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J Thorac Cardiovasc Surg 1994;108:21-28
© 1994 Mosby, Inc.

SURGERY FOR CONGENITAL HEART DISEASE

Pathology of coronary arteries, myocardium, and great arteries in supravalvular aortic stenosisReport of five cases with implications for surgical treatment

Rochester, Minn.

From the Division of Thoracic and Cardiovascular Surgery and the Division of Anatomic Pathology, Mayo Clinic, Rochester, Minn.

Received for publication Oct. 1, 1993. Accepted for publication Dec. 8, 1993. Address for reprints: William D. Edwards, MD, Hilton (11) Pathology, Mayo Clinic, Rochester, MN 55905.

Abstract

Among five patients with supravalvular aortic stenosis in whom autopsy tissues were available, all were male, 1 to 39 years old (mean 10 years, median 3 years), and the four children had Williams-Beuren syndrome (two familial, two sporadic). Medial thickening and dysplasia (disorganization) characterized the aortic sinotubular junction of three patients with discrete disease and the entire ascending aorta and arch branches of the two with diffuse disease. Medial dysplasia also involved the pulmonary arteries in each case, but less severely than the aorta. Dysplasia of coronary arteries was observed in all five hearts and was more obstructive proximally than distally, in cases with diffuse than discrete aortic disease, and in the adult than in the two children with discrete supravalvular aortic stenosis. All major epicardial arteries were involved, without predilection for any particular vessel. In contrast to the great arteries, coronary artery dysplasia involved all three layers, not just the media. To varying degrees, vessels showed intimal hyperplasia, fibrosis, and disorganization (dysplasia); disruption and loss of the internal elastic membrane, with indistinct intimal-medial junctions; medial hypertrophy and dysplasia; and adventitial fibroelastosis. In severe cases, the microscopic structure resembled that of the ductus arteriosus. Acute intramedial dissections were observed in the ascending aorta and distal right coronary artery in one patient each. Chronic microfocal ischemic fibrosis was identified in the subendocardium and papillary muscles of the left ventricle in four patients, and the adult patient also had an acute myocardial infarction. In summary, these findings emphasize the extraaortic extent of supravalvular aortic stenosis and the development of ischemic heart disease even in childhood. The presence of severe coronary obstruction in the adult with discrete aortic disease suggests that chronic high pulsatile coronary blood pressure may favor the proliferation of dysplastic tissue. Early surgical intervention may minimize the degree of proliferation, as well as allow regression of left ventricular hypertrophy, thereby lessening the risk of myocardial ischemia and aortic dissection. (J THORAC CARDIOVASC SURG 1994;108:21-8)

Congenital supravalvular aortic stenosis represents a developmental complex that is characterized by localized or diffuse narrowing of the ascending aortic lumen commencing at the sinotubular junction (Fig. 1). Additional manifestations of the complex include stenoses in the pulmonary arteries and proximal aortic arch vessels, aortic valve dysplasia, and coronary ostial stenoses. ^1-5 In a recent review of the Mayo Clinic experience with the surgical treatment for supravalvular aortic stenosis, ostial and distal coronary arterial lesions and myocardial scarring were described from the autopsy reports from patients who died. ⁶ These findings prompted us to perform a detailed histologic investigation of the coronary arteries, myocardium, and great arteries in supravalvular aortic stenosis.

View larger version (39K): [in this window] [in a new window]   Fig. 1. Schematic diagram of discrete and diffuse forms of supravalvular aortic stenosis.

From the tissue registry of the Mayo Clinic, five hearts with supravalvular aortic stenosis were identified and reviewed by a cardiac pathologist (W.D.E.). The histologic findings in one heart (Table I, case 2) have been reported previously. ⁴ Multiple sections were taken for microscopic examination from the left main coronary artery and from the proximal, middle, and distal regions of the left anterior descending, left circumflex, and right coronary arteries. In addition, in each specimen, myocardial samples were obtained from the anteroseptal, anterolateral, and inferior walls of the left ventricle, including both mitral papillary muscles. Sections from the ascending aorta, aortic arch vessels, descending thoracic aorta, main pulmonary artery, and right and left pulmonary arteries were also processed for evaluation of arterial dysplasia or other abnormalities.

RESULTS

Clinical features
All five patients were male. The mean age at the time of death was 10 years (range 1 to 39 years, median 3 years). The four children had Williams-Beuren syndrome, two familial and two sporadic (see Table I). Additional patient data including the year of autopsy, the type of supravalvular aortic stenosis, and associated cardiovascular and noncardiovascular lesions are summarized in Table I.

Three patients had the discrete form of supravalvular aortic stenosis (Fig. 2). Two of these had a history of sudden death, one during repair of hypospadia (case 4) and the other spontaneously (case 3). Patient 5 died of an acute myocardial infarction on the first day after aortic valve replacement and mitral valvuloplasty, and 9 years after enlargement of the ascending aorta with a teardrop-shaped pericardial patch and decalcification of a focally calcified bicuspid aortic valve.

View larger version (140K): [in this window] [in a new window]   Fig. 2. Gross pathology of supravalvular aortic stenosis. A and B, Discrete form shows external constriction (A, arrows) and internal thickening at level of aortics inotubular junction (B,*). Note focal fusion of aortic cusp to junctional ridge (arrow). C. Diffuse form exhibits marked thickening of aortic wall and walls of brachiocephalic branches. Asc Ao, Ascending aorta; AS, aortic sinus; LV, left ventricle; PT, pulmonary trunk; SVC, superior vena cava.

Pathologic features
Coronary arterial lesions were categorized as congenital or acquired. Congenital lesions consisted of intimal hyperplasia (n = 5), intimal fibrosis (n = 4), indistinct intimal-medial junction with loss of internal elastic lamina (n = 5), medial hypertrophy (n = 5), medial disorganization with "woven" fibroelastic pattern (n = 5), and adventitial fibroelastosis (n = 5) (Fig. 3). In severe cases, this constellation of lesions resulted in a thickened arterial wall that appeared similar in structure to the ductus arteriosus.

View larger version (1081K): [in this window] [in a new window]   Fig. 3. Photomicrographs of coronary arteries in supravalvular aortic stenosis. A. Normal coronary artery, for comparison. B. Distinct intima (Int), media (Med), and adventitia (Adv), with thickening of all three layers. C. Severe luminal obstruction caused by wall thickening, with loss of internal elastic membrane, loss of distinction between intima and media, and disorganized (dysplastic) intimal-medial proliferation. D. Severe stenosis caused by dysplasia and atherosclerosis in 39-year-old man. E. Transition from three distinct arterial layers (right) into thickened and disorganized wall with loss of distinction between intima and media (left). F. Arterial dysplasia associated with focal acute intimal tear (*) and minor intramedial dissection (arrow). (Elastic-van Gieson; A, x35; B and C,x30; D, x15; E, x60; F, x20.)

Table II

View larger version (164K): [in this window] [in a new window]   Fig. 4. Photomicrograph of myocardium in supravalvular aortic stenosis with coronary artery obstruction. Chronic ischemic changes include replacement fibrosis (left) and sarcoplasmic vacuolization of myocytes (right) from mitral papillary muscle. (Hematoxylin and eosin; x200.)

View larger version (170K): [in this window] [in a new window]   Fig. 5. Photomicrograph of ascending aorta in supravalvular aortic stenosis. A, Marked disorganization and loss of elastic elements. B, Normal tissue, from distal portion of descending thoracic aorta in same patient, for comparison (Elastic-van Gieson; x260.)

In patients with supravalvular aortic stenosis, blood flow to the aortic sinuses and coronary ostia may be obstructed because of adhesion of the valve cusps to the stenotic supravalvular ridge. ^5-11 Left ostial stenosis caused by this mechanism was observed in one of the specimens in the present series. In the absence of such ostial obstruction, the coronary arteries are exposed to both an elevated systolic pressure and a high pulse pressure, which represent appreciable distending forces that may lead to dilatation and tortuosity. In our recently reported series of 80 patients with supravalvular aortic stenosis, dilatation of the right coronary artery was found in 29% of the patients and dilatation of the left coronary artery in 20%. ⁶ As in other series, the higher incidence of dilatation of the right versus the left coronary artery was due to the higher prevalence of left ostial stenosis. ^6,8-11

Other secondary structural changes in the coronary arteries that are caused by high systolic pressure in the aortic root include intimal hyperplasia and atherosclerosis. The high smooth muscle content of the media of the coronary artery (as opposed, for instance, to the media of the internal mammary artery, which is mainly elastic) may predispose to these early occurring and progressive processes. ^12,13 The spectrum of coronary artery disease in supravalvular aortic stenosis, as observed in the current series, may be explained by the difference in exposure time among the cases. An additional potential complication of the high pressure to which the coronary arteries are exposed is focal dissection of the arterial wall, as occurred in the 39-year-old patient in the present series.

Data from this study illustrate the prevalence of ischemic heart disease among patients with supravalvular aortic stenosis. With coexistent left ventricular hypertrophy, lesions of myocardial ischemia often begin to develop in early childhood.

In patients with supravalvular aortic stenosis as part of the Williams-Beuren syndrome, the most common associated anomalies consist of stenoses in the proximal aortic arch vessels and pulmonary arteries. ^1-3,5 In the present study, stenoses of the innominate, left common carotid, and left subclavian arteries were observed in two patients with the Williams-Beuren syndrome and the diffuse form of supravalvular aortic stenosis. Proximal and distal pulmonary artery stenoses, extending beyond the first lobar branches, were found in the specimens of all four patients with the Williams-Beuren syndrome. Severe flow disturbance distal to the obstructing ridge at the sinotubular junction may cause dissection of the dysplastic aortic wall, as was seen in a 2-year-old boy in the present series.

In addition, supravalvular aortic stenosis has been reported to be associated with abnormalities of the mitral valve. Becker and colleagues ¹⁴ reported on three patients who had uniform thickening of the mitral valve and protrusion of the mitral valve toward the left atrium. The thickening was caused by an increase in fibrous tissue, and two of their three patients also had fibrous chordal thickening. Similar findings have been reported by others. ^5,15 In our series, two patients with Williams-Beuren syndrome had mitral valve abnormalities consisting of thickening of both leaflets and the attached chordae tendineae.

On the basis of the pathologic findings in the coronary arteries, myocardium, and ascending aorta as presented in this study, we recommend operative treatment of supravalvular aortic stenosis in early childhood, to prevent accelerated coronary artery disease, its detrimental ischemic effects on the myocardium, and dissection of the ascending aorta or coronary arteries. Our experience ^6,10 and that of others ^16-18 indicate that enlargement of the aortic root with a teardrop-shaped or pantaloon-shaped patch leads to excellent long-term results. Alternatively, patching of the three aortic sinuses ¹⁹ or circular excision of the stenosis at the level of the sinotubular junction followed by end-to-end anastomosis of the ascending aorta to the aortic root ²⁰ may restore a more anatomic configuration to the aortic root, but long-term results are not available. In diffuse supravalvular aortic stenosis, the entire ascending aorta should be enlarged with a patch, often with extension into the aortic arch and one or more of the proximal aortic arch vessels. ⁶ Alternatively, a conduit may be inserted from the ascending to descending aorta with side branches to stenotic arch vessels. ⁶

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Jacques A. M. van Son William D. Edwards Gordon K. Danielson Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Son, J. A. M. Articles by Danielson, G. K. Search for Related Content PubMed PubMed Citation Articles by van Son, J. A. M. Articles by Danielson, G. K.