AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Until the 1950s, isolated pulmonary stenosis was considered to be a rare congenital abnormality.¹ A review of the literature in 1949 yielded just 68 cases. However, as physiologic testing has improved, this condition has been more frequently recognized.

Pulmonary valve stenosis (PVS) is described as those lesions that collectively are associated with obstruction to right ventricular outflow. PVS may be valvular, subvalvular, or supravalvular. PVS is the cause of isolated right ventricular outflow obstruction in 80% of cases.²

Pathophysiology

The pulmonic valve develops between the 6th and 9th week of gestation. Normally, the pulmonic valve is formed from 3 swellings of subendocardial tissue called the semilunar valves. These tubercles develop around the orifice of the pulmonary tree. The swellings are normally hollowed out and reshaped to form the 3 thin-walled cusps of the pulmonary valve.

Failure to develop normally can result in the following malformations: fusion of 2 of the cusps, 3 leaflets that are thickened and partially fused at the commissures, or a single cone-shaped valve. In Noonan syndrome, tissue pads within the sinuses interfere with the normal mobility and function of the valve.

The most common pathology is valvular pulmonic stenosis, which accounts for more than 80% of cases of pulmonary stenosis. Most cases are isolated valvular conditions, but they may be associated with a ventricular septal defect or secondarily lead to right ventricular infundibular hypertrophy.³

Isolated infundibular or subvalvular pulmonic stenosis is less common and is usually associated with a ventricular septal defect.

Most cases are congenital and sporadic. PVS is not understood to have significant inheritance, but its concordance among siblings is higher than would be expected. Rarely, pulmonic stenosis is associated with recessively transmitted conditions such as Laurence-Moon-Biedl syndrome. Isolated pulmonic stenosis has been reported in association with trisomy 21, and infundibular stenosis has been associated with trisomy 18, 15, and 13. In patients with Noonan syndrome, pulmonic stenosis, classically with dysplastic valves, can be present. Additionally, in the congenital rubella syndrome, supravalvular pulmonic and pulmonary artery branch stenoses are frequently present.

Acquired valvular disease is rare. The two most common etiologies are carcinoid and rheumatic fever.

Frequency

United States

PVS accounts for 10% of cases of congenital heart disease. Prevalence of pulmonary stenosis is 8-12% of all congenital heart defects. Isolated PVS with intact ventricular septum is the second most common congenital cardiac defect. PVS may occur in as many as 30% of all patients with congenital heart disease when associated with other congenital cardiac lesions.

Mortality/Morbidity

Much of what is known about the morbidity and mortality of PVS comes from the Natural History Study of Congenital Heart Defects and the Second Natural History Study of Congenital Heart Defects. The Natural History Study of Congenital Heart Defects included an initial cardiac catheterization and then follow-up for events over an 8-year period. The Second Natural History Study of Congenital Heart Defects reported on 16-27 years of follow up from the same cohort. The studies demonstrated that adverse outcomes directly relate to the right ventricular systolic pressure gradient.

• Mild (<50 mm Hg) PVS is well tolerated. Trivial differences were noted in the frequency of electrocardiographic abnormalities, exercise tolerance, echocardiographic findings, and adverse cardiac outcomes for those with pressure gradients less than 50 mm Hg. Of these patients, 94% were asymptomatic, without cyanosis or congestive heart failure.^{4, 5}
• Moderate to severe PVS (>50 mm Hg) can be associated with decreased cardiac output, right ventricular hypertrophy, early congestive heart failure (CHF), and cyanosis.
• The impact of this valvular lesion on pregnancy and fetal outcomes has not been rigorously studied. A case-control study of 17 patients in 2007 suggested that there is no adverse impact on either the mother or the fetus.⁶

Sex

The male-to-female ratio is approximately 1:1.

Age

PVS most commonly presents in newborns. It can be asymptomatic for years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• History of a heart murmur since birth
• Acyanosis
• Dyspnea
• Fatigue
• Dizziness or syncope, occasionally
• Chest pain

Physical

Physical examination findings correlate with the severity of right ventricular outflow obstruction.

• The first heart sound is normal and followed by a systolic ejection click. The systolic ejection click is variable with respiration and louder on expiration. It is loudest over the left upper sternal border.
• • Patients with dysplastic valves may not have a systolic ejection click.
  • The second heart sound is split. This is due to delayed closing of the pulmonic valve at the end of systole. The pulmonic component of the second heart sound may be diminished in intensity.
• Systolic ejection murmur (crescendo-decrescendo), grade 2-5/6, is audible at the left upper sternal border, transmitting into the back and posterior lung fields. The murmur is heard best in the 1st to 3rd intercostal spaces.
• Severity of valvular disease is related directly to the intensity and duration of the murmur. When severe, murmur extends into diastole (beyond the second heart sound).
• Hepatosplenomegaly may develop in cases of CHF.
• Severe PVS is associated with tricuspid insufficiency and may be associated with elevated central venous pressure, hepatosplenomegaly, a pulsatile liver, jugular venous pulsations, and hepatojugular reflux.
• Murmur of peripheral pulmonary stenosis (commonly encountered in neonates) is a grade 2/6 systolic murmur that radiates into the posterior lung fields.
• • Pathology of peripheral pulmonic stenosis is secondary to the acute angular takeoff of the branch pulmonary arteries from the main pulmonary arteries specific to a neonatal anatomy. This condition and associated murmur usually resolve spontaneously in the first month of life.
• Myocardial infarction of hypertrophied right ventricle may occur.
• Prominent A wave of the jugular venous pulse is observed.
• Tricuspid regurgitation occasionally is present.
• The murmur usually radiates to the clavicles, the suprasternal area, and left neck. Radiation down the left sternal border is less common.

Causes

• PVS primarily results from a maldevelopment of the pulmonic valve tissue and the distal portion of the bulbus cordis. One maldevelopment is characterized by fusion of leaflet commissures, resulting in a domed appearance to the valve. Other etiologies result in dysplastic valves, which do not open and close normally.
• Coexisting cardiac malformations (eg, ventricular septal defect, atrial septal defect, patent ductus arteriosus) may complicate the anatomy, physiology, and clinical picture.
• Aberrant flow patterns in utero also may be associated, in part, with maldevelopment of the pulmonary valve.
• Rubella embryopathy may cause PVS.
• Family history is a mild risk factor.⁷
• Cases have been reported in the setting of Mayer-Rokitansky-Kuster-Hauser syndrome.⁸

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Complex congenital heart disease associated with findings of pulmonary stenosis
Infundibular/subinfundibular stenosis
Supravalvular pulmonary stenosis
Dysplastic pulmonic valve stenosis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Laboratory evaluation usually is not helpful.
• Oximetry provides information on possible right-to-left shunting in borderline cyanotic lesions or in patients with anemia but does not identify the cause of the shunt (pulmonary, interatrial, interventricular, great arterial).
• Although arterial blood gases (ABG) analysis usually is not needed, one notable exception is the hyperoxia test in newborns with cyanosis of undetermined origin.
• Administered 100% FIO₂ generally does not increase the partial pressure of oxygen to levels much greater than 100 mm Hg in patients with a cyanotic congenital heart defect.

Imaging Studies

• Chest radiography
• • Chest radiographs demonstrate a prominent main pulmonary artery segment but a normal heart size.
  • Pulmonary vascular markings are usually normal but may be decreased in severe PVS.
  • CHF presents as cardiomegaly with right ventricular and right atrial enlargement in severe valvular pulmonary stenosis with or without tricuspid insufficiency.
• Echocardiography^{9, 10, 11}
• • The transthoracic approach provides valuable information about the site of obstruction and other possible congenital abnormalities.
  • Valve surface area is not used to determine the severity of stenosis. Rather, the peak gradient across the pulmonic valve is used as an indicator of disease severity. Doppler studies can accurately determine velocity of flow across the valve. The gradient is calculated from 4 times the peak systolic velocity squared:

Pressure gradient = 4 X velocity squared

• • Multiple views and measurements increase the accuracy of the predicted peak systolic pressure gradient.
  • A thickened pulmonic valve with restricted systolic motion (doming) in the parasternal short axis view is apparent.
  • Frequently, the main pulmonary artery is dilated distal to the stenotic orifice.
  • Most children with pulmonary stenosis do not require further evaluation beyond echocardiography.
• Whole-heart MRI
• • A case report from 2007 described the identification of a patient with isolated subvalvular pulmonary stenosis using whole-heart MRI.¹² This imaging tool is noninvasive and has the added benefit of creating a 3-dimensional representation of the heart and surrounding structures.
  • Other reports have described the use of whole-heart MRI as a presurgical adjunct.¹³

Other Tests

• Electrocardiography
• • ECG reflects the degree of right ventricular involvement.
  • ECG confirms right axis deviation and right ventricular hypertrophy in moderate valvular pulmonary stenosis.
  • Degree of right ventricular hypertrophy correlates with the severity of PVS.
  • Right atrial hypertrophy and right ventricular hypertrophy with strain pattern are observed when pulmonary stenosis is severe. A tall R wave in V₁ more than 10 mm suggests severe stenosis.
  • ECG confirms superior QRS axis (left axis deviation) with dysplastic pulmonary valve and Noonan syndrome.
  • In the Second Natural History Study of Congenital Heart Defects, the rates of arrhythmias in patients with PVS were higher than expected compared with historical controls. The prevalence of "serious arrhythmias" was lower in patients with PVS than either aortic stenosis or ventricular septal defect.¹⁴

Procedures

• Cardiac catheterization
• • The technique for angioplasty was described in 1982.¹⁵
  • This procedure is not indicated for mild PVS but is essential in severe stenosis.
  • Catheterization assesses the morphology of the right ventricle, pulmonary outflow tract, degree of tricuspid regurgitant flow, and pulmonary arteries.
• Patients with echocardiographic evidence of significant PVS (>50 mm Hg) should undergo diagnostic and therapeutic cardiac catheterization. Percutaneous balloon dilatation, stenting, and pulmonic valve replacement¹⁶ are increasingly being performed with high success rates.¹⁷
• Patients with infundibular or supravalvular pulmonic stenosis, if severe, require operative and invasive surgical interventions.
• A surgical approach is often preferred in patients with Noonan syndrome because of to the degree of immobility that is often present.¹⁸

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• If patient has a large left-to-right shunt, such as patent ductus arteriosus or ventricular septal defect, and is in respiratory distress, diuresis is effective in reducing the cyanosis secondary to pulmonary edema.
• Use of oxygen may reduce pulmonary artery pressure in patients with a reactive pulmonary vasculature, thus increasing pulmonary blood flow.
• Oxygen should be administered to any cyanotic patient in respiratory distress.

Emergency Department Care

• Patients with mild PVS usually do not require any treatment.
• Patients with severe or symptomatic infundibular or supravalvular pulmonary stenosis require intervention.
• Frequently, cyanotic infants with respiratory distress and hypotension/shock undergo a workup as for septic patients.
• Bacterial endocarditis prophylaxis
• • During the Second Natural History Study of Congenital Heart Defects, 592 patients with PVS were followed for 10,688 person-years; only one patient had an episode of bacterial endocarditis.¹⁹
  • PVS is not specifically mentioned in the 2007 American Heart Association (AHA) guidelines for antibiotic prophylaxis to prevent bacterial endocarditis. This guideline calls for endocarditis prophylaxis in the 6 months following repair of a congenital heart defect. Additionally, prophylaxis is required lifetime for individuals who have prosthetic valves.²⁰

Consultations

• Pediatric cardiologist
• Intensivist

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

No medications are useful in isolated PVS.

Patients with CHF may benefit from anticongestive therapy.

Cyanotic patients may benefit from oxygen and prostaglandin E1. Patients with cyanosis from a large right-to-left shunt require a definitive surgical procedure.

Drug Category: Prostaglandin

This agent is used as a smooth muscle relaxer.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients with mild PVS rarely require treatment.
• Intervention with either balloon angioplasty or valve repair is indicated for patients with peak valve gradients more then 50 mm Hg or for patients with angina, syncope, exertional dyspnea, or presyncope. Corrective options include open heart surgery, balloon angioplasty, percutaneous stenting, percutaneous valve replacement, or percutaneous conduit placement.
• Patients with severe or symptomatic infundibular or supravalvular pulmonary stenosis require surgical intervention.
• Critical PVS may present with near pulmonary atresia (a cyanotic lesion) with a small and often inadequate right ventricle.
• • These patients survive because of a patent ductus arteriosus.
  • Pulmonary valve atresia or critical PVS with inadequate right ventricle requires a shunt (usually modified Blalock-Taussig or central shunt) after the ductus is kept patent pharmacologically with prostaglandin E1.
  • Definitive repair may not be possible if the right ventricle is hypoplastic, requiring a single ventricular palliation, such as the Fontan procedure, or a variation, such as a direct right atrial appendage to main pulmonary artery anastomosis.
  • Frequently, the main and branch pulmonary arteries require augmentation.

Further Outpatient Care

• Patient should maintain normal physical activity.
• Most patients with murmurs are given prophylaxis against infective subacute bacterial endocarditis (SBE).
• Opinions differ about the need for SBE prophylaxis recommendations for patients with PVS because of the extremely low incidence of endocarditis in this relatively large subpopulation.
• For patients older than 6 months with a gradient less than 40 mm Hg at the time of diagnosis, follow up can safely be performed at intervals of 2 years or more.

Transfer

• Patients with symptomatic PVS should be transferred to a tertiary care center offering pediatric cardiology and pediatric cardiothoracic surgery.

Complications

• One complication of acute palliation or relief of severe PVS involves hypercontractile, residual, obstructing muscular hypertrophy in the infundibulum.
• • Infundibular obstruction after valvular stenosis repair by surgery or valvuloplasty has led to the designation of suicide right ventricle.
  • This complication is more frequent in older patients with long-standing pulmonary stenosis.
• Other complications include the following:
• • Late atrial arrhythmias
  • Persistent repolarization abnormalities
  • Iatrogenic injury from balloon angioplasty or stent delivery

Prognosis

• Mild PVS usually does not progress. However, patients with moderately severe to severe disease tend to progress.
• After relief of the stenosis, it does not usually recur, and right ventricular hypertrophy frequently regresses.
• Following balloon or surgical valvulotomy, outcome generally is excellent.
• A 2007 study presented long-term follow-up data on 90 adult patients who had pulmonary balloon valvuloplasty. In this cohort, outcome data were excellent; this study supports the use of balloon angioplasty in these patients, even if there is an associated tricuspid regurgitant lesion or infundibular stenosis.²¹

Patient Education

• Patients and parents of those with mild PVS should be reassured that this condition is not related to, or associated with, coronary artery disease, dysrhythmia, or sudden death. Patients are no more at risk for disastrous health consequences than the general population.
• Insurability may become a factor in obtaining further care.
• If the patient is asymptomatic and acyanotic and has mild PVS evinced by initial Doppler echocardiography, an annual screening examination and ECG would be prudent follow-up.
• If no significant change in the condition appears for a few years after the initial evaluation, the patient can be discharged reasonably for follow-up care over extended periods of 3-5 years.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose a more serious congenital heart defect, such as tetralogy of Fallot (tet), could yield disastrous consequences.
• Acyanotic patients with tet and mild right ventricular outflow tract obstruction may have a similar presentation and physical examination findings.
• Tet is a lesion that is surgically correctable; the repair can be performed safely even in the neonatal period.
• Echocardiography can reliably confirm the precise diagnosis and differentiate between PVS and tet.
• Echocardiography should not be withheld if any suspicion exists of a more complex anatomy.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Blount SG, Komesu S, McCord MC. Asymptomatic isolated valvular pulmonary stenosis; diagnosis by clinical methods. N Engl J Med. Jan 1 1953;248(1):5-11. [Medline].
2. Fyler DC. Pulmonary stenosis. In: Nadas Pediatric Cardiology. 1992:459-70.
3. Moore K, Persaud T. The Developing Human. In: Clinically Oriented Embryology. 1998.
4. Driscoll DJ, Wolfe RR, Gersony WM, et al. Cardiorespiratory responses to exercise of patients with aortic stenosis, pulmonary stenosis, and ventricular septal defect. Circulation. Feb 1993;87(2 Suppl):I102-13. [Medline].
5. Ardura J, Gonzalez C, Andres J. Does mild pulmonary stenosis progress during childhood? A study of its natural course. Clin Cardiol. Sep 2004;27(9):519-22. [Medline].
6. Hameed AB, Goodwin TM, Elkayam U. Effect of pulmonary stenosis on pregnancy outcomes--a case-control study. Am Heart J. Nov 2007;154(5):852-4. [Medline].
7. Driscoll DJ, Michels VV, Gersony WM, et al. Occurrence risk for congenital heart defects in relatives of patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect. Circulation. Feb 1993;87(2 Suppl):I114-20. [Medline].
8. Kula S, Saygili A, Tunaoglu FS, et al. Mayer-Rokitansky-Küster-Hauser syndrome associated with pulmonary stenosis. Acta Paediatr. Apr 2004;93(4):570-2. [Medline].
9. Nishimura RA, Pieroni DR, Bierman FZ, et al. Second natural history study of congenital heart defects. Pulmonary stenosis: echocardiography. Circulation. Feb 1993;87(2 Suppl):I73-9. [Medline].
10. Silverman NH. Right heart obstructive lesions. In: Pediatric Echocardiography. 1993;327.
11. Snider AR, Serwer GA. Abnormalities to right ventricular outflow. In: Echocardiography in Pediatric Heart Disease. 1990:231-41.
12. Sato Y, Komatsu S, Matsuo S, et al. Isolated subvalvular pulmonary stenosis: depiction at whole heart magnetic resonance imaging. Int J Cardiovasc Imaging. Feb 2007;23(1):49-52. [Medline].
13. Seibt C, Flender B, Gutberlet M. Comprehensive non-invasive pre-surgical magnetic resonance imaging in a patient with LEOPARD's syndrome cardiomyopathy. Eur Heart J. Jun 2006;27(12):1407. [Medline].
14. Wolfe RR, Driscoll DJ, Gersony WM, et al. Arrhythmias in patients with valvar aortic stenosis, valvar pulmonary stenosis, and ventricular septal defect. Results of 24-hour ECG monitoring. Circulation. Feb 1993;87(2 Suppl):I89-101. [Medline].
15. Kan JS, White RI Jr, Mitchell SE, et al. Percutaneous balloon valvuloplasty: a new method for treating congenital pulmonary-valve stenosis. N Engl J Med. Aug 26 1982;307(9):540-2. [Medline].
16. Bonhoeffer P, Boudjemline Y, Qureshi SA, et al. Percutaneous insertion of the pulmonary valve. J Am Coll Cardiol. May 15 2002;39(10):1664-9. [Medline].
17. Block PC, Bonhoeffer P. Percutaneous approaches to valvular heart disease. Curr Cardiol Rep. Mar 2005;7(2):108-13. [Medline].
18. Castenada AR, Jonas RA, Meyer JE. Surgery for infants with congenital heart defects. In: Cardiac Surgery. 1993:1013-35.
19. Gersony WM, Hayes CJ, Driscoll DJ, et al. Bacterial endocarditis in patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect. Circulation. Feb 1993;87(2 Suppl):I121-6. [Medline].
20. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. Oct 9 2007;116(15):1736-54. [Medline].
21. Fawzy ME, Hassan W, Fadel BM, et al. Long-term results (up to 17 years) of pulmonary balloon valvuloplasty in adults and its effects on concomitant severe infundibular stenosis and tricuspid regurgitation. Am Heart J. Mar 2007;153(3):433-8. [Medline].
22. Almeda FQ, Kavinsky CJ, Pophal SG, et al. Pulmonic valvular stenosis in adults: diagnosis and treatment. Catheter Cardiovasc Interv. Dec 2003;60(4):546-57. [Medline].
23. Park MK. Pulmonary stenosis. In: Pediatric Cardiology for Practitioners. 145-7.
24. Rocchini AP, Emmanouilides GC. Pulmonary stenosis. In: Heart Disease in Infants, Children and Adolescent: Including the Fetus and Young Adult. 930-62.

Article Last Updated: Jul 3, 2008