Congenital pulmonary stenosis and regurgitation

Incidence and prevalence

Typical mobile dome-shaped pulmonary valve stenosis is relatively common with a prevalence as high as 10% of cases of congenital heart disease. ^, Sex distribution is equal or with female prevalence. This is also the case in dysplastic pulmonary valve stenosis.

Anatomic considerations

Congenital obstruction to right ventricular outflow in hearts with two non-inverted ventricles originates in, below or above the pulmonary valve. Three morphologic types of pulmonary stenosis involve the pulmonary valve: (1) typical mobile dome-shaped, (2) dysplastic, and (3) bicuspid. Dome-shaped pulmonary valve stenosis is characterized by a thin mobile valve mechanism with a narrow central opening at its apex ( Fig. 10.1 ). Three rudimentary raphes extend from the central opening to the wall of the pulmonary artery, but separate leaflets and separate commissures cannot be identified. Pinpoint dome-shaped pulmonary valve stenosis in neonates is sometimes referred to as functional pulmonary atresia (see Fig. 10.1 , lower, A and B). The pulmonary trunk is consistently dilated because an inherent medial abnormality is coupled with the mobile dome-shaped valve, but not with its functional state (see Fig. 10.1 ). The jet from the stenotic valve breaks up upon striking the apex of the pulmonary trunk. The pressure component of total energy increases with a proportionate increase pressure in the left branch ( Fig. 10.2 A). The physics of jet dispersion is believed to account for the larger size of the left branch. Calcification of a dome-shaped stenotic pulmonary valve is exceptional and is reserved for older patients. Dysplastic pulmonary valve stenosis is much less common and is characterized by myomatous thickening of three separate but poorly mobile leaflets without commissural fusion ( Fig. 10.3 and Box 10.1 ). ^, Bicuspid pulmonary valve stenosis is a feature of Fallot’s tetralogy (see Chapter 13 ). Isolated bicuspid pulmonary valves are rare and are of little or no functional significance.

Subvalvular pulmonary stenosis can be infundibular or subinfundibular . The infundibular variety is caused by anterior and rightward deviation (malalignment) of the infundibular septum and is dealt with in Chapter 13 . Secondary hypertrophic infundibular pulmonary stenosis accompanies—is secondary to—severe pulmonary valve stenosis ( Figs. 10.4 and 10.5 ). Stenosis of the ostium of the infundibulum is a rare form of fixed obstruction to right ventricular outflow ( Figs. 10.6 and 10.7 ). Subinfundibular stenosis or double-chambered right ventricle is a rare form of congenital obstruction to right ventricular outflow. Obstructing muscle bundles within the right ventricular cavity result in a double-chambered right ventricle; the right ventricle is hence divided into a high-pressure inlet portion and a low-pressure outlet portion by normal or anomalous muscle bundles ^, or by apical trabecular muscle sequestered from the rest of the right ventricle. The degree of obstruction varies from nil to severe to virtually complete. Double-chambered right ventricle usually coexists with a ventricular septal defect. ^,

Pulmonary artery stenosis (supravalvular ) is caused by narrowing of the pulmonary trunk, its bifurcation, or its primary or intrapulmonary branches ( Figs. 10.8 and 10.9 ). Stenosis of the pulmonary artery and its branches usually occurs as an isolated malformation and can be unilateral or bilateral, single or multiple, and segmental or tubular (see Figs. 10.8 and 10.9 ). Intrapulmonary arteries distal to the stenoses tend to be dilated (see Figs. 10.8 and 10.9 ). Rarely, a membranous form of obstruction occurs immediately above the valve.

Neonates, especially premature, normally exhibit a disparity in size between the pulmonary trunk and its proximal branches. Angulations at the origins of the branches cause a drop in systolic pressure in the absence of morphologic pulmonary artery stenosis (see Chapter 2 and Fig. 2.4 ). ^, The small pulmonary trunk and small proximal branches in Fallot’s tetralogy are discussed in Chapter 15 . In Williams syndrome, bilateral stenosis of pulmonary artery branches is associated with supravalvular aortic stenosis (see Chapter 7 ). Experimental constriction of the pulmonary trunk in fetal lambs results in thin-walled intrapulmonary resistance vessels.

Physiologic consequences

The physiological consequences of pulmonary stenosis result from increased resistance to right ventricular discharge. Systolic pressure is elevated proximal to the obstruction and is normal or reduced distally. Pulmonary artery stenosis causes an increase in systolic pressure in the pulmonary trunk which is proximal to the obstruction ( Fig. 10.10 ). Valvular and subvalvular pulmonary stenosis increase the systolic pressure in the right ventricle that is proximal to the obstruction. The gross morphologic response of the right ventricle to pressure overload is new sarcomeres in parallel, hence an increase in thickness of the free wall and ventricular septum, adaptive responses appropriate for developing power. Cavity size remains normal. In neonates with pinpoint pulmonary stenosis, cavity size is reduced.

The ultrastructural response to mechanical stress depends on myocyte maturity or immaturity at the time the inciting stimulus of overload becomes operative. In pulmonary stenosis, the inciting stimulus is present at birth when cardiomyocytes are immature and capable of replication which is accompanied by capillary angiogenesis. Accordingly, each replicated normal-sized myocyte is paired with its own capillary, so myocyte/capillary ratio (capillary density) is normal. However, a morphologic right ventricle is perfused by a morphologic right coronary artery which imposes an inherent limitation.

Children and young adults with mild to moderate pulmonary valve stenosis have normal or near-normal right ventricular function and can increase their cardiac output with exercise. In severe pulmonary valve stenosis, however, stroke volume and cardiac output are fixed. Systolic contraction of hypertrophied infundibular muscle (see Fig. 10.4 ) is reinforced by exercise.

Pressure overload of the right ventricle can result in systolic and diastolic dysfunction of the left ventricle. ^, Systolic dysfunction has been ascribed to chronic underfilling of the left ventricle, and diastolic dysfunction has been ascribed to displacement of the hypertrophied septum into the left ventricular cavity.

The history

Patients with isolated pulmonary stenosis tend to have a favorable long-term prognosis with little progression of disease in those with mild valvar pulmonary stenosis. Even so, great strides have been made in diagnostic capabilities and therapeutic options for patients with obstruction of the right ventricular outflow tract further optimizing outcomes. ^,

Familial recurrence of isolated pulmonary valve stenosis is uncommon if not rare ( Fig. 10.11 ). In dysplastic pulmonary valve stenosis, the converse is the case. Some family members have a dysplastic valve, while others have a mobile dome-shaped valve. Familial Noonan syndrome frequently occurs with dysplastic pulmonary valve stenosis and has appeared in three generations. ^, Successful pregnancy is possible in females with Noonan syndrome. Familial pulmonary artery stenosis occurs as an isolated anomaly or with coexisting supravalvular aortic stenosis. Members of the same family may have either or both anomalies.

Genetic anomalies have been associated with pulmonary stenosis with and without Noonan syndrome. Cardio-facio-cutaneous syndrome occurs sporadically with multiple congenital anomalies where pulmonary stenosis is more common in individuals with a BRAF mutation. PTPN11 mutations cause LEOPARD syndrome and Noonan syndrome, both of which are part of a family of autosomal dominant syndromes termed “RASopathies,” which are developmental diseases caused by mutations in genes encoding for signal transducers of the RAS-MAPK cascade. ^, Cardiac defects occur in 80% of these with worst outcomes described in those with Noonan syndrome and pulmonary stenosis who carry the PTPN11 mutations.

Normal birth weights and normal growth and development are characteristic of mobile dome-shaped pulmonary valve stenosis. However, in Noonan syndrome with dysplastic pulmonary valve stenosis, growth and development are poor. ^{, ,} Pulmonary artery stenosis is associated with low birth weights and retarded physical and mental development in the rubella syndrome and in Williams syndrome (see Chapter 7 ). ^,

Neonates with pinpoint pulmonary valve stenosis experience rapidly progressive cardiac failure. However, the majority of patients with mobile dome-shaped pulmonary valve stenosis experience little or no difficulty in infancy and childhood. In a review of 69 cases, the average age at death was 26 years, seven patients survived to age 50 years, and three survived to 70 and 75 years. In 21 adults, the average follow-up was 50 years. There are examples of survival into the sixth, seventh, and eighth decade, with one patient reaching 78 years. Longevity depends on three variables: (1) the initial severity of stenosis, (2) whether a given degree of stenosis remains constant or progresses, and (3) whether the function of the afterloaded right ventricle is preserved. ^{, ,}

The normal pulmonary valve orifice increases linearly with age and body surface area. The orifice of a stenotic mobile dome-shaped pulmonary valve increases with age, but not necessarily at the rate of somatic growth. ^, Mild pulmonary valve stenosis in infancy usually remains mild, but moderate to severe pulmonary stenosis tends to progress. Stenosis of the pulmonary artery and its branches is not progressive. Fibrous thickening and occasionally calcification are responsible for increasing the degree of stenosis in older adults.

Equivalent degrees of pulmonary stenosis may handicap one patient in childhood but leave another relatively free of symptoms in adulthood. It is not surprising that mild pulmonary stenosis is asymptomatic, but it is surprising that an appreciable number of patients with moderate to severe pulmonary stenosis claim to be virtually asymptomatic. Patients with right ventricular systolic pressures between 50 and 100 mm Hg include a New Zealand long-distance swimmer, a long-distance runner, and an English hockey captain. My patients include a 17-year-old boy who played baseball despite a right ventricular systolic pressure of nearly 200 mm Hg, a 32-year-old male who had run the quarter mile in high school despite a right ventricular systolic pressure of 75 mm Hg, and a female with a right ventricular pressure of nearly 200 mm Hg who worked full-time and had recurrent ascites for 7 years before death at age 60 years. Dyspnea and fatigue are mild as long as the right ventricle maintains a normal stroke volume at rest and augments its stroke volume with exercise. ^, However, relatively asymptomatic patients can deteriorate rapidly. Cardiac output is inadequate even at rest when the hemodynamic burden imposed on the right ventricle leads to right ventricular failure, the commonest cause of death.

Giddiness and light-headedness with effort prefigure syncope. Children as well as adults occasionally experience the chest pain of right ventricular myocardial ischemia. ^, A 3-year-old with severe pulmonary artery stenosis died during an episode of chest pain and at necropsy had infarction of the right ventricular free wall and interventricular septum. Sudden death has been associated with right ventricular infarction and an abnormal right coronary artery. Dilated thin-walled intrapulmonary artery aneurysms distal to the stenoses of pulmonary artery branches (see Fig. 10.9 B) are sources of hemoptyses that can be intermittent and mild or recurrent and brisk.

Severe pulmonary stenosis is accompanied by giant jugular venous A waves ( Fig. 10.12 ) that patients are subjectively aware of especially during effort or excitement. These neck pulsations can be seen in the mirror. A 13-year-old girl with pulmonary valve stenosis and congenital complete heart block was aware of intermittent amplification of A waves as her right atrium randomly contracted against a closed tricuspid valve, and a 15-year-old boy was unpleasantly aware of intermittent amplification of jugular venous A waves caused by premature ventricular beats.

Mobile dome-shaped pulmonary valve stenosis is a substrate for infective endocarditis that can induce a medical valvotomy when tissue is interrupted and orifice size increases. Jet lesions in pulmonary artery stenosis can serve as substrates for infective endarteritis.

Physical appearance

Six physical appearances are relevant in patients with congenital pulmonary stenosis: (1) the round bloated facies in infants with mobile dome-shaped pulmonary valve stenosis, (2) Noonan syndrome, (3) the rubella syndrome, (4) Williams syndrome, (5) Alagille syndrome, and (6) the Cornelia de Lange syndrome.

Infants with mobile dome-shaped pulmonary valve stenosis occasionally have chubby round bloated facies with highly colored cheeks ( Fig. 10.13 A) and well-developed fat deposits. The digits may be erythematous or frankly red in response to a small or intermittent right-to-left shunt through a patent foramen ovale. Noonan syndrome ^{, ,} (see Fig. 10.13 C) is characterized by short stature, webbed neck, pterygium colli, ptosis, hypertelorism, lymphedema, low-set ears, low anterior and posterior hairlines, flat or shield chest, pectus excavatum or carinatum, hyperelastic skin, inguinal hernia, nevi, dystrophic nails, micrognathia, hypospadias, and small undescended or cryptorchid testes, ^, foramen ovale (see Chapter 12 ).

About one-third of Noonan patients are intellectually disabled, and approximately two-thirds have congenital heart disease, especially dysplastic pulmonary valve stenosis (60%) or hypertrophic cardiomyopathy (20%). ^{, ,} Mild pulmonary stenosis in patients with Noonan syndrome is typically nonprogressive. Malignant tumor development is a complication encountered in other RASopathies, though the neoplastic risks and incidence of malignant tumors are less clearly defined in Noonan syndrome and related disorders of the Noonan spectrum.

The rubella syndrome is characterized by cataracts, retinopathy, deafness, hypotonia, dermatoglyphic abnormalities, and intellectual disability. Height and weight are usually normal for age despite intrauterine growth retardation. Stenosis of the pulmonary artery and its branches and patent ductus arteriosus (see Chapter 17 ) are the most frequent types of coexisting congenital heart disease.

Williams syndrome includes a small chin, large mouth, patulous lips, blunt upturned nose, wide-set eyes, broad forehead, baggy cheeks, and malformed teeth (see Chapter 7 ). The most frequent coexisting congenital heart disease is pulmonary artery stenosis with supravalvular aortic stenosis (see Chapter 7 ).

Alagille syndrome, also called arteriohepatic dysplasia or the Alagille-Watson syndrome, is an autosomal dominant disorder with abnormalities of liver, eyes, kidneys, and skeleton. ^, Facial appearance is characterized by a prominent overhanging forehead, deep-set eyes, and a small pointed chin (see Fig. 10.13 B). The most frequent coexisting congenital heart disease is stenosis of the pulmonary artery and its branches.

Cornelia de Lange syndrome expresses itself as low birth weight; slow growth; small stature; microcephaly; thin eyebrows that meet at midline; long eyelashes; short upturned nose; thin, downturned lips; hirsutism; small hands and feet; in-curved fifth fingers; cleft palate; and missing limbs or portions of limbs. The incidence of pulmonary valve stenosis is reportedly 39%.

Pulmonary stenosis also occurs in the LEOPARD syndrome that is characterized by multiple lentigines and café-au-lait spots.

The arterial pulse

When severe pulmonary stenosis is accompanied by right ventricular failure, especially with coexisting left ventricular dysfunction, the arterial pulse is reduced. Asymmetry of right and left brachial and carotid arterial pulses (right greater than left) is a feature of supravalvular aortic stenosis that may accompany stenosis of the pulmonary artery and its branches (see Chapter 7 ).

The jugular venous pulse

The jugular venous A wave is distinctive, increasing progressively as the stenosis increases ( Fig. 10.14 ; see also Fig. 10.12 A), culminating in a giant A wave that leaps to the eye, towering above and dwarfing the other waves of the venous pulse. Powerful right atrial contraction generates a giant A wave via the superior vena cava and a presystolic liver pulse via the inferior cava. With the advent of right ventricular failure and tricuspid regurgitation, the large A wave is accompanied by an increase in the V wave. The liver then manifests presystolic and systolic pulsations.