I. INTRODUCTION. The pulmonary valve is a trileaflet valve that lies anterior and to the left of the aortic valve and separates the right ventricular outflow tract (RVOT) from the pulmonary trunk. The three pulmonary leaflets are semilunar in shape and are thinner than the aortic leaflets.

Primary abnormalities of the pulmonic valve are often congenital and are usually diagnosed in childhood. In adults, pulmonary valve disease is more commonly due to pulmonary hypertension from left-sided heart disease.

A. Pulmonary regurgitation (PR). A mild degree of PR is a common finding in healthy adults. In adults, the most common cause of moderate PR is pulmonary hypertension. Severe PR is most commonly a complication of corrective interventions for congenital heart disease.

1. PR is the most common complication after repair of tetralogy of Fallot. It has been shown to be associated with the use of a transannular patch to reconstruct the RVOT, and was more liberally utilized in an earlier surgical era. PR is also commonly seen postvalvotomy for pulmonary stenosis (balloon or surgical).

2. Other causes of PR are rare and include endocarditis, rheumatic heart disease, carcinoid, pulmonary artery (PA) and annular dilatation as seen in Marfan syndrome, and congenital anomalies (e.g., absent pulmonary valve syndrome, malformed or fenestrated leaflets, and trauma).

B. Pulmonary stenosis (PS). Congenital PS is by far the most frequent cause. It is relatively common, with an estimated prevalence of about 10% of children with congenital heart disease. It is most commonly an isolated lesion but may be associated with other conditions: tetralogy of Fallot, congenital rubella syndrome, Noonan syndrome, Williams syndrome, Alagille syndrome, and LEOPARD syndrome. Other rare causes include rheumatic heart disease, carcinoid, and extrinsic obstruction by cardiac tumors or sinus of Valsalva aneurysms.

1. Pulmonary stenosis can occur at three levels.

a. Valvular—seen in >90% of cases, most commonly because of restricted leaflets from fibrous thickening and commissural fusion. A bicuspid valve is seen in less than 20% of cases. A dysplastic valve is commonly encountered in patients with Noonan syndrome, often associated with hypoplastic annulus and proximal PA.

b. Subvalvular—PS is extremely rare and results from narrowing of the RVOT as seen in double-chambered RV or from septal malalignment.

c. Supravalvular—PS is related to narrowing of the main PA or its branches, which can occur as part of another congenital abnormality (as seen in Williams syndrome) or as an isolated defect.

A. Pulmonary regurgitation. PR causes volume overload on the RV, the severity of which depends on the degree and duration of the regurgitant flow. The low pulmonary vascular resistance allows blood to easily pass through the lungs despite severe PR, thus limiting significant RV volume overload and allowing this lesion to be tolerated for longer periods. Ultimately, severe chronic RV volume overload leads to RV dilatation and dysfunction with resultant right-sided heart failure symptoms. The RV volume overload when severe manifests as “paradoxical” septal motion during diastole on echocardiography. After intervention and correction of the PR, the RV typically improves; however, an irreversible decline in contractility may occur.

B. Pulmonary stenosis. The RV initial response to the pressure overload created by PS is an increase in its wall thickness with resultant RV hypertrophy. RV pressure overload is associated with paradoxical septal motion during systole, evidenced by echocardiography. If left uncorrected, depending on the severity and chronicity of the pressure overload, RV dilatation and dysfunction may occur. After correction of the pulmonic stenosis with relief of the increased RV afterload, an improvement in RV hypertrophy and function is expected.

A. Pulmonary regurgitation. From a pathology perspective, PR can be divided into two major categories.

1. Conditions associated with anatomically abnormal valve cusps as seen in:

a. Congenital etiologies such as absent, hypoplastic, bicuspid, malformed tricuspid, or quadricuspid valves.

b. Rheumatic disease leading to morphologic alterations of the valve leaflets.

c. Carcinoid syndrome.

d. Trauma, which may result from external blunt/injury or iatrogenic causes (PA catheters).

e. Infective endocarditis.

2. Conditions associated with anatomically normal valve cusps as a result of:

a. PA hypertension with subsequent dilatation of the pulmonary trunk.

b. Idiopathic dilated pulmonary trunk.

c. Marfan syndrome with resultant dilatation of the pulmonary annulus.

B. Pulmonary stenosis. Congenital causes of pulmonic stenosis constitute well over 95% of these conditions.

1. Congenital types of pulmonic stenosis include (Fig. 7.1):

a. Acommissural: usually dome-shaped valve with a central aperture. Ridges mark sites of apparently malformed commissures.

b. Unicommissural: with a single asymmetric commissure.

c. Bicuspid: associated with tetralogy of Fallot.

d. Dysplastic: all three cusps are greatly thickened and rubbery. There is no commissural fusion, but the valve annulus is small.

A. Pulmonary regurgitation. Congenitally malformed valves producing isolated pure PR are exceedingly rare. Of the 116 operatively excised pulmonic valves reported by Altrichter and colleagues, 5 (˜4%) had pure pulmonary regurgitation. The majority of patients had pure pulmonary stenosis.

B. Pulmonary stenosis. Congenital PS is far more common than the acquired form. It is frequently an isolated lesion. In a minority of cases, it is associated with other congenital conditions including the following:

1. Noonan syndrome: This is an autosomal dominant disorder with an estimated incidence of 1 in 1,000 to 2,500 live births. Approximately 50% of cases have a
mutation in the PTPN11 gene on chromosome 12, which encodes the nonreceptor protein tyrosine phosphatase SHP2. Noonan syndrome is characterized by facial dysmorphism (downward eye slant and low-set ears), proportionate short stature, and heart disease, most often pulmonic stenosis. In a report of 118 patients with Noonan syndrome, a dysplastic pulmonary valve was found in approximately 7% and significant PS in approximately 24% of cases.

2. Williams syndrome: Also known as Williams-Beuren syndrome, this is a multisystem genetic disorder caused by hemizygous deletion on chromosome 7, encompassing about 28 genes including the elastin gene ELN. Affected patients present with variable phenotypic expression of the following manifestations: “elfin” facies, supravalvular aortic stenosis, branch PA stenosis or other vascular anomalies, hypertension, cognitive impairment, short stature, and endocrine, genitourinary, and other systemic abnormalities.

3. Congenital rubella syndrome: Approximately half of children infected during the first 2 months of gestation have congenital heart disease, with the most common lesions being branch PA stenosis and patent ductus arteriosus. Other lesions, including pulmonary valvular stenosis, aortic valve stenosis, tetralogy of Fallot, coarctation of the aorta, and ventricular septal defect, have also been reported.

A. Pulmonary regurgitation. The clinical course of pulmonic regurgitation is related to its severity and to the underlying etiology. Mild PR is generally benign, and progression to more severe forms is uncommon. Chronic severe PR is usually well tolerated for years until marked RV dilatation from chronic volume overload occurs, with resultant RV dysfunction and right-sided heart failure symptoms (dyspnea on exertion, fatigue, lower extremity swelling). RV failure is associated with increased morbidity and mortality.

B. Pulmonary stenosis. The natural course of patients with PS varies with the severity of the disease, with event-free survival inversely related to the pressure gradient (PG) across the valve—that is, the higher the gradient, the higher the incidence of events.

1. For mild PS (PG <30 mm Hg): The course of the disease is generally benign and unlikely to progress to more serious disease. Patients with mild PS are asymptomatic. In the Natural History Study of Congenital Heart Defects, among patients with valve gradient <25 mm Hg, 96% were free of operation at 10-year follow-up.

2. For moderate PS (PG 30 to 50 mm Hg): Patients are frequently symptomatic. Most of these patients are detected in childhood and treated with valvotomy (either surgical or percutaneous). The probability of their survival is similar to that of the general population, and only 5% will require reoperation. Asymptomatic, medically treated patients also fare well into adulthood, although some may show evidence of progression of stenosis, and approximately 24% will require intervention.