outflow tract obstruc artery stenosis is well these lesions may occur s

gressive (41, but is amena- ble to surgical correction (5, ~mo~ary artery stenosis is

for surgical correction, although newer sur- s and the recent i~tro~~ctioQ of balloon

yielded promising results in occasional patients (7,g). The natural history of ~~~mo~ary artery stenosis with or without associated supravalvular aortic stenosis has not been described. This study was undertaken to define the natural his and clinical interrelati supravalv~lar aortic and onary artery stenosis P

From the Department of Paediatric Cardiology. Freeman Hospital, New- castle upon Tyne and *The Hospital for Sick Children, London, England.

Manuscript received September 28, 1989; revised manuscript received December 20, 1989, accepted January 10, l!I90.

: Christopher Wren, MB. ChB. Department of Pae- diatric Cardiology, Freeman Hospital, Newcastle upon Tyne NE7 7DN. England.

Ql990 by the American College of Cardiology

-

artery stenosis relief 0F suprav

nts with suprav~~~v~lar tenosis, or both, tmder-

atheterization between 1973 and I98

and had been referred for inve stigation of a heart murmur. Eighteen had clinically dominant aortic stenosis; the other 17 presented with signs of pulmonary artery stenosis. ‘The

ductus arteriosus in one, coarctation of the aorta in one, both

1626 WRENETAL. SUPRAVALVULARAORTICANDPULMONARYSTENOSI

JACC Vol. 15. No. 7 s June I :16X5-30

patent ductus and coarctation of the aorta in one, pulmonary valve stenosis in one and asymptomatic carotid artery ste- nosis in one.

Twenty-three patients had only one cardiac catheteriza- tion prcgedure; 11 of these underwent surgical relief Of supravalvular aortic stenosis after the first study and 1 other died during the follow-up period. Twelve patients underwent at least two cardiac catheterization procedures; the age at tit catheterization ranged from 2 weeks to 15 years, and the interval between studies ranged from 8 to 105 months.

Cardiac ~~~~~~e~~o~ and a@ pby. All data were reviewed retrospectively, having been obtained during rou- tine clinical investigation. Blood pressures were measured with fluid-filled catheters and recorded on a multichannel ink jet recorder. The severity of pulmonary artery stenosis was assessed from the right ventricular systolic pressure because it was not possible to record distal pulmonary artery pres- sure in all cases. Supravalvular aortic stenosis was assessed from the peak to peak pressure decrease recorded during catheter withdrawal from the left ventricle to the aorta. Cardiac output was not measured routinely; only one patient had clinical evidence of low cardiac output and a low mixed venous oxygen saturation.

All patients with supravalvular aortic stenosis had a 1e.B ventricular angiogram or aortogram in the posteroanterior or left anterior oblique projection (1). In some of those with pulmonary artery stenosis and no left-sided pressure gradi- ent, the ascending aorta was visualized on the right ventric- ular or pulmonary artery angiogram. Supravalvular aortic stenosis was identified as being of either hourglass or tubular (hypoplastic) type, although these are probably different degrees of the same disease process (I). The diameter of the aortic valve and the minimal diameter of the ascending aorta (that is, maximal stenosis) were measured in systole from a projected cineangiogram (Fig. I). Catheter diameter was used to correct for magnification.

Twelve patients with normal right ventricular pressure did not have a right heart angiogram. In all other patients, a right ventricular or pulmonary artery angiogram was per- forned in the posteroanterior projection, usually with cra- nial angulation, and in the lateral projection (2). The char- acteristic appearance of the pulmonary arteries in these patients is diffuse hypoplasia of the right and left branch arteries (Fig. 2) rather than discrete stenosis, although subtle stenoses may be present at distal branches (2). Pulmonary artery growth was assessed from the diameter, *the right and left pulmonary arteries measured during both systole and diastole, midway between the origin and the first bifur- cation (Fig. 2), In three cases, the left pulmonary artery could be measured only on the lateral projection. Note was taken of the age and body surface area at the time of investigation. The diameters of the ascending aorta, the aortic valve and the right and left pulmonary arteries were compared with normal ranges reported by Sievers et al. (9).

Figure 1. Lateral aortogram,! showing supravalvular aoruc stenosis of the hourglass type. although the stenosis extends a EElle way up ascending aorta. The dia;meters of the aortic valve and of supravalvular aortic stenosis were measured during systole rows).

treasures. Supravalvular aortic stenosis was present in 27 (77%) of the 35 patients. Eleven had a left ventricle to aorta pressure decrease >70 study and were referred for surgical relic (Fig. 3). Their ages ranged from 2 to IS years patients had an elevated right ventricular pressure.

Serial catheterization in nine paGeNts showed an increase in the aortic pressure gradient in all except two cases. Four of the youngest patients, all with pulmonary artery stenosis, had a strikingly similar increase in the pressure gradient over the first few years (Fig. 3). One patient with very poor left ventricular function from the time of his first investigation 4 years of age had no increase in pressure gradient at rescu 4 years later, a few months before he died. One boy died suddenly at the age of 4 years despite having a pressure gradient of only 24 mm Hg at the study performed 1 year previously. Another patient had an aortic that increased from 45 mm Hg at 1 year of at 2 years of age but subsequently decrea age 3. No other patient showed a reduction in pressure gradient on repeat catheterization. On1 had no pressure gradient at the first cat quently developed a gradient within the ascending aorta: the gradient did not become surgically significant in either patient during the follow-up period.

aorta was seen in 3.

ventricle &VI to aorta pressure

those who have no?

same patient are joined.

5 10 15

AGE yean

ective sf the severity

am-tic stenosis, but could

wo patients still had hi

ight ventricular or pM~~~~ary a~~io~~ap~y in the patients with elevated right veWicu!ar

1628 WREN ET AL. JACC Vol. 15, No. 7

SUPRAVALVULAR AORTIC AND PULMONARY STENOSIS June 1990: 1625-30

8 5 10 15

AGE years

Figure 5. Relation between right ventricular (RV) systc5.: pressure and age. Open squares show patients with angiographic evidence of severe multiple peripheral pulmonary artery stenosis. Closed circles indicate patients without obvious peripheral pulmonary artery ste- nosis. Open circles show the patient with persisting severe pulmo- nary artery hypoplasia who died from right ventricular failure at operation. Serial results in the same patient are joined.

pressure showed that pulmonary artery diameters were well below normal during both systole and diastole at the first study and the systolic expansion of the arteries was minimal. Figure 6 shows results from the right pulmonary artery; measurements from the left pulmonary artery were similar.

In three patients, the pulmonary artery diastolic diameter remained below normal, but increased at a normal rate. The diastolic diameter increased in proportion to body surface area in only one patient. This child also had a ventricular septal defect, and as her pulmonary artery diameter in- creased, the pulmonary to systemic fiow ratio also increased from 1.6:1 to 2.6: 1. In two patients, the diastolic pulmonary artery diameter per unit surface area decreased as the child grew (Fig. 6).

At restudy, there was a true increase in the systolic diameter of the pulmonary arteries (that is, an increase in

proportion to the body surface area) in a (Fig. 6). The exception was the patient w increase in right ventricular pressure who The increase in systolic diameter carrel decrease in right ventricular pressure. tensibility was most marked in tho crease in right ventricular pressure was small in the only patient whose right ventricular pressure increased (Fig. 7).

In two patients with persisting righ hyperte~~si~~ at ages 9 cand Myears, th pulmonary artery diastolic and systolic ilar to those in the rest of the group, b multiple peripheral pulmonary artery parent. Although minor angiographic narrowing at pulmo- nary artery branches was seen in several other patients, these were not hemodynamically dominant. No a signs that might predict the development of significant pe- ripheral pulmonary artery stenosis were found.

Only two patients with normal right ventri underwent right ventricular aagiography. The monary arteries were of normal size in both, b had an appearance similar to that in patients with significant pulmonary artery steaosis.

Supravalvular Aortic Stenosis Follow-u ks. Supravalvular aortic stenosrs is a pro-

gressive lesion. Our results show t&-the left ventricle to aorta pressure gradient had increased in most patients un- dergoing repeat cardiac catheterization. Serial angiography showed that the increase in pressure gradient is related to failure of normal growth of the supravalvular aortic region. The rate of increase in diameter of the supravalvular aortic stenosis is below normal. Because area is proportional to the square of diameter, the cross-sectional area of the ascending aortic stenosis effectively becomes even less with growth (in

Figure 6. Log-log graph of the diameter of the right pulmonary artery during diastole (left) and systole (right) against body surface area obtained from mea- surements of right ventricular or pulmonary artery angiograms (see text for details). Serial measurements in the same patient are joined. The dashed line and shaded area indicate the mean and range of normal values taken from the study of Sievers et al. (9).

1.0 1.5 0.2 0.5 1.0 1.5

Body Surlaf~ Area m2

and sapravalvular amtic steoQsis. At 3

aortic pressure gradi-

selected for initial ve survey, our patients were t catheterization on clinical supravalvu~ar aortic stenosis

underwent surgery after the initial investigation. Patients being restudied therefore, those with mild or moderate left ventricular w tract obstruction at the first study. The most rapid change in the aortic pressure gradient was seen in patients referred early with asymptomatic pulmonary artery stenosis. This finding probably represents an ascer- tainment bias because these were the only patients with s~~ravalvu~ar aortic stenosis nndergoi~g serial study earl lie. A similar rate of early rogression may have occurre patients without ~u~rno~~y artery stenosis who thus did not present until their su~rava~v~lar aortic stenosis was clini- cally apparent. Those with little or no pulmonary artery stenosis presented later, once the aortic stenosis had become

. Few previous studies have examined the progression of supravalvular aortic stenosis, either an- giographically or hemodynamically. Giddins et al. (4) found

Keane et al. (IC) found no change in pressure gradient in four der children who were restudied after owever, as we have shown, the most

increase in aortic pressure gradient occurs in the first few years of life dllring the period of most rapid growth.

We found that the sapvavalvuiaar aortic diameter was below rtormal in all patients, even those with no outflow tract pressare gradient. Thus, the underlying structural abnormal- ity of the aorta is always present, even though it may not be

valvular aortic stenosis.

~~~0~~~ Arhvy Stenosis

ies. In contrast to supravalvular aortic stenosis, pulmonary artery stenosis is usually diffuse or

1630 WREN ET AL. SUPRAVALWLAR AORTIC AND PULMONARY STENOSIS

JACC Vail. is. No. 7 June 1 : 1625-30

tubular rather than discrete and improves hemodynamically in most patients. Right ventricular pressure decreased on serial catheterization in all but two patients, and the de- crease was reldted to an increase in the systolic distensibility of the pulmonary arteries rather than true luminal growth. Angiographic evidence of peripheral pulmonary artery ste- nosis was seen in several patients, but the lesions were not hemodynamically significant in the majority. The two pa- tients whose right ventricular pressure did not decrease were a girl in whom severe multiple peripheral pulmonary artery stenosis developed or became dominant and a child with very severe persistent pulmonary artery hypoplasia. The latter wdS the only patient in whom the right-sided lesion limited the prognosis.

Previous studies. Giddins et al. (4) found that the pressure gradient between proximal and distal pulmonary artcries decreased in 3 of 6 patients with Williams’ syndrome studied after a mean period of 7 years; mean right ventricular pressure became normal in 9 of 10 patients, decreasing from 52 to 28 mm Hg. We are not aware of any other report of serial right heart catheterization in children with pulmonary artery stenosis.

C!onclnsions. This study has shown that supravalvular aortic stenosis is usually a progressive lesion. An increase in the left ventricular outflow tract pressure gradient is likely in those patients whose supravalvular aortic stenosis does not warrant surgery after the first investigation. They should, therefore, be kept under close long-term follow-up evB!ua- t&s. It is noteworthy thal Doppler estimation of the de- crease in aortic pressure may be inaccurate in those with supravalvular aortic stenosis and may overestimate the catheter-measured pressure gradient because the modified Bernoulli equation fails to take into account the pressure recovery distal to a streamlined stenosis (t 2). Noninvasive estimation of serial right-sided pressure gradients may also be inaccurate. We have also shown that, with rare excep tions, associated pulmonary artery stenosis improves with time and is unlikely to be a limiting factor in the patient’s prognosis.

We are grateful to Hugh Bain, MB, ChB, FRCP, John MRCP, Stewart Hunter, MB, ChB, FRCP, Fergus BChir. FRCP, FACC, Philip Rees. MB, BCh, FRCP and James Taylor, MD, FRCP for permission to include details of patients under their c&e.

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Martin EC, Moseley IF. Supravalvar aortic stenosis. 2r 758-65.

Giddins NG. Finley JP, Nanton MA. Roy DL. The natural course of supravalvar aortic stenosis and peripheral pulmonary artery stenosis in Williams’ syndrome. Br Heart J 1989;62:315-9.

Doty DB. Polansky DB, Jenson CB. Supravalvular aortic stctosis: repair by extended aortoplasty. 3 Thorac Cardiovasc Suq 1977;74:362-71.

Raker G. Teske D, Kilman 9, Hosier D, Wooley C. SupravaJvularaonic stenosis: a 28-year clinical perspective and experience with patch aorto- plasty. Am J Cardiol 1983:51:256-60.

Yamaguchi M, Tachibana H, Hosokawa Y. Qhashi repair of supravalvular aortic stenosis associated with severe multiple peripheral pulmonwi stenoses: report of extended peripheral pulmonary arterioplasty. 3 Thorac Cardiovasc Surg 1987:93:785-93.

Ring JC. Bass JL, Marvin W, et al. Management of congenital stenosis of a branch pulmonary artery with balloon dilation angioplasty. J Thorac Cardiovasc Surg 1985;90:35-44.

Sievers HH. Onnasch W, Lan8e PE. Bernhard A. Hcictzen PH. Dimensions of the great arteries. semilunar valve roots, and right ventric- ular outflow tract during growth: normative angiocardiographic data. Pediatr Cardiol 1983;4:189-%.

IO. Keane JF. Fellows KE. LaFarge CG. Nadas AS. Bernhard WF. The surgical management of discrete and diffuse supravalvar aortic stenosis. Circulation 197&54: 112-7.

I I. Hallidie-Smith KA, Karas S. Cardiac abnormalities in Williams-Beuren syndrome. Arch Dis Child 1988;63:889-13.

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