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Education in Heart
Congenital heart disease in adult patients
Pulmonary valve stenosis in the adult patient: pathophysiology, diagnosis and management
  1. Emily Ruckdeschel,
  2. Yuli Y Kim
  1. Philadelphia Adult Congenital Heart Center, Penn Medicine and the Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  1. Correspondence to Dr Emily Ruckdeschel, Philadelphia Adult Congenital Heart Center, Philadelphia PA 19104, USA; ruckdesche{at}email.chop.edu

https://doi.org/10.1136/heartjnl-2017-312743

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    Learning objectives

    • Know the epidemiology and presentation of pulmonary valve disease in adults.

    • Understand the long-term sequelae of untreated and treated pulmonary valve disease.

    • Recognise the indications for intervention in pulmonary valve disease in adults.

    Introduction

    The most common form of right ventricular outflow tract (RVOT) obstruction is pulmonary valve stenosis. Pulmonary stenosis (PS) occurs in isolation in 8%–10% of congenital heart disease but is often associated with other congenital lesions1 Subvalvar and supravalvar PS are less common but also seen in adults. PS and supravalvar PS are most often congenital and can be associated with genetic syndromes including Noonan, Alagille and Williams syndromes as well as congenital rubella. PS can also be an acquired condition such as rheumatic heart disease, carcinoid, infective endocarditis or result from trauma. Pulmonary valve disease is often accompanied by pulmonary regurgitation (PR) as a result of inherent abnormalities of the valve or from prior intervention. This review will focus primarily on isolated forms of pulmonary valve disease in adults.

    Physiology

    Abnormalities of the pulmonary valve, subvalvar or supravalvar region can lead to RVOT obstruction. The primary consequence of PS is pressure overload of the right ventricle, the degree of which is dependent on the severity of the stenosis. Pressure overload of the right ventricle results in increased contractility and dilation leading to increased wall stress and compensatory right ventricular hypertrophy. Increased muscle mass allows for the right ventricle to maintain a normal cardiac output. Right ventricular hypertrophy may cause a decrease in ventricular compliance and result in increased right ventricular end-diastolic pressures and increased right atrial pressures. Right-to-left shunting may occur if there is an interatrial communication. Over time, progressive right ventricular hypertrophy and stiffness can give rise to right ventricular diastolic and systolic dysfunction.

    Chronic severe PR results in right ventricular dilation. Increased right ventricular end-diastolic volume allows for a compensatory increase in stroke volume to maintain cardiac output. Long-standing right ventricular volume load can result in right ventricular diastolic dysfunction with elevation in right ventricular end-diastolic pressure. Dilation of the right ventricle and tricuspid annulus forms the substrate for functional tricuspid regurgitation which compounds the volume load.

    Pathology

    Pulmonary valve stenosis

    A pulmonary valve which is conical or dome shaped is considered the classic form of PS. Raphe may be present but there is no separation of cusps resulting in a small central orifice. Less commonly, PS is the result of a dysplastic pulmonary valve that is typically trileaflet but with markedly thickened and myxomatous cusps. Dysplastic valves are often found in association with a hypoplastic annulus, supravalvar stenosis and in the setting of other cardiac and non-cardiac anomalies. Unicuspid or bicuspid pulmonic valves are rarely isolated and are usually found in complex congenital heart disease such as tetralogy of Fallot (figure 1). Aneurysmal dilation of the pulmonary artery is seen in association with PS. Dilation tends to affect the main pulmonary artery and left pulmonary artery secondary to the poststenotic jet but is not consistently associated with the degree of PS.

    Figure 1
    Figure 1

    Classification of pulmonary valve stenosis. The pulmonary valve can be (A) a commissural or (B) unicommissural with prominent systolic doming of the cusps and an eccentric orifice. (C) Bicuspid pulmonary valve is shown with fused commissures. (D) Dysplastic pulmonary valve is severely thickened with deformed valve cusps.

    Subpulmonic stenosis

    The outflow portion of the right ventricle, also known as the infundibulum, may be a location of RVOT obstruction. Obstruction in the subpulmonary region may be secondary to a discrete fibromuscular ridge/ring or hypertrophied muscle bundles. Alternatively, hypertrophied supporting bands of the right ventricle may occur, resulting in obstruction at the infundibular ostium and effectively dividing the right ventricle into two chambers. This is referred to as a double-chambered right ventricle (DCRV) and is relatively rare occurring in only 0.2%–2.0% of all cases of congenital heart disease.2 The DCRV consists of a high-pressure proximal chamber and a low-pressure distal chamber below the pulmonary valve. DCRV is often seen in association with other congenital lesions such as tetralogy of Fallot, ventricular septal defects (VSD) or transposition of the great arteries. The exact mechanism for hypertrophy of the muscles bundles is not well understood.

    Pulmonary regurgitation

    PR is most often the result of prior intervention on the pulmonary valve and is not typically seen in isolation. It is common after both percutaneous and surgical interventions on the pulmonary valve. The right ventricle adapts to chronic volume loading with progressive dilation and eventual deterioration of ventricular function. Historically considered benign, it is now understood that long-term chronic severe PR as seen in tetralogy of Fallot results in progressive RV dilation with eventual RV dysfunction and associated exercise intolerance, ventricular tachycardia and risk of sudden cardiac death.3 PR in an anatomically normal pulmonic valve can result from pulmonary hypertension or dilated pulmonary artery in Marfan syndrome.4

    Clinical manifestations

    Pulmonary stenosis

    Presentation of PS is dependent on the severity of the disease. Mild and moderate PS are often incidentally diagnosed after a murmur is auscultated. Symptoms may develop in patients with moderate to severe stenosis as they age and include dyspnoea and fatigue with exertion. In severe stenosis, the right ventricle is unable to augment cardiac output which may lead to exertional chest pain, syncope and rarely sudden cardiac death. The mechanism may be secondary to decreased myocardial perfusion in the setting of significant right ventricular hypertrophy leading to ischaemia and resultant arrhythmia. Desaturation may occur from right-to-left shunting across an atrial level communication such as atrial septal defect or patent foramen ovale. Right heart failure is uncommon in adults but may occur if severe disease is left untreated.

    Pulmonary regurgitation

    PR is typically tolerated well for many years and is more likely to present symptomatically later in life in those without other associated lesions.5 Though physiologically distinct, lessons learnt from the effects of chronic aortic regurgitation on the left ventricle have suggested that chronic severe PR may follow a similar course. After an asymptomatic compensatory phase in which semilunar valve regurgitation is well tolerated for many years, there is a maladaptive phase consisting of progressive ventricular remodelling and eventually ventricular dysfunction that can be accompanied by symptoms.6 Symptoms of severe PR include exercise intolerance and arrhythmias. In the long term, patients may develop signs and symptoms of right heart failure including oedema, elevated jugular venous pressure. Long-term outcomes in patients with PR are primarily derived from patients with tetralogy of Fallot who have undergone different surgical interventions (ie, VSD closure, RVOT augmentation) than those with isolated pulmonary valve disease. Sudden death in the tetralogy of Fallot population is likely mediated by ventricular tachycardia7 and is therefore not clear that this risk exists to the same extent in patients with isolated pulmonary valve disease.

    Diagnosis

    Physical examination

    The physical examination findings in PS are dependent on the severity of the disease. There is a systolic crescendo–decrescendo murmur heard in the pulmonic position that increases with inspiration and usually ends in mid-systole in mild stenosis but can extend further with increasing severity of obstruction. Mild PS typically has a murmur of grade 3 or lower with moderate to severe stenosis characterised by grade 4 or higher with right ventricular lift and associated thrill which radiates to the back. The murmur may be soft if there is associated right heart failure and low cardiac output. There may be a pulmonic ejection click that decreases with inspiration. An earlier click is consistent with more significant stenosis and the click will merge with the first heart sound in severe stenosis. The second heart sound is usually split. The degree of S2 splitting is proportional to the degree of stenosis and may be widely split and fixed. The P2 component may be reduced or absent with severe stenosis, however, which can make S2 splitting difficult to appreciate (figure 2). A right-sided S4 gallop may be auscultated. In severe pulmonic stenosis, the jugular venous pressure can be elevated with a prominent ‘a’ wave.

    Figure 2
    Figure 2

    Phonographic assessment of pulmonary stenosis. Note prolongation of the murmur and increased width of splitting with progressively severe pulmonary stenosis. The aortic component (A2) is obscured in severe stenosis with associated present but softer pulmonary component (P2). The ejection click (C) occurs after the first heart sound (S1) in mild stenosis but progressively merges with the first heart sound with increasing severity (adapted from Vogelpoel and Schrire45). RV, right ventricular.

    The murmur of PR is auscultated over the pulmonic area and starts after a brief pause following P2. It is characterised as a low frequency decrescendo murmur that augments with inspiration. The pitch and length of the diastolic murmur depend on pulmonary arterial and right ventricular end-diastolic pressure. With right ventricular hypertrophy, there can be rapid deceleration of regurgitant blood flow from the pulmonary artery which can produce a right-sided S3 gallop.

    ECG/chest X-ray

    ECG is often normal in mild stenosis or show subtle right axis deviation. In moderate and severe PS, there is increased right axis deviation from right ventricular hypertrophy with associated high amplitude R waves in V1, deep S waves in V6 and R:S ratio of <1. Patients with associated severe PR may have prolonged QRS duration reflective of volume loading and enlargement of the right ventricle. Chest X-ray may demonstrate enlargement of the pulmonary artery and in severe stenosis there may be mild cardiomegaly. Patients with right heart failure can demonstrate a larger cardiac silhouette.

    Echocardiography

    Echocardiogram is the most common imaging technique and allows for the assessment of location of obstruction, valve morphology and degree of stenosis. In addition, information can be obtained about the RVOT, pulmonary annulus, pulmonary arteries and right ventricular size and function. The pulmonary valve is best seen in the parasternal short-axis view (figure 3). Transoesophageal echocardiography can be challenging for examination of the pulmonary valve and it is typically seen in the mid-oesophageal window with transducer positions from 50 to 90.8 Doppler interrogation of the pulmonary valve can estimate the systolic pressure gradient using the simplified Bernoulli equation. Assessment of the gradient in DCRV can be challenging secondary to difficulty aligning the Doppler angle and the gradient may be underestimated in some cases. Assessment of right ventricular hypertrophy is best done through parasternal and subcostal long-axis views. Right ventricular dilation is best assessed from apical four-chamber views. Quantification of right ventricle dilation is challenging by echocardiography and typically advanced imaging is required for accurate assessment.

    Figure 3
    Figure 3

    Cardiac MRI in severe pulmonary regurgitation. Short-axis stack of cine steady-state free precession cardiac MRI in repaired tetralogy of Fallot. Right ventricular volume and ejection fraction is calculated by tracing the endocardial border at end-diastole and end-systole for each slice. Note the severely dilated right ventricle and diastolic flattening of the interventricular septum.

    The definition of severe PS according to the 2014 American Heart Association (AHA)/American College of Cardiology (ACC) guidelines for the management of patients with valvular heart disease is a Vmax greater than 4 m/s or peak instantaneous gradient greater than 64 mm Hg6 (table 1). In the ACC/AHA 2008 guidelines for the management of adults with congenital heart disease, severe pulmonic stenosis is defined as a peak gradient greater than 50 mm Hg, moderate when the gradient is 30–50 mm Hg and mild when less than 30 mm Hg.9

    View this table:
    Table 1

    Severity of pulmonic valve stenosis

    Physiological conditions which alter flow across the pulmonary valve affect the accuracy of calculated gradient by the modified Bernoulli equation. For example, if there is severe right ventricular systolic dysfunction, the right ventricle cannot generate sufficient pressure to overcome significant stenosis. Lower flow across the valve will yield a peak instantaneous gradient that underestimates the true severity of the stenosis. Similarly, left-to-right flow across a septal defect or concomitant PR increases flow across the pulmonic valve, thereby increasing the transpulmonary gradient and overestimating the severity of pulmonic valve stenosis. Long-segment stenosis and serial obstructions (ie, associated subvalvar and/or supravalvar pulmonary artery stenosis) are also other conditions in which Doppler-derived gradients are less reliable.

    Peak instantaneous gradients by echocardiography overestimate peak-to-peak gradients in the catheterisation laboratory and may be exaggerated by effects of sedation. Right ventricular systolic pressure estimates by tricuspid regurgitation peak velocity, qualitative assessment of septal position, as well as degree of right ventricular hypertrophy can provide additional information on pulmonic stenosis severity. Correlation between the Doppler gradient derived by echocardiography with clinical findings is recommended.

    Echocardiographic assessment of pulmonary valve regurgitation can at times be challenging and has not been well studied. Assessment techniques typically used for aortic regurgitation are applied with varying degrees of success.10 The proximal jet width of PR seen with colour Doppler is commonly used to grade regurgitation and can be expressed as a ratio relative to the pulmonary valve annulus diameter. A ratio of >0.5 is correlated with severe PR as measured by cardiac MRI (CMR).11 Severe PR in the setting of normal pulmonary artery pressures can be difficult to assess secondary to rapid equalisation of pressures across the pulmonary valve and brief duration of a colour flow jet. Secondary evidence of right ventricular volume overload such as septal flattening during diastole should be used as supportive evidence of severe PR. Other evidence of severe PR is a dense jet with rapid deceleration seen on pulsed or continuous wave Doppler and diastolic flow reversal in the branch pulmonary arteries.10

    Cardiac CT

    CT is excellent for assessing anatomy, particularly of the branch pulmonary arteries where echocardiography is inadequate. Though modern CT protocols allow for assessment of ventricular size and function it often requires increased doses of radiation. In patients with metal artefact or devices CT can be a helpful adjunct to echocardiography when MRI is not feasible.

    Cardiac MRI

    CMR is useful for assessing anatomy and for quantification of PR as well as RV size and function and is considered the imaging modality of choice for these reasons (figure 3). Cine imaging, phase contrast techniques and MR angiography allow for more precise quantification compared with echocardiography.12 CMR is well suited for the evaluation of right ventricular volumes and function given that geometry of the right ventricle is better viewed in three dimensions. Grading of PR by CMR is typically reported as mild if regurgitation fraction is <20%, moderate if 20%–40% and severe if >40%, though some would suggest >35% as severe.10 13 The degree of stenosis can also be assessed using velocity mapping but gradients determine by echocardiography are typically preferred.

    Cardiac catheterisation

    Historically, cardiac catheterisation was the gold standard for diagnosing PS but now no longer required for diagnostic purposes with the advent of other imaging techniques. Haemodynamic assessment can be helpful when other forms of imaging are limited or the severity of disease is in question. At the time of cardiac catheterisation, haemodynamic data including pressure gradient across the pulmonary valve, right ventricular systolic pressure compared with systemic pressures and right-sided filling pressures are obtained. In patients with normal cardiac output, mild stenosis is defined as a gradient <35 to 40 mm Hg or right ventricular pressure less than half systemic. Moderate stenosis is a gradient between 40 and 60 mm Hg with right ventricular pressures between half to three-quarters systemic. Severe PS is defined as a gradient >60 mm Hg or a right ventricular pressure at least three-quarters systemic.1 Angiography can demonstrate the morphological characteristics of the pulmonary valve including cusp thickening, mobility and excursion or cusp tethering as well as associated lesions including annular hypoplasia, infundibular obstruction or distal main or branch pulmonary artery stenosis (figure 4).

    Figure 4
    Figure 4

    Valvar pulmonary stenosis. (A) Parasternal short-axis view by echocardiogram focused over the MPA showing a thickened pulmonic valve that domes in systole (arrow) by transthoracic echocardiography. (B) Anteroposterior and (C) lateral projections of a right ventriculogram demonstrating doming pulmonic valve cusps (arrow). Note the dilated main pulmonary artery. MPA, main pulmonary artery; RA, right atrium; RV, right ventricle; RVOT, right ventricular outflow tract.

    There is mixed data on the accuracy of peak instantaneous gradients derived by echocardiography compared with invasive gradients by cardiac catheterisation for pulmonic stenosis. Some studies have demonstrated excellent correlation with peak-to-peak gradients14 15 whereas others have shown peak instantaneous gradients to overestimate peak-to-peak gradients but are comparable to catheter-derived maximal instantaneous gradient.16 17 More recently, mean Doppler gradients were shown to have the best correlation with peak-to-peak gradient in isolated18 and complex19 PS.

    Treatment/management

    Pulmonary stenosis

    There is no standard medical management for patients with PS. If symptoms of right heart failure are present it may be reasonable to consider the use of diuretics.

    The natural history of mild PS is typically benign. Those patients with gradients <25 mm Hg in childhood almost never require intervention in early adulthood and had equivalent survival to those without PS. Those with gradients of 25–49 mm Hg had a 20% of requiring intervention in follow-up. Most patients with gradients of 50–79 mm Hg required intervention.20

    Indications for intervention in pulmonic valve stenosis are summarised in table 2. It is recommended that patients with peak instantaneous Doppler gradients less than 30 mm Hg be followed at 5-year intervals and every 2–5 years with echocardiography in the asymptomatic patients with gradients greater than 30 mm Hg.9 Successful percutaneous balloon valvuloplasty was initially reported in 1982 and is the treatment of choice for classic domed PS.21 The mechanism for relief of stenosis is commissural splitting with generally excellent outcomes.22 Though outcomes are not as optimal compared with classic domed pulmonic valve stenosis, balloon valvuloplasty may provide some degree of relief for dysplastic pulmonic valves and is a reasonable first-line option.23

    View this table:
    Table 2

    Recommendations for intervention in right ventricular outflow tract obstruction, pulmonic valve and supravalvar pulmonary stenosis9 48

    A large multicentre registry of 533 patients followed for a median of 33 months (range 1 month to 8.7 years) after balloon valvuloplasty showed that 23% had suboptimal results (residual gradient >36 mm Hg, repeat valvuloplasty or surgical valvotomy). Predictors of suboptimal outcome included earlier study year of intervention, higher residual postprocedural gradient or valvar anatomy.24 More recently, outcomes were reported on 139 patients who underwent balloon valvuloplasty with a median follow-up of 6 years (range 0–21 years) which showed reintervention was required in only 9.4% of patients, mostly for restenosis. On longer follow-up, mild PR is common but at least moderate PR was observed in up to 60% of patients after a median follow-up of 15.1 years (range 10.1–26.3 years).25 26

    When balloon valvuloplasty is not sufficient, surgical intervention can be considered. And for isolated forms of infundibular obstruction, surgery is the only option in which obstructing muscle bundles or discrete fibrous tissue are resected. Surgical relief of pulmonic stenosis involves commissurotomy or valvotomy via an incision through the pulmonary trunk using an open or closed technique. Valvectomy is reserved for situations in which simple valvotomy is inadequate, that is, dysplastic pulmonic valves. A transannular patch using autologous pericardium may be required to enlarge the annulus and supravalvar area. Outcomes of surgical valvotomy demonstrate excellent survival but there is a significant incidence of PR necessitating repeat surgical intervention such as pulmonary valve replacement (PVR) later in life.27

    Worsening of infundibular obstruction after relief of pulmonic valve stenosis is a well-documented phenomenon after surgical valvotomy and balloon valvuloplasty but improves over time with regression of right ventricular hypertrophy.28 29

    Pulmonary regurgitation

    PR is common after intervention of PS as noted above. PVR leads to decreases in right ventricular size and improvements in symptoms. Indications for PVR for asymptomatic severe PR in the setting of isolated pulmonary valve disease are not well established, but recent research suggests that size thresholds used for tetralogy of Fallot may be reasonable.30 In patients with severe right ventricular dilation or decreased ejection fraction, PVR may not improve right ventricular size or function if performed too late. Current guidelines are geared towards intervening prior to development of irreversible changes and are based on size thresholds determined by CMR. Size thresholds beyond which RV size has less chance of reverse remodelling have evolved to current values with a push towards earlier surgery: right ventricular end-diastolic volume of 150 mL/m2, end-systolic volume of 80 mL/m2 or right ventricular end-diastolic volume to left ventricular end-diastolic volume ratio >2.31–33 Despite this approach on timing of PVR, there is no current evidence to support mortality benefit PVR in patients with tetralogy of Fallot,34 though long-term data are lacking.

    Surgical PVR

    Historically, PVR has been performed surgically with low morbidity and mortality. Prosthetic pulmonic valve dysfunction and valve durability is limited with the average lifespan estimated to be 10–15 years.35 36 Though the right ventricle initially improves in size, there is evidence of progressive prosthetic pulmonic valve dysfunction and right ventricular deterioration with return to preoperative right ventricular size over the ensuing 10 years.37 Given this and the variability of right ventricular remodelling after restoration of RVOT and pulmonic valve competence, it is difficult to know what criteria clinicians should use to refer for repeat PVR in the absence of symptoms.

    Transcatheter pulmonary valve implantation

    Since its inception in 2000, there is increasing availability of and experience with transcatheter pulmonary valves.38 Historically, these were only available for use in those with prior right ventricle to pulmonary artery conduits or those with prior surgically placed prosthetic pulmonary valves. Though no head-to-head studies have directly compared transcatheter versus surgically implanted pulmonic valves, reductions in PR and right ventricular size appear to be comparable.39 40 Earlier studies have suggested a rate of endocarditis above what is expected in surgical PVR, estimated to be as high as 10%–15% in the medium term compared with 1%–2% in surgically implanted valves, though recent data are mixed.41–44 The newer development of larger transcatheter valves and stents (Harmony Valve, Venus-P valve and Alterra stent) are all designed for use in native or surgically augmented RVOTs (without prior pulmonary valve implantation) and employ self-expanding technology. With increasing use of transcatheter technology, it is important that heart teams comprised cardiologists, cardiovascular surgeons, interventionalists and anaesthesiologists work together to determine the best intervention for patients and to ensure that procedures are done safely and effectively. At the time of writing, thresholds for transcatheter pulmonary valve implantation are similar to those for surgical PVR though this may change in the future. Currently, available transcatheter devices are detailed in table 3.

    View this table:
    Table 3

    Transcatheter pulmonic valve implantation options

    Summary

    RVOT obstruction in the form of pulmonary valve stenosis is a relatively common form of congenital heart disease in adults. Intervention may be required in symptomatic or severe valvar PS and is often done via a catheter-based procedure. Outcomes from balloon valvuloplasty are good but long term issues with PR are common and may later require PVR. Transcatheter pulmonary valve implantation is quickly evolving as an option for many.

    Key messages

    • Congenital valvar pulmonary stenosis (PS), that is, mild in severity is well tolerated with a benign natural history.

    • Balloon angioplasty is the first-line treatment for severe valvar PS, especially for doming pulmonic valves.

    • Double-chambered right ventricle is an uncommon form of right ventricular outflow tract obstruction in which the right ventricle is divided into a proximal high-pressure and distal low-pressure chamber. Surgical repair is effective with low morbidity and mortality.

    • Assessment of right ventricular size and function is best done with cardiac MRI as imaging and geometry limit evaluation of the right ventricle using echocardiography.

    • Indications for pulmonic valve replacement (PVR) are continuing to evolve and are currently based on symptoms, right ventricular size and systolic function with a heavy reliance on cardiac MRI assessment.

    • PVR has been shown to improve symptoms but does not consistently improve right ventricular systolic function and there is no data demonstrating mortality benefit.

    • Transcatheter pulmonary valve implantation has emerged as an alternative therapy for some patients and rapidly evolving technologies hold promise for expanding eligibility to others. No head-to-head studies have directly compared surgical versus transcatheter approaches but short-term to mid-term outcomes regarding right ventricular remodelling and symptomatic improvement are similar.

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    References

    1. 1.↵
      2. Prieto LR ,
      3. Latson LA
      . Pulmonary Stenosis. In: Allen HD , Shaddy RE , Penny DJ , eds. Moss and Adams' Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adult. Phildadelphia: Lippincott Williams & Wilkins, 2016:983–1007.
    2. 2.↵
      2. Loukas M ,
      3. Housman B ,
      4. Blaak C , et al
      . Double-chambered right ventricle: a review. Cardiovasc Pathol 2013;22:417–23.doi:10.1016/j.carpath.2013.03.004
      OpenUrlCrossRefPubMed
    3. 3.↵
      2. Bouzas B ,
      3. Kilner PJ ,
      4. Gatzoulis MA
      . Pulmonary regurgitation: not a benign lesion. Eur Heart J 2005;26:433–9.doi:10.1093/eurheartj/ehi091
      OpenUrlCrossRefPubMedWeb of Science
    4. 4.↵
      2. Waller BF ,
      3. Howard J ,
      4. Fess S
      . Pathology of pulmonic valve stenosis and pure regurgitation. Clin Cardiol 1995;18:45–50.doi:10.1002/clc.4960180112
      OpenUrlCrossRefPubMedWeb of Science
    5. 5.↵
      2. Shimazaki Y ,
      3. Blackstone EH ,
      4. Kirklin JW
      . The natural history of isolated congenital pulmonary valve incompetence: surgical implications. Thorac Cardiovasc Surg 1984;32:257–9.doi:10.1055/s-2007-1023399
      OpenUrlCrossRefPubMedWeb of Science
    6. 6.↵
      2. Nishimura RA ,
      3. Otto CM ,
      4. Bonow RO , et al
      . AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;2014:2438–88.
      OpenUrl
    7. 7.↵
      2. Khairy P
      . Ventricular arrhythmias and sudden cardiac death in adults with congenital heart disease. Heart 2016;102:1703–9.doi:10.1136/heartjnl-2015-309069
      OpenUrlAbstract/FREE Full Text
    8. 8.↵
      2. Baumgartner H ,
      3. Hung J ,
      4. Bermejo J , et al
      . Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. J Am Soc Echocardiogr 2009;22:1–23.doi:10.1016/j.echo.2008.11.029
      OpenUrlCrossRefPubMedWeb of Science
    9. 9.↵
      2. Warnes CA ,
      3. Williams RG ,
      4. Bashore TM , et al
      . ACC/AHA 2008 Guidelines for the management of adults with congenital heart disease: Executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to develop guidelines for the management of adults with congenital heart disease). Circulation 2008;118:2395–451.doi:10.1161/CIRCULATIONAHA.108.190811
      OpenUrlFREE Full Text
    10. 10.↵
      2. Zoghbi WA ,
      3. Adams D ,
      4. Bonow RO , et al
      . Recommendations for noninvasive evaluation of native valvular regurgitation: A report from the american society of echocardiography developed in collaboration with the society for cardiovascular magnetic resonance. J Am Soc Echocardiogr 2017;30:303–71.doi:10.1016/j.echo.2017.01.007
      OpenUrl
    11. 11.↵
      2. Renella P ,
      3. Aboulhosn J ,
      4. Lohan DG , et al
      . Two-dimensional and Doppler echocardiography reliably predict severe pulmonary regurgitation as quantified by cardiac magnetic resonance. J Am Soc Echocardiogr 2010;23:880–6.doi:10.1016/j.echo.2010.05.019
      OpenUrlCrossRefPubMed
    12. 12.↵
      2. Saremi F ,
      3. Gera A ,
      4. Ho SY , et al
      . CT and MR imaging of the pulmonary valve. Radiographics 2014;34:51–71.doi:10.1148/rg.341135026
      OpenUrl
    13. 13.↵
      2. Kawel-Boehm N ,
      3. Maceira A ,
      4. Valsangiacomo-Buechel ER , et al
      . Normal values for cardiovascular magnetic resonance in adults and children. J Cardiovasc Magn Reson 2015;17:29.doi:10.1186/s12968-015-0111-7
      OpenUrlCrossRefPubMed
    14. 14.↵
      2. Lima CO ,
      3. Sahn DJ ,
      4. Valdes-Cruz LM , et al
      . Noninvasive prediction of transvalvular pressure gradient in patients with pulmonary stenosis by quantitative two-dimensional echocardiographic Doppler studies. Circulation 1983;67:866–71.doi:10.1161/01.CIR.67.4.866
      OpenUrlAbstract/FREE Full Text
    15. 15.↵
      2. Frantz EG ,
      3. Silverman NH
      . Doppler ultrasound evaluation of valvar pulmonary stenosis from multiple transducer positions in children requiring pulmonary valvuloplasty. Am J Cardiol 1988;61:844–9.doi:10.1016/0002-9149(88)91077-6
      OpenUrlCrossRefPubMedWeb of Science
    16. 16.↵
      2. Aldousany AW ,
      3. DiSessa TG ,
      4. Dubois R , et al
      . Doppler estimation of pressure gradient in pulmonary stenosis: maximal instantaneous vs peak-to-peak, vs mean catheter gradient. Pediatr Cardiol 1989;10:145–9.doi:10.1007/BF02081678
      OpenUrlCrossRefPubMedWeb of Science
    17. 17.↵
      2. Currie PJ ,
      3. Hagler DJ ,
      4. Seward JB , et al
      . Instantaneous pressure gradient: a simultaneous Doppler and dual catheter correlative study. J Am Coll Cardiol 1986;7:800–6.doi:10.1016/S0735-1097(86)80339-4
      OpenUrlFREE Full Text
    18. 18.↵
      2. Silvilairat S ,
      3. Cabalka AK ,
      4. Cetta F , et al
      . Echocardiographic assessment of isolated pulmonary valve stenosis: which outpatient Doppler gradient has the most clinical validity? J Am Soc Echocardiogr 2005;18:1137–42.doi:10.1016/j.echo.2005.03.041
      OpenUrlCrossRefPubMedWeb of Science
    19. 19.↵
      2. Silvilairat S ,
      3. Cabalka AK ,
      4. Cetta F , et al
      . Outpatient echocardiographic assessment of complex pulmonary outflow stenosis: Doppler mean gradient is superior to the maximum instantaneous gradient. J Am Soc Echocardiogr 2005;18:1143–8.doi:10.1016/j.echo.2005.04.003
      OpenUrlPubMed
    20. 20.↵
      2. Hayes CJ ,
      3. Gersony WM ,
      4. Driscoll DJ , et al
      . Second natural history study of congenital heart defects. Results of treatment of patients with pulmonary valvar stenosis. Circulation 1993;87:I28–37.
      OpenUrlPubMed
    21. 21.↵
      2. Kan JS ,
      3. White RI ,
      4. Mitchell SE , et al
      . Percutaneous balloon valvuloplasty: a new method for treating congenital pulmonary-valve stenosis. N Engl J Med 1982;307:540–2.doi:10.1056/NEJM198208263070907
      OpenUrlCrossRefPubMedWeb of Science
    22. 22.↵
      2. Ananthakrishna A ,
      3. Balasubramonium VR ,
      4. Thazhath HK , et al
      . Balloon pulmonary valvuloplasty in adults: immediate and long-term outcomes. J Heart Valve Dis 2014;23:511–5.
      OpenUrl
    23. 23.↵
      2. Feltes TF ,
      3. Bacha E ,
      4. Beekman RH , et al
      . Indications for cardiac catheterization and intervention in pediatric cardiac disease: a scientific statement from the American Heart Association. Circulation 2011;123:2607–52.doi:10.1161/CIR.0b013e31821b1f10
      OpenUrlFREE Full Text
    24. 24.↵
      2. McCrindle BW
      . Independent predictors of long-term results after balloon pulmonary valvuloplasty. Valvuloplasty and Angioplasty of Congenital Anomalies (VACA) Registry Investigators. Circulation 1994;89:1751–9.doi:10.1161/01.CIR.89.4.1751
      OpenUrlAbstract/FREE Full Text
    25. 25.↵
      2. Voet A ,
      3. Rega F ,
      4. de Bruaene AV , et al
      . Long-term outcome after treatment of isolated pulmonary valve stenosis. Int J Cardiol 2012;156:11–15.doi:10.1016/j.ijcard.2010.10.038
      OpenUrlCrossRefPubMed
    26. 26.↵
      2. Devanagondi R ,
      3. Peck D ,
      4. Sagi J , et al
      . Long-Term Outcomes of Balloon Valvuloplasty for Isolated Pulmonary Valve Stenosis. Pediatr Cardiol 2017;38:247–54.doi:10.1007/s00246-016-1506-4
      OpenUrl
    27. 27.↵
      2. Nielsen EA ,
      3. Hjortdal VE
      . Surgically treated pulmonary stenosis: over 50 years of follow-up. Cardiol Young 2016;26:860–6.doi:10.1017/S1047951115001158
      OpenUrl
    28. 28.↵
      2. Engle MA ,
      3. Holswade GR ,
      4. Goldberg HP , et al
      . Regression after open valvotomy of infundibular stenosis accompanying severe valvular pulmonic stenosis. Circulation 1958;17:862–73.doi:10.1161/01.CIR.17.5.862
      OpenUrlAbstract/FREE Full Text
    29. 29.↵
      2. Ben-Shachar G ,
      3. Cohen MH ,
      4. Sivakoff MC , et al
      . Development of infundibular obstruction after percutaneous pulmonary balloon valvuloplasty. J Am Coll Cardiol 1985;5:754–6.doi:10.1016/S0735-1097(85)80407-1
      OpenUrlFREE Full Text
    30. *30.↵
      2. Bokma JP ,
      3. Winter MM ,
      4. Oosterhof T , et al
      . Pulmonary valve replacement after repair of pulmonary stenosis compared with tetralogy of fallot. J Am Coll Cardiol 2016;67:1123–4.doi:10.1016/j.jacc.2015.12.032
      OpenUrlFREE Full Text
    31. *31.↵
      2. Therrien J ,
      3. Provost Y ,
      4. Merchant N , et al
      . Optimal timing for pulmonary valve replacement in adults after tetralogy of Fallot repair. Am J Cardiol 2005;95:779–82.doi:10.1016/j.amjcard.2004.11.037
      OpenUrlCrossRefPubMedWeb of Science
    32. 32.↵
      2. Geva T
      . Indications and timing of pulmonary valve replacement after tetralogy of Fallot repair. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2006:11–22.doi:10.1053/j.pcsu.2006.02.009
    33. 33.↵
      2. Oosterhof T ,
      3. van Straten A ,
      4. Vliegen HW , et al
      . Preoperative thresholds for pulmonary valve replacement in patients with corrected tetralogy of Fallot using cardiovascular magnetic resonance. Circulation 2007;116:545–51.doi:10.1161/CIRCULATIONAHA.106.659664
      OpenUrlAbstract/FREE Full Text
    34. 34.↵
      2. Bokma JP ,
      3. Geva T ,
      4. Sleeper LA , et al
      . A propensity score-adjusted analysis of clinical outcomes after pulmonary valve replacement in tetralogy of Fallot. Heart 2018;104:738–44.doi:10.1136/heartjnl-2017-312048
      OpenUrlAbstract/FREE Full Text
    35. 35.↵
      2. Geva T
      . Indications for pulmonary valve replacement in repaired tetralogy of fallot: the quest continues. Circulation 2013;128:1855–7.doi:10.1161/CIRCULATIONAHA.113.005878
      OpenUrlFREE Full Text
    36. 36.↵
      2. Ferraz Cavalcanti PE ,
      3. Sá MP ,
      4. Santos CA , et al
      . Pulmonary valve replacement after operative repair of tetralogy of Fallot: meta-analysis and meta-regression of 3,118 patients from 48 studies. J Am Coll Cardiol 2013;62:2227–43.doi:10.1016/j.jacc.2013.04.107
      OpenUrlFREE Full Text
    37. 37.↵
      2. Hallbergson A ,
      3. Gauvreau K ,
      4. Powell AJ , et al
      . Right ventricular remodeling after pulmonary valve replacement: early gains, late losses. Ann Thorac Surg 2015;99:660–6.doi:10.1016/j.athoracsur.2014.09.015
      OpenUrlCrossRefPubMed
    38. 38.↵
      2. Bonhoeffer P ,
      3. Boudjemline Y ,
      4. Saliba Z , et al
      . Percutaneous replacement of pulmonary valve in a right-ventricle to pulmonary-artery prosthetic conduit with valve dysfunction. The Lancet 2000;356:1403–5.doi:10.1016/S0140-6736(00)02844-0
      OpenUrl
    39. *39.↵
      2. McElhinney DB ,
      3. Hellenbrand WE ,
      4. Zahn EM , et al
      . Short- and medium-term outcomes after transcatheter pulmonary valve placement in the expanded multicenter US melody valve trial. Circulation 2010;122:507–16.doi:10.1161/CIRCULATIONAHA.109.921692
      OpenUrlAbstract/FREE Full Text
    40. 40.↵
      2. Fraisse A ,
      3. Aldebert P ,
      4. Malekzadeh-Milani S , et al
      . Melody ® transcatheter pulmonary valve implantation: results from a French registry. Arch Cardiovasc Dis 2014;107:607–14.doi:10.1016/j.acvd.2014.10.001
      OpenUrlCrossRefPubMed
    41. 41.↵
      2. McElhinney DB ,
      3. Benson LN ,
      4. Eicken A , et al
      . Infective endocarditis after transcatheter pulmonary valve replacement using the Melody valve: combined results of 3 prospective North American and European studies. Circ Cardiovasc Interv 2013;6:292–300.doi:10.1161/CIRCINTERVENTIONS.112.000087
      OpenUrlAbstract/FREE Full Text
    42. 42.↵
      2. Van Dijck I ,
      3. Budts W ,
      4. Cools B , et al
      . Infective endocarditis of a transcatheter pulmonary valve in comparison with surgical implants. Heart 2015;101:788–93.doi:10.1136/heartjnl-2014-306761
      OpenUrlAbstract/FREE Full Text
    43. 43.↵
      2. Sharma V ,
      3. Griffiths ER ,
      4. Eckhauser AW , et al
      . Pulmonary valve replacement: A single-institution comparison of surgical and transcatheter valves. Ann Thorac Surg 2018;106:807–13.doi:10.1016/j.athoracsur.2018.04.002
      OpenUrl
    44. 44.↵
      2. Lluri G ,
      3. Levi DS ,
      4. Miller E , et al
      . Incidence and outcome of infective endocarditis following percutaneous versus surgical pulmonary valve replacement. Catheter Cardiovasc Interv 2018;91:277–84.doi:10.1002/ccd.27312
      OpenUrl
    45. 45.↵
      2. Vogelpoel L ,
      3. Schrire V
      . Auscultatory and phonocardiographic assessment of pulmonary stenosis with intact ventricular septum. Circulation 1960;22:55–72.doi:10.1161/01.CIR.22.1.55
      OpenUrlAbstract/FREE Full Text
    46. 46.
      2. Roos-Hesselink JW ,
      3. Meijboom FJ ,
      4. Spitaels SE , et al
      . Long-term outcome after surgery for pulmonary stenosis (a longitudinal study of 22-33 years). Eur Heart J 2006;27:482–8.doi:10.1093/eurheartj/ehi685
      OpenUrlCrossRefPubMed
    47. 47.
      2. Cuypers JA ,
      3. Witsenburg M ,
      4. van der Linde D , et al
      . Pulmonary stenosis: update on diagnosis and therapeutic options. Heart 2013;99:339–47.doi:10.1136/heartjnl-2012-301964
      OpenUrlFREE Full Text
    48. 48.↵
      2. Baumgartner H ,
      3. Bonhoeffer P ,
      4. De Groot NM , et al
      . ESC Guidelines for the management of grown-up congenital heart disease (new version 2010). Eur Heart J 2010;31:2915–57.doi:10.1093/eurheartj/ehq249
      OpenUrlCrossRefPubMedWeb of Science

    Footnotes

    • Contributors ER and YYK have contributed equally to this manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient consent Not required.

    • Provenance and peer review Commissioned; externally peer reviewed.