time. In the group of patients who presented in infancy, over 50 per cent died.l3 Greater than 50 per cent mortality is associated with complete endocardial cushion defect and isolated ventricular septal defect who do not undergo surgical treatment. Pulmonary artery hypertension is also reported to occur more frequently in patients with Down syndrome with and without congenital cardiac malformations. 8, 41 The etiologies of this pulmonary artery hypertension are incompletely understood at present; yet it remains a significant cause of morbidity and mortality in patients with or without underlying congenital cardiac malformations. The following discussion presents the clinical, noninvasive, and cardiac catheterization characteristics of the major cardiac defects associated with Down syndrome. ENDOCARDIAL CUSHION DEFECT Complete Atrioventricular Canal Complete endocardial cushion defect is the most common form of congenital cardiac malformation associated with Down syndrome. 1, 13, 24, 26 Of 141 patients with Down syndrome undergoing cardiac evaluation at the University of Michigan since 1977, 42 per cent were found to have this defect. Alterations in the embryologic development of the endocardial cushions result in abnormalities of the atrial septum, the atrioventricular valves (mitral and tricuspid), and the ventricular septum. The degree of ventricular septal deficiency leads to the categorization of endocardial cushion defect into complete, transitional, and partial forms. In the com-
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plete form of endocardial cushion defect, there is deficiency of the atrial septum, both atrioventricular valves, and the ventricular septum. The clinical manifestations of this malformation usually are present in infancy and occur as a result of a large left-to-right shunt. Symptoms may include poor feeding, poor growth, dyspnea, cyanosis, easy fatigability, and diaphoresis. Cardiovascular examination in the newborn period or infancy may be entirely normal. However, more often on physical examination there may be a prominence of the left precordium. The cardiac impulse will be .hyperactive both at the xiphoid and apical regions. The first heart sound is usually normal, the second heart sound may split on inspiration. If pulmonary hypertension is present, the pulmonary component of the second heart sound will be accentuated. A systolic murmur present along the left sternal border is most commonly ejection in nature as a result of the large left-to-right shunt. An apical holosystolic murmur may be present in patients with mitral insufficiency. The presence of a low frequency, mid-diastolic murmur over the xiphoid or cardiac apex suggests a large left-to-right shunt. The characteristic electrocardiographic finding is a superiorly directed QRS axis, usually occurring between - 30 and - 90° (Fig. 1). Atrial hypertrophy has been reported to occur in approximately 60 per cent of patients and first degree heart block is often noted. Patterns of right ventricular or left ventricular hypertrophy will most likely depend on the degree of pulmonary artery hypertension and left-to-right shunt respectively. Chest x-ray evaluation often reveals cardiomegaly with enlargement of the left and right atrium and left ventricle. Dilatation of the main pulmonary artery segment and increased pulmonary vascular markings occur with large left-to-right shunts (Fig. 2). The development of echocardiography has had a dramatic impact in the evaluation of patients with complete atrioventricular canal deformities. M-mode echocardiographic characteristics include mitral valve displacement with multiple echoes, narrow left ventricular outflow tract, and continuity of the mitral and tricuspid valves which seem to "walk through" the interventricular septum. 4O Large regions of interventricular septal dropout can be detected as well. Two-dimensional echocardiography, however, has supplanted M-mode in the diagnosis, classification, and detailed analysis of complete atrioventricular canal deformities.28 Two-dimensional echo will reveal the size and location of atrial and ventricular defects and define tricuspid and mitral valve morphology (Fig. 3). Associated defects such as multiple atrial or ventricular defects, double orifice mitral valve, and left ventricular papillary muscle abnormalities can be detected with this technique. More recently, Doppler echocardiographic analysis has been shown to determine the presence of mitral regurgitation and may be able to quantify left-to-right shunt. Cardiac catheterization remains useful in documenting intracardiac anatomy using axial angiography techniques ..30 The characteristic left ventricular angiographic appearance is that of a "goose neck" deformity of the outflow tract, which occurs as a result of the abnormally positioned mitral valve (Fig. 4). Catheterization is also effective in quantifying left-to-right shunts, determining pulmonary artery pressures and resistances, and in
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ELECTROCARDIOGRAPHIC REPORT
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Figure 1. Characteristic superior QRS axis on the electrocardiogram of a patient with a complete atrioventricular canal deformity.
detecting associated malformations such as patent ductus arteriosus and mitral insufficiency. Transitional Endocardial Cushion Defects The so-called transitional form of endocardial cushion deformity refers to those defects in which there are atrial and ventricular defects of the endocardial cushion type, with involvement of both mitral and tricuspid leaflets. The degree of ventricular septal deficiency is not as great as in the complete form, as there is a bridge of tissue that extends between the anterior and posterior AV valve leaflets.1 These patients tend to have symptoms similar to those of patients with complete endocardial cushion deformity. Likewise, chest x-ray and electrocardiographic findings may not distinguish this type of atrioventricular canal. Two-dimensional echocardiography and cineangiography are useful in identifying those patients with lesser degrees of ventricular septal deficiency. Angiography will reveal goose neck deformity of the left ventricular outflow tract as in the complete form. Catheterization demonstrates large left-to-right shunt, but pulmo-
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Figure 2. Chest x-ray of a patient with a complete atrioventricular canal, showing cardiomegaly and increased pulmonary blood How.
nary artery pressures and resistances will often be less than in the complete form. Partial Atrioventricular Canal Defects (Ostium Primum Atrial Septal Defect) This form of atrial septal defect is present in a small number of patients with Down syndrome. These patients often present with signs of a large left-to-right shunt. Hyperactive right and left ventricular impulses are often noted. The first heart sound is normal, and in distinction to the second heart sound in patients with complete form of atrioventricular canal, patients of this type will have fixed splitting of the second heart sound. The intensity of the pulmonic closure sound (P2) relates to the degree of pulmonary artery hypertension present. A right ventricular outflow
Figure 3. Two-dimensional echocardiogram of a patient with atrioventricular canal. RA = right atrium, LA = left atrium, RV = right ventricle, LV = left ventricle, S = superior, L = leftward. Arrow points to common AV valve (tricuspid and mitral).
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Figure 4. Typical "goose neck" left ventricular outflow tract deformity in a patient with endocardial cushion defect seen on left ventricular angiogram.
tract murmur and an early or mid-diastolic rumble at the left lower sternal border occur secondary to excessive blood flow across the pulmonary and tricuspid valves. Mitral insufficiency or left ventricular to right atrial shunt is suggested by an apical/axillary holosystolic murmur. The electrocardiogram and chest x-ray reveal the previously mentioned abnormal QRS axis and signs of cardiac chamber enlargement. The echocardiographic appearance is that of deficiency of the inferior-most portion of the atrial septum. Right-sided atrial and ventricular enlargement is present and the ventricular septal motion may be flattened or paradoxical. Additionally, the anterior mitral valve leaflet cleft can be demonstrated. At catheterization, these patients have evidence of a large left-to-right shunt occurring at the atrial level, typical goose neck outflow tract appearance on left ventricular angiogram, but usually less than 60 per cent of systemic pressure in the right ventricle and pulmonary artery. VENTRICULAR SEPTAL DEFECT This cardiac defect is nearly as common as endocardial cushion defect in Down syndrome. It was diagnosed in one third of all Down syndrome patients seen at the University of Michigan since 1977. The clinical manifestations of a ventricular septal defect relate directly to the size of the defect itself. The majority of ventricular septal defects in infants and children with Down syndrome are large,16 and are therefore associated with a large left-to-right shunt and pulmonary artery hypertension. As a result of the large left-to-right shunt, similar symptoms to those of atrioventricular canal of the complete form may be noted, such as dyspnea, poor feeding, diaphoresis, and failure to thrive. Likewise, the physical examination of an infant or child with a large ventricular septal defect will be similar to that of a child with an endocar-
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dial cushion deformity. Thus, it may be very difficult after history and physical examination to predict whether there is an endocardial cushion deformity or a large ventricular septal defect. The electrocardiogram is helpful in distinguishing the two. Patients with isolated ventricular septal defect (of the nonendocardial cushion type) usually have a normal QRS axis (0 to + 180°). Biventricular hypertrophy will be present in the majority of patients with large ventricular septal defect. The chest x-ray findings parallel those of the endocardial QUshion deformity in that cardiomegaly and increased pulmonary vascular markings are the rule. Two-dimensional echocardiography can accurately distinguish endocardial cushion defects from other septal defects and can detect associated malformations. Cardiac catheterization data will reveal evidence for a large left-toright shunt occurring at the ventricular level. Right ventricular and pulmonary artery pressures will be increased in large defects, and pulmonary resistances may be elevated as well. Axial angiographic techniques can distinguish endocardial cushion deformities from nonendocardial cushion type of ventricular defects and can identify other associated defects. OTHER DEFECTS The other forms of cardiac malformation associated with Down syndrome include tetralogy of Fallot, patent ductus arteriosus, and atrial septal defect of the secundum type. Each of these deformities have their own unique clinical, electrocardiographic, echocardiographic, and angiographic findings. The findings in these defects associated with patients having Down syndrome is not unlike that seen in the normal population. Finally, nearly all forms of cardiovascular malformation have been described in patients with Down syndrome, such as transposition of the great arteries, hypoplastic left heart, anomalous pulmonary venous return, etc. However, the incidence of these defects in patients with Down syndrome does not appear to be different than that in the general population. PULMONARY ARTERY HYPERTENSION AND PULMONARY VASCULAR DISEASE Studies of children with Down syndrome and congenital heart disease have suggested that an unusually high incidence of pulmonary artery hypertension and pulmonary vascular obstructive disease exists in this population. 8 Other studies indicate that, although there is a very significant increase in pulmonary artery hypertension and pulmonary vascular disease in patients with Down syndrome and congenital heart disease, this may not be more severe than that which occurs in patients with similar cardiac malformations. 41 Numerous reports exist, however, of the development of pulmonary vascular obstructive disease in patients with Down syndrome who have little or no congenital cardiac malformations. 17. 18.26. 41 Several hypotheses have been entertained to explain the development of significant pulmonary artery hypertension and pulmonary vascular obstructive disease
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in these children. Chronic upper airway obstruction with resultant pulmonary hypertension and cor pulmonale can occur secondary to tonsilar and adenoidal hypertrophy, 27 laryngomalacia,3 obstructive sleep apnea, 18 enlarged tongue, and midfacial (nose) hypoplasia. 36 All of these mechanisms of upper airway obstruction, known to occur more frequently in patients with Down syndrome, result in alveolar hypoventilation, hypoxemia, and hypercapnia, which may chronically or acutely result in elevation of pulmonary artery pressures and resistances. In addition, the lung parenchyma itself may be abnormal in patients with Down syndrome. 15 Patients with Down syndrome may have diminished numbers of alveoli and decreased alveolar surface area.l O The loss of capillary surface area secondary to this alveolar diminution can result in the development of pulmonary artery hypertension and pulmonary vascular disease. Also, there may be less muscular hypertrophy than expected in the pulmonary arteries of patients with Down syndrome and large leftto-right shunts, suggesting a qualitative pulmonary arterial abnormality that may fail to protect the lung parenchyma from the damaging effects of high flow and pressure. 42 Additional pulmonary complications occur in patients with Down syndrome and can aggravate pulmonary artery hypertension. Gastroesophageal reflux has been associated with congenital heart defects and Down syndrome. 38 Reflux results in numerous pulmonary complications including infection and bronchospasm. These may aggravate pulmonary artery hypertension acutely and chronically. In addition, children with Down syndrome have been shown to have Band T lymphocyte abnormalities that can result in an increased incidence of pulmonary infections. 4 , 31 These infections may aggravate existing symptoms of pulmonary congestion, result in pulmonary parenchymal damage, aggravate upper airway obstruction, and ultimately play a role in the development and propagation of pulmonary artery hypertension and pulmonary vascular disease. The identification of patients with pulmonary artery hypertension and pulmonary vascular obstructive disease is critical in establishing treatment and prognosis for this group of patients. Clinical findings to suggest the presence of pulmonary artery hypertension include a prominent right ventricular impulse, increased intensity of the pulmonic closure sound, decreased intensity of systolic murmurs, disappearance of the diastolic rumble, and perhaps improvement in symptoms and signs of congestive heart failure. Electrocardiographically, right ventricular hypertrophy will be present in all patients with significant pulmonary artery hypertension, but is not an accurate predictor of the degree of hypertension. Echocardiographic techniques have not yet been reliable in predicting accurately the degree of pulmonary artery hypertension or pulmonary resistance. The chest x-ray in patients with severe pulmonary hypertension and pulmonary vascular disease may demonstrate a dilated main pulmonary artery segment and a disorganized "pruning" pattern of the pulmonary blood flow (Fig. 5). The development of clinical evidence of right-to-left shunting (i.e., cyanosis), a palpable pulmonary closure sound on palpation of the chest, and auscultation of a pulmonary insufficiency (Graham-Steele) murmur are signs of severe pulmonary vascular obstructive disease and Eisenmenger's
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Figure 5. Prominent main and proximal pulmonary arteries and multiple areas of atelectasis seen in the chest x-ray of a patient with Down syndrome and pulmonary vascular disease.
physiology. These changes of severe pulmonary vascular disease have been noted to occur in children with Down syndrome who are less than one year of age. 22 This illustrates the necessity of early cardiac evaluation in the children with Down syndrome and congenital heart malformations in order to assess pulmonary artery pressures and resistances. MANAGEMENT The most critical point in evaluation and management of the child with Down syndrome is recognizing those patients with underlying cardiovascular malformations and in identifying those with pulmonary artery hypertension. Clearly, the identification of these patients is the responsibility of the primary pediatrician. Any patient suspected of having Down syndrome should have chromosomal studies performed and, if trisomy 21 is documented, cardiovascular workup should be undertaken. Careful history and physical examination will frequently reveal those patients with significant cardiac malformation. Numerous cases of patients without signs or symptoms of heart failure have been identified to later have severe intracardiac malformations. The electrocardiogram and echocardiogram, two relatively inexpensive, noninvasive screening tests, are useful in identifying the majority of the patients with Down syndrome who have a congenital heart defect. These two tests should be performed in all neonates with documented trisomy 21. Should electrocardiographic or echocardiographic abnormalities be present or if there are clinical signs of hemodynamic compromise, the infant should be referred to a pediatric cardiologist. The management of congestive heart failure in patients with Down syndrome has changed very little in recent years. Digitalis and diuretic therapy are indicated for patients with signs or symptoms of congestive
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heart failure. Afterload reduction therapy (e. g., hydralazine) may also be useful, but is not used in the "routine" management of congestive heart failure. As mentioned previously, cardiac catheterization is necessary to assess pulmonary artery pressures and resistances. In the presence of pulmonary hypertension and increased resistance, administration of pulmonary vasodilators (e. g., oxygen and/or tolazoline) may be useful in assessing the degree of damage to the pulmonary vasculature. In those patients who require relief of pulmonary artery hypertension, surgical intervention is necessary. Banding (constriction) of the pulmonary artery has been effective in treating congestive heart failure, preventing pulmonary vascular disease, 12, 14, 29, 33 and increasing patient survival. Unfortunately, pulmonary artery banding may not alter the progression of pulmonary vascular disease, and, in patients with significant atrioventricular valve regurgitation or left ventricular to right atrial shunt, may not be effective in improving hemodynamics. Postoperative complications such as severe cyanosis, sub aortic stenosis, and severe mitral regurgitation can occur. With advances in complete surgical repair, pulmonary artery banding has become a less frequent mode of therapy for infants with large ventricular septal defects or complete endocardial cushion defects. Pulmonary artery banding is still indicated in children with complex cardiac malformations such as those with hypoplastic right ventricle, those with large ventricular communications and coarctation of the aorta, and in those who for a variety of reasons, (e.g., associated anomalies, infection, severe respiratory compromise) would not tolerate an open heart procedure. Surgical correction is now the procedure of choice for the treatment of patients with refractory congestive failure and/or pulmonary hypertension. Successful transatrial closure of ventricular septal defects can be undertaken safely in children using cardiopulmonary bypass techniques and in infants utilizing hypothermia and circulatory arrest. 2, 5, 25 Postoperative hemodynamics in these patients are excellent. 2, 25 Surgical repair of complete atrioventricular canal has resulted in a significant change in the approach to patients with this cardiac malformation.22, 33 Medically managed, there is a high incidence of morbidity and mortality occurring even under one year of age, 6 and morbidity and mortality secondary to pulmonary artery banding are excessively high as well. U sing techniques of cardiopulmonary bypass, deep hypothermia, and cardioplegia, complete intracardiac repair of complete endocardial cushion defects have been performed in patients as young as one month of age.5, 9, 11, 19, 21 Surgical mortality, however, remains high (20 to 30 per cent). The technique presently employed can be done transatrially, hopefully reducing the incidence of postoperative heart block, right bundle branch block, right ventricular dysfunction, and ventricular ectopy. Residual hemodynamic problems include mitral insufficiency, left-toright shunt, and pulmonary artery hypertension. Mitral insufficiency is common (60 to 80 per cent 9, 19), is moderate or severe in many cases, and may infrequently necessitate valve replacement. Residualleft-to-right shunt is infrequent and rarely large enough to require reoperation. Persistent pulmonary hypertension is becoming less of a problem as successful sur-
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gical intervention is performed in younger patients. Clinically, the majority of patients show dramatic improvement following surgery. Although the child or adolescent with severe pulmonary vascular disease may be inoperable, symptoms secondary to right heart failure, cyanosis, and polycythemia can be severe and progressive, and warrant continued medical treatment. Erythropheresis, home oxygen administration, and restriction of physical activities may palliate symptoms of headache, chest pain, respiratory compromise, syncope, and exercise intolerance. Regulation of participation in Special Olympics to those events requiring limited physical exertion is often a practical concern in those patients.
PROGNOSIS
Children with Down syndrome may have many potentially life-threatening complications secondary to their chromosomal abnormality. Intestinal obstruction, leukemia, and severe congenital heart defects make up the majority of directly life-threatening illnesses. The incidence of survival in patients with Down syndrome and cardiovascular malformation is approximately 60 per cent at one year of age, compared with an 85 per cent 1 year survival of children with Down syndrome without heart malformations. The degree of severity of cardiovascular malformation has direct impact on their prognosis as well. In patients with complete atrioventricular canal, managed nonsurgically, there is a 96 per cent mortality by 5 years of age. 7 Surgical management of patients with Down syndrome and severe congenital cardiac malformations dramatically improves the prognosis. Present operative techniques would suggest approximately a 75 per cent survival following surgical repair of endocardial cushion defect, and greater in those with isolated ventricular septal defect and atrial septal defect. Following successful surgery, an improvement in signs and symptoms of congestive failure can be expected. Growth will improve, although it should be remembered that children with Down syndrome are shorter and lighter than age-matched normals, and special growth charts are available when assessing their height and weight.
SUMMARY
There is a high incidence of congenital heart disease in patients with Down syndrome. The most frequent cardiac malformations are endocardial cushion defect, ventricular septal defect, patent ductus arteriosus, and atrial septal defect. The majority of these defects are hemodynamically significant and result in clinical signs and symptoms of cardiopulmonary compromise. Medical management is effective temporarily in many cases, but does not affect the development of pulmonary artery hypertension or pulmonary vascular disease. Surgical management of these patients is indicated. Improvement in surgical techniques has allowed intervention in infancy with satisfactory long-term results. The development of pulmonary artery hypertension and pulmonary vascular disease is Significant in pa-
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tients with Down syndrome and often affects the long-term prognosis of these children. Fortunately, improvement in the medical and surgical management of patients with serious heart defects has advanced to the point where most cardiac centers in this country are able to perform surgical procedures with an acceptable risk. Children with Down syndrome and congenital heart disease can be successfully treated early in life. Future concerns, in the light of a changing sociolegal environment, center around possible prevention, early recognition, and improved management.
REFERENCES 1. Adams, F. H., and Emmanouilides, G. C.: Heart Disease in Infants, Children, and Adolescents, 3rd ed. Baltimore and London, Williams and Wilkins, 1983. 2. Arciniegas, E., Farooki, Z. Q., Hakimi, M., et al.: Surgical closure of ventricular septal defect during the first twelve months of life. J. Thorac. Cardiovasc. Surg., 80:921-928, 1980. 3. Aggarwal, K. C., Rastogi, A., and Singhi, S.: Cor pulmonale due to laryngomalacia in Down syndrome. Indian Pediatr. 18:914--916, 1981. 4. Barroeta, 0., Nungaray, L., Lopez-Osuna, A., et al.: Defective monocyte chemotaxis in children with Down syndrome. Pediatr. Res., 17:292--295, 1983. 5. Bender, H. W., Fisher, R. D., Walker, W. D., et al.: Reparative cardiac surgery in infants and small children: Five years experience with profound hypothermia and circulatory arrest. Ann. Surg., 190:437-443, 1979. 6. Berger, T. J., Kirklin, J. W., Blackstone, E. H., et al.: Primary repair of complete atrioventricular canal in patients less than two years old. Am. J. Cardiol., 41:906--913, 1978. 7. Berger, T. J., Blackstone, E. H., Kirklin, J. W., et al.: Survival and probability of cure without and with operation in complete atrioventricular canal. Ann. Thorac. Surg., 27:104--111, 1979. 8. Chi, Tp. L., Krovetz, L. J.: The pulmonary vascular bed in children with Down syndrome. J. Pediatr., 86:533--538, 1975. 9. Chin, A. J., Keane, J. F., Norwood, W. 1., et al.: Repair of complete common atrioventricular canal in infancy. J. Thorac. Cardiovasc. Surg., 84:437-445, 1982. 10. Conney, T. P., and Thurlbeck, W. M.: Pulmonary hypoplasia in Down's syndrome. N. Engl. J. Med., 307:1170-1173, 1982. 11. Culpepper, W., Koff, J., Lin, C-Y, et al.: Complete common atrioventricular canal in infancy-surgical repair and postoperative hemodynamics. Circulation, 58:550-558, 1978. 12. Epstein, M. L., Moller, J. H., Amplatz, K., et al.: Pulmonary artery banding in infants with complete atrioventricular canal. J. Thorac. Cardiovasc. Surg., 78:28--31, 1979. 13. Greenwood, R. D., and Nadas, A. S.: The clinical course of cardiac disease in Down syndrome. Pediatrics, 58:89~97, 1976. 14. Hunt, C. E., Formanek, G., Levine, M. A., et al.: Banding of the pulmonary artery, results in ill children, Circulation, 43:395-406, 1971. 15. Kontras, S. B., and Bodenbender, J. G.: Abnormal capillary morphology in congenital heart disease. Pediatrics, 37:316--322, 1966. 16. Laursen, H. B., Congenital heart disease in Down syndrome. Br. Heart J., 38:32--38, 1976. 17. Levine, O. R., and Simpser, M.: Alveolar hypoventilation and cor pulmonale associated with chronic airway obstruction in infants with Down syndrome. Clin. Pediatr., 21:2529, 1982. 18. Loughlin, G. N., Wynne J. W., and Victorica, B. E.: Sleep apnea as a possible cause of pulmonary hypertension in Down syndrome. J. Pediatr., 98:435-437, 1981. 19. Mair, D. D., and McGoon, D. C.: Surgical correction of atrioventricular canal during the first year of life. Am. J. Cardiol., 40:66--69, 1977.
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20. Masaki, M., Higurashi, M., Iijima, K., et al.: Mortality and survival for Down syndrome in Japan. Am. J. Hum. Genet., 33:629-639, 1981. 21. Matthews, J., Bromberg, J., Spicer, R. L., et a1.: Repair of complete atrioventricular canal in the first two years oflife (abstract) Circulation, 64:237, 1981. 22. McCabe, J. C., Engle, M. A., and Gay, W. A.: Surgical treatment of endocardial cushion defects. Am. J. Cardio\., 39:72-77, 1977. 23. Newfeld, E. A., Sher, M., Paul, M. H., et al.: Pulmonary vascular disease in complete atrioventricular canal defect. Am. J. Cardio\., 39:721-726, 1977. 24. Park, S. C., Mathews, R. A., and Zuberbuhler, J. R.: Down syndrome with congenital heart malformation. Am. J. Dis. Child., 131:29--33, 1977. 25. Rein, J. G., Freed, M. D., Norwood, W. 1., et al.: Early and late results of closure of ventricular septal defect in infancy. Ann. Thorac. Surg., 24:19--26, 1977. 26. Rowe, R. D., and Uchida, 1. A.: Cardiac malformation in mongolism: A prospective study of 184 mongoloid children. Am. J. Med., 31:726--735, 1961. 27. Rowland, T. W., Nordstrom, L. G., Bean, M. S., et al.: Chronic upper airway obstruction and pulmonary hypertension in Down syndrome. Am. J. Dis. Child., 135:10501052, 1981. 28. Silverman, N. H., and Snider, A. R.: Two dimensional echocardiography in congenital heart disease. Norwalk, Conn., Appleton-Century Crofts, 1982. 29. Somerville, J., Agnew, T., Stark, J., et aI.: Banding of the pulmonary artery for common atrioventricular canal. Br. Heart J., 29:816--828, 1967. 30. Soto, B., Bargeron, L. M., Pacifico, A. D., et aI.: Angiography of atrioventricular canal defects. Am. J. Cardiol., 48:492-499, 1981. 31. Spina, C. A., Smith, D., Korn, E., et al.: Altered cellular immune functions in patients with Down syndrome. Am. J. Dis. Child., 135:251-255, 1981. 32. Stark, J., Aberdeen, E., and Waterston, D. J.: Pulmonary artery constriction (banding): A report of 146 cases. Surgery, 65:808-818, 1969. 33. Stewart, S., Harris, P., and Manning, J.: Complete endocardial cushion defect: Operative technique and results. J. Thorac. Cardiovasc Surg., 78:914-919, 1979. 34. Strain, J. E.: The decision to forgo life-sustaining treatment for newborns. Pediatrics, 72:572-573, 1983. 35. Strain, J. E.: The American Academy of Pediatrics Comments on the "Baby Doe II" Regulations. N. Eng\. J. Med., 309:443--444, 1983. 36. Strome, M.: Down syndrome: A modern otorhinolaryngological perspective. Laryngoscope, 91:1581, 1594, 1981. 37. Tandon, R., and Edwards, J. E.: Cardiac malformations associated with Down syndrome. Circulation, 47:1349--1355, 1973. 38. Weesner, K. M., and Rosenthal, A.: Gastroesophageal reflux in association with congenital heart disease. Clin. Pediatr., 22:424-426, 1983. 39. Will, G. F.: The case of Phillip Becker. Newsweek, 112, 1980. 40. Williams, R. G., and Rudd, M.: Echocardiographic features of endocardial cushion defects. Circulation, 49:418-422, 1974. 41. Wilson, S. K., Hutchins, G. N., and Neill, C. A.: Hypertensive pulmonary vascular disease in Down syndrome. J. Pediatr., 95:722-726, 1979. 42. Yamaki, S., Horiuschi, T., and Sekino, Y.: Quantitative analysis of pulmonary vascular disease in simple cardiac anomalies with the Down syndrome. Am. J. Cardio\., 51:1502-1506, 1983. Department of Pediatrics William Beaumont Hospital 3601 W. 13 Mile Road Royal Oak, Michigan 48072
Cardiovascular Disease in Down Syndrome Robert L. Spicer, M.D. *
The association of cardiovascular disease in patients with Down syndrome has been recognized for nearly 100 years. A wide variety of cardiovascular malformations have been identified in these patients, 13. 16,24, 26, 37 and the majority of malformations are acutely or chronically life-threatening. Prior to the development of advanced cardiac surgery techniques, severe defects led invariably to death. Recent advances in the surgical management of patients with severe cardiac malformations have resulted in improved survival of these patients. In addition, new techniques of ultrasonography and angiography have aided in the diagnosis, therapy, and follow-up of these patients. Perhaps even more relevant is the recent change in social attitudes toward patients with physical and mental abnormalities. This social awareness has found its way into courts of law, where two cases that have made national headlines have involved children with Down syndrome. 34, 35, 39 This article will discuss the cardiovascular diseases associated with Down syndrome. The highlights of clinical evaluation of these children will be presented. Recent advances in diagnosis and management will be discussed, and the medical or surgical approach to the patient with severe cardiovascular malformations will be presented. In view of the social concerns regarding these patients, the present discussion will provide assistance in caring for these children. INCIDENCE Down syndrome occurs in approximately 1 in 800 live births; it is the most common chromosomal abnormality. The incidence of cardiovascular malformations in Down syndrome is about 40 per cent. 26 Of patients with Down syndrome who were hospitalized, the incidence of congenital heart disease is much greater (62 per cent),13 The cardiac malformations associated with Down syndrome are predominantly endocardial cushion defect Clinical Assistant Professor of Pediatrics, University of Michigan, Ann Arbor, Michigan, Director of Pediatric Cardiology, William Beaumont Hospital, Royal Oak, Michigan
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and ventricular septal defect. In the prospective study reported by Rowe in 1961, endocardial cushion defects made up approximately 36 per cent of the patients with Down syndrome who were found to have congenital heart disease. 26 Ventricular septal defect was present in 33 per cent of this population. In studies performed reviewing cardiac disease in patients with Down syndrome followed by cardiology centers, endocardial cushion defect was found to be the most common cardiac malformation (43 to 49 per cent). 13, 24 In these studies, isolated ventricular septal defects were present in 28 to 32 per cent of patients with Down syndrome. Autopsy studies suggest a higher incidence of endocardial cushion defect (60 per cent) as opposed to isolated ventricular septal defects (30 per cent).37 Other cardiovascular malformations occur much less often. Atrial septal defects of the secundum type, tetralogy of Fallot, and patent ductus arteriosus are found in less than 10 per cent of patients. It is important to note that approximately 30 per cent of patients with Down syndrome and congenital heart malformation have multiple cardiac defects. 24 The most commonly associated defects are patent ductus arteriosus (5 to 15 per cent) and pulmonic stenosis (9 per cent). Without treatment, there is very high mortality and morbidity in the form of congestive failure, pulmonary hypertension, and pulmonary vascular obstructive disease. 13, 20, 24, 26 Of all patients seen at Children's Hospital in Boston between 1962 and 1973 who had Down syndrome and congenital heart disease, 33 per cent had died over that period of time. In the group of patients who presented in infancy, over 50 per cent died.l3 Greater than 50 per cent mortality is associated with complete endocardial cushion defect and isolated ventricular septal defect who do not undergo surgical treatment. Pulmonary artery hypertension is also reported to occur more frequently in patients with Down syndrome with and without congenital cardiac malformations. 8, 41 The etiologies of this pulmonary artery hypertension are incompletely understood at present; yet it remains a significant cause of morbidity and mortality in patients with or without underlying congenital cardiac malformations. The following discussion presents the clinical, noninvasive, and cardiac catheterization characteristics of the major cardiac defects associated with Down syndrome. ENDOCARDIAL CUSHION DEFECT Complete Atrioventricular Canal Complete endocardial cushion defect is the most common form of congenital cardiac malformation associated with Down syndrome. 1, 13, 24, 26 Of 141 patients with Down syndrome undergoing cardiac evaluation at the University of Michigan since 1977, 42 per cent were found to have this defect. Alterations in the embryologic development of the endocardial cushions result in abnormalities of the atrial septum, the atrioventricular valves (mitral and tricuspid), and the ventricular septum. The degree of ventricular septal deficiency leads to the categorization of endocardial cushion defect into complete, transitional, and partial forms. In the com-
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plete form of endocardial cushion defect, there is deficiency of the atrial septum, both atrioventricular valves, and the ventricular septum. The clinical manifestations of this malformation usually are present in infancy and occur as a result of a large left-to-right shunt. Symptoms may include poor feeding, poor growth, dyspnea, cyanosis, easy fatigability, and diaphoresis. Cardiovascular examination in the newborn period or infancy may be entirely normal. However, more often on physical examination there may be a prominence of the left precordium. The cardiac impulse will be .hyperactive both at the xiphoid and apical regions. The first heart sound is usually normal, the second heart sound may split on inspiration. If pulmonary hypertension is present, the pulmonary component of the second heart sound will be accentuated. A systolic murmur present along the left sternal border is most commonly ejection in nature as a result of the large left-to-right shunt. An apical holosystolic murmur may be present in patients with mitral insufficiency. The presence of a low frequency, mid-diastolic murmur over the xiphoid or cardiac apex suggests a large left-to-right shunt. The characteristic electrocardiographic finding is a superiorly directed QRS axis, usually occurring between - 30 and - 90° (Fig. 1). Atrial hypertrophy has been reported to occur in approximately 60 per cent of patients and first degree heart block is often noted. Patterns of right ventricular or left ventricular hypertrophy will most likely depend on the degree of pulmonary artery hypertension and left-to-right shunt respectively. Chest x-ray evaluation often reveals cardiomegaly with enlargement of the left and right atrium and left ventricle. Dilatation of the main pulmonary artery segment and increased pulmonary vascular markings occur with large left-to-right shunts (Fig. 2). The development of echocardiography has had a dramatic impact in the evaluation of patients with complete atrioventricular canal deformities. M-mode echocardiographic characteristics include mitral valve displacement with multiple echoes, narrow left ventricular outflow tract, and continuity of the mitral and tricuspid valves which seem to "walk through" the interventricular septum. 4O Large regions of interventricular septal dropout can be detected as well. Two-dimensional echocardiography, however, has supplanted M-mode in the diagnosis, classification, and detailed analysis of complete atrioventricular canal deformities.28 Two-dimensional echo will reveal the size and location of atrial and ventricular defects and define tricuspid and mitral valve morphology (Fig. 3). Associated defects such as multiple atrial or ventricular defects, double orifice mitral valve, and left ventricular papillary muscle abnormalities can be detected with this technique. More recently, Doppler echocardiographic analysis has been shown to determine the presence of mitral regurgitation and may be able to quantify left-to-right shunt. Cardiac catheterization remains useful in documenting intracardiac anatomy using axial angiography techniques ..30 The characteristic left ventricular angiographic appearance is that of a "goose neck" deformity of the outflow tract, which occurs as a result of the abnormally positioned mitral valve (Fig. 4). Catheterization is also effective in quantifying left-to-right shunts, determining pulmonary artery pressures and resistances, and in
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ELECTROCARDIOGRAPHIC REPORT
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!., '! .• ; .!: :: :i Iii 11 II' II :Uri!II·;:!'·I!·11 ~,
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.
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Figure 1. Characteristic superior QRS axis on the electrocardiogram of a patient with a complete atrioventricular canal deformity.
detecting associated malformations such as patent ductus arteriosus and mitral insufficiency. Transitional Endocardial Cushion Defects The so-called transitional form of endocardial cushion deformity refers to those defects in which there are atrial and ventricular defects of the endocardial cushion type, with involvement of both mitral and tricuspid leaflets. The degree of ventricular septal deficiency is not as great as in the complete form, as there is a bridge of tissue that extends between the anterior and posterior AV valve leaflets.1 These patients tend to have symptoms similar to those of patients with complete endocardial cushion deformity. Likewise, chest x-ray and electrocardiographic findings may not distinguish this type of atrioventricular canal. Two-dimensional echocardiography and cineangiography are useful in identifying those patients with lesser degrees of ventricular septal deficiency. Angiography will reveal goose neck deformity of the left ventricular outflow tract as in the complete form. Catheterization demonstrates large left-to-right shunt, but pulmo-
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Figure 2. Chest x-ray of a patient with a complete atrioventricular canal, showing cardiomegaly and increased pulmonary blood How.
nary artery pressures and resistances will often be less than in the complete form. Partial Atrioventricular Canal Defects (Ostium Primum Atrial Septal Defect) This form of atrial septal defect is present in a small number of patients with Down syndrome. These patients often present with signs of a large left-to-right shunt. Hyperactive right and left ventricular impulses are often noted. The first heart sound is normal, and in distinction to the second heart sound in patients with complete form of atrioventricular canal, patients of this type will have fixed splitting of the second heart sound. The intensity of the pulmonic closure sound (P2) relates to the degree of pulmonary artery hypertension present. A right ventricular outflow
Figure 3. Two-dimensional echocardiogram of a patient with atrioventricular canal. RA = right atrium, LA = left atrium, RV = right ventricle, LV = left ventricle, S = superior, L = leftward. Arrow points to common AV valve (tricuspid and mitral).
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Figure 4. Typical "goose neck" left ventricular outflow tract deformity in a patient with endocardial cushion defect seen on left ventricular angiogram.
tract murmur and an early or mid-diastolic rumble at the left lower sternal border occur secondary to excessive blood flow across the pulmonary and tricuspid valves. Mitral insufficiency or left ventricular to right atrial shunt is suggested by an apical/axillary holosystolic murmur. The electrocardiogram and chest x-ray reveal the previously mentioned abnormal QRS axis and signs of cardiac chamber enlargement. The echocardiographic appearance is that of deficiency of the inferior-most portion of the atrial septum. Right-sided atrial and ventricular enlargement is present and the ventricular septal motion may be flattened or paradoxical. Additionally, the anterior mitral valve leaflet cleft can be demonstrated. At catheterization, these patients have evidence of a large left-to-right shunt occurring at the atrial level, typical goose neck outflow tract appearance on left ventricular angiogram, but usually less than 60 per cent of systemic pressure in the right ventricle and pulmonary artery. VENTRICULAR SEPTAL DEFECT This cardiac defect is nearly as common as endocardial cushion defect in Down syndrome. It was diagnosed in one third of all Down syndrome patients seen at the University of Michigan since 1977. The clinical manifestations of a ventricular septal defect relate directly to the size of the defect itself. The majority of ventricular septal defects in infants and children with Down syndrome are large,16 and are therefore associated with a large left-to-right shunt and pulmonary artery hypertension. As a result of the large left-to-right shunt, similar symptoms to those of atrioventricular canal of the complete form may be noted, such as dyspnea, poor feeding, diaphoresis, and failure to thrive. Likewise, the physical examination of an infant or child with a large ventricular septal defect will be similar to that of a child with an endocar-
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dial cushion deformity. Thus, it may be very difficult after history and physical examination to predict whether there is an endocardial cushion deformity or a large ventricular septal defect. The electrocardiogram is helpful in distinguishing the two. Patients with isolated ventricular septal defect (of the nonendocardial cushion type) usually have a normal QRS axis (0 to + 180°). Biventricular hypertrophy will be present in the majority of patients with large ventricular septal defect. The chest x-ray findings parallel those of the endocardial QUshion deformity in that cardiomegaly and increased pulmonary vascular markings are the rule. Two-dimensional echocardiography can accurately distinguish endocardial cushion defects from other septal defects and can detect associated malformations. Cardiac catheterization data will reveal evidence for a large left-toright shunt occurring at the ventricular level. Right ventricular and pulmonary artery pressures will be increased in large defects, and pulmonary resistances may be elevated as well. Axial angiographic techniques can distinguish endocardial cushion deformities from nonendocardial cushion type of ventricular defects and can identify other associated defects. OTHER DEFECTS The other forms of cardiac malformation associated with Down syndrome include tetralogy of Fallot, patent ductus arteriosus, and atrial septal defect of the secundum type. Each of these deformities have their own unique clinical, electrocardiographic, echocardiographic, and angiographic findings. The findings in these defects associated with patients having Down syndrome is not unlike that seen in the normal population. Finally, nearly all forms of cardiovascular malformation have been described in patients with Down syndrome, such as transposition of the great arteries, hypoplastic left heart, anomalous pulmonary venous return, etc. However, the incidence of these defects in patients with Down syndrome does not appear to be different than that in the general population. PULMONARY ARTERY HYPERTENSION AND PULMONARY VASCULAR DISEASE Studies of children with Down syndrome and congenital heart disease have suggested that an unusually high incidence of pulmonary artery hypertension and pulmonary vascular obstructive disease exists in this population. 8 Other studies indicate that, although there is a very significant increase in pulmonary artery hypertension and pulmonary vascular disease in patients with Down syndrome and congenital heart disease, this may not be more severe than that which occurs in patients with similar cardiac malformations. 41 Numerous reports exist, however, of the development of pulmonary vascular obstructive disease in patients with Down syndrome who have little or no congenital cardiac malformations. 17. 18.26. 41 Several hypotheses have been entertained to explain the development of significant pulmonary artery hypertension and pulmonary vascular obstructive disease
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in these children. Chronic upper airway obstruction with resultant pulmonary hypertension and cor pulmonale can occur secondary to tonsilar and adenoidal hypertrophy, 27 laryngomalacia,3 obstructive sleep apnea, 18 enlarged tongue, and midfacial (nose) hypoplasia. 36 All of these mechanisms of upper airway obstruction, known to occur more frequently in patients with Down syndrome, result in alveolar hypoventilation, hypoxemia, and hypercapnia, which may chronically or acutely result in elevation of pulmonary artery pressures and resistances. In addition, the lung parenchyma itself may be abnormal in patients with Down syndrome. 15 Patients with Down syndrome may have diminished numbers of alveoli and decreased alveolar surface area.l O The loss of capillary surface area secondary to this alveolar diminution can result in the development of pulmonary artery hypertension and pulmonary vascular disease. Also, there may be less muscular hypertrophy than expected in the pulmonary arteries of patients with Down syndrome and large leftto-right shunts, suggesting a qualitative pulmonary arterial abnormality that may fail to protect the lung parenchyma from the damaging effects of high flow and pressure. 42 Additional pulmonary complications occur in patients with Down syndrome and can aggravate pulmonary artery hypertension. Gastroesophageal reflux has been associated with congenital heart defects and Down syndrome. 38 Reflux results in numerous pulmonary complications including infection and bronchospasm. These may aggravate pulmonary artery hypertension acutely and chronically. In addition, children with Down syndrome have been shown to have Band T lymphocyte abnormalities that can result in an increased incidence of pulmonary infections. 4 , 31 These infections may aggravate existing symptoms of pulmonary congestion, result in pulmonary parenchymal damage, aggravate upper airway obstruction, and ultimately play a role in the development and propagation of pulmonary artery hypertension and pulmonary vascular disease. The identification of patients with pulmonary artery hypertension and pulmonary vascular obstructive disease is critical in establishing treatment and prognosis for this group of patients. Clinical findings to suggest the presence of pulmonary artery hypertension include a prominent right ventricular impulse, increased intensity of the pulmonic closure sound, decreased intensity of systolic murmurs, disappearance of the diastolic rumble, and perhaps improvement in symptoms and signs of congestive heart failure. Electrocardiographically, right ventricular hypertrophy will be present in all patients with significant pulmonary artery hypertension, but is not an accurate predictor of the degree of hypertension. Echocardiographic techniques have not yet been reliable in predicting accurately the degree of pulmonary artery hypertension or pulmonary resistance. The chest x-ray in patients with severe pulmonary hypertension and pulmonary vascular disease may demonstrate a dilated main pulmonary artery segment and a disorganized "pruning" pattern of the pulmonary blood flow (Fig. 5). The development of clinical evidence of right-to-left shunting (i.e., cyanosis), a palpable pulmonary closure sound on palpation of the chest, and auscultation of a pulmonary insufficiency (Graham-Steele) murmur are signs of severe pulmonary vascular obstructive disease and Eisenmenger's
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Figure 5. Prominent main and proximal pulmonary arteries and multiple areas of atelectasis seen in the chest x-ray of a patient with Down syndrome and pulmonary vascular disease.
physiology. These changes of severe pulmonary vascular disease have been noted to occur in children with Down syndrome who are less than one year of age. 22 This illustrates the necessity of early cardiac evaluation in the children with Down syndrome and congenital heart malformations in order to assess pulmonary artery pressures and resistances. MANAGEMENT The most critical point in evaluation and management of the child with Down syndrome is recognizing those patients with underlying cardiovascular malformations and in identifying those with pulmonary artery hypertension. Clearly, the identification of these patients is the responsibility of the primary pediatrician. Any patient suspected of having Down syndrome should have chromosomal studies performed and, if trisomy 21 is documented, cardiovascular workup should be undertaken. Careful history and physical examination will frequently reveal those patients with significant cardiac malformation. Numerous cases of patients without signs or symptoms of heart failure have been identified to later have severe intracardiac malformations. The electrocardiogram and echocardiogram, two relatively inexpensive, noninvasive screening tests, are useful in identifying the majority of the patients with Down syndrome who have a congenital heart defect. These two tests should be performed in all neonates with documented trisomy 21. Should electrocardiographic or echocardiographic abnormalities be present or if there are clinical signs of hemodynamic compromise, the infant should be referred to a pediatric cardiologist. The management of congestive heart failure in patients with Down syndrome has changed very little in recent years. Digitalis and diuretic therapy are indicated for patients with signs or symptoms of congestive
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heart failure. Afterload reduction therapy (e. g., hydralazine) may also be useful, but is not used in the "routine" management of congestive heart failure. As mentioned previously, cardiac catheterization is necessary to assess pulmonary artery pressures and resistances. In the presence of pulmonary hypertension and increased resistance, administration of pulmonary vasodilators (e. g., oxygen and/or tolazoline) may be useful in assessing the degree of damage to the pulmonary vasculature. In those patients who require relief of pulmonary artery hypertension, surgical intervention is necessary. Banding (constriction) of the pulmonary artery has been effective in treating congestive heart failure, preventing pulmonary vascular disease, 12, 14, 29, 33 and increasing patient survival. Unfortunately, pulmonary artery banding may not alter the progression of pulmonary vascular disease, and, in patients with significant atrioventricular valve regurgitation or left ventricular to right atrial shunt, may not be effective in improving hemodynamics. Postoperative complications such as severe cyanosis, sub aortic stenosis, and severe mitral regurgitation can occur. With advances in complete surgical repair, pulmonary artery banding has become a less frequent mode of therapy for infants with large ventricular septal defects or complete endocardial cushion defects. Pulmonary artery banding is still indicated in children with complex cardiac malformations such as those with hypoplastic right ventricle, those with large ventricular communications and coarctation of the aorta, and in those who for a variety of reasons, (e.g., associated anomalies, infection, severe respiratory compromise) would not tolerate an open heart procedure. Surgical correction is now the procedure of choice for the treatment of patients with refractory congestive failure and/or pulmonary hypertension. Successful transatrial closure of ventricular septal defects can be undertaken safely in children using cardiopulmonary bypass techniques and in infants utilizing hypothermia and circulatory arrest. 2, 5, 25 Postoperative hemodynamics in these patients are excellent. 2, 25 Surgical repair of complete atrioventricular canal has resulted in a significant change in the approach to patients with this cardiac malformation.22, 33 Medically managed, there is a high incidence of morbidity and mortality occurring even under one year of age, 6 and morbidity and mortality secondary to pulmonary artery banding are excessively high as well. U sing techniques of cardiopulmonary bypass, deep hypothermia, and cardioplegia, complete intracardiac repair of complete endocardial cushion defects have been performed in patients as young as one month of age.5, 9, 11, 19, 21 Surgical mortality, however, remains high (20 to 30 per cent). The technique presently employed can be done transatrially, hopefully reducing the incidence of postoperative heart block, right bundle branch block, right ventricular dysfunction, and ventricular ectopy. Residual hemodynamic problems include mitral insufficiency, left-toright shunt, and pulmonary artery hypertension. Mitral insufficiency is common (60 to 80 per cent 9, 19), is moderate or severe in many cases, and may infrequently necessitate valve replacement. Residualleft-to-right shunt is infrequent and rarely large enough to require reoperation. Persistent pulmonary hypertension is becoming less of a problem as successful sur-
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gical intervention is performed in younger patients. Clinically, the majority of patients show dramatic improvement following surgery. Although the child or adolescent with severe pulmonary vascular disease may be inoperable, symptoms secondary to right heart failure, cyanosis, and polycythemia can be severe and progressive, and warrant continued medical treatment. Erythropheresis, home oxygen administration, and restriction of physical activities may palliate symptoms of headache, chest pain, respiratory compromise, syncope, and exercise intolerance. Regulation of participation in Special Olympics to those events requiring limited physical exertion is often a practical concern in those patients.
PROGNOSIS
Children with Down syndrome may have many potentially life-threatening complications secondary to their chromosomal abnormality. Intestinal obstruction, leukemia, and severe congenital heart defects make up the majority of directly life-threatening illnesses. The incidence of survival in patients with Down syndrome and cardiovascular malformation is approximately 60 per cent at one year of age, compared with an 85 per cent 1 year survival of children with Down syndrome without heart malformations. The degree of severity of cardiovascular malformation has direct impact on their prognosis as well. In patients with complete atrioventricular canal, managed nonsurgically, there is a 96 per cent mortality by 5 years of age. 7 Surgical management of patients with Down syndrome and severe congenital cardiac malformations dramatically improves the prognosis. Present operative techniques would suggest approximately a 75 per cent survival following surgical repair of endocardial cushion defect, and greater in those with isolated ventricular septal defect and atrial septal defect. Following successful surgery, an improvement in signs and symptoms of congestive failure can be expected. Growth will improve, although it should be remembered that children with Down syndrome are shorter and lighter than age-matched normals, and special growth charts are available when assessing their height and weight.
SUMMARY
There is a high incidence of congenital heart disease in patients with Down syndrome. The most frequent cardiac malformations are endocardial cushion defect, ventricular septal defect, patent ductus arteriosus, and atrial septal defect. The majority of these defects are hemodynamically significant and result in clinical signs and symptoms of cardiopulmonary compromise. Medical management is effective temporarily in many cases, but does not affect the development of pulmonary artery hypertension or pulmonary vascular disease. Surgical management of these patients is indicated. Improvement in surgical techniques has allowed intervention in infancy with satisfactory long-term results. The development of pulmonary artery hypertension and pulmonary vascular disease is Significant in pa-
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tients with Down syndrome and often affects the long-term prognosis of these children. Fortunately, improvement in the medical and surgical management of patients with serious heart defects has advanced to the point where most cardiac centers in this country are able to perform surgical procedures with an acceptable risk. Children with Down syndrome and congenital heart disease can be successfully treated early in life. Future concerns, in the light of a changing sociolegal environment, center around possible prevention, early recognition, and improved management.
REFERENCES 1. Adams, F. H., and Emmanouilides, G. C.: Heart Disease in Infants, Children, and Adolescents, 3rd ed. Baltimore and London, Williams and Wilkins, 1983. 2. Arciniegas, E., Farooki, Z. Q., Hakimi, M., et al.: Surgical closure of ventricular septal defect during the first twelve months of life. J. Thorac. Cardiovasc. Surg., 80:921-928, 1980. 3. Aggarwal, K. C., Rastogi, A., and Singhi, S.: Cor pulmonale due to laryngomalacia in Down syndrome. Indian Pediatr. 18:914--916, 1981. 4. Barroeta, 0., Nungaray, L., Lopez-Osuna, A., et al.: Defective monocyte chemotaxis in children with Down syndrome. Pediatr. Res., 17:292--295, 1983. 5. Bender, H. W., Fisher, R. D., Walker, W. D., et al.: Reparative cardiac surgery in infants and small children: Five years experience with profound hypothermia and circulatory arrest. Ann. Surg., 190:437-443, 1979. 6. Berger, T. J., Kirklin, J. W., Blackstone, E. H., et al.: Primary repair of complete atrioventricular canal in patients less than two years old. Am. J. Cardiol., 41:906--913, 1978. 7. Berger, T. J., Blackstone, E. H., Kirklin, J. W., et al.: Survival and probability of cure without and with operation in complete atrioventricular canal. Ann. Thorac. Surg., 27:104--111, 1979. 8. Chi, Tp. L., Krovetz, L. J.: The pulmonary vascular bed in children with Down syndrome. J. Pediatr., 86:533--538, 1975. 9. Chin, A. J., Keane, J. F., Norwood, W. 1., et al.: Repair of complete common atrioventricular canal in infancy. J. Thorac. Cardiovasc. Surg., 84:437-445, 1982. 10. Conney, T. P., and Thurlbeck, W. M.: Pulmonary hypoplasia in Down's syndrome. N. Engl. J. Med., 307:1170-1173, 1982. 11. Culpepper, W., Koff, J., Lin, C-Y, et al.: Complete common atrioventricular canal in infancy-surgical repair and postoperative hemodynamics. Circulation, 58:550-558, 1978. 12. Epstein, M. L., Moller, J. H., Amplatz, K., et al.: Pulmonary artery banding in infants with complete atrioventricular canal. J. Thorac. Cardiovasc. Surg., 78:28--31, 1979. 13. Greenwood, R. D., and Nadas, A. S.: The clinical course of cardiac disease in Down syndrome. Pediatrics, 58:89~97, 1976. 14. Hunt, C. E., Formanek, G., Levine, M. A., et al.: Banding of the pulmonary artery, results in ill children, Circulation, 43:395-406, 1971. 15. Kontras, S. B., and Bodenbender, J. G.: Abnormal capillary morphology in congenital heart disease. Pediatrics, 37:316--322, 1966. 16. Laursen, H. B., Congenital heart disease in Down syndrome. Br. Heart J., 38:32--38, 1976. 17. Levine, O. R., and Simpser, M.: Alveolar hypoventilation and cor pulmonale associated with chronic airway obstruction in infants with Down syndrome. Clin. Pediatr., 21:2529, 1982. 18. Loughlin, G. N., Wynne J. W., and Victorica, B. E.: Sleep apnea as a possible cause of pulmonary hypertension in Down syndrome. J. Pediatr., 98:435-437, 1981. 19. Mair, D. D., and McGoon, D. C.: Surgical correction of atrioventricular canal during the first year of life. Am. J. Cardiol., 40:66--69, 1977.
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20. Masaki, M., Higurashi, M., Iijima, K., et al.: Mortality and survival for Down syndrome in Japan. Am. J. Hum. Genet., 33:629-639, 1981. 21. Matthews, J., Bromberg, J., Spicer, R. L., et a1.: Repair of complete atrioventricular canal in the first two years oflife (abstract) Circulation, 64:237, 1981. 22. McCabe, J. C., Engle, M. A., and Gay, W. A.: Surgical treatment of endocardial cushion defects. Am. J. Cardio\., 39:72-77, 1977. 23. Newfeld, E. A., Sher, M., Paul, M. H., et al.: Pulmonary vascular disease in complete atrioventricular canal defect. Am. J. Cardio\., 39:721-726, 1977. 24. Park, S. C., Mathews, R. A., and Zuberbuhler, J. R.: Down syndrome with congenital heart malformation. Am. J. Dis. Child., 131:29--33, 1977. 25. Rein, J. G., Freed, M. D., Norwood, W. 1., et al.: Early and late results of closure of ventricular septal defect in infancy. Ann. Thorac. Surg., 24:19--26, 1977. 26. Rowe, R. D., and Uchida, 1. A.: Cardiac malformation in mongolism: A prospective study of 184 mongoloid children. Am. J. Med., 31:726--735, 1961. 27. Rowland, T. W., Nordstrom, L. G., Bean, M. S., et al.: Chronic upper airway obstruction and pulmonary hypertension in Down syndrome. Am. J. Dis. Child., 135:10501052, 1981. 28. Silverman, N. H., and Snider, A. R.: Two dimensional echocardiography in congenital heart disease. Norwalk, Conn., Appleton-Century Crofts, 1982. 29. Somerville, J., Agnew, T., Stark, J., et aI.: Banding of the pulmonary artery for common atrioventricular canal. Br. Heart J., 29:816--828, 1967. 30. Soto, B., Bargeron, L. M., Pacifico, A. D., et aI.: Angiography of atrioventricular canal defects. Am. J. Cardiol., 48:492-499, 1981. 31. Spina, C. A., Smith, D., Korn, E., et al.: Altered cellular immune functions in patients with Down syndrome. Am. J. Dis. Child., 135:251-255, 1981. 32. Stark, J., Aberdeen, E., and Waterston, D. J.: Pulmonary artery constriction (banding): A report of 146 cases. Surgery, 65:808-818, 1969. 33. Stewart, S., Harris, P., and Manning, J.: Complete endocardial cushion defect: Operative technique and results. J. Thorac. Cardiovasc Surg., 78:914-919, 1979. 34. Strain, J. E.: The decision to forgo life-sustaining treatment for newborns. Pediatrics, 72:572-573, 1983. 35. Strain, J. E.: The American Academy of Pediatrics Comments on the "Baby Doe II" Regulations. N. Eng\. J. Med., 309:443--444, 1983. 36. Strome, M.: Down syndrome: A modern otorhinolaryngological perspective. Laryngoscope, 91:1581, 1594, 1981. 37. Tandon, R., and Edwards, J. E.: Cardiac malformations associated with Down syndrome. Circulation, 47:1349--1355, 1973. 38. Weesner, K. M., and Rosenthal, A.: Gastroesophageal reflux in association with congenital heart disease. Clin. Pediatr., 22:424-426, 1983. 39. Will, G. F.: The case of Phillip Becker. Newsweek, 112, 1980. 40. Williams, R. G., and Rudd, M.: Echocardiographic features of endocardial cushion defects. Circulation, 49:418-422, 1974. 41. Wilson, S. K., Hutchins, G. N., and Neill, C. A.: Hypertensive pulmonary vascular disease in Down syndrome. J. Pediatr., 95:722-726, 1979. 42. Yamaki, S., Horiuschi, T., and Sekino, Y.: Quantitative analysis of pulmonary vascular disease in simple cardiac anomalies with the Down syndrome. Am. J. Cardio\., 51:1502-1506, 1983. Department of Pediatrics William Beaumont Hospital 3601 W. 13 Mile Road Royal Oak, Michigan 48072