Subvalvar aortic stenosis (subaortic stenosis)

INTRODUCTION — Left ventricular outflow tract (LVOT) obstructive lesions account for approximately 6 percent of cases of congenital heart disease in children; in one series, the incidence was estimated to be 6 in 10,000 live births [1,2]. Obstruction may occur at valvar (which is by far the most common), subvalvar, and supravalvar levels.

Subvalvar aortic stenosis (also called subaortic stenosis) will be reviewed here. Valvar and supravalvar aortic stenosis are discussed separately. (See "Valvar aortic stenosis in children".)

Subvalvar aortic stenosis can be induced by a fixed stenosis or may have a dynamic component that is primarily due to the genetic disease hypertrophic cardiomyopathy (previously called idiopathic hypertrophic subaortic stenosis). Only fixed stenosis will be reviewed here; subvalvar obstruction due to hypertrophic cardiomyopathy is discussed separately. (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction".)

EPIDEMIOLOGY — Subvalvar aortic stenosis (AS) is the second most common form of AS. Among children with congenital AS, subvalvar AS accounts for 10 to 14 percent of cases [2,3]. Similar to valvar AS, subvalvar AS is more common in males, who account for 67 to 75 percent of cases [2,3].

Other cardiac malformations occur in 50 to 65 percent of cases [4-6]. One report of 35 patients found the following lesions: patent ductus arteriosus (34 percent), ventricular septal defect (VSD, 20 percent), aortic coarctation (23 percent), pulmonic stenosis (9 percent), and miscellaneous other lesions (14 percent) [4].

Subvalvar AS is seldom encountered in newborns and is rare in infants [4,6]. In clinical practice, subvalvar AS develops and progresses over time so that most consider it an acquired rather than congenital lesion [4,6-8]. In some patients, it is not detected until one to six years after surgical correction of a VSD or aortic coarctation [7,9]. One hypothesis is that an underlying abnormality in left ventricular outflow tract (LVOT) architecture creates turbulence, which then contributes to progressive LVOT thickening, fibrosis, and scarring, with scarring of an otherwise normal aortic valve as well [10]. At least two observations are consistent with a congenital predisposition:

●Among children who undergo surgery for a VSD or aortic coarctation, specific LVOT geometric abnormalities, most notably the angle between the aortic outflow and the long axis of the ventricular septum [11], have been identified on echocardiography that predict the subsequent development of subvalvar AS [9].

●Familial occurrence of subvalvar AS has been described in humans and Newfoundland dogs [12,13], which indicates a genetic predisposition.

ANATOMY — Subvalvar aortic stenosis encompasses a variety of lesions, which can occur alone or in combination. These include a thin membrane (the most common lesion), thick fibromuscular ridge, diffuse tunnel-like obstruction, abnormal mitral valve attachments, and, occasionally, accessory endocardial cushion tissue.

●In the majority of patients, obstruction is caused by a membrane that is attached to the ventricular septum or completely encircles the left ventricular outflow tract (LVOT) (movie 1) [5,14-16]. Its location ranges from immediately below the aortic valve to a point further down into the left ventricle. The aortic valve is usually tricommissural [17]. In some cases, this subaortic tissue has been noted to progressively involve the undersurface of the aortic valve leaflets, limiting mobility and contributing to the LVOT and/or aortic regurgitation. Some degree of muscular ventricular septal hypertrophy is present in up to 75 percent of cases [18].

●Diffuse, "tunnel-like" narrowing of the LVOT is rare and is characterized by marked myocardial hypertrophy and, often, aortic annular hypoplasia [19].

PHYSIOLOGY — As noted above, it has been suggested that subaortic stenosis results from an underlying abnormality in left ventricular outflow tract (LVOT) architecture, with turbulence leading to progressive LVOT fibrosis [4,10]. Significant obstruction of the LVOT leads to ventricular hypertrophy and hyperdynamic function.

Many patients have associated aortic regurgitation (AR). The mechanism is thought to be thickening of the valve leaflets due to trauma from the high velocity jets caused by the subaortic lesion, as well as restricted leaflet motion due to encroaching subvalvar tissue in some patients. In one study of 220 patients with subaortic stenosis, a peak Doppler gradient ≥50 mmHg at diagnosis was a significant predictor of at least moderate AR, while patients with no or trivial AR tended to have thin, mobile valve leaflets [20].

CLINICAL FEATURES — Clinically significant subvalvar aortic stenosis (AS) is an isolated lesion that is rare in newborns and unusual in infants [4]. Patients with mild or moderate obstruction are typically asymptomatic. The lesion is often uncovered during evaluation of other associated cardiac defects. When uncomplicated, it is generally identified when echocardiography is performed for evaluation of a murmur, which is occurring more frequently at earlier ages.

Physical examination — More than one-half of affected patients have a cardiac murmur during the first year of life, which becomes more typical of left ventricular outflow tract obstruction as the patient gets older [5]. Physical examination in fixed subvalvar AS reveals the following features (table 1):

●A characteristic harsh "shrieking" systolic ejection type murmur heard best at the mid-left sternal border. A thrill is sometimes palpable at the same site.

●A preceding ejection click is rare unless a bicommissural aortic valve is also present.

●An early diastolic high frequency murmur of aortic regurgitation is heard in some patients, typically at the right sternal border but also commonly at the left lower sternal border due to the apically directed regurgitant jet.

The physical examination can also help distinguish fixed from dynamic subaortic stenosis in hypertrophic cardiomyopathy (HCM) (table 1). In patients who are able to cooperate with a Valsalva maneuver, the intensity of the murmur typically decreases in fixed subvalvar AS and increases in HCM.

DIAGNOSIS — As noted above, the physical examination can help to distinguish subaortic stenosis from other causes of left ventricular outflow tract (LVOT) obstruction, and echocardiography confirms the diagnosis.

Echocardiography — Echocardiography characterizes the anatomy of the subaortic lesion and is useful to assess dimensions and function of the left ventricle (LV) and integrity of the aortic and mitral valves. Associated congenital lesions and nonobstructive membranes can also be visualized. As echocardiography has become more commonplace, thin nonobstructive membranes and septal protrusions have been found in those without clinically significant subaortic stenosis.

Thin fibrous membranes are typically seen just proximal to the junction of the aortic root with the septum. On echocardiogram, such membranes typically appear to arise from the membranous septum, although they may arise from a thickened muscular ridge slightly further down into the ventricle (movie 2). Attachments to the anterior leaflet of the mitral valve are frequently seen. (See "Echocardiographic evaluation of the aortic valve".)

The degree of obstruction to outflow in subvalvar aortic stenosis (AS) is often difficult to appreciate on the two dimensional echocardiogram, and Doppler examination is indicated. Continuous wave Doppler is used to estimate the gradient and therefore the extent of obstruction across the LVOT. The measurement of the maximum instantaneous gradient by echocardiogram is often higher (as much as 37 percent) than the peak-to-peak gradient at catheterization [21]. Some investigators have noted a high correlation between mean gradient values estimated by Doppler and peak-to-peak LVOT gradients directly measured by catheter [21,22], but in our clinical experience we have not found this to be a consistent finding.

Other tests — Electrocardiogram (ECG) and chest radiography are not diagnostic but are often performed in patients with subvalvar AS. Cardiac catheterization is frequently performed for further elucidation of the anatomy, particularly in patients with multiple levels of obstruction.

Electrocardiogram — The ECG is usually abnormal in subvalvar AS. Although the ECG remains normal in some patients with severe obstruction, the majority have LV hypertrophy with decreased anterior forces and, less often, a strain pattern. Signs of LV hypertrophy are seen in up to one-half of those with mild subaortic stenosis [14].

Chest radiograph — The chest radiograph is often normal. Some patients, including those with mild stenosis, have mild cardiomegaly or LV prominence. Dilation of the ascending aorta is uncommon [14].

Cardiac catheterization — Cardiac catheterization is frequently performed to further elucidate the mechanism and extent of subaortic obstruction, especially when multiple levels of obstruction are suspected. We do not usually perform catheterization in patients with simple membranes or ridges.

Catheterization provides both hemodynamic and anatomic data, such as the gradient across the valve, measurement of cardiac output, and estimates of the degree of aortic regurgitation. Associated lesions, such as aortic coarctation, can be defined. However, fine anatomic details of nearby structures, such as the mitral valve apparatus, are better shown by echocardiography.

COURSE — Patients with subvalvar aortic stenosis (AS) often have rapidly progressive obstruction in infancy and early childhood [6,8,23,24]. However, the disorder may remain stable for years, and some adults have only mild obstruction, especially those who do not have associated congenital heart defects [4,25-27].

One report described the course of subvalvar AS in 83 patients (age 11 months to 25 years) who were followed for a median of 6.1 years [23]. Additional cardiac malformations were present in 47 (57 percent), and 14 (17 percent) had significant noncardiac lesions. Surgery was performed in 74 patients at a median age of 12 years. The following findings were noted:

●The left ventricular outflow tract (LVOT) gradient increased in 25 of 26 patients who had cardiac catheterization more than once before surgery.

●Aortic regurgitation (AR) that was usually mild was present before surgery in 55 percent and was absent or mild in most patients after surgery.

●Infectious endocarditis occurred in 12 percent but did not occur when the gradient was decreased to <80 mmHg after surgery unless there were other residual lesions.

Not surprisingly, progression of subvalvar AS appears to be slower in patients who do not present until adulthood, since they have presumably been selected out as having less severe disease. This was illustrated in a series of 134 patients (mean age 31 years) with discrete subaortic stenosis [26]. The mean LVOT gradient increased from 39.2 to 46.8 mmHg over five years, a rate of change of 2.25 mmHg per year [26]. Moderate to severe AR was present in only 19 percent, and significant progression of AR was not seen. A multicenter study of 149 adults (median age 20 years) with unoperated subvalvar AS demonstrated similar findings with a median follow-up of 6.3 years; baseline LVOT gradient was 32 mmHg and increased by 0.8±0.1 mmHg/year [27]. Baseline LVOT gradient and age were not associated with more rapid progression, although patients with other congenital heart defects tended to have more rapid progression. Mild AR was common (present in 58 percent) but did not progress over time.

MANAGEMENT

Surgical repair — Definitive therapy for subvalvar aortic stenosis (AS) consists of surgical correction of the obstruction, which may range from simple membrane removal to extensive ring resection, with or without myectomy, to a Konno procedure.

Timing — Because of the high rate of recurrence, the timing of surgery, especially in the first decade of life, is controversial. Recommendations range from early operation to longer periods of observation, dependent upon patient characteristics [15,28-32].

Our approach to the timing of surgery in patients with subaortic stenosis is as follows:

●We defer surgery in the first decade of life if the obstruction is moderate or less (ie, maximum instantaneous Doppler gradient ≤50 mmHg) and regurgitation is no more than trivial. This peak Doppler gradient is similar to the threshold mean Doppler gradient for surgical intervention of >30 mmHg advocated by another large referral center [33]. Others recommend surgical intervention in any patient who has an left ventricular outflow tract (LVOT) gradient ≥50 mmHg and in infants or young children (up to school age) with a well-defined gradient ≥30 mmHg [34].

●Children with an LVOT gradient <30 mmHg and no significant left ventricular hypertrophy are followed closely for progression, especially in the first several years of life. We usually see toddlers at least twice each year and more often if there is evidence of progression. Older children are followed at less frequent intervals. We perform echocardiography for any change in symptoms or the examination.

●An older child with a gradient <30 mmHg may be followed medically until there is significant progression of the obstruction documented by echocardiography or catheterization, or definite progression of aortic regurgitation (AR) to at least a mild degree. The inexactness of predictions of gradient by Doppler must always be considered in the decision making process. We often perform catheterization in children with borderline values or with multiple levels of obstruction.

●Unoperated adults with stable gradients <50 mmHg and without significant left ventricular (LV) hypertrophy are also followed closely, since some of these patients will eventually require surgery.

●"Prevention" of AR alone is not a criterion for surgery, although, as noted below, the appearance and worsening of regurgitation is frequently used as a criterion for surgery.

The development of significant AR is considered an indication for surgery because it is an acquired lesion, although the extent rarely progresses to or beyond moderate in young children. Significant AR appears to be more common in postoperative patients and following balloon dilation attempts [20,26,31].

The recommendation to observe patients with LVOT gradients <30 mmHg is supported by a large retrospective study of 313 children diagnosed with subaortic stenosis between 1975 and 1998 at a single Canadian tertiary center [33]. Surgery was performed in 159 (51 percent), of whom 23 (14 percent) required reoperation. Patients who underwent surgical resection more commonly had a mean LVOT gradient by echocardiogram Doppler >30 mmHg, which was associated with accelerated gradient progression and progressive AR. Of the 238 patients with echographic data available who had a mean Doppler LVOT gradient <30 mmHg, freedom from intervention was 49 percent at 15-years follow-up.

This study must be interpreted carefully due to its retrospective design, the lack of standardized quantitative assessment of AR by echocardiogram, the lack of adequate echo data in 75 patients (24 percent of the study cohort), and the fact that this was a single institution with adoption of the mean LVOT gradient of >30 mmHg as an indication for operation. However, despite these limitations, these results nevertheless confirm that a sizeable subset of patients with subaortic stenosis will have stable gradients for years. In this study, the mean Doppler LVOT gradient >30 mmHg was a powerful distinguishing tool for both the risk of progression of subaortic obstruction and worsening AR [33].

Earlier investigators also noted that patients vary in their rates of progression, with some remaining stable for long periods [4,25,26], with slower progression in patients presenting as adults, presumably due to selection for less severe disease [26]. Progression of AR was also noted to be more common in patients with mean Doppler LVOT gradients >30 mmHg [28].

Method of correction — In contrast to valvar AS, subvalvar AS does not respond to balloon dilation. Thus, the appropriate intervention for patients with significant obstruction is surgical resection of the subvalvar membrane or fibrous crescent, with myectomy for those with significant muscular or tunnel-like obstruction [15,34,35]. For patients with diffusely narrow LVOTs, the Konno procedure and its modifications, which involve incision of the ventricular septum and patch augmentation of the LVOT, may be necessary.

Outcome — Mortality following surgery for subvalvar AS is very low [15,36]. In a study of 155 patients who underwent subvalvar AS resection at a single institution between 1984 and 2009 and were followed for a median of 10.9 years, survival at 10 and 20 years was 98.6 and 86.3 percent, respectively [36].

Recurrent obstruction occurs in 20 to 30 percent of patients following surgery, and reoperation is required in 15 to 20 percent [35-40]. Reported risk factors for recurrence include younger age at initial surgery, closer lesion proximity to the aortic valve (<7 mm), peak LV outflow Doppler gradient ≥60 mmHg, and intraoperative peeling of the membrane from the aortic or mitral valves [15,36,40].

The reported rate of reoperation was considerably lower in one report when surgery was performed when the peak LVOT gradient was ≤40 mmHg (0.9 versus 6.5 percent per year in patients with a higher gradient), as was the need for concomitant repair of the aortic valve (20 versus 49 percent), although this may reflect differences in the substrate rather than timing of the surgery alone [15]. However, the median age was only six years, follow-up was only six years, and peak gradients were calculated rather than measured in some patients [15]. Indeed, many centers would not recommend surgery for peak gradients <40 mmHg alone, as many remain stable for many years. (See 'Timing' above.)

The recurrence risk for adult patients following initial surgical resection had previously been thought to be low, based upon limited data from small, single-center series. However, in a large (313 patients) multicenter study with a median duration of follow-up of 12.9 years, 26 percent of patients required reoperation during the follow-up period of the study [41]. In this cohort, nearly all patients were noted to have adequate surgical relief (median 76 mmHg preoperatively to 15 mmHg postoperatively) and there was an overall increase in the gradient of 1.3 mmHg per year. Mild AR was present in most patients (68 percent) but generally did not progress over time. Predictors for reoperation included female sex (hazard ratio [HR] 1.53, 95% CI 1.02-2.30) and progression of left ventricular outflow tract gradient (HR 1.45, 95% CI 1.31-1.62). In this study, additional myectomy did not reduce the risk for reoperation but increased the risk of complete heart block requiring pacemaker (8.1 versus 1.7 percent of patients).

In addition to recurrent obstruction, reported postoperative complications that occurred primarily in earlier surgical case series included mitral valve damage, AR, ventricular septal defect creation, or bundle branch or complete heart block. In one single-center case series of 185 patients undergoing subaortic stenosis surgery, 11 percent developed permanent complete heart block requiring pacemaker implantation [42]. Risk factors included more complex subaortic obstruction and more aggressive surgical resection techniques.

In earlier case series, complications, such as high residual gradients and death, were also more frequently seen in the rare tunnel-like obstruction than in simple membrane resection [35]. However, in a case series of 46 patients with complex and tunnel-like subaortic stenosis, there were no deaths, and only two patients developed recurrent obstruction over a median three-year follow-up [43].

Endocarditis prophylaxis — In the 2007 American Heart Association guidelines, antibiotic prophylaxis to prevent bacterial endocarditis is no longer recommended in patients with subvalvar AS, except in those with a prior history of endocarditis or with a repair that required prosthetic material or device. In the latter, antibiotic prophylaxis is recommended for the first six months after repair unless a residual defect is present, in which case prophylactic antibiotics are continued beyond the six-month period. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

SUMMARY AND RECOMMENDATIONS — Subvalvar aortic stenosis (AS) is the second most common form of AS.

●Subvalvar AS is rare in newborns and infants. It develops and progresses over time so that most experts in the field consider it an acquired rather than a congenital lesion. It has been proposed that subvalvar AS is due to progressive left ventricular outflow tract (LVOT) thickening and scarring due to turbulence caused by an underlying abnormality in LVOT architecture. (See 'Epidemiology' above and 'Physiology' above and "Valvar aortic stenosis in children".)

●A variety of lesions can cause subvalvar AS, including a thin membrane (most common), thick fibromuscular ridge, diffuse tunnel-like obstruction, abnormal mitral valve attachments, and occasionally, accessory endocardial cushion tissue. (See 'Anatomy' above.)

●Patients with mild or moderate obstruction are typically asymptomatic. The lesion is often uncovered during evaluation of other associated cardiac defects. When uncomplicated, it is generally identified when echocardiography is performed for evaluation of a murmur. More than one-half of affected patients have a harsh systolic ejection murmur heard best at the midleft sternal border. Many patients also have associated aortic regurgitation (AR). (See 'Clinical features' above.)

●The diagnosis of subvalvar AS is made by echocardiography (movie 1 and movie 2). Electrocardiogram and chest radiography are not diagnostic but are often performed in patients with subvalvar AS. Cardiac catheterization is frequently performed to provide more information regarding the anatomy and the hemodynamic effects of the lesion, particularly in patients with multiple levels of obstruction. (See 'Diagnosis' above and "Valvar aortic stenosis in children".)

●The clinical course of subvalvar AS varies from stable asymptomatic disease to rapidly progressive obstructive severe disease. (See 'Course' above and "Valvar aortic stenosis in children".)

●The definitive treatment for subvalvar AS is surgical correction of the obstruction. Recommendations for the need and timing of surgery vary because of a high rate of recurrence. (See 'Timing' above and 'Method of correction' above.)

●In our practice, we use the following management approach (see 'Management' above and 'Timing' above):

•We defer surgery in the first decade of life if the obstruction is moderate or less (maximum instantaneous Doppler gradient ≤50 mmHg or mean LVOT gradient <30 mmHg) and regurgitation is no more than trivial.

•Patients with more severe obstruction or with progressive AR are surgically corrected.

•Children with a LVOT gradient <30 mmHg and no significant left ventricular hypertrophy are followed closely for progression of obstruction.

●Mortality following surgery for subvalvar AS is very low. Recurrent obstruction occurs in 20 to 30 percent of patients following surgery, and reoperation is required in 15 to 20 percent. (See 'Outcome' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge John Keane, MD, who contributed to an earlier version of this topic review.