Pulmonic Valvular Stenosis
- Author: Melanie A Loewenthal, MD; Chief Editor: Robert E O'Connor, MD, MPH more...
Pulmonic valvular stenosis (PVS) is described as lesions that collectively are associated with obstruction to the right ventricular outflow tract. Stenosis may be valvular, subvalvular, or supravalvular. Isolated pulmonary stenosis is considered to be a rare congenital abnormality. It is the most common cause of congenital outflow tract obstruction, resulting in decreased flow from the right ventricle to the pulmonary arteries. Isolated right ventricular outflow tract obstruction is pulmonic valvular stenosis in 80% of cases.
Pulmonic valvular disease is clinically detected at different stages of life. The more severe the obstruction, the earlier the valvular abnormality is detected. Pulmonic valvular stenosis is most often associated with the failure of the valvular leaflets to fuse and less commonly is caused by dysplastic thickening of the valves.
Neonates with critical stenosis typically present with central cyanosis at birth. Infants and children with ejection murmurs auscultated in the pulmonic area are often evaluated, and stenosis is discovered during this period. Symptoms of pulmonic stenosis have been observed to progress with time. Adults present with symptoms of congestive heart failure (CHF) and right ventricular outflow obstruction that is progressive in nature. Many of these congenital valvular malformations occur in the setting of well-defined syndromes. Examples of such syndromes involving stenosis of the pulmonic valves are Holt-Oram syndrome, Noonan syndrome, and Leopard syndrome.[5, 7] Eisenmenger syndrome associated with trisomy 13 also results in pulmonary outflow tract obstruction; however, often, other cardiac malformations are involved as well.
A large study called the Second Natural History Study of Congenital Heart Defects analyzed the treatment, quality of life, echocardiography findings, complications, exercise responses, and predisposition to endocarditis with regards to cardiac valvular disease, and pulmonary stenosis was found to be the most benign valvular lesion.
Supravalvular, valvular, and subvalvular lesions are associated with pulmonic valvular stenosis. Lesions vary in severity, from with simple valvular hypertrophy to complete outflow obstruction and atresia. The trileaflet pulmonic valve ranges from thickened or partially fused commissures to an imperforate valve.
Most cases of pulmonic valvular stenosis are congenital. Often times, the valvular abnormality is associated with syndromes such as Noonan syndrome and Leopard syndrome. The inheritance pattern of pulmonic valvular stenosis is poorly understood, although these syndromes display an autosomal dominant pattern. Rarely, pulmonic stenosis is associated with recessively transmitted conditions such as Laurence-Moon-Biedl syndrome. Mutations in germlines PTPN1 and RAF1 have been associated with these valvular abnormalities. Supravalvular lesion may occur in the setting of tetralogy of Fallot, Williams syndrome, Alagille syndrome, as well as Noonan syndrome.
The myocardial cushion begins as a matrix of endothelial cells and an outer mitochondrial layer separated by cardiac jelly. After endocardial cushion formation, the endothelial mesenchymal transformation (EMT), which are specified endothelial cells, differentiate and migrate into the cardiac jelly. Through a poorly understood process, the cardiac jelly goes through local expansion and bolus swelling, and cardiac valves are formed. The aortic and pulmonic valves develop from the outflow tract of the endocardial cushion, also believed to have neural crest cell migration from the brachial crest during development.
Research suggests that the vascular endothelial growth factor (VEGF), a pleiotropic factor, is responsible for signaling the development of the endocardial cushion. Hypoxia and glucose have regulatory effects on this factor. Infants born to hyperglycemic mothers have a 3-fold increase in cardiovascular abnormalities. There has been correlation between intrapartum hypoxic events and valvular disease. Additionally, numerous signaling molecules contribute to VEGF and EMT such as the ERB-B signaling in the cardiac jelly, transforming growth factor (TGF)/cadherin, and BMP/TGF-beta.
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. In Noonan syndrome, tissue pad overgrowth within the sinuses interferes with the normal mobility and function of the 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 the congenital rubella syndrome, supravalvular pulmonic and pulmonary artery branch stenoses are frequently present. Acquired valvular disease is rare. The most common etiologies are carcinoid syndrome, rheumatic fever, and homograft dysfunction.
Years of stenosis can result in subendocardial hypertrophy causing significant outflow obstruction and resulting in right ventricular pressure overload and pulmonary hypertension. As this process worsens, the asymptomatic adult becomes gradually symptomatic.[11, 12]
Approximately 5 out of 1000 infants are born with a congenital cardiac malformation. Cardiac malformation is the most common congenital abnormality. Among cardiac malformations, valvular defects are the most common subtype, accounting for 25% of all malformations involving the myocardium. Prevalence of pulmonary stenosis is 8-12% of all congenital heart defects.
Isolated pulmonic valvular stenosis with intact ventricular septum is the second most common congenital cardiac defect. Pulmonic valvular stenosis may occur in as many as 30% of all patients who have other congenital heart defects.
Sixty percent of patients with Noonan syndrome are found to have some degree of pulmonic valvular stenosis.
Mild pulmonic valvular stenosis has a good overall prognosis. Life expectancy approaches that of someone without valvular disease.
Patients with moderately severe to severe stenosis have clinically progressing disease. The survival rate for severe stenosis is 96%; however, mean follow-up over a period of 33 years suggest that 53% of patients had required further intervention. Forty percent may have atrial or ventricular arrhythmias.[6, 11]
Following balloon or surgical valvulotomy, outcome generally is excellent. After interventions to relieve the stenosis, stenosis usually does not recur and right ventricular hypertrophy often regresses.
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.
Valvular disease in general has high morbidity and mortality rates. Isolated pulmonic valvular disease has been found to be the most benign. In the United States, about 82,000 valvular replacements are performed per year. Survival to adulthood is most common, as symptoms and extent of disease progress with time.
Much of what is known about the morbidity and mortality of pulmonic valvular stenosis 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 pulmonic valvular stenosis with pressure gradient across the valve less than 50 mm Hg was found to be well tolerated clinically and subjectively. Of these patients, 94% were asymptomatic, without cyanosis or congestive heart failure.[15, 16] Moderate-to-severe pulmonic valvular stenosis, with pressure gradient greater than 50 mm Hg is more often associated with decreased cardiac output, right ventricular hypertrophy, early congestive heart failure (CHF), and cyanosis. Valvulotomy has been shown to improve morbidity and mortality and is indicated with these gradients.
The morbidity and mortality of valvular lesions in regards to pregnancy and fetal outcomes has not been rigorously studied. A case-control study of 17 patients suggested that there is no adverse impact on either the mother or the fetus.
Complications of pulmonic valvular stenosis may include the following:
Sustained infundibular obstruction after valvular stenosis repair by surgery or valvuloplasty 
Late atrial arrhythmias 
Persistent repolarization abnormalities
Iatrogenic injury from balloon angioplasty or stent delivery
The male-to-female ratio of pulmonic valvular stenosis is approximately 1:1.
Pulmonic valvular stenosis most commonly presents in newborns. It can be asymptomatic for years.
Blount SG, Komesu S, McCord MC. Asymptomatic isolated valvular pulmonary stenosis; diagnosis by clinical methods. N Engl J Med. 1953 Jan 1. 248(1):5-11. [Medline].
Perloff JK, Child JS, Aboulhosn J. Pulmonic valvular disease. Congenital Heart Disease in Adults. 3rd ed. Saunders; 2008.
Fyler DC. Pulmonary stenosis. Nadas Pediatric Cardiology. 1992. 459-70.
Inglessis I, Landzberg MJ. Interventional catheterization in adult congenital heart disease. Circulation. 2007 Mar 27. 115(12):1622-33. [Medline].
Libby P, Bonow RO, Mann DL, Zipes DP. Braunwald's Heart Disease; A Textbook of Cardiovascular Medicine. 8th ed. Saunders Inc; 2007.
Hatemi AC, Gursoy M, Tongut A, Bicakhan B, Guzeltas A, Cetin G. Pulmonary stenosis as a predisposing factor for infective endocarditis in a patient with Noonan syndrome. Tex Heart Inst J. 2010. 37(1):99-101. [Medline].
Diller GP, van Eijl S, Okonko DO, Howard LS, Ali O, Thum T. Circulating endothelial progenitor cells in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension. Circulation. 2008 Jun 10. 117(23):3020-30. [Medline].
Nishimura RA, Gersony et al. Second Natural History Study of Congenital Heart Defects. Circulation. Feb 1993. 87:89-137.
Jorge AA, Malaquias AC, Arnhold IJ, Mendonca BB. Noonan syndrome and related disorders: a review of clinical features and mutations in genes of the RAS/MAPK pathway. Horm Res. 2009. 71(4):185-93. [Medline].
Crawford. Pulmonic stenosis. Cardiology. 3rd ed. Mosby Inc; 2009.
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. 2007 Mar. 153(3):433-8. [Medline].
Nishimura RA, Pieroni DR, Bierman FZ, et al. Second natural history study of congenital heart defects. Pulmonary stenosis: echocardiography. Circulation. 1993 Feb. 87(2 Suppl):I73-9. [Medline].
Driscoll DJ, Wolfe RR, Gersony WM, et al. Cardiorespiratory responses to exercise of patients with aortic stenosis, pulmonary stenosis, and ventricular septal defect. Circulation. 1993 Feb. 87(2 Suppl):I102-13. [Medline].
Ardura J, Gonzalez C, Andres J. Does mild pulmonary stenosis progress during childhood? A study of its natural course. Clin Cardiol. 2004 Sep. 27(9):519-22. [Medline].
Hameed AB, Goodwin TM, Elkayam U. Effect of pulmonary stenosis on pregnancy outcomes--a case-control study. Am Heart J. 2007 Nov. 154(5):852-4. [Medline].
De Meester P, Buys R, Van De Bruaene A, et al. Functional and haemodynamic assessment of mild-to-moderate pulmonary valve stenosis at rest and during exercise. Heart. 2014 Sep. 100(17):1354-9. [Medline].
Moore K, Persaud T. The Developing Human. Clinically Oriented Embryology. 1998.
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. 1993 Feb. 87(2 Suppl):I114-20. [Medline].
Kula S, Saygili A, Tunaoglu FS, Olguntürk R. Mayer-Rokitansky-Küster-Hauser syndrome associated with pulmonary stenosis. Acta Paediatr. 2004 Apr. 93(4):570-2. [Medline].
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. 1993 Feb. 87(2 Suppl):I89-101. [Medline].
Silverman NH. Right heart obstructive lesions. Pediatric Echocardiography. 1993. 327.
Snider AR, Serwer GA. Abnormalities to right ventricular outflow. Echocardiography in Pediatric Heart Disease. 1990. 231-41.
Kilner PJ. Imaging congenital heart disease in adults. Br J Radiol. 2011 Dec. 84 Spec No 3:S258-68. [Medline].
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. 2006 Jun. 27(12):1407. [Medline].
Bettencourt N, Rocha J, Carvalho M, Leite D, Toschke AM, Melica B, et al. Multislice computed tomography in the exclusion of coronary artery disease in patients with presurgical valve disease. Circ Cardiovasc Imaging. 2009 Jul. 2(4):306-13. [Medline].
Sato Y, Komatsu S, Matsuo S, et al. Isolated subvalvular pulmonary stenosis: depiction at whole heart magnetic resonance imaging. Int J Cardiovasc Imaging. 2007 Feb. 23(1):49-52. [Medline].
Kan JS, White RI Jr, Mitchell SE, Gardner TJ. Percutaneous balloon valvuloplasty: a new method for treating congenital pulmonary-valve stenosis. N Engl J Med. 1982 Aug 26. 307(9):540-2. [Medline].
Bonhoeffer P, Boudjemline Y, Qureshi SA, et al. Percutaneous insertion of the pulmonary valve. J Am Coll Cardiol. 2002 May 15. 39(10):1664-9. [Medline].
Block PC, Bonhoeffer P. Percutaneous approaches to valvular heart disease. Curr Cardiol Rep. 2005 Mar. 7(2):108-13. [Medline].
Violini R, Vairo U, Hijazi ZM. Stent strut breakage using high-pressure balloons for bifurcation stenting and subsequent percutaneous pulmonary valve replacement using the Edwards Sapien THV. Catheter Cardiovasc Interv. 2012 Sep 13. [Medline].
Roselli EE, Abdel Azim A, Houghtaling PL, Jaber WA, Blackstone EH. Pulmonary hypertension is associated with worse early and late outcomes after aortic valve replacement: Implications for transcatheter aortic valve replacement. J Thorac Cardiovasc Surg. 2012 Sep 6. [Medline].
Liu S, Xu X, Liu G, Ding X, Zhao X, Qin Y. Comparison of Immediate and Long-term Results between the Single Balloon and Inoue Balloon Techniques for Percutaneous Pulmonary Valvuloplasty. Heart Lung Circ. 2015 Jan. 24(1):40-5. [Medline].
Castenada AR, Jonas RA, Meyer JE. Surgery for infants with congenital heart defects. Cardiac Surgery. 1993. 1013-35.
Gersony WM, Hayes CJ, Driscoll DJ, et al. Bacterial endocarditis in patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect. Circulation. 1993 Feb. 87(2 Suppl):I121-6. [Medline].
[Guideline] 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. 2007 Oct 9. 116(15):1736-54. [Medline].
Almeda FQ, Kavinsky CJ, Pophal SG, Klein LW. Pulmonic valvular stenosis in adults: diagnosis and treatment. Catheter Cardiovasc Interv. 2003 Dec. 60(4):546-57. [Medline].
Park MK. Pulmonary stenosis. Pediatric Cardiology for Practitioners. 145-7.
Rocchini AP, Emmanouilides GC. Pulmonary stenosis. Heart Disease in Infants, Children and Adolescent: Including the Fetus and Young Adult. 930-62.