Sandbox:Pulmonary valve stenosis

Epidemiology and Demographics

• Pulmonary stenosis accounts for 8% of all congenital heart disease.
• Worldwide, the prevalence of pulmonic stenosis is 1 per 2000 births.
• The prevalence of pulmonic stenosis and tetralogy of fallot is higher in Asian countries.

Causes

Pulmonary valve stenosis is due to a structural changes resulting from thickening and fusion of the pulmonary valve. The valve pathology can be congenital or acquired. The following is the list of causes:

• Congenital causes: These account for 95% of the cases with pulmonic stenosis which include isolated pulmonic valve pathologies and its associations with other congenital heart diseases.
  • Associated with congenital heart disease:
    • Tetralogy of Fallot
    • Double outlet right ventricle
    • Univentricular atrio-ventricular connection
    • Atrioventricular canal defect
    • Bicuspid pulmonary valve: Frequently associated with Tetralogy of Fallot.
    • Quadricuspid pulmonary valve: It is a benign and an incidental finding.

  • Isolated pulmonic stenosis: The causes include as follows:
    • Acommissural pulmonary valves: Valve has a prominent systolic doming of the cusps and an eccentric orifice.
    • Dysplastic pulmonary valves: Thickened and deformed cusps with no commissural fusion.
    • Less common malformations include of commissural malformation include: unicommissural pulmonary valve, bicuspid valve with fused commissures.
• Acquired Causes: These are less frequent and account for less than 5% of the cases.
  • Carcinoid Syndrome: It is the most common acquired cause of Pulmonic stenosis.
  • Post infectious: Infective endocarditis
  • Calcification of the pulmonary valve
  • Rheumatic heart disease
  • Following Ross procedure for correction of right ventricular outlet obstruction

• Functional Pulmonic Stenosis:

Risk Factors

Common risk factors in the development of congenital heart disease apply for pulmonic stenosis and include:

• Maternal pre-gestational diabetes mellitus
• Consanguineous marriage
• Phenylketonuria
• Febrile illness
• Vitamin A use
• Marijuana use
• Exposure to organic solvents

Pathophysiology

Anatomy

• Pulmonary valve is located at the distal part of the right ventricular outflow tract at the junction of the pulmonary artery.
• It is located anterior and superior to the aortic valve at the level of the third intercostal space and separated from the tricuspid valve by the infundibulum of the right ventricle.
• It is comprised of three equal sized, semilunar cusps or leaflets (right, left, anterior), nomenclature based on the corresponding aortic valve.
• The three cusps are joined by commissures and the cusps are thinner when compared to the aortic valve, due to a low pressure in the right ventricle.
• The area of the valve is related to body surface area and men usually have greater valve area when compared with women.
• The normal orifice area is approximately around 3cm².
• The pulmonary valve opens in the right ventricular systole allowing the deoxygenated blood to be delivered to the lungs.
• During the right ventricular diastole the pulmonary valves close completely to prevent regurgitation of blood into the right ventricle.

Pathogenesis

• Pulmonic valve stenosis can result from structural alterations resulting from congenital and acquired causes.

Associated Conditions

These are a common genetic disorders associated with pulmonic stenosis:

Syndrome	Genetic Defect	Cardiac features	Other features
Noonan	PTPN11, SOS1 Heterogeneous trait Aberrant RAS-MAPK-signaling	Dysplastic pulmonary valve stenosis Supravalvular pulmonary stenosis Hypertrophic cardiomyopathy	Short stature Hypertelorism Downward eye slant Low set ears
Williams Beuren	7Q11.23 deletions Autosomal dominant trait	Supravalvular aortic or pulmonary stenosis	Elfin face Short stature Impaired cognition and development Endocrine disorders and genitourinary abnormalities
Leopard	PTPN11, RAF-1 Autosomal dominant trait	Electrocardiographic abnormalities Supravalvular or valvular pulmonary stenosis	Lentigines Ocular hypertelorism Abnormal genitalia Retardation of growth Deafness
DiGeorge	22Q11 deletion Autosomal dominant trait	Conotruncal defects such as tetralogy of Fallot Interrupted aortic arch Truncus arteriosus Vascular rings ASD/VSD	Hypertelorism Low set and posteriorly rotated ears Palatal abnormalities Micrognathia Developmental delay Hypoplastic thymus Hypocalcaemia Immunological abnormalities
Allagile	AG-1, NOTCH-2 Dominant trait	Peripheral pulmonary stenosis	Facial dysmorphias (triangular face, wide nasal bridge, deep set eyes) Intrahepatic cholestasis Butterfly vertebrae
Keutel	MGP mutations Autosomal recessive trait	Multiple peripheral pulmonary stenosis	Abnormal cartilage calcifications Brachytelephalangy Subnormal IQ and hearing loss
Congenital Rubella	N/A	Peripheral pulmonary stenosis Open ductus Botalli	Congenital cataract/glaucoma Deafness Pigmentary retinopathy