Pulmonary valve stenosis

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Pulmonary valve stenosis
Pulmonary valve stenosis
ICD-10 I37.0, I37.2, Q22.1
ICD-9 424.3, 746.02
OMIM 265500
DiseasesDB 11025
MedlinePlus 001096

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]

Synonyms and keywords: Valvular Pulmonary Stenosis, Pulmonic Stenosis, Right Ventricular Outlet Obstruction, supravalvular pulmonic stenosis, infundibular pulmonic stenosis, Narrowing of pulmonary valve, PS

Overview

Pulmonary valve stenosis accounts for 8% of all congenital heart disease and worldwide the prevalence of pulmonary valve stenosis is 1 per 2000 births.[1] The pulmonic valve stenosis is classified into 3 different subtypes based on the location of the stenosis. Isolated valvular stenosis is the most common sub-type, with dome shaped morphology and dysplastic valves. Patients with mild stenosis usually have a beningn course and do not progress, patients with moderate to severe stenosis manifest symptoms of dyspnea, chest pain, fatigue and syncope. If left untreated patients progress to right heart failure. 2D Echo is the standard diagnostic test to identify the location and to assess the severity of the stenosis. Symptomatic patients undergo valvulotomy or balloon valvuloplasty based on the morphology of the affected valves. Timely intervention in patients with valvular stenosis has good outcomes and excellent prognosis. Guidelines for evaluation, approach and treatment are well-defined.

Historical Perspective

  • The pulmonary valve and its function of allowing blood to the lungs for nourishment was first described by Hippocrates. [2]
  • Erasistratus, mentioned the function of the pulmonary valve in the unidirectional flow. [3]
  • Galen described the membranes of the valves and named them as "semilunar". [4]
  • Mondino de Luzzi designed the sketch of the pulmonary valves in the anatomical position for the first time. [5]
  • Realdo Colombo described the pulmonary circulation for the first time. [6]
  • Aortic stenosis was probably first described by Lazare Riviere (1589-1655), a French physician in 1663. [7]
  • The first transcatheter aortic valve replacement procedure in the world was performed on 16 April 2002 in a 57-year-old inoperable patient with severe aortic stenosis. The procedure was done by the Interventional Cardiologist Professor Alain Cribier at the Charles Nicolle University Hospital in Rouen, France.

Classification

Based on the anatomic location

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.[8] [9]

  • 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.[10]
  • 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 defect, Ebstein’s anomaly, double outlet right ventricle, and transposition of the great arteries.[9]
  • 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 syndrome, DiGeorge, and Leopard syndrome. [9]

Based on the severity of the stenosis

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:[11]


  • Mild: Peak velocity less than 3m/s and peak gradient is less than 36 mm Hg.[11]
  • 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. [9]
  • According to 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease, stages of severe pulmonic stenosis are defined as follows: This form of aortic stenosis presents later in life, usually after the age of 75. [12]
Stage Definition Valve Anatomy Valve Hemodynamics Hemodynamic Consequences Symptoms
C,D Severe pulmonic stenosis
  • Thickened, distorted, possibly calcified leaflets with systolic doming and/or reduced excursion
  • Other anatomic abnormalities may be present, such as narrowed RVOT.
  • Vmax >4 m/s; peak instantaneous gradient >64 mm Hg
  • None or variable and dependent on severity of obstruction
  • According to 2014 AHA/ACC Guidelines for the Management of Patients With Valvular Heart Disease, progression of valvular heart disease (VHD) are defined as follows:[13]
Stage Definition Description
A At risk Patients with risk factors for development of valvular heart disease
B Progressive Patients with progressive valvular heart disease (mild-to-moderate severity and asymptomatic)
C Asymptomatic severe Asymptomatic patients who have the criteria for severe valvular heart disease:
  • C1: Asymptomatic patients with severe VHD in whom the left or right ventricle remains compensated
  • C2: Asymptomatic patients with severe VHD with decompensation of the left or right ventricle
D Symptomatic severe Patients who have developed symptoms as a result of valvular heart disease

Pathophysiology

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. The valve problems develop 5 - 10 years after the rheumatic fever, a tiny nodule forms along the valve leaflets. The degree of leaflet thickening and calcification and the severity of chordal involvement are variable. Rheumatic fever is becoming rare in the United States, so mitral stenosis is also less common.[14]
  • These morphological changes affect the complete opening of the pulmonic valve during the ventricular systole causing elevated right ventricular systolic pressures and leading to right ventricular remodelling.[15]
  • The obstruction leads to increased pressure overload on the right ventricle as it has to push the blood against resistance. [9]

Genetics

These are a common genetic disorders associated with pulmonic stenosis:[16]

Syndrome Genetic Defect Cardiac features Other features
Noonan syndrome[17]
  • PTPN11, SOS1
  • Heterogeneous trait
  • Aberrant RAS-MAPK-signaling
  • Short stature
  • Hypertelorism
  • Downward eye slant
  • Low set ears
Williams Beuren[18]
  • Supravalvular aortic or pulmonary stenosis
  • Elfin face
  • Short stature
  • Impaired cognition and development
  • Endocrine disorders and genitourinary abnormalities
Leopard syndrome[19]
  • Electrocardiographic abnormalities
  • Supravalvular or valvular pulmonary stenosis
  • Lentigines[20]
  • Ocular hypertelorism
  • Abnormal genitalia
  • Growth retardation
  • Deafness
DiGeorge syndrome[21]
  • Hypertelorism
  • Low set and posteriorly rotated ears
  • Palatal abnormalities
  • Micrognathia
  • Developmental delay
  • Hypoplastic thymus
  • Hypocalcaemia
  • Immunological abnormalities
Allagile[22]
  • Peripheral pulmonary stenosis[23]
  • Facial dysmorphias (triangular face, wide nasal bridge, deep set eyes)
  • Intrahepatic cholestasis
  • Butterfly [vertebra]]
Keutel[24]
  • Multiple peripheral pulmonary stenosis
Congenital rubella syndrome[25] N/A
  • Peripheral pulmonary stenosis
  • Open ductus Botalli

Associated conditions

A rare association of pulmonic stenosis with an unrepaired ASD is reported.[26] [27] [28]

Epidemiology and Demographics

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: [33][34].

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.[35]

Associated with congenital heart disease

Acquired Causes

These are less frequent and account for less than 5% of the cases. [48]

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.[54]

Risk Factors

Common risk factors in the development of congenital heart disease apply for pulmonic stenosis and include:[56]

Natural History, Complications and Prognosis

Natural History

Patients with congenital pulmonary stenosis manifest clinical features few hours after birth, in childhood or in adulthood. Manifestation of symptoms, symptom severity and the outcomes are dependent on the severity of stenosis. Patients with mild pulmonic stenosis have a benign course and do not progress and patients with moderate and severe stenosis have dyspnea with exertion and syncope.[61]

Prognosis

Patients with moderate to severe pulmonic valve stenosis are managed well with surgery or balloon valvuloplasty and have very good prognosis. [62]

Complications

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.[63]

Diagnosis

Gold standard diagnosis of pulmonic stenosis and assessment of severity is done by 2D echocardiography.[64]

History and Symptoms

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

Mild valvular

PS

Moderate Valvular

PS

Severe Valvular PS Infundibular

Pulmonic Stenosis

Supravalvular

Pulmonic Stenosis

Right Heart Failure
Clinical Features

Asymptomatic

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.[68]
  • 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: [70]


Mild valvular

PS

Severe Valvular

PS

Physical Examination Findings
  • 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.

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:[73]

Chest X-Ray

Echocardiography

Transthoracic 2D Echo and Doppler imaging is the standard diagnostic test to detect and assess the severity of the stenosis.[75]

  • Echo shows thickened and dome shaped valves, peak and mean gradients to assess the severity can be measured by Doppler imaging. [76]
  • Dysplastic valves are well visualized on echo.[77]
  • Always calculate the tricuspid regurgitation gradient to rule out overestimation of the pulmonary stenosis gradient.[78]
  • Right ventricular function and ejection fraction is better measured by a 3D echo when compared to a 2D echo.[79]
  • 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.[80]

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.[81]

Dual-Source Computed Tomography

It is an accurate imaging technique to evaluate the function and anatomy of the pulmonary valve.[82]

Evaluation of Pulmonary Stenosis in Adolescents and Young Adults

According to 2008 ACC/AHA guidelines, following are the guidelines for evaluation of patients with pulmonary stenosis:

Class I
"1. An ECG is recommended for the initial evaluation of pulmonic stenosis in adolescent and young adult patients and serially every 5 to 10 years for follow-up examinations.(Level of Evidence: C) "
"2.Transthoracic Doppler echocardiography is recommended for the initial evaluation of pulmonic stenosis in adolescent and young adult patients, and serially every 5 to 10 years for follow-up examinations.(Level of Evidence: C)"
"3.Cardiac catheterization is recommended in the adoles- cent or young adult with pulmonic stenosis for evalu- ation of the valvular gradient if the Doppler peak jet velocity is greater than 3 m per second (estimated peak gradient greater than 36 mm Hg) and balloon dilation can be performed if indicated.(Level of Evidence: C) "
Class III
"1.Diagnostic cardiac catheterization is not recommended for the initial diagnostic evaluation of pulmonic stenosis in adolescent and young adult patients.(Level of Evidence: C).(Level of Evidence: C) "

Treatment

Medical Therapy

There is no specific medical therapy for the treatment of pulmonic stenosis. However, patients diagnosed with right heart failure diuretics are recommended to decrease the fluid overload. [83]

Surgery

Indications For Intervention

Surgical correction is recommended based on the peak gradient and other associated clinical features:[84] [85]

  • Surgery is advised regardless of the symptoms if the doppler derived peak instantaneous gradient greater than 64 mm Hg (peak velocity >4 m/s). [86]
  • 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:[83]
  • Asymptomatic patients with a systolic RV pressure greater than 80 mm Hg (TR jet velocity >4.3 m/s).

2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines[87]

Recommendations for Valvular Pulmonary Stenosis

Class I
1. In adults with moderate or severe valvular pulmonary stenosis and otherwise unexplained symptoms of HF, cyanosis from interatrial right-to-left communication, and/or exercise intolerance, balloon valvuloplasty is recommended..(Level of Evidence: B-NR)
2.In adults with moderate or severe valvular pulmonary stenosis and otherwise unexplained symptoms of HF, cyanosis, and/ or exercise intolerance who are ineligible for or who failed balloon valvuloplasty, surgical repair is recommended(Level of Evidence: B-NR)
Class IIa
1.In asymptomatic adults with severe valvular pulmonary stenosis, intervention is reasonable. (Level of Evidence: C-EO)"

According to 2010, ESC Guidelines for the management of grown-up congenital heart disease, Indications for intervention in Right Ventricular Outlet Obstruction are as follows:[88]

Class I
"1.RVOTO at any level should be repaired regardless of the symptoms when the doppler peak gradient is >64mm Hg(peak velocity >4.0m/s), provided that the RV function is normal and no valve substitute is required(Level of Evidence: C)"
"2.In valvular PS, balloon valvulotomy should be the intervention of choice.(Level of Evidence: C) "
"3.In asymptomatic patients in whom balloon valvulotomy is ineffective and the surgical valve replacement is the only option, surgery should be performed in the presence of a systolic right ventricular pressure greater than 80mm Hg ( TR velocity >4.3m/s)(Level of Evidence: C) "
Class IIa
"1.Intervention in patients with gradient <64 mm Hg should be considered in the presence of:
  • Symptoms related to PS or
  • Decreased RV function or
  • Double chambered RV ( which is usually progressive) or
  • Important arrythmias (Level of Evidence: C)"
"2.Peripheral PS, regardless of the symptoms, should be considered for repair if :
  • >50% diameter narrowing and RV systolic pressure >50 mm of Hg and/or
  • Lung perfusion abnormalities are present.(Level of Evidence: C)"

Intervention Options

  • Percutaneous balloon pulmonary valvulotomy (BPV) has widely replaced surgical valvulotomy as a treatment option for pulmonary valve stenosis.[89][90]
  • Catheter intervention is recommended for patients with doming valves which are not dysplastic.[91]
  • Surgery is recommended for patients with:
    • Subinfundibular or infundibular pulmonic stenosis and hypoplastic pulmonary annulus
    • Dysplastic pulmonary valves
    • Patients with associated lesions which need a surgical approach, such as severe PR or severe TR.
  • 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.

Intervention Outcome

  • Surgical outcomes in patients with valvular stenosis is good with survival rate of 90 to 96% 25 years after the surgery when its done in the childhood.[92][93]
  • Survival is around 70% at 25 years when 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.[94][95][96]
  • BPV has shown to have sub-optimal results in patients with dysplastic valves when compared to doming valves.[97]

Complications

  • Post procedural pulmonary regurgitation is a common complication and occurs in 10 to 40% patients. Majority of the patients remain asymptomatic and only few patients develop hemodynamically significant pulmonary regurgitation.[98]
  • Bradycardia and hypotension at the time of balloon inflation
  • Transient permanent right bundle branch block or atrioventricular block
  • Higher mortality rates reported after surgical decompression in patients with RV-dependent coronary circulation.[99]
  • Balloon rupture
  • Tricuspid papillary muscle rupture
  • Perforation of the RV outflow tract

Follow up

Patients with pulmonic stenosis 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:[100]

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

According to 2008 ACC/AHA guidelines[100], 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 2011, Indications for Cardiac Catheterization and Intervention in Pediatric Cardiac Disease, A Scientific Statement From the American Heart Association.[101]

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

Prevention

  • There are no specific primary preventive measures.
  • Patients with diagnosed pulmonary valvar stenosis are not candidates for infective endocarditis prophylaxis.
  • Infective endocarditis prophylaxis is recommended only in patients with prosthetic valves.

Participation In Sports

According to 2005 Task Force 2: Congenital Heart Disease, guidelines for participation in sports are as follows:[102]

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 operative 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 participate 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 recommendations as those for patients before treatment."
"3.Athletes with severe pulmonary incompetence characterized by a marked right ventricular enlargement can participate in class IA and IB competitive sports."

SupraValvular Pulmonic Stenosis

According to 2008 ACC/AHA Guidelines, Recommendations for Evaluation of Patients With Supravalvular, Branch, and Peripheral Pulmonary Stenosis (DO NOT EDIT)[103]

Class I
"1. Patients with suspected supravalvular, branch, or peripheral PS should have baseline imaging with echocardiography- Doppler plus 1 of the following: MRI angiography, CT angiography, or contrast angiography. (Level of Evidence: C)"
"2. Once the diagnosis is established, follow-up echocardiography- Doppler to assess RV systolic pressure should be performed periodically, depending on severity. (Level of Evidence: C)"

Recommendations for Interventional Therapy in the Management of Branch and Peripheral Pulmonary Stenosis (DO NOT EDIT)[103]

Class I
"1. Percutaneous interventional therapy is recommended as the treatment of choice in the management of appropriate focal branch and/or peripheral pulmonary artery stenosis with greater than 50% diameter narrowing, an elevated RV systolic pressure greater than 50 mm Hg, and/or symptoms. (Level of Evidence: B)"
"2. In patients with the above indications for intervention, surgeons with training and expertise in CHD should perform operations for management of branch pulmonary artery stenosis not anatomically amenable to percutaneous interventional therapy. (Level of Evidence: B)"

Recommendations for Evaluation and Follow-Up (DO NOT EDIT)[103]

Class I
"1. Patients with peripheral PS should be followed up every 1 to 2 years, on the basis of severity, with a clinical evaluation and echocardiography-Doppler to evaluate RV systolic pressure and RV function. (Level of Evidence: C)"
"2. Discussion with a cardiac surgeon with expertise in CHD should take place before percutaneous peripheral pulmonary artery interventions are undertaken. (Level of Evidence: C)"

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