INTRODUCTION — Nearly all cases of valvular pulmonic stenosis are congenital in origin, and most cases occur as an isolated lesion. Acquired cases of stenosis of the native pulmonary valve are encountered less commonly but may be caused by the carcinoid syndrome or rheumatic fever (in which case pulmonic stenosis is always associated with other valve abnormalities). (See "Clinical manifestations and diagnosis of pulmonic stenosis in adults", section on 'Introduction'.)
Congenital valvular pulmonic stenosis exists in three predominant forms [1]:
●Most cases involve dome-type pulmonic valve stenosis, which is characterized by a narrow central opening with preserved valve motion. Three rudimentary raphes are generally present without clear-cut commissures. The pulmonary trunk may be dilated due to a medial abnormality and eccentric flow from the stenotic valve. Calcification of the valve is rare but is noted in some older patients.
●Approximately 20 percent of cases involve pulmonary valve dysplasia, with thickened valve leaflets and relative immobility of the valve (image 1). Pulmonary artery dilation is not commonly associated with dysplastic valves. Dysplastic pulmonary valves are a common component of Noonan syndrome, occurring in up to half of patients in some studies. (See "Clinical manifestations and diagnosis of pulmonic stenosis in adults", section on 'Introduction' and "Noonan syndrome".)
●More complex congenital heart disease, such as cases of tetralogy of Fallot or transposition of the great arteries, may be associated with a unicuspid or bicuspid pulmonary valve, which may be obstructive. (See "Pathophysiology, clinical features, and diagnosis of tetralogy of Fallot", section on 'Right ventricular outflow tract obstruction'.)
Acquired right ventricular outflow obstruction may occur after surgical reconstruction for congenital cardiac disorders such as tetralogy of Fallot, pulmonary atresia, truncus arteriosus, double outlet right ventricle, or transposition of the great arteries with pulmonic stenosis. Reconstruction often entails the placement of a pulmonary valve prosthesis, right ventricle-to-pulmonary artery homograft, or valved conduit, which degenerates over time, manifesting as stenosis, regurgitation, or both. Treatment of valve, homograft, or conduit dysfunction may be amenable to surgery or percutaneous valve replacement [2,3]. There are increasing numbers of patients with stenosis of bioprosthetic or valved conduits used in repair of more complex congenital lesions affecting the pulmonary valve, such as tetralogy of Fallot, pulmonary atresia, or truncus arteriosus, and these are discussed separately. (See "Management and outcome of tetralogy of Fallot", section on 'Chronic postoperative complications' and "Pulmonary atresia with intact ventricular septum (PA/IVS)" and "Truncus arteriosus", section on 'Management'.)
The natural history and treatment of valvular pulmonic stenosis will be reviewed here. While valvular stenosis in the context of other congenital lesions or more complex congenital heart disease may have similarities, the natural history, clinical consequence, and concomitant lesions may not be the same, which may limit the direct extrapolation of diagnostic strategies and treatment options. Diagnosis and evaluation of pulmonic stenosis and management of pregnancy and pulmonic stenosis are discussed separately. (See "Clinical manifestations and diagnosis of pulmonic stenosis in adults" and "Pregnancy and valve disease", section on 'Pulmonic stenosis'.)
GRADING SEVERITY — The natural history and approach to therapy of valvular pulmonic stenosis are determined by the hemodynamic severity of the obstruction.
The severity of pulmonic stenosis is classified by major society guidelines using the following criteria, which vary depending on which guidelines are used:
●Mild pulmonic stenosis is identified by a peak Doppler gradient across the valve <36 mmHg (equal to peak Doppler jet velocity <3 m/sec) [1,4].
●Moderate stenosis is identified by a peak Doppler gradient of 36 to 64 mmHg (peak jet velocity of 3 to 4 m/sec) [1,4].
●Severe pulmonic stenosis is identified by a peak Doppler gradient >64 mmHg (peak jet velocity of >4 m/sec) [1,4] or mean Doppler gradient >35 mmHg [4].
Although mean gradients have been less commonly used to quantify pulmonic stenosis, the 2018 American Heart Association/American College of Cardiology (AHA/ACC) guidelines for adults with congenital heart disease include a mean gradient criterion for severe pulmonic stenosis since this may reflect the catheter-derived peak-to-peak gradients more accurately than do peak Doppler gradients [4]. A study of 90 patients with isolated pulmonic stenosis found that the mean Doppler gradient more accurately reflected the catheter-derived peak-to-peak gradient [5]. The peak Doppler gradient averaged 24 mmHg higher than the catheter-derived peak-to-peak gradient. Additionally, the studies that demonstrated the effectiveness of transcatheter pulmonary valve replacement in patients with prosthetic pulmonary valves or pulmonary homografts (Melody trial) used mean gradients as an inclusion criterion. Consequently, mean gradient is commonly used when deciding treatment timing for patients with right ventricular outflow obstruction. (See "Percutaneous pulmonic valve implantation".)
MONITORING — We agree with the 2018 American Heart Association/American College of Cardiology (AHA/ACC) adult congenital heart disease guideline recommendations for monitoring asymptomatic patients [4]. For patients with pulmonic stenosis with no symptoms and normal exercise capacity, follow-up with an adult congenital heart disease cardiologist, electrocardiogram, and Doppler echocardiography are recommended at three- to five-year intervals, with exercise testing performed as needed.
NATURAL HISTORY — The probability of survival in patients with isolated valvular pulmonic stenosis is similar to that of the general population. The majority of patients with valvular pulmonic stenosis are asymptomatic [6].
Mild stenosis — Patients with mild pulmonic stenosis are asymptomatic of their valve disease. If symptoms occur, they should not be attributed to pulmonic stenosis. Some adults with mild stenosis will have been diagnosed during childhood [7], but many cases will have gone undetected.
The course during adulthood is generally benign with little progression of stenosis and a persistently high functional status in most patients. In the Natural History Study of Congenital Heart Defects (NHS), for example, among patients with baseline peak systolic valve gradient <25 mmHg, 96 percent were free of operation at 10-year follow-up [6].
Moderate stenosis — Moderate pulmonic stenosis is often detected in childhood and is frequently symptomatic. Dyspnea on exertion and fatigue may occur due to the limitation of right ventricular cardiac output.
A large number of patients with moderate stenosis, particularly symptomatic cases, receive definitive therapy during childhood. These individuals survive into adulthood with life expectancies that are not different from the general population [6]. Long-term follow-up of patients in the NHS found that only 5 percent who had surgical valvotomy or balloon valvotomy in childhood required reoperation [6].
Patients with moderate stenosis treated medically in childhood may fare well into adulthood, although some may show evidence of progression of stenosis [7,8]. Approximately 24 percent of initially asymptomatic patients in the NHS ultimately required a pulmonic valve procedure for progressive symptoms or right ventricular failure; independent predictors of the need for intervention included more severe elevation in the peak systolic gradient and a reduction in cardiac output [6].
Overall, there were few differences between surgically and medically treated patients with moderate pulmonic stenosis in the NHS [6]. Both groups had low levels of cardiac drug use (4 percent) and excellent clinical status as defined by New York Heart Association criteria (97 percent were in class I) (table 1).
Severe stenosis — Severe pulmonic stenosis most often presents in childhood and presents with right ventricular failure and cyanosis. Adults will have usually been treated early in life with either surgical or balloon valvotomy, regardless of symptomatology [7]. The prognosis continues to be good into adulthood after successful treatment [6].
INDICATIONS FOR INTERVENTION — We agree with the 2018 American Heart Association/American College of Cardiology (AHA/ACC) adult congenital heart disease recommendations for intervention in patients with pulmonic stenosis [4]:
●For symptomatic patients (otherwise unexplained symptoms of heart failure, cyanosis from interatrial right-to-left communication, and/or exercise intolerance) with a domed pulmonic valve with moderate or severe valvular stenosis and less than moderate pulmonic valve regurgitation, balloon valvotomy is recommended.
●For symptomatic patients with moderate or severe valvular pulmonic stenosis who are ineligible for or who have failed balloon valvotomy, surgical repair is recommended. This includes patients with severe pulmonic stenosis and an associated hypoplastic pulmonary annulus, severe pulmonary regurgitation, subvalvular pulmonic stenosis, or supravalvular pulmonic stenosis. Surgery is also preferred for most dysplastic valves and when there is associated severe tricuspid regurgitation, the need for a surgical Maze procedure or other cardiac surgical procedure that warrants operative intervention. Balloon valvotomy is less effective in patients with a dysplastic valve (with or without Noonan syndrome), so surgery is generally preferred.
●For asymptomatic patients with a domed pulmonic valve and severe valvular stenosis with less than moderate pulmonic valve regurgitation, balloon valvotomy is suggested.
There are no definite indications for intervening for an asymptomatic dilated pulmonary artery, as these are low pressure aneurysms with an extremely low risk of dissection or rupture. Repair for evidence of symptomatic compression of neighboring structures and repair at the time of valve replacement are reasonable approaches.
LONG-TERM SURGICAL FOLLOW-UP — Long-term follow-up of surgical intervention from the era of the NHS cohort, which was before the current use of percutaneous balloon valvotomy, comes from a report of 53 patients who were initially treated between 1951 and 1982 at a mean age of 10 years; their status was determined 33 years later [9]. Forty of the patients were treated with open valvotomy, with infundibular resection in 13. The following findings were noted:
●Thirty-five reinterventions were performed in 28 patients (53 percent), including pulmonary valve replacement for regurgitation in 21, open valvotomy in five, and balloon valvotomy in three. Most of the reinterventions were performed more than 25 years after the initial procedure. The only predictor of the need for reintervention was closed valvotomy.
●Twenty patients developed an atrial arrhythmia, six of whom had radiofrequency ablation, and three patients developed a ventricular arrhythmia.
Similar outcomes were noted at 22- to 33-year follow-up in a later cohort of 90 consecutive patients who underwent surgery between 1968 and 1980 [10]:
●Survival was 93 percent at 25 years. At last follow-up, 67 percent of patients were in NYHA class I (table 1) and maximal exercise capacity was 90 percent of normal.
●Reintervention was required in 15 percent, primarily for pulmonary regurgitation. Reoperation for pulmonary regurgitation was required in nine percent, particularly after use of the transannular patch technique. At last follow-up, moderate to severe pulmonary regurgitation was present in 37 percent.
●Supraventricular arrhythmias occurred only in patients with severe pulmonary regurgitation and disappeared after reoperation. There were no major ventricular arrhythmias.
BALLOON VALVOTOMY — When intervention is required and pulmonary valve anatomy is suitable (eg, domed), percutaneous balloon valvotomy is the procedure of choice, with excellent short- and long-term results (figure 1). As discussed above, the NHS found that intervention was rarely needed in long-term follow-up of patients with baseline mild disease and that intervention was eventually required in approximately one-quarter of initially asymptomatic patients with moderate disease because of progressive symptoms or right heart failure [6]. Children with severe disease are usually treated early in life but require ongoing follow-up either for regurgitation or residual stenosis. (See 'Natural history' above.)
Procedural considerations — Use of an oversized balloon (approximately 1.2 to 1.25 times the measured pulmonary annulus ) aids in achieving a successful result (defined as a final peak valvular gradient of <20 mmHg) [11].
Acute response — The procedure is generally well tolerated. A mortality rate of 0.2 percent and major complication of 0.6 percent were reported by the Valvuloplasty and Angioplasty of Congenital Anomalies registry [12]. Acute complications are generally minor and include a vagal response, catheter induced ventricular ectopy, right bundle branch block, and transient or permanent high grade AV nodal block [11]. Other complications include pulmonary valve regurgitation, tricuspid regurgitation, stroke, syncope, pulmonary artery rupture, pulmonary edema, cardiac perforation, and tamponade.
Transient severe right ventricular outflow tract obstruction ("suicidal right ventricle") has been reported after the pulmonic valvular obstruction has been relieved [11,13,14]. This may be treated by volume expansion and beta blocker therapy and tends to regress with time [14].
A pooled analysis of studies involving 784 patients of all ages showed that clinical success was achieved with balloon valvotomy in 98 percent, with a fall in the systolic outflow gradient from 71 to 28 mmHg [12]. Procedural mortality was less than 0.5 percent. Among the 196 patients in whom such data could be obtained, transvalvular and infundibular obstruction were each responsible for approximately one-half of the total residual gradient. After balloon valvuloplasty, a residual infundibular gradient tended to decline over several months as right ventricular hypertrophy diminished. Other studies reported similar reductions in the systolic outflow gradient (eg, 91 to 38 mmHg and 93 versus 19 mmHg) [15-17].
Long-term efficacy — The long-term efficacy of percutaneous balloon valvotomy was evaluated in a series of 53 adolescent and adult patients 13 to 55 years of age treated between 1985 and 1995 [15]. The systolic pressure gradient across the pulmonary valve fell from 91 to 38 mmHg after the procedure and had fallen further at late follow-up an average of seven years later. In 7 of 53 patients who developed pulmonary insufficiency immediately after balloon valvotomy, none had this complication at late follow-up.
In another report, 62 patients 9 months to 44 years of age were followed for 1 to 10 years (mean 6.4 years) after percutaneous balloon valvotomy [16]. The mean transvalvular gradient fell from 93 to 19 mmHg immediately after the procedure, and was 18 mmHg at follow-up. Progressive spontaneous regression of infundibular hypertrophy was noted. Restenosis occurred in less than 5 percent and was more likely in patients with dysplastic valves.
Similar findings were noted in a series of 85 patients followed for up to 10 years [18]. Repeat balloon dilation was required in 11 percent and surgical intervention for subvalvular or supravalvular stenosis in 5 percent. Although residual pulmonary regurgitation was noted in the majority of patients, it was mild and right ventricular volume overload did not ensue.
Longer-term follow-up is available after surgical correction than after balloon valvotomy. As noted above, patients who underwent surgical valvotomy had, at 33-year follow-up, a 53 percent likelihood of reintervention; most reinterventions were performed more than 25 years after the procedure [9]. The applicability of these findings to balloon valvotomy is uncertain. Surgery tended to produce lower long-term gradients but a higher rate of pulmonary insufficiency (45 versus 11 percent in one series) [19]. This may be important since pulmonary insufficiency requiring pulmonary valve replacement was the indication for reintervention in three-quarters of the patients in the surgical series.
Pulmonary regurgitation following valvotomy — Though concomitant stenosis and regurgitation occur in acquired or degenerative valve disease, it is relatively uncommon in isolated untreated pulmonary stenosis. The prevalence and severity of pulmonary regurgitation (PR) are higher in patients with pulmonic stenosis who have undergone balloon valvotomy. While mild degrees of pulmonary regurgitation are well tolerated, more significant pulmonary regurgitation may result in right ventricular enlargement and dysfunction, sufficient to consider pulmonary valve replacement. Echocardiographic or cardiac magnetic resonance indication for pulmonic regurgitation in asymptomatic patients is not known. While some practitioners may utilize criteria for other diseases for which pulmonary regurgitation is a common sequela, such as tetralogy of Fallot, data are lacking to support such an approach.
In patients with PR following valvotomy, we assess PR severity and right ventricular size (algorithm 1) [4].
●In patients with no or mild PR, we perform routine follow-up. For patients with mild PR clinical and imaging follow-up every two years is reasonable.
●In patients with moderate or greater PR and right ventricular enlargement, we assess for the presence of symptoms caused by PR.
•We refer patients with symptomatic PR for pulmonic valve replacement.
•For patients with no or uncertain symptoms due to PR, we perform serial imaging and cardiopulmonary exercise testing. Patients should receive follow-up imaging at least every 12 months.
-For patients with RV dysfunction, progressive RV dilation, or progressive decrease in exercise capacity, we refer to a heart valve team for individualized assessment of the benefit/risk of pulmonary valve replacement.
-For patients without the above changes, we follow-up according to the patient’s physiologic stage (at least every 12 months).
If the pulmonary valve must be replaced, surgery is the available option, though there is an ongoing clinical trial of percutaneous pulmonary valve replacement in native outflow tracts.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)
SUMMARY AND RECOMMENDATIONS
●The severity of pulmonic stenosis is classified echocardiographically according to either the peak or mean Doppler gradients across the valves. Although peak gradients have been more commonly used, the mean gradients may more accurately reflect catheter-derived peak-to-peak gradients. (See 'Grading severity' above.)
●The majority of adult patients with valvular pulmonic stenosis have mild stenosis and are asymptomatic. Patients with moderate pulmonic stenosis frequently develop dyspnea and fatigue. Patients with severe stenosis may develop early right ventricular failure and cyanosis. (See 'Natural history' above.)
●For symptomatic patients (otherwise unexplained symptoms of heart failure, cyanosis from interatrial right-to-left communication, and/or exercise intolerance) with a domed pulmonic valve with moderate or severe valvular stenosis and less than moderate pulmonic valve regurgitation, balloon valvotomy is recommended.
●For symptomatic patients with moderate or severe valvular pulmonic stenosis who are ineligible for or who have failed balloon valvotomy, surgical repair is recommended. This includes patients with severe pulmonic stenosis and an associated hypoplastic pulmonary annulus, severe pulmonary regurgitation, subvalvular pulmonic stenosis, or supravalvular pulmonic stenosis. Surgery is also preferred for most dysplastic valves and when there is associated severe tricuspid regurgitation, the need for a surgical Maze procedure or other cardiac surgical procedure that warrants operative intervention. Balloon valvotomy is less effective in patients with a dysplastic valve (with or without Noonan syndrome), so surgery is generally preferred.
●For asymptomatic patients with a domed pulmonic valve and severe valvular stenosis with less than moderate pulmonic valve regurgitation, balloon valvotomy is suggested.
●Dynamic right ventricular outflow obstruction has been reported after surgical or percutaneous treatment of pulmonic stenosis and tends to regress with time. (See 'Acute response' above.)
