The progressive nature of subaortic stenosis in congenital heart disease

Internatronal

137

Journal of Cardiology, 8 (1985) 137-143

Elsevier

IJC 00263

The progressive nature of subaortic stenosis in congenital heart disease Robert M. Freedom 1*2,Andrew Pelech ‘, Abe Brand I, Michael Vogel ‘, Peter M. Olley ‘, Jeffrey Smallhorn ’ and Richard D. Rowe ’ Division of Cardiology, Departments of ’ Pediatrics and ’ Pathology, The Hospital for Sick Children. and Departments of Pedratrics and Pntho/ogy, The University of Toronto Faculty of Medicine (Received

5 March 1984; revision accepted

8 November

1984)

Freedom RM, Pelech A, Brand A, Vogel M, Olley PM, Smallhorn J, Rowe RD. The progressive nature of subaortic stenosis in congenital heart disease. Int J Cardiol 1985;8:137-143. Data derived from serial hemodynamic and angiocardiographic investigations on pediatric patients not subjected to intervening intracardiac operations support the view that subaortic stenosis in congenital heart disease tends to be a progressive disorder. Our data are obtained from two groups of patients. The first comprised 22 patients with discrete subaortic stenosis in relative isolation. The second was made up of 19 patients with the fibrous or fibromuscular forms of discrete subaortic stenosis associated with a perimembranous ventricular septal defect. The results from both groups support our initial contention. The progressive character of subaortic stenosis in these two situations illustrates the dynamic nature of congenital heart disease, and the tendency of a changing form and function. (Key words: heart defects; natural history; septal defect; subaortic diaphragmatic shelf)

congenital

heart

disease;

ventricular

Introduction There is now rather extensive clinical and morphological evidence that some congenitally malformed hearts can and do undergo changes in form and function, with profound effects on the natural history of the specific lesion [l]. Spontaneous closure or diminution in size of a perimembranous or muscular ventricular septal Reprint requesrs to: Robert M. Freedom, Toronto, Ontario, Canada M5G 1X8. 0167-5273/85/$03.30

M.D.. The Hospital

0 1985 Elsevier Science Publishers

for Sick Children,

B.V. (Biomedical

555 University

Division)

Avenue.

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defect in isolation [2-61; diminution or closure of an atria1 septal defect within the fossa ovalis [7]; closure or diminution in size of the so-called physiologically advantageous ventricular septal defect [8-lo]; progression of the severity of isolated valvular aortic or pulmonary stenosis [2,11]: the mechanism and incidence of acquired right ventricular outflow obstruction in patients with ventricular septal defect [12]; and the development of hypertrophic obstructive cardiomyopathy among patients with congenital heart defects are but some of the examples of the dynamic nature of congenital heart disease [13-151. There is now little doubt that subaortic stenosis tends to be a progressive disorder [16624]. We wish to focus this report on the progressive character of the discrete form of subaortic stenosis in relative isolation and in its association with ventricular septal defect.

Patient Material Between 1960 and 1983, 22 children with subaortic stenosis and intact ventricular septum and 19 with an additional ventricular septal defect have undergone 2 or more cardiac catheterizations during medical follow-up. Serial investigations were carried out to assess the severity of the outflow tract obstruction and/or change in size of the associated ventricular septal defect. Some aspects of these patients have been briefly reviewed in papers previously published from this institution [12,16,21,24]. Patients with hypertrophic obstructive cardiomyopathy have been excluded.

Group 1: the Progressive Nature of Discrete Subaortic Stenosis Twenty-two patients had undergone serial hemodynamic and angiocardiographic evaluations in the absence of other significant intracardiac pathology prior to operative repair of discrete subaortic stenosis. Sixteen patients were boys (73%) and the remainder girls. Associated anomalies included coarctation in 8 patients (36%) an arterial duct in 5 patients (23%) and mitral valve anomalies in 2 patients (9%). All 8 patients underwent repair of the coarctation of the aorta and ligation of the duct (2 patients) before intracardiac repair. The age range at the initial catheterization was from 1 month to 11.1 years, mean 4.8 years. At the second catheterization the ages ranged from 4 months to 15.1 years, mean 9.2 years. All catheter studies were performed with the patients lightly sedated with demerol, phenerzan, and thorazine. Cardiac outputs were not routinely measured. The pressure gradients were recorded with fluid-filled catheters from a left ventricle to ascending aorta pressure withdrawal. The majority of children had an angiographic appearance of a diaphragm-like shelf, 17 patients (77%) with a minority having either fibromuscular obstruction (3 patients), or tunnel malformation (2 patients). The mean of the resting peak systolic left ventricular outflow tract gradient increased from 22.3 f 20.1 mm Hg to 66.6 + 36.2 mm Hg. Seventeen patients (76%) showed a hemodynamically significant increased gradient (i.e. arbitrarily chosen as

139 diaphragm-

17 pts

flbromuscular ridgem-----m 3 pts

tunnelo-----o 2 pts

6

8 10 12 age m years

14

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Fig. 1. Graph depicting serial change in LVOT gradient forms of discrete subaortic stenosis in isolation.

18

among

22 patients

with the three pathologic

20 mm Hg) while 5 patients (23%) showed no alteration over a mean period of 4.6 years (range 6 months to 12.8 years). The progression of the left ventricular outflow tract gradients with time is shown in Fig. 1. The progressive nature of the subaortic gradient was most evident in the two patients with the “tunnel” malformation. One patient progressed from 0 to 177 mm Hg over a period of 4 months, the other from 30 mm Hg to 71 mm Hg in 3 months. This result was markedly different from the progression seen with the shelf-like diaphragms (40.3 + 34.1 mm Hg over a mean period of 4.9 years - P > 0.05) and fibromuscular ridges (25.3 k 25.0 mm Hg over a mean period of 3.1 years - P = 0.10). Coincident with the increase in pressure gradient, 7 patients (33%) developed a murmur of aortic regurgitation. Three patients developed evidence of aortic regurgitation in the absence of a progressive gradient. Group 2: Ventricular Septal Defect and Subaortic Stenosis We have previously reported 41 patients from this institution with ventricular septal defect and subaortic stenosis (excluding those patients with associated interruption of the aortic arch, atrioventricular septal defect, abnormal ventriculoarterial connexion, and univentricular atrioventricular connexion [24]. Nineteen of these patients underwent serial cardiac catheterizations without intervening intracardiac surgery. The male to female ratio is 2.2 : 1. The mean age at the initial investigation was 18.3 months, ranging from 2 days to 11.1 years. The mean age at the second study was 7.6 years, with an age range from 10 months to 16.8 years. The mean interval between the first and subsequent study was 5.9 years. The mean pressure left ventricular outflow gradient at the initial catheterization was only 9.3 mm Hg,

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Fig. 2. Graph depicting serial change in LVOT gradient among patients with fibrous or fibromuscular forms of subaortic stenosis associated with perimembranous ventricular septal defect. (Reproduced from [24] with permission.)

ranging from O-90 mm Hg. At the second investigation the mean pressure gradient had increased to 35.8 mm Hg ranging from 0 to 110 mm Hg. However, this increment was only observed in 14 of the 19 patients (Fig. 2). In 5 of the patients, no increase in gradient was recorded. The mean pressure gradients of these 14 patients was 48.6 mm Hg, ranging from 10 to 110 mm Hg. The pulmonary to systemic blood ratio at the initial investigations ranged from 1.1 to 3, with a mean of 1.48, and at the second investigation, the mean Qp/Qs was 1.19, ranging from unity to 1.7.

Discussion There is clinical and experimental evidence that physiological significant discrete subaortic stenosis is an acquired lesion [25]. It is rarely identified in neonates and young children and indeed has not been reported in the developing heart. In a study on the Newfoundland dog, Pyle and colleagues concluded that subaortic stenosis developed post-natally on top of an underlying genetic predisposition. The morphogenetic basis remains unknown. Rosenquist et al. have shown increased mitral-aortic separation in patients with discrete subaortic stenosis due to a muscular wedge [27,28]. They suggested this might alter both the angle and the flow pattern at which blood is injected from the left ventricle during a critical period of development. They further speculate that a hemodynamic alteration could cause embryonic cells near the crest of the ventricular septum to accumulate with an eventual potential to differentiate into a fibro-muscular ridge. What is not conjectural is the tendency for the discrete forms of subaortic stenosis to progress in severity. Substantial serial increments in pressure gradients across the left ventricular outflow tract have been documented in this and other reports [11,17,19-231. Yet despite such observations of progression in some of any cohorts of patients, we are cognizant that some patients with trivial pressure gradients will

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remain clinically stable for years. Among those patients who do demonstrate longitudinal increments in pressure gradients, there is little clinical evidence to suggest that the tunnel form of subaortic stenosis evolves from a fibrous or fibromuscular obstruction [29] (although this can happen). We have provided a substantial data base to indicate the progressive nature of subaortic stenosis in association with ventricular septal defect [24]. The serial increase in pressure gradients in these patients could result from firstly an increase in the severity of left ventricular outflow tract obstruction; secondly, diminution in the size of the ventricular septal defect; thirdly, acquisition of right ventricular outflow tract obstructions; or a combination of these three events. Previous scrutiny of the data obtained from these patients suggested to us that progression of the severity of the left ventricular outflow tract obstruction was primarily responsible for the increased pressure gradient [24]. The luxury of longitudinal non-invasive imaging of intracardiac structure and function as now facilitated by cross-sectional echocardiography may clarify those mechanisms responsible for the molding or generation of structural alterations of the left ventricular outflow tract. In this regard, we have already imaged in some neonates and young infants a tiny, subaortic muscular ridge that may well be the harbinger of true subaortic stenosis (Fig. 3). Furthermore, the serial applications of pulsed Doppler-derived velocity shifts may also provide information about hemodynamic progression in these same patients [30-331. This academic “voyeurism” has

Fig. 3. Precordial long axis cut in a neonate demonstrating LA = left atrium: LV = left ventricle; SR = subaortic ridge.

a small

subaortic

ridge.

AOv = aorta;

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set the stage for exciting revelations as the natural history of some congenital cardiac malformations continue to be unraveled. In conclusion, we have provided further data documenting the dynamic nature of congenital heart defects in general. Specifically, our data supports the view that subaortic stenosis tends to be a progressive disorder, both in relative isolation or in association with ventricular septal defect. Despite the tendency of the discrete types of subaortic stenosis to progress in severity, we have been reluctant to make global recommendations in suggesting surgical intervention for patients with trivial gradients. Yet we are cognizant of the expressed concerns of Somerville and her colleagues about the future of patients with small pressure gradients across the left ventricular outflow tract and the possibility of progressive damage to the aortic valve [19]. For these reasons, we lean towards surgical intervention in patients with unequivocal anatomic evidence of left ventricular fibrous or fibromuscular outlet obstruction even in the absence of substantial resting pressure gradients.

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gradients

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stenotic

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by Doppler