Sandbox:Pulmonary valve stenosis

Classification

• Pulmonic stenosis is classified into valvular, subvalvular (infundibular) and supravalvular based on the location of the stenosis in relation to the pulmonary valve. Valvular stenosis is most common of the three sub-types.
  • Sub-valvular stenosis: It can be infudibular or sub-infundibular. Infundibular stenosis is a feature of tetralogy of fallot. Sub-infundibular pulmonic stenosis is known as ‘double chambered right ventricle’ dividing the right ventricle into a high pressure inlet and a low pressure outlet causing a progressive right ventricular outflow tract obstruction.
  • Valvular stenosis: It is the most common cause of pulmonic stenosis. The valves are usually dome shaped or dysplastic affecting the movement of the cusps. It can be isolated or associated with other congenital heart diseases such as atrial septal defects, Ebstein’s anomaly, double outlet right ventricle, and transposition of the great arteries.
  • Supravalvular stenosis: The obstruction is usually in the common pulmonary trunk or in the bifurcation or the pulmonary branches. It is commonly associated with other congenital syndromes such as Williams–Beuren, Noonan, Allagile, DiGeorge, and Leopard syndrome.

• Severity of pulmonary stenosis is classified based on the estimated peak velocity and peak resting gradient calculated using modified Bernoulli equation. It is classified into:
  • Mild: Peak velocity less than 3m/s and peak gradient is less than 36 mm Hg.
  • Moderate: Peak velocity is 3 to 4m/s and peak gradient is 36 to 64mm Hg.
  • Severe: Peak velocity is greater than 4m/s and peak gradient is greater than 64mm Hg.

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. It is a common finding associated with Noonan syndrome.
    • 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: Primary cardiac tumours obstructing the right ventricular outflow tract such as leiomyosarcoma.

Differentiating from other diseases

Right ventricular outflow tract obstruction must be distinguished from an ASD, a small VSD, aortic stenosis, and acyanotic or pink tetralogy of Fallot.

• Atrial septal defect: Presence of systolic ejection murmur, wide fixed split S2, EKG showing RVH. In ASD the split of the S2 is fixed, there is no ejection click.
• Small Ventricular septal defect: Amyl nitrate increases venous return and increases the murmur of pulmonary stenosis, in VSD the murmur becomes softer.
• Mild left-sided outflow obstruction: With valsalva maneuver the murmur of aortic stenosis becomes softer after about 5 beats, with pulmonary stenosis it becomes softer within 3 beats.
• Acyanotic or pink tetralogy of Fallot: with amyl nitrate and increased venous return the murmur of PS increases, and the murmur of tetralogy decreases because of peripheral dilation and an increase in right to left shunting.

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

Natural History, Complications and Prognosis

Patients with congenital pulmonary stenosis manifest clinical features few hours after birth or in childhood or in adulthood. Manifestation of symptoms, symptom severity and the outcomes are dependent on the severity of the disease.

• Patients with mild pulmonic stenosis have a benign course and do not progress.
• Patients with moderate and severe stenosis have dynpnea with exertion and syncope, and is managed well with surgery or balloon valvuloplasty carries very good prognosis.
• If left untreated, patients with moderate to severe stenosis progress to develop tricuspid regurgitation and right ventricular dysfunction leading to right ventricular failure and arrhythmias.

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 with fused commisures affect the flexibility of the valve causing obstruction of the outflow tract. In patients with dysplastic valves, the cusps are not fused but they are rigid from intrinsic thickening resulting in the narrowing of the outflow tract.
• These morphological changes affect the complete opening of the pulmonic valve in ventricular systole causing elevated right ventricular systolic pressures and leading to right ventricular remodelling.
• The obstruction leads to increased pressure overload in the right ventricle as it has to push the blood against resistance.

Genetics

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

Associated conditions

A rare association of pulmonic stenosis with an unrepaired ASD is reported.

History and Symptoms

The severity of symptoms and age of symptom onset depends on the severity of the stenosis. Clinical presentations of various degrees of severity is as follows:

• Critical pulmonary stenosis:It presents in first few hours to days of life with cyanosis. It is a condition with a very small or pin-hole orifice in the pulmonary valve which can be diagnosed prenatally. These patients have an intact interventricular septum, poorly complaint hypoplastic right ventricle and are ductus dependent. Cyanosis in these patients is due to the right to left shunting at the level of the foramen ovale.
• Mild Pulmonic Stenosis: Patients with mild stenosis are asymptomatic and are diagnosed by routine examination with an ejection systolic murmur.
• Moderate Pulmonic Stenosis: Patients present with exertional dyspnea and fatigue.
• Severe Pulmonic Stenosis: Patients present with exertional dyspnea, chest pain and syncope.
• Untreated patients develop features of right ventricular failure which include:
  • Exercise intolerance
  • Fatigue
  • Shortness of breath
  • Swelling of the feet or ankles
  • Abdominal discomfort
  • Chest pain

Physical Examination

The common examination findings include:

• Patients with isolated pulmonary stenosis usually appear normal. In patients diagnosed with syndromes associated with pulmonic stenosis syndrome specific physical examination findings are demonstrated.
• Cardiac examination findings are dependent on the degree of the pulmonary stenosis, the pathology of the valve and associated cardiac lesions. The common findings include as follows:
  • In mild stenosis findings include normal jugular venous pulse, absent right ventricle lift, ejection click in the pulmonary area which decreases with inspiration, ejection systolic murmur in the pulmonary area heard in the ending of mid systole increasing in intensity during inspiration.
  • In severe stenosis findings include:
    • Elevated JVP with a prominent "A" wave
    • Right ventricular heave
    • Louder and longer ejection murmur in the left parasternal area in second and third intercostal space
    • Ejection click is softer and absent with increasing severity
    • Wide split S2 with reduced or absent P2 component
    • Right sided S4 can be audible.

Diagnosis

Diagnosis of pulmonic stenosis and assessment of severity is done by 2D echocardiography.

EKG

Patients with mild stenosis usually do not show any EKG changes excepting for right axis deviation of -100° to -110° which is considered normal in children and adults.
In case of severe stenosis the following changes can be noted, which include:

• Features of right ventricular hypertrophy
• Rightward axis deviation
• High R wave amplitude in lead V1
• Deep S waves in the left precordial leads with <1 R:S ratio in lead V6

Echocardiography

Transthoracic 2D Echo and Doppler imaging is the standard to detect and assess the severity of the stenosis.

• Echo shows thickened and dome shaped valves, peak and mean gradients to assess the severity can be measured by Doppler imaging.
• Dysplastic valves are well visualized on echo.
• Always calculate the tricuspid regurgitation gradient to rule out overestimation of the pulmonary stenosis gradient.
• Right ventricular function and ejection fraction is better measured by a 3D echo when compared to a 2D echo.

• Pulmonic Stenosis 1

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• Pulmonic Stenosis 2

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MRI

Cardiac MRI is very useful to study the anatomy of the right ventricular outflow tract, pulmonary artery and to locate the exact level of stenosis.

Cardiac Catheterization

Cardiac catheterization is useful to measure the pressure gradients directly, but its not performed on a regular basis as echo is a reliable and non-invasive test to measure the pressure gradients.

Dual-Source Computed Tomography

It is an accurate imaging technique to evaluate the function and anatomy of the pulmonary valve.

ACC / AHA Guidelines - Indications for balloon valvotomy in Pulmonary Stenosis (DO NOT EDIT)

According to 2008 ACC/AHA guidelines, following are the indications for balloon valvotomy in pulmonary stenosis:

Class I

"1.Balloon valvotomy is recommended in adolescent and young adult patients with pulmonic stenosis who have exertional dyspnea, angina, syncope, or presyncope and an RV–to–pulmonary artery peak-to-peak gradient greater than 30 mm Hg at catheterization.(Level of Evidence: C) "

"2.Balloon valvotomy is recommended in asymptomatic adolescent and young adult patients with pulmonic stenosis and RV–to–pulmonary artery peak-to-peak gradient greater than 40 mm Hg at catheterization.(Level of Evidence: C) "

Class III

"1.Balloon valvotomy is not recommended in asymptomatic adolescent and young adult patients with pulmonic stenosis and RV–to–pulmonary artery peak-to-peak gradient less than 30 mm Hg at catheterization.(Level of Evidence: C) "

Class IIb

"1.Balloon valvotomy may be reasonable in asymptomatic adolescent and young adult patients with pulmonic stenosis and an RV–to–pulmonary artery peak-to-peak gradient 30 to 39 mm Hg at catheterization.(Level of Evidence: C) "

Recommendations For Pulmonary Valvuloplasty

According to Indications for Cardiac Catheterization and Intervention in Pediatric Cardiac Disease, A Scientific Statement From the American Heart Association, 2011.

Class I

"1. Pulmonary valvuloplasty is indicated for a patient with critical valvar pulmonary stenosis (defined as pulmonary stenosis present at birth with cyanosis and evidence of patent ductus arteriosus dependency), valvar pulmonic stenosis, and a peak-to-peak catheter gradient or echocardiographic peak instantaneous gradient of >40 mm Hg or clinically significant pulmonary valvar obstruction in the presence of RV dysfunction.(Level of Evidence: A) "

Class IIa

"1.It is reasonable to perform pulmonary valvuloplasty on a patient with valvar pulmonic stenosis who meets the above criteria in the setting of a dysplastic pulmonary valve.(Level of Evidence: C) "

"2. It is reasonable to perform pulmonary valvuloplasty in newborns with pulmonary valve atresia and intact ventricular septum who have favorable anatomy that includes the exclusion of RV-dependent coronary circulation.(Level of Evidence: C) "

Class IIb

"1. Pulmonary valvuloplasty may be considered as a palliative procedure in a patient with complex cyanotic CHD, including some rare cases of tetralogy of Fallot.(Level of Evidence: C) "

[[Class III

"1.Pulmonaryvalvuloplasty should not be performed in patients with pulmonary atresia and RV-dependent coronary circulation.(Level of Evidence: B) "

Medical Therapy

There are no specific measures for the treatment of pulmonic stenosis.

• In patients diagnosed with right heart failure diuretics are recommended to decrease the fluid overload.

Surgical Therapy

Indications for surgical therapy

Surgical correction is recommended based on the peak gradient and other associated clinical features:

• Surgery is advised regardless of the symptoms if the Doppler derived peak instantaneous gradient greater than 64 mm Hg (peak velocity >4 m/s).
• In patients with Doppler derived peak instantaneous gradient less than 64 mm Hg (peak velocity >4 m/s), surgery is advised if any of the following is present:
  • Symptomatic patient
  • Decreased right ventricular function
  • Double chambered right ventricle
  • Arrhythmias
  • Right to left shunting via the VSD or ASD
• Asymptomatic patients with a systolic RV pressure greater than 80 mm Hg (TR velocity >4.3 m/s).

Surgical Options

• Balloon pulmonary valvuloplasty (BPV)has replaced surgical valvulotomy as a treatment option for pulmonary valve stenosis.
• In patients with significant residual PS after BPV, a redo BPV can be performed with a larger balloon to avoid valve replacement.
• In patients with hemodynamically significant pulmonary regurgitation after valvulotomy or BPV, surgical valve replacement is recommended.

Surgical Outcome

• Surgical outcomes in patients with valvular stenosis is good with survival rate of 90 to 96% 25 years after the surgery, if surgery is done in the childhood.
• Survival is around 70% at 25 years if the surgery is performed in adulthood.
• BPV has shown to have good outcomes in long term follow up with very low rate of re-intervention requirement.
• BPV has shown to have sub-optimal results in patients with dysplastic valves when compared to doming valves.

Complications of the surgery

• Post procedural pulmonary regurgitation is a common complication. Majority of the patients remain asymptomatic and only few patients develop hemodynamically significant pulmonary regurgitation.
• Bradycardia and hypotension at the time of balloon inflation
• Permanent right bundle branch block or atrioventricular block
• Balloon rupture
• Tricuspid papillary muscle rupture

Follow up

Patients with PS are recommended for a regular echocardiography to evaluate the degree of pulmonary regurgitation, RV pressure, RV function and tricuspid regurgitation. The frequency of visits is dependent on the degree of stenosis and is as follows:

• Mild untreated or residual pulmonic stenosis: Follow up once every 5 years.
• Moderate pulmonic stenosis: Annual visit with echocardiography every 2 years.

Prevention

• Endocarditis prophylaxis is not recommended in patients with pulmonary stenosis, except in patients with valvular prosthesis.

Participation In Sports

Pulmonary valve stenosis in untreated patients

"1.Athletes with a peak systolic gradient less than 40 mm Hg and normal right ventricular function can participate in all competitive sports if no symptoms are present. Annual re-evaluation is recommended. "

"2.Athletes with a peak systolic gradient greater than 40 mm Hg can participate in low-intensity competitive sports (classes IA and IB). Patients in this category usually are referred for balloon valvuloplasty or op- erative valvotomy before sports participation. "

Pulmonary valve stenosis treated by operation or balloon valvuloplasty

"1.Athletes with no or only residual mild PS and normal ventricular function without symptoms can partici- pate in all competitive sports. Participation in sports can begin two to four weeks after balloon valvuloplasty. After operation, an interval of approximately three months is suggested before resuming sports participation. "

"2.Athletes with a persistent peak systolic gradient greater than 40 mm Hg should follow the same recommenda- tions as those for patients before treatment."

"3.Athletes with severe pulmonary incompetence charac- terized by a marked right ventricular enlargement can participate in class IA and IB competitive sports."

References

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