Aortic regurgitation in children

INTRODUCTION — Aortic regurgitation (AR) is a common finding in children undergoing echocardiography. It rarely occurs as an isolated lesion since it is usually associated with aortic stenosis (AS) or a ventricular septal defect (VSD). The latter disorders are discussed separately. (See "Valvar aortic stenosis in children" and "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis".)

PHYSIOLOGY — All forms of AR produce a similar hemodynamic abnormality. The inability of the aortic valve leaflets to remain closed during diastole results in a portion of the left ventricular (LV) stroke volume leaking back from the aorta into the LV. The added volume of regurgitant blood produces an increase in LV end-diastolic volume. According to Laplace's law, the increase in LV end-diastolic volume causes an elevation in wall stress. The heart responds with compensatory myocardial hypertrophy, referred to as eccentric LV hypertrophy. Eccentric LV hypertrophy is characterized by elevated LV mass, but normal mass-to-volume ratio, and returns wall stress towards a normal level [1].

The combination of hypertrophy and chamber enlargement raises the total stroke volume. The net effect is that forward stroke volume and, therefore, cardiac output are initially maintained despite the regurgitant lesion. Although the LV volume is increased, end-diastolic pressure is normal due to an increase in ventricular compliance. Thus, the heart initially adapts well to chronic AR, functioning as a very efficient and compliant high-output pump.

Severe AR results in increased end-diastolic and end-systolic volumes. When compensatory eccentric hypertrophy eventually fails to maintain normal wall stress in the face of increasing volumes, systolic function becomes impaired [1]. Without intervention, progressive LV dysfunction develops. Reduced aortic diastolic pressures from excessive runoff, especially during exercise, may impair coronary perfusion. Increased left atrial pressure may lead to pulmonary edema. (See "Clinical manifestations and diagnosis of chronic aortic regurgitation in adults".)

ETIOLOGY — AR rarely occurs as an isolated lesion. There are many etiologies of AR, including the following [2]:

●Associated with aortic stenosis (AS) and/or bicuspid aortic valve:

•Bicuspid aortic valve is a common cause of AR. (See "Valvar aortic stenosis in children".)

•AR commonly occurs following surgical or transcatheter intervention for AS. Among patients with congenital valvar AS who are treated with transcatheter balloon aortic valvulotomy (BAV), most have new or increased AR that, in one report, was moderate to severe in 13 percent after the procedure and in 38 percent at almost four years [3]. The risk is increased in patients undergoing repeat BAV. (See "Subvalvar aortic stenosis (subaortic stenosis)".)

•AR is also common in children with subaortic stenosis. (See "Valvar aortic stenosis in children".)

●Associated with other congenital heart defects, including:

•Ventricular septal defect (VSD; typically membranous or subpulmonary), in which AR may occur due to prolapse of an aortic leaflet through the defect. (See "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis".)

•Tetralogy of Fallot. (See "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis".)

•Truncus arteriosus. (See "Truncus arteriosus".)

●Connective tissue disorders, such as Marfan syndrome, Loeys-Dietz, and Ehlers-Danlos syndromes. However, as described below, AR in this setting is more common in adults in association with progressive aortic root dilation. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders" and "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes".)

●Other genetic syndromes, such as Turner syndrome and osteogenesis imperfecta. (See "Clinical manifestations and diagnosis of Turner syndrome", section on 'Aortic valve disease and coarctation' and "Osteogenesis imperfecta: An overview".)

●Acquired infectious causes, such as infectious endocarditis or rheumatic heart disease (the latter is uncommon in developed countries). (See "Infective endocarditis in children" and "Clinical manifestations and diagnosis of rheumatic heart disease".)

PHYSICAL EXAMINATION — The physical examination in children with AR is often subtle because most have mild disease. In addition, some of the classic findings in adults are seldom found in children, even in those with moderate to severe AR. Nevertheless, it is useful to review the classic findings that are seen in more severe disease because they can often establish the clinical diagnosis.

Pulses — Both examination of the peripheral pulses and auscultation of the heart are particularly important. The increased stroke volume results in abrupt distension of the peripheral arteries and an elevation in systolic pressure. Regurgitation back into the left ventricle (LV) then leads to a rapid decline in pressure, with quick collapse of the arteries, and a low diastolic pressure that can fall below 30 mmHg in severe disease.

The net effect is a wide pulse pressure, which is manifested on examination as a "water hammer" or Corrigan pulse. This finding may be best appreciated by palpation of the radial or brachial arteries (exaggerated by raising the arm) or the carotid pulses. (See "Examination of the arterial pulse", section on 'Water hammer pulse'.)

Other findings are associated with a hyperdynamic pulse:

●De Musset sign – A head bob occurring with each heartbeat

●Traube sign – A pistol shot pulse (systolic and diastolic sounds) heard over the femoral arteries

●Duroziez sign – A systolic and diastolic bruit heard when the femoral artery is partially compressed

●Quincke pulses – Capillary pulsations in the fingertips or lips

●Mueller sign – Systolic pulsations of the uvula

●Becker sign – Visible pulsations of the retinal arteries and pupils

●Hill sign – Popliteal cuff systolic pressure exceeding brachial pressure by more than 60 mmHg

Exaggerated or bounding pulses and these physical signs are not specific for AR, since they can be seen in any condition associated with a marked increase in stroke volume, other aortic runoff lesions, or a hyperdynamic circulation. Causes of a hyperdynamic circulation include anemia, fever, thyrotoxicosis, large arteriovenous fistula, patent ductus arteriosus, and severe bradycardia.

The combination of LV enlargement and forceful systolic function results in the apical impulse being displaced laterally and inferiorly as well as being diffuse and hyperdynamic. A prominent pulsation (and occasionally a thrill) may be felt at the sternal notch due to concurrent dilatation of the ascending aorta.

Cardiac auscultation — Chronic AR is associated with changes in the heart sounds and a distinctive murmur. The heart sounds typically have the following characteristics (see "Approach to the infant or child with a cardiac murmur" and "Common causes of cardiac murmurs in infants and children"):

●First heart sound (S1) may be soft, often reflecting a long PR interval

●An early ejection click following S1 may be present in the setting of bicuspid aortic valve (movie 1)

●Second heart sound (S2) is variable; it may be soft, absent, or single

●A2 is often soft or absent, while P2 may be normal but obscured by the diastolic murmur

●A systolic ejection sound may be due to abrupt aortic distension caused by the large stroke volume

●A third heart sound (S3 gallop) is heard when LV function is severely depressed

Mild or more AR is invariably accompanied by a diastolic murmur. In a review of the literature, the presence of an early diastolic murmur, as heard by a cardiologist, was the most useful finding for establishing the presence of AR [4].

The diastolic murmur of AR begins immediately after A2 (movie 2 and movie 3 and movie 4). It is high pitched, often blowing in quality, and may be sustained in intensity or decrescendo. It may be soft and barely audible, often appreciated only when the patient is sitting up, leaning forward, and holding his or her breath in expiration.

The intensity of the murmur does not correlate well with the severity of AR. However, the timing and duration of the murmur may be helpful.

●In mild AR, the murmur occurs only in early diastole and is blowing.

●As the regurgitation becomes more severe, the murmur extends through more of diastole, may become holodiastolic, and is often rougher in quality.

●In very severe regurgitation with ventricular decompensation, the murmur may become soft or even absent. This change in character reflects the near equivalence of aortic diastolic and LV end-diastolic pressures, which markedly diminishes regurgitant flow. A similar situation can occur when AR is acute and the LV end-diastolic pressure is very high.

The site at which the murmur is best heard varies with the cause. The murmur is heard best along the left sternal border, at the third and fourth intercostal space, when AR is due to valvular disease. In contrast, abnormalities of the aortic root produce murmurs that are best heard at the right sternal border and apex.

A systolic murmur can be heard in many patients. It typically resembles the ejection type of murmur heard in aortic stenosis (AS), ie, a crescendo-decrescendo harsh murmur beginning after S1. This murmur does not necessarily reflect concurrent AS, since the increased ejection rate and large stroke volume across the aortic valve can lead to a "functional" stenosis. However, as noted above, AR often occurs in association with other cardiac lesions that produce a systolic murmur, such as valvar AS or ventricular septal defect (VSD). (See "Valvar aortic stenosis in children".)

A second type of diastolic murmur (the Austin Flint murmur) may also be appreciated. This murmur is a mid- to late-diastolic rumble, heard at the apex. It is the result of antegrade turbulent diastolic blood flow from the left atrium competing with the retrograde regurgitant flow from the aorta. The latter impinges upon the anterior mitral valve leaflet opening, causing some functional stenosis. The murmur may be confused with that of mitral stenosis. Distinguishing features from mitral stenosis include the absence of both a loud S1 and an opening snap of the mitral valve. (See "Auscultation of cardiac murmurs in adults" and "Auscultation of heart sounds".)

DIAGNOSIS — Echocardiography is used to diagnose and evaluate the degree of regurgitation. It also evaluates the anatomy of the lesion, identifies any accompanying disorders, and assesses ventricular function (movie 5 and figure 1 and movie 6).

Serial echocardiographic assessments are used to guide management, including timing of aortic valve surgery, if necessary [5]. (See 'Monitoring' below.)

Cardiac magnetic resonance imaging (CMR) is a useful adjunctive imaging test, particularly for patients with poor acoustic windows or those with equivocal findings on echocardiography. CMR provides accurate measurement of the degree of regurgitation (regurgitant fraction), left ventricle (LV) chamber volumes, and systolic function. In a series of adult patients with chronic AR, CMR resulted in the reclassification of AR severity in some patients compared with echocardiography and had the potential to add important diagnostic and prognostic information [6].

Other noninvasive tests reveal abnormalities but provide only adjunctive additional information to echocardiography. The chest radiograph is often remarkable for a prominent ascending aorta. An enlarged LV may be seen with significant regurgitation. With moderate or greater regurgitation, the electrocardiogram frequently reveals LV hypertrophy and, with advanced disease, ST-T changes due to ischemia. Cardiac catheterization is usually unnecessary; it is used only to evaluate associated lesions.

CLINICAL COURSE — Few studies are available on the clinical course of AR. Most cases of AR are mild, symptoms are unusual, and the patient remains stable for many years. Progression occurs in some patients, while infective endocarditis may cause acute progression.

The natural history of isolated congenital AR was described in seven children who did not have Marfan syndrome [2]. The diagnosis was made in infancy in five. Three patients were asymptomatic through follow-up at 8, 10, and 20 years, while four required valve replacement at age 3, 10, 15, and 20 years for progressive severity.

Dilatation of the aorta is common in children with Marfan syndrome and other connective tissue disorders such as Loeys-Dietz and Ehlers-Danlos syndromes and may progress with time. One report followed 52 patients with Marfan syndrome through childhood and adolescence [7]. Aortic root dilation was present in 43 and AR in 13 (25 percent). The AR was diagnosed at a mean age of 14.6 years (none before five years) and was initially mild in all but one patient. At a mean follow-up of 7.9 years, aortic abnormalities progressed in 13, requiring aortic surgery in 10 for aortic root dilation or dissection. There is further progression in adulthood [8]. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders".)

Dilation of the aortic root and/or the ascending aorta are also frequently encountered in patients with bicuspid aortic valve and can similarly contribute to progressive AR. (See "Clinical manifestations and diagnosis of bicuspid aortic valve in adults", section on 'Aortic regurgitation'.)

As noted above, AR can occur in association with ventricular septal defect (VSD) (see 'Etiology' above). One report described long-term follow-up (1946 to 1989) in 92 patients who had VSD and audible AR [9]. Onset of AR occurred at a median age of 5.3 years. The aortic valve was bicuspid in 10 percent and tricuspid in the remainder. Surgery was performed in 72 patients, including VSD closure and valvuloplasty in 50, VSD closure and aortic valve replacement in 15, and VSD closure alone in seven. (See "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis", section on 'Natural history'.)

MONITORING — Children with AR should be followed by a pediatric cardiologist at least yearly to monitor for the development of symptoms, increasing left ventricular (LV) dilation, or worsening LV systolic function. More frequent evaluation is recommended in patients with moderate to severe AR or for those in whom the rate of change in their regurgitation is unclear.

The majority of children remain asymptomatic, even with severe AR. As a result, serial echocardiographic assessment, including measurement of ventricular dimensions, volumes, and function, is crucial in determining the timing of surgical repair. As discussed above, monitoring with cardiac magnetic resonance imaging (CMR) provides more accurate measurement of the degree of regurgitation, particularly in patients with poor acoustic windows.

Patients who develop symptoms of heart failure, develop signs or symptoms of ischemia with exertion, or have a decline in LV function are generally referred for surgical intervention, as discussed below. (See 'Surgery' below.)

Children with AR do not require endocarditis prophylaxis. This issue is discussed separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

MANAGEMENT

Medical therapy — For children with any of the following, we suggest vasodilator therapy:

●Moderate or greater AR

●Symptomatic AR

●AR with concurrent hypertension

Angiotensin-converting enzyme (ACE) inhibitors (eg, captopril, enalapril) are generally the first-line choice for vasodilator therapy in this setting since they are well tolerated in children. Nifedipine or hydralazine are second-line options.

The use of ACE inhibitors in this setting is supported by limited observational data in children and by indirect evidence from studies in adults with chronic AR. Limited pediatric data suggest ACE inhibitors may result in partial reversal of left ventricular (LV) dilation and hypertrophy. In a report of 20 children (mean age 14.3 years) with asymptomatic chronic AR who were treated with captopril for one year, the mean reduction in regurgitant fraction was 28 percent [10]. Captopril therapy was also associated with significant reductions in LV end-diastolic and end-systolic dimensions, end-diastolic and end-systolic indexes, and LV mass index. There are no published data supporting the long-term use of vasodilators in patients with less severe AR in the absence of clinically significant LV enlargement.

The evidence supporting use of vasodilator therapy in adults with chronic AR is discussed separately. (See "Natural history and management of chronic aortic regurgitation in adults", section on 'Pharmacologic therapy'.)

Surgery — Indications for aortic valve repair or replacement include:

●Symptoms of heart failure

●Signs or symptoms of ischemia with exertion

●First indication of a decline in LV systolic function

Unlike in adults, ventricular volumes have not been incorporated into the guidelines for aortic valve surgery in children. This is because threshold values for Z-scores of LV short-axis dimensions or LV volumes as an indication for surgery have not been established in pediatric patients [11].

The choice of procedure (valve repair or replacement) depends upon the cause of AR and the possible presence of other anatomic abnormalities.

●Valve repair – Valve repair is effective for AR caused by balloon aortic valvulotomy (BAV) in children with congenital aortic stenosis (AS). Valve repair can also be used for truncal valves or prolapse of one or more cusps associated with a ventricular septal defect (VSD) [9,12-14].

In one report, 21 patients ages 9 months to 15 years had surgical repair of AR following BAV [12]. The extent of AR, LV end-diastolic dimension, and proximal regurgitant jet/aortic annulus diameter ratio were significantly decreased following repair. All patients survived and were asymptomatic at an average follow-up of 30 months. None required reoperation for late failure, although 20 percent needed reintervention by three years.

Techniques for aortic valve repair continue to evolve and improve. In particular, "bicuspidization" reconstruction techniques may be associated with better long-term results. In a series of 18 patients who underwent symmetric bicuspidization aortic valve repair at the author's institution, 88 percent were free of moderate or worse AR at 21 months follow-up versus 43 percent in patients with other types of reconstruction [15]. Longer-term follow-up of this and other novel techniques are necessary before this approach can be used routinely.

●Valve replacement – Aortic valve replacement usually requires a mechanical prosthesis and systemic anticoagulation. Bioprosthetic valves reduce the need for anticoagulation but have a failure rate in children as high as 20 percent due to valve degeneration and progressive calcification [16,17]. A promising novel technique, known as the Ozaki procedure, involves replacing all three leaflets with pericardium [18,19]. Variations of this technique that include single-leaflet replacements have been described. A small case series in pediatric patients showed encouraging early results [19]. In a study from our center including 57 patients (making it the pediatric largest series to date) who underwent three-leaflet Ozaki repair, there was no early mortality or conversion to aortic valve replacement [20]. Freedom from moderate AR at a median follow-up of eight months was 96 percent. However, longer follow-up studies are necessary before this approach can be routinely recommended.

●Ross or Ross/Konno procedure – An alternative to valve replacement with a mechanical valve or bioprosthesis is the Ross or Ross/Konno procedure [21-23]. With this procedure, the pulmonary valve is transplanted to the aortic position and a homograft conduit is implanted from the right ventricle to the pulmonary artery. Use of this technique has been limited by the high rates of failure of the pulmonary autograft in the aortic position, typically related to neo-aortic root dilation and progressive neo-AR, as well as deterioration of the right heart homografts.

Aortic valve repair and replacement and the Ross procedure in children are discussed in greater detail separately. (See "Subvalvar aortic stenosis (subaortic stenosis)".)

SUMMARY AND RECOMMENDATIONS

●Causes – Aortic regurgitation (AR) is a common finding in children undergoing echocardiography. It rarely occurs as an isolated lesion. AR is most commonly associated with bicuspid aortic valve, aortic stenosis (AS; particularly in children who have undergone balloon valvotomy), or a ventricular septal defect (VSD). AR also can be seen in patients with Marfan syndrome and other connective tissue disorders, genetic disorders (eg, Turner syndrome and osteogenesis imperfecta), other congenital heart defects (eg, tetralogy of Fallot, truncus arteriosus), and acquired infections such as endocarditis or rheumatic heart disease. (See 'Etiology' above.)

●Physical findings – The physical examination varies depending upon the degree of AR. The classical findings of AR consist of wide pulse pressure, lateral and inferior displacement of a diffuse and hyperdynamic apical pulse, and the presence of a high-pitched diastolic murmur (which is often blowing in quality) (movie 2 and movie 3 and movie 4). (See 'Physical examination' above.)

●Diagnosis – The diagnosis of AR is made by echocardiography. Serial echocardiographic assessments are used to guide management, including the need and timing of aortic valve surgery. Cardiac magnetic resonance imaging (CMR) is a useful adjunctive imaging test, particularly in patients with poor acoustic windows or those with equivocal findings on echocardiography. (See 'Diagnosis' above.)

●Clinical course – Most pediatric cases of AR are mild, asymptomatic, and remain stable over many years. In children with bicuspid aortic valve or connective tissue disorder (eg, Marfan syndrome), AR may be associated with dilatation of the aorta, which can progress over time. (See 'Clinical course' above.)

●Management – Children with AR should be followed yearly by a pediatric cardiologist for the development of symptoms, increasing left ventricular (LV) dilation, or worsening LV systolic function. More frequent evaluation is recommended in patients with moderate to severe AR or for those in whom the rate of change in their regurgitation is unclear. (See 'Monitoring' above.)

•Medical management – For children with moderate or greater AR, symptomatic AR, and/or AR associated with hypertension, we suggest vasodilator therapy (Grade 2C). We suggest an angiotensin-converting enzyme (ACE) inhibitor (eg, captopril or enalapril) rather than other agents (Grade 2C). This is because ACE inhibitors are usually are well tolerated in children. Nifedipine or hydralazine are second-line options. (See 'Medical therapy' above.)

•Surgical management – For children with signs or symptoms of heart failure, evidence of ischemia with exertion, or decline in LV systolic function, we suggest surgical valve intervention (ie, valve repair or replacement) (Grade 2C). The choice between repair and replacement depends upon the cause of AR and the presence of other anatomic abnormalities. (See 'Surgery' above.)

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