Functional Pulmonary Valve Stenosis / Atresia

Description

Functional pulmonary valve atresia (FPVA) and functional pulmonary stenosis (FPS) describe dynamic hemodynamic states in which antegrade systolic flow across the pulmonary valve is absent or markedly reduced despite a structurally normal pulmonary valve and right ventricular outflow tract. Unlike anatomic obstruction, these conditions reflect a failure of right ventricular–pulmonary arterial coupling rather than a fixed valvar lesion. It is accompanied by markedly decreased right ventricular output. In this situation, the right atrial pressure increases and is often decompressed via the inter-atrial shunt creating a right to left shunt and preductal desaturation. In the presence of a ductus, there is left to right shunting at the ductal level to provide pulmonary blood flow. In this case, there is no pre- and post-ductal saturation differences. 

Functional Pulmonary Valve Stenosis / Atresia describes a dynamic (and often reversible) transitional state in which a structurally normal pulmonary valve appears “closed,” or opens only minimally, because the right ventricle cannot effectively couple to the pulmonary circulation. In this setting, elevated PVR—often compounded by excessive mean airway pressure—together with RV dysfunction and progressive tricuspid regurgitation promotes a shunt pattern that is right-to-left (or bidirectional) at the atrial level, with pulmonary blood flow becoming ductal-dependent when a PDA is present. Echocardiography helps differentiate functional obstruction from true anatomic pulmonary valve atresia/stenosis by demonstrating a thin, mobile valve; absent or very low antegrade systolic RVOT velocities without a fixed high gradient; and, importantly, the (often) presence of even trivial pulmonary regurgitation, which confirms valve patency. Management is framed around restoring physiology rather than “treating a valve lesion,” with attention to maintaining ductal patency when needed, optimizing ventilation/oxygenation and acid–base status to lower PVR, and supporting RV preload and contractility as ventriculo-vascular coupling recovers.

FPVA represents the extreme end of this spectrum, characterized by little or no forward systolic pulmonary flow, whereas FPS denotes partial valve opening with low-velocity antegrade flow. These entities exist along a continuum and commonly evolve toward normal flow as pulmonary vascular resistance (PVR) falls and right ventricular (RV) performance improves. In some cases (especially with extreme prematurity and RV vulnerability), such as the example illustrated below, impaired cardiopulmonary transition or excessive mean airway pressure from positive pressure ventilation can precipitate right ventricular strain and progressive tricuspid regurgitation. Severe ongoing tricuspid regurgitation promotes right-to-left interatrial shunting, resulting in systemic desaturation and decreased pulmonary blood flow (since a large fraction of the RV output is directed into the right atrium instead of the pulmonary artery). In the setting of reduced pulmonary blood flow and elevated intrapulmonary pressures, pulmonary vascular resistance may rise reactively in an attempt to maintain pulmonary perfusion pressure in the context of low flow. This effect is further compounded by extravascular compression of the pulmonary vasculature from elevated intra-alveolar pressure. Together, these mechanisms create a physiology in which pulmonary blood flow becomes ductal-dependent. In this context, reduction of mean airway pressure is a key component of management, as it lowers right ventricular afterload and facilitates restoration of antegrade pulmonary blood flow—particularly important given the right ventricle’s limited tolerance to acute afterload and its tendency to recover more slowly once strained.

Ductal and Inter-Atrial Shunt(s) effects

• In functional pulmonary valve atresia with both a patent foramen ovale and a patent ductus arteriosus, there is no effective antegrade systolic flow across the pulmonary valve, so pulmonary blood flow is entirely dependent on ductal flow from the aorta into the pulmonary arteries. The right ventricle is uncoupled with the pulmonary artery and is unable to overcome pulmonary arterial afterload, rendering its stroke volume ineffective. The presence of a PFO allows right-to-left atrial shunting, providing a relief pathway for the right atrium but at the cost of systemic desaturation, as venous blood bypasses the lungs. Oxygenation is therefore moderately to severely reduced and highly sensitive to ductal patency and pulmonary vascular resistance. Clinically, these infants may appear temporarily stable while the ductus remains widely patent, but they are extremely vulnerable to abrupt deterioration if ductal constriction occurs. Reduction in pulmonary vascular resistance with oxygen or inhaled nitric oxide often leads to rapid improvement and restoration of pulmonary valve opening. If the culprit was in part the excessive mean airway pressure that created excessive strain on the right ventricle, one of the first management strategy is to drop acutely the mean airway pressure - especially when there is concomittant hyperinflation on chest radiography, and to optimize ventilatory management. Refer to the Cardio-Respiratory section. 

• When functional pulmonary valve atresia is present with a patent ductus arteriosus but with a restrictive small inter-atrial shunt (which is rarer in neonatal life but could happen), the pulmonary blood flow remains entirely ductal-dependent, but the absence of an atrial decompression pathway fundamentally alters the physiology. Right atrial and right ventricular pressures rise, and the right heart becomes trapped without an effective pop-off. Although systemic oxygenation may initially appear less compromised than in the presence of a large PFO, overall cardiac output is often more fragile. These infants are prone to low systemic flow, hypotension, and progressive right ventricular ischemia or dysfunction, particularly during periods of stress or increased pulmonary vascular resistance. These infants often have significant hepatomegaly and can shift rapidly in a low cardiac output syndrome since the preload of the left ventricle is dependent on the pulmonary blood flow which is reduced due to near absent antegrade flow by the RV outflow tract. Ductal constriction in this setting can precipitate rapid cardiovascular collapse, and tolerance of transitional instability is generally poor. 

• In functional pulmonary valve atresia with a patent foramen ovale but no (or a very restrictive/small) patent ductus arteriosus, pulmonary blood flow is critically reduced or absent, as there is neither antegrade flow across the pulmonary valve nor a ductal source of pulmonary perfusion. Systemic venous blood preferentially shunts right-to-left across the atrial septum, bypassing the lungs almost entirely. This results in profound hypoxemia, severe metabolic acidosis, and critically reduced left ventricular preload. The clinical presentation is immediately life-threatening, with rapid progression to shock and cardiovascular collapse. This physiology is not compatible with survival unless pulmonary blood flow is urgently re-established, typically by reopening the ductus or restoring pulmonary valve opening through rapid reduction in pulmonary vascular resistance. 

• In functional pulmonary valve stenosis with both a patent foramen ovale and a patent ductus arteriosus, antegrade systolic flow across the pulmonary valve is present but markedly reduced and highly variable. Pulmonary blood flow arises from a combination of limited right ventricular ejection and supplemental ductal flow, with the relative contribution of each fluctuating according to loading conditions, ventilation, and pulmonary vascular tone. Atrial-level shunting is right to left or bidirectional (depending on left atrial preload / pulmonary blood flow; and degree of right atrial pressure from tricuspid regurgitation), reflecting dynamic right-sided pressures. Systemic oxygenation is usually mildly to moderately reduced and labile, particularly during agitation or changes in ventilatory support. Clinically, these infants often display transitional instability rather than fixed cyanosis, and pulmonary valve opening frequently improves as pulmonary vascular resistance falls and right ventricular–pulmonary arterial coupling recovers. 

Echocardiographic features

Echocardiography is essential for distinguishing functional from anatomic pulmonary valve obstruction. On two-dimensional imaging, the pulmonary valve in FPVA or FPS typically appears thin, mobile, and normally sized, without doming, dysplasia, or leaflet thickening. Doppler interrogation demonstrates absent or very low-velocity antegrade systolic flow, often without the high gradients seen in fixed pulmonary stenosis. A key diagnostic feature confirming valve patency is pulmonary regurgitation: even a trivial regurgitant jet establishes that the valve is anatomically open. Right ventricular systolic indices may appear preserved in this setting, often as a consequence of significant tricuspid regurgitation, whereby a substantial proportion of right ventricular stroke volume is directed backward into the low-pressure right atrium rather than forward into the right ventricular outflow tract. Because commonly used RV systolic indices are highly load-dependent, an RV ejecting predominantly into a low-impedance atrial chamber may demonstrate seemingly normal values (e.g., TAPSE, fractional area change). These measurements can therefore mask substantial intrinsic RV strain and do not accurately reflect the ventricle’s true contractile performance were it required to generate effective forward flow against normal or increased pulmonary afterload. It is important to rule out structural anomalies of the tricuspid valve (such as tricuspid valve dysplasia or Ebstein's anomaly).

Examples of functional pulmonary valve atresia

Example 1

Example 2

The tricuspid regurgitation jet velocity provides an estimate of the right ventricle–right atrium (RV–RA) systolic pressure gradient and therefore informs on right ventricular systolic pressure (RVSP). However, in this physiology, RVSP does not reflect systolic pulmonary arterial pressure because there is uncoupling between the right ventricle and the pulmonary artery. When the pulmonary valve does not open (FPVA), or opens only minimally (FPS), systolic pressure does not equalize between the RV and PA. As a result, pressure generation within the RV becomes dissociated from effective valve opening, and RVSP may be normal or only modestly elevated despite severely impaired pulmonary blood flow. In this setting, pulmonary blood flow is frequently maintained via the ductus arteriosus, typically with left-to-right shunting from the aorta into the pulmonary circulation. Administration of inhaled nitric oxide or high–fraction inspired oxygen may acutely lower pulmonary vascular resistance, allowing improved pulmonary valve opening during echocardiographic assessment and thereby confirming a functional, rather than fixed, mechanism of obstruction. As antegrade flow across the pulmonary valve recovers, ductal shunting may evolve from purely left-to-right to bidirectional or even right-to-left, reflecting the recovering contribution of the RV to main pulmonary artery filling. Paradoxically, once the right ventricle begins to contribute to pulmonary blood flow, the appearance of bidirectional or right-to-left ductal shunting may be associated with the emergence of pre- and post-ductal oxygen saturation differences—differences that were previously absent when the ductus was left-to-right and solely supplying an underfilled pulmonary artery due to absent or near-absent RV forward flow. In the earlier left-to-right ductal state, there is often no pre-/post-ductal saturation gradient, and the infant may be profoundly cyanotic as a result of significant right-to-left interatrial shunting. If the interatrial shunt becomes restrictive, systemic output may fall precipitously, leading to a low–cardiac output state. In this scenario, the infant may appear deceptively well saturated but be markedly hypoperfused, with a gray or shock-like clinical picture and evidence of systemic venous congestion, including hepatomegaly. FPVA and FPS result in dependence on ductal flow for pulmonary perfusion, often accompanied by systemic desaturation and reduced effective RV stroke volume. Persistent RV–pulmonary artery uncoupling may lead to secondary myocardial dysfunction if not corrected. Abrupt ductal constriction can precipitate rapid cardiovascular collapse.

Management principles

Management focuses on restoration of favorable physiology rather than relief of a fixed anatomic obstruction. In the acute phase, maintenance of ductal patency with prostaglandin E1 should be strongly considered, unless the patent ductus arteriosus (PDA) is already wide open and unrestrictive, in which case close monitoring may be appropriate. A large, unrestrictive PDA equalizes pressure between the main pulmonary artery and the aorta and can act as a “competitor” to right ventricle–pulmonary artery (RV–PA) coupling in the setting of a severely compromised right ventricle. In some cases, partial ductal restriction may facilitate antegrade RV contribution to pulmonary artery filling by limiting excessive pressure transmission from the systemic circulation into the pulmonary circuit, thereby reducing RV afterload and promoting recovery. Conversely, if the PDA becomes overly restrictive and pulmonary blood flow is insufficient, prostaglandin E1 should be promptly initiated or re-escalated to augment pulmonary blood flow, improve left atrial preload, reduce right-to-left interatrial shunting, and preserve left ventricular preload and systemic cardiac output. Management should also prioritize reduction of pulmonary vascular resistance through optimization of oxygenation, ventilation, and acid–base balance, while avoiding excessive mean airway pressures that impair venous return and further increase RV afterload. Right ventricular preload and contractility should be supported judiciously. Inotropic therapy may be tailored to the hemodynamic profile—for example, dobutamine in the absence of significant tachycardia to enhance RV contractility, milrinone when systemic blood pressure is adequate and urine output is preserved, or epinephrine in cases of severe ventricular dysfunction requiring additional inotropic support and systemic vascular resistance augmentation. Serial echocardiographic assessment is essential, as antegrade pulmonary blood flow frequently improves with falling pulmonary vascular tone and recovery of RV–PA coupling.

Coronary perfusion

One of the most critical repercussions of severe RV dysfunction is impaired coronary perfusion. Coronary circulation is diastolic-dependent, with perfusion occurring when aortic diastolic pressure exceeds RA pressure, allowing coronary blood to perfusion the myocardium and drain into the RA via the coronary sinus. When diastolic aortic pressure is low and RA pressure is high, the trans-coronary pressure gradient drops, severely compromising myocardial perfusion. This is particularly detrimental in the setting of increased myocardial oxygen demand from inotropic and vasopressor support. In this case, there was hepatomegaly, dilated subhepatic veins with retrograde flow and a dilated RA, suggesting markedly elevated RA pressure. The presence of a right-to-left interatrial shunt indicates that RA pressure is high enough to drive systemic venous blood into the left atrium. However, the shunt is unlikely to be fully decompressing the RA, leaving persistently elevated RA pressure that further impacts overall coronary sinus drainge. One critical consequence of this is impaired coronary perfusion. Coronary sinus pressure is likely elevated due to high RA pressure, which reduces the trans-coronary pressure gradient, making it more difficult for coronary blood flow to adequately perfuse the myocardium (dilated coronary arteries are often seen because of this). This is further exacerbated by low systemic diastolic pressure, which diminishes the driving force for coronary circulation. Additionally, severe RV dilation increases transmural pressure, further restricting subendocardial coronary flow. This is compounded by the cardiac hypertrophy, likely a result of maternal diabetes, which increases myocardial oxygen demand. The hypertrophied myocardium, combined with a high endogenous adrenergic load from stress and exposure to cardiovascular medications for the management, significantly raises metabolic demand, worsening the supply-demand mismatch. Ultimately, this constellation of factors—impaired coronary perfusion, increased myocardial oxygen demand, and restricted oxygenation due to compromised pulmonary circulation—creates the perfect storm for myocardial ischemia and dysfunction. The result is a vicious cycle in which worsening myocardial ischemia further reduces cardiac function, exacerbating hemodynamic instability and perpetuating the cycle of RV failure, poor LV output, and systemic hypoperfusion.

Associated conditions

Although FPVA and FPS may occur in otherwise normal cardiac anatomy—most commonly in persistent pulmonary hypertension of the newborn, transient neonatal RV dysfunction or sometime secondary to high ventilatory pressures after an adverse perinatal transition—similar physiology is frequently seen in congenital heart disease. In Ebstein anomaly or Tricuspid Valve Dysplasia, severe tricuspid regurgitation and a functionally ineffective RV can produce FPVA despite a normal pulmonary valve, sometimes resulting in a circular shunt with profound systemic hypoperfusion. Severe RV hypertrophy or cardiomyopathy can also limit effective RV–pulmonary coupling by limiting filling, limiting effective RV cardiac output and promote tricuspid regurgitation. One must rule out: true pulmonary valve atresia, critical pulmonary valve stenosis, pulmonary atresia with intact ventricular septum, RV cardiomyopathy and tricuspid valve stenosis.

RV-PA Coupling and Uncoupling

Right ventricle-pulmonary artery (RV-PA) coupling describes the physiological interaction and balance between right ventricular contractility and the afterload imposed by the pulmonary vascular system. In a healthy, well-coupled state, the right ventricle (RV) successfully adapts its contractile performance to match the resistance it faces in the pulmonary arteries, thereby maintaining efficient stroke volume and cardiac output. This harmonious relationship is essential for the RV to pump blood into the lungs without undergoing pathologic changes in geometry or function. RV-PA uncoupling refers to the state of maladaptation that occurs when the pulmonary afterload becomes so high—or the myocardial function so impaired—that the RV can no longer increase its contractility to compensate. This failure of adaptation leads to RV dilatation, systolic dysfunction, and a subsequent drop in pulmonary perfusion. Clinical evidence of uncoupling often includes increased right heart dimensions and inferior vena cava dilation, which are markers of the transition toward right heart failure. Echocardiography provides a reliable non-invasive method to assess this relationship through the ratio of the tricuspid annular plane systolic excursion (TAPSE) to the estimated systolic pulmonary arterial pressure (sPAP). The TAPSE/sPAP ratio serves as a surrogate for RV-PA coupling, where lower values indicate significant uncoupling. A ratio below 0.19 mm/mmHg is frequently used in risk stratification to identify patients with severe haemodynamic impairment and a high risk of clinical failure. However, this can only be evaluated when there is preserved pulmonary valvular opening and cannot be interpreted when there is a FPVA or FPS physiology. Consequently, RV-PA coupling is regarded as a critical independent predictor of mortality in patients with pulmonary arterial hypertension or heart failure secondary to left heart disease. To help visualize this concept, think of RV-PA coupling as a cyclist (the right ventricle) pedalling up a hill (the pulmonary afterload). In a coupled state, as the hill gets steeper, the cyclist pushes harder on the pedals to maintain their speed. Uncoupling occurs when the hill becomes so steep that the cyclist's strength is exhausted; they can no longer match the resistance of the incline, their pace drops, and they eventually begin to wobble and fail.

In summary, right ventricular–pulmonary arterial (RV–PA) coupling refers to the ability of the right ventricle to generate sufficient pressure and flow to effectively open the pulmonary valve and deliver blood into the pulmonary circulation in the face of a given afterload. In the normal transitional circulation, a rapid postnatal fall in pulmonary vascular resistance allows efficient RV–PA coupling, with modest RV systolic pressure translating into forward pulmonary blood flow. In the setting of functional pulmonary valve atresia or severe functional pulmonary stenosis, this coupling is lost. Markedly elevated pulmonary vascular resistance, excessive intrathoracic pressure, or impaired RV systolic performance prevent RV pressure generation from being effectively transmitted across the pulmonary valve, resulting in absent or severely reduced antegrade flow despite a structurally normal valve. In this uncoupled state, RV systolic pressure may be normal or only mildly elevated, yet pulmonary blood flow remains critically low. RV–PA uncoupling has important physiological and clinical implications. Because the RV is unable to eject forward, pulmonary blood flow becomes ductal-dependent, and RV stroke volume is often redirected backward through tricuspid regurgitation into the low-pressure right atrium. Standard echocardiographic indices of RV systolic function may therefore appear preserved, masking significant RV strain. Restoration of RV–PA coupling requires reduction of pulmonary vascular resistance, optimization of lung volumes and intrathoracic pressures, and support of RV preload and contractility. As coupling improves, even modest increases in RV systolic performance can result in reopening of the pulmonary valve and re-establishment of antegrade pulmonary blood flow, underscoring the dynamic and reversible nature of functional pulmonary valvular atresia and stenosis.

Targeted Neonatal Echocardiography Example of Functional Pulmonary Valve Stenosis

Example 3

Following a reduction in mean airway pressure—thereby lowering PVR by relieving intra-alveolar, pressure-related compression of the pulmonary vascular bed—low-dose iNO was introduced stepwise to achieve transient pulmonary vasodilation. This aimed to counter reactive pulmonary vasoconstriction that likely developed after prolonged exposure to high MAP, with progressive RV pressure load and strain culminating in tricuspid regurgitation, and to support the circulation until RV recovery. The hemodynamic response was immediate: the atrial shunt across the PFO shifted to predominantly left-to-right, consistent with improved RV emptying and increased antegrade flow from the RV to the MPA. The resulting rise in pulmonary blood flow increased LA preload, reduced the right-to-left atrial gradient, and effectively reversed the interatrial shunt (with only brief, residual right-to-left flow). Clinically, both pre- and post-ductal saturations rapidly rose to 100%, allowing prompt weaning of supplemental oxygen. On re-evaluation, RV systolic function had recovered and tricuspid regurgitation had decreased—improving effective forward RV output—so iNO was subsequently weaned.