Clinical manifestations and diagnosis of pulmonic stenosis in adults

INTRODUCTION — Stenosis of the pulmonary valve is a relatively common congenital defect, occurring in approximately 7 percent of children with congenital heart disease [1-3]. There is a slight female predominance, and familial occurrence has been reported in 2 percent of cases in the absence of a genetic disorder [4].

Pulmonic stenosis in children is usually associated with a benign clinical course, and excellent treatment options are available for severe cases. Thus, there is a high rate of survival into adulthood. This topic will review the pathophysiology, clinical manifestations, and diagnosis of pulmonic stenosis in adults. The natural history and treatment of this disorder in adults are discussed separately. (See "Pulmonic valve stenosis in adults: Management".)

PATHOPHYSIOLOGY — Pulmonic stenosis can occur at three locations:

●Valvular

●Subvalvular

●Supravalvular

Valvular pulmonic stenosis — A tricuspid valve is present in patients with typical valvular pulmonic stenosis, with varying degrees of fibrous thickening and fusion of the commissures [5]. The restricted leaflets typically have a conical or dome-shaped appearance during systole, with an orifice in a shape similar to a "fish mouth." Calcification of the stenotic valve is rare [6]. Bicuspid pulmonic valves have been described but occur in less than 20 percent of cases [7]. In addition to pulmonary stenosis, there may be pulmonary artery dilation as a consequence of underlying connective tissue abnormality and eccentric flow due to the stenotic valve. If pulmonic valve stenosis is sufficiently severe, right ventricular hypertrophy may occur over time. Right ventricular chamber enlargement is not expected in patients with pulmonic stenosis unless there is associated pulmonary regurgitation or longstanding systolic dysfunction.

A small proportion of patients (particularly those with Noonan syndrome) have a markedly dysplastic valve, with prominent leaflet thickening, little commissural fusion, and often a hypoplastic annulus and proximal pulmonary artery [8,9]. These valves are often severely stenotic and usually require intervention during childhood.

Most patients with congenital pulmonic stenosis do not have significant pulmonary regurgitation; mixed pulmonary stenosis and pulmonary regurgitation is more commonly seen with acquired pulmonary valve disease or after intervention for pulmonic stenosis. (See "Pulmonic valve stenosis in adults: Management", section on 'Management of postvalvotomy PR'.)

Associated conditions — Valvular pulmonic stenosis is most commonly an isolated lesion. In a minority of cases it is associated with other conditions including the following:

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

●Congenital rubella syndrome [10]. (See "Congenital rubella", section on 'Clinical features'.)

●Noonan syndrome. (See "Causes of short stature", section on 'Noonan syndrome'.)

●Acquired pulmonic stenosis is most often due to carcinoid syndrome [11]. (See "Carcinoid heart disease".)

Subvalvular pulmonic stenosis — Primary fibromuscular narrowing limited to the right ventricular outflow tract is an extremely rare phenomenon that is probably part of the spectrum of illness associated with a double-chambered right ventricle [12]. By comparison, varying degrees of secondary outflow tract narrowing are commonly seen as part of the overall muscular hypertrophy of the right ventricle induced by pulmonic stenosis. This secondary obstruction often regresses following valvotomy or valvuloplasty [13]. (See "Pulmonic valve stenosis in adults: Management".)

Right ventricular outflow tract obstruction at any level is one of the cardinal features of tetralogy of Fallot. (See "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis".)

Supravalvular pulmonic stenosis — Isolated or multiple areas of narrowing of the main pulmonary artery or branches may occur. It is rare as a de novo finding in adults but can be seen in children either as part of another congenital defect or as an isolated abnormality. Right ventricular pressure overload is recognized by echo Doppler or catheterization, and computed tomography of the pulmonary arteries or pulmonary artery angiography usually demonstrates multiple focal or diffuse areas of stenosis. When isolated, it occurs most often at the left pulmonary artery takeoff, presumably due to changes related to the insertion of the ductus arteriosus. Balloon pulmonary angioplasty or stent placement may offer these patients successful short-term reduction in right ventricular hypertension and alleviation of symptoms.

Pulmonary arterial stenosis often occurs in association with other cardiac or noncardiac congenital defects. These include tetralogy of Fallot and the congenital rubella syndrome as well as rarer disorders such as Williams syndrome, Noonan syndrome, Alagille syndrome, and LEOPARD syndrome. Branch pulmonary stenosis are a potential sequelae of prior Blalock-Thomas-Taussig shunts (commonly called Blalock-Taussig shunt) and both main and branch pulmonary stenosis may result from the arterial switch repair of transposition of the great arteries. (See "D-transposition of the great arteries (D-TGA): Management and outcome".)

CLINICAL MANIFESTATIONS — Survival into adulthood is common in patients with pulmonic stenosis, even in the absence of surgical or percutaneous intervention. However, fibrous thickening and rarely calcification of the valve with age may result in decreased valve mobility and increased obstruction. Thus, the patient who is initially asymptomatic may begin to experience symptoms that vary from mild exertional dyspnea to signs and symptoms of right heart failure, depending upon the severity of obstruction and the degree of myocardial compensation. Moderate to severe obstruction may lead to an inability to augment pulmonary blood flow during exertion, resulting in exercise-induced fatigue, dyspnea, syncope, or chest pain. Diastolic right ventricular dysfunction as a consequence of hypertrophy may also contribute to symptoms but is more difficult to accurately assess. (See "Pulmonic valve stenosis in adults: Management".)

Physical findings are related to severity of stenosis, thus the findings in adults with pulmonic stenosis are often subtle, since most patients have mild to moderate disease. The typical constellation includes:

●Prominence of the jugular venous "A" wave, although overall jugular venous pressure is usually normal. (See "Examination of the jugular venous pulse".)

●Prominent right ventricular systolic impulse with a left parasternal lift.

●A systolic ejection murmur with maximal intensity at the left upper sternal border. The murmur duration increases with increasing degrees of stenosis at valve level, and its peak intensity occurs later in systole (see "Auscultation of cardiac murmurs in adults"). In patients with milder stenosis, the murmur will vary with respiration. The murmur radiates to the back, particularly the posterior lung fields.

●A pulmonary ejection sound (or click). Presence of this high frequency component usually denotes a mild or moderate degree of stenosis, since it occurs earlier in systole with severe stenosis, and eventually becomes "buried" in the first heart sound [14]. The ejection click decreases in intensity with inspiration. (See "Auscultation of heart sounds".)

●Splitting of the second heart sound results from prolonged ejection and delay in the pulmonic component. The degree of splitting increases with more severe stenosis, and may become fixed in the most severe forms due to a fixed right ventricular output or development of conduction delay. (See "Auscultation of heart sounds".)

●A right-sided fourth heart sound may be heard over the left sternal border in cases of right ventricular hypertrophy and diminished compliance.

●Varying degrees of tricuspid regurgitation may be detected. Pulmonic regurgitation may also be detected as a decrescendo, diastolic murmur; this finding is more prevalent following valvotomy or valvuloplasty [15]. (See "Auscultation of cardiac murmurs in adults".)

●Cyanosis occurs only in the most severe cases and is indicative of right to left shunting at the atrial level through a septal defect or patent foramen ovale, generally in the face of elevated right atrial pressures.

DIAGNOSIS — Echocardiography is the key test for diagnosis and evaluation of pulmonic stenosis [16,17]. (See "Echocardiographic evaluation of the pulmonic valve and pulmonary artery".)

Echocardiography — Two- and three-dimensional echocardiography are excellent modalities for assessment of pulmonary valvular anatomy (image 1), localization of the stenosis, assessment of severity, and evaluation of right ventricular size and function. Echocardiography (generally transthoracic echocardiography) is the preferred test for evaluating the severity of pulmonic stenosis [16,17]. (See "Echocardiographic evaluation of the pulmonic valve and pulmonary artery".)

●Typical valvular stenosis is characterized by mildly thickened leaflets with restricted systolic excursion, leading to a domed appearance [18].

●Presystolic doming of the valve may be seen during atrial contraction in patients with more severe stenosis who have a noncompliant right ventricle [18]; doming correlates with the progressive decrease in the systolic ejection click [14].

●Truly dysplastic valves are characterized by markedly thickened and seemingly immobile leaflets, hypoplasia of the valve annulus, and often supra-annular narrowing [19]. The ability to identify dysplastic valves is essential since balloon valvuloplasty in these patients may achieve less than optimal results. (See "Pulmonic valve stenosis in adults: Management", section on 'Balloon valvotomy'.)

●Echocardiographic detection of pulmonic valve calcification is rare [20].

Echocardiography may also reveal changes secondary to the hemodynamic effects of pulmonic stenosis, including right ventricular hypertrophy (including narrowed right ventricular outflow tract), right ventricular/right atrial enlargement, and poststenotic dilation of the main pulmonary artery [16,17].

Continuous wave Doppler measurement of peak systolic velocities provides estimates of the transpulmonic gradient that are correlated closely with simultaneous values obtained at cardiac catheterization (image 2) [21,22].

Doppler echocardiography is particularly useful for the detection and assessment of pulmonic regurgitation severity using jet width, jet density and contour, deceleration/pressure half-time, and diastolic flow reversal in the pulmonary arteries [23]. This technique is of particular importance in the assessment of residual insufficiency in patients who have undergone balloon valvuloplasty [13,24]. Color Doppler is also useful for identification of the location of obstruction. Flow acceleration proximal to valve level suggests subvalvar pulmonic stenosis.

Transesophageal echocardiography is not indicated in the routine evaluation of pulmonic stenosis. However, it may be helpful if the diagnosis of pulmonic valve endocarditis is suspected [25], though the localization of the pulmonary valve relatively far from the TEE probe may make visualization of the pulmonary valve difficult.

Classification of the severity of pulmonic stenosis and relationship to prognosis is discussed separately. (See "Pulmonic valve stenosis in adults: Management", section on 'Grading severity'.)

ADDITIONAL TESTS

Electrocardiogram — The baseline electrocardiogram is often normal, particularly in cases of mild or moderate pulmonic stenosis. In more severe cases, the mean frontal axis may deviate to the right and varying degrees of right ventricular hypertrophy may be detected. Right bundle branch block is also seen.

Cardiac catheterization — Diagnostic cardiac catheterization is rarely required in patients with pulmonic stenosis due to the extensive characterization of valvular structure, severity of stenosis, and right ventricular size and function derived from echocardiography [16,17]. Invasive hemodynamic measurements and ventriculography may be useful when the severity of stenosis is unclear or a significant secondary infundibular stenosis is suspected in addition to the valvular stenosis.

Cardiac catheterization is primarily performed in patients who are candidates for balloon valvotomy for confirmation of gradients meriting intervention immediately prior to the procedure. (See "Pulmonic valve stenosis in adults: Management", section on 'Balloon valvotomy'.)

Cardiac magnetic resonance imaging — Cardiac magnetic resonance imaging (CMR) is commonly used to assess patients with right ventricular abnormalities and congenital heart disease and may have a role in selected patients with isolated pulmonary stenosis. If echocardiography image quality is inadequate, CMR is an option to assess severity of valve disease and impact on the right ventricle. For those patients who may have complex anatomy, MRI can more accurately delineate anatomy of the right heart and pulmonary arteries. In patients with pulmonary regurgitation, CMR is valuable in clinical decision making because it allows measurement of right ventricular volume and function. Additionally, CMR can be used to measure differential branch pulmonary artery blood flow, which can help in assessment of the severity of branch pulmonary artery stenosis [26,27].

Cardiac computed tomography — Cardiac computed tomography (CCT) is another means of assessing pulmonary arterial anatomy and right ventricular size and function. The angiography afforded by CT is excellent, but the ability to perform accurate right ventricular volumes and assessment of systolic function is available in more limited settings; thus, CMR remains the preferred modality for right ventricular size and function. However, for patients who cannot undergo CMR, CT may be an option in centers with the capability of performing volume and function analysis. CT can be particularly valuable in assessing main or branch pulmonary artery stenosis.

COMPLICATIONS — Several clinical concerns are shared equally among those with varying severity of pulmonic stenosis, regardless of the type of treatment given (medical or surgical).

Infective endocarditis — The incidence of infective endocarditis in patients with pulmonic stenosis followed to adulthood is very low compared with other types of valvular heart disease (0.9 per 10,000 person-years versus 27.1 for those with aortic stenosis) [28]. Nevertheless, the risk is a little more than twice that in the general population (0.38 per 10,000 person-years).

Antimicrobial prophylaxis is suggested for patients with cardiac conditions that confer the highest risk of adverse outcome from infective endocarditis. Most patients with valvular heart disease, including those with pulmonic stenosis, are not included in this group unless they have had prior endocarditis or have a prosthetic valve. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

Arrhythmia — There is an increased incidence of arrhythmia in patients with pulmonic stenosis; these include supraventricular premature beats, ventricular premature beats, and ventricular couplets [29]. Only those with symptomatic palpitations require evaluation. Electrophysiologic testing is generally not necessary since the incidence of malignant arrhythmias is low.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)

SUMMARY AND RECOMMENDATIONS

●Stenosis of the pulmonary valve is a relatively common congenital defect, occurring in approximately 7 percent of children with congenital heart disease. (See 'Introduction' above.)

●A tricuspid valve is present in patients with typical valvular pulmonic stenosis, with varying degrees of fibrous thickening and fusion of the commissures. A small proportion of patients (particularly those with Noonan syndrome) have a markedly dysplastic valve associated with severe stenosis. (See 'Valvular pulmonic stenosis' above.)

●Primary fibromuscular narrowing limited to the right ventricular outflow tract is an extremely rare phenomenon that is probably part of the spectrum of illness associated with a double-chambered right ventricle. In contrast, secondary outflow tract narrowing is commonly seen as part of the hypertrophy of the right ventricle induced by pulmonic stenosis. (See 'Subvalvular pulmonic stenosis' above.)

●Pulmonary arterial stenosis often occurs in association with other cardiac or noncardiac congenital defects. These include tetralogy of Fallot and the congenital rubella syndrome as well as rarer disorders such as Williams syndrome, Noonan syndrome, Alagille syndrome, and LEOPARD syndrome. (See 'Supravalvular pulmonic stenosis' above.)

●Symptoms of pulmonic stenosis with severe obstruction include exertional dyspnea, fatigue, syncope, and chest pain. (See 'Clinical manifestations' above.)

●The systolic ejection murmur of pulmonic stenosis becomes later peaking and louder as the stenosis worsens, assuming preserved right ventricular function. (See 'Clinical manifestations' above.)

●The treatment of pulmonic stenosis is discussed separately. (See "Pulmonic valve stenosis in adults: Management".)