Pulmonary atresia with intact ventricular septum (PA/IVS)

INTRODUCTION — Pulmonary atresia with intact ventricular septum (PA/IVS) (figure 1) is characterized by complete obstruction to right ventricular (RV) outflow with varying degrees of RV and tricuspid valve (TV) hypoplasia. Blood is thus unable to flow from the RV to the pulmonary artery and lungs, and an alternative source of pulmonary blood flow is required for survival. If untreated, PA/IVS is almost always fatal. Outcomes of surgical interventions are improving, with a five-year survival rate of approximately 80 percent.

The definition, anatomy, physiology, clinical presentation, management (including follow-up care), and outcome of PA/IVS will be reviewed here.

DEFINITION — PA/IVS is a rare congenital cardiac defect that consists of atresia of the pulmonary valve resulting in an absent connection between the right ventricular outflow tract (RVOT) and pulmonary arteries as well as an IVS that allows no connection between the right and left ventricles.

PA/IVS is distinctive from PA with a ventricular septal defect (PA/VSD; often called tetralogy of Fallot [TOF]/PA) and from severe forms of Ebstein anomaly of the tricuspid valve (TV). Although all of these defects can result in complete obstruction of the RVOT, they have different morphologic anatomic features (eg, RV size and function, presence of pulmonary and/or TV abnormalities, and status of the ventricular septum), which significantly impact management decisions.

●PA/IVS features developmental abnormalities of the RV and TV that are "upstream" of pulmonary outflow. The pulmonary arteries may be small, but their architecture and branching patterns are usually otherwise normal.

●PA/VSD (or TOF/PA) more often features a normally-formed RV and TV with "downstream" abnormalities of the pulmonary artery architecture, in addition to the VSD. Major aortopulmonary collateral arteries that supply blood to the pulmonary vascular bed are often present. (See "Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries (TOF/PA/MAPCAs)".)

●Ebstein anomaly of the TV is primarily characterized by abnormalities of the TV and RV, as discussed separately. (See "Ebstein anomaly: Clinical manifestations and diagnosis".)

EPIDEMIOLOGY — The reported incidence of PA/IVS based on registries and population-based studies of children born with congenital heart disease (CHD) is approximately 4 to 8 per 100,000 live births [1-8]. PA/IVS accounts for 1 to 3 percent of all congenital cardiac defects in children. One small study reported a slight male predominance and recurrence of the defect in siblings [9].

These studies may underestimate the true incidence of PA/IVS because of spontaneous abortions (which may occur, especially if there is severe tricuspid regurgitation and hydrops fetalis) and elective termination (which may take place when an early diagnosis is made by fetal echocardiography) [10,11].

PATHOGENESIS — The pathogenesis of PA/IVS is unknown, but, compared with other cardiac lesions, identifiable genetic syndromes and other cardiac malformations are less common. There are isolated reports of familial cases of PA/IVS, including one publication that implicates a single gene [12,13]. A study involving human pluripotent stem cells from PA/IVS patients suggests an intrinsic abnormality in cardiomyocyte contractile function [14]. However, the current evidence is insufficient to establish a consistent genetic association.

It has been proposed that PA/IVS is an acquired lesion due to perturbation in fetal blood flow. This concept is based on reports of serial ultrasound studies demonstrating the development (or serial worsening) of pulmonary valve obstruction in fetuses [15-17]. It has led clinicians to pursue fetal interventions including in utero dilation of the pulmonary valve to promote blood flow through the right ventricular outflow tract (RVOT). (See 'Fetal intervention' below.)

In some cases, it has been proposed that viral infection or inflammatory disease in mid-term gestation creates fusion of the pulmonary valve leaflets, eventually progressing to an atretic pulmonary valve and the subsequent abnormalities of fetal blood flow that ultimately results in PA/IVS. However, no relationship has been established between PA/IVS and maternal rubella, despite the reported associations between pulmonary stenosis and maternal rubella [18,19]. Coxsackievirus B infection during pregnancy also has been reported to be associated with increased risk of pulmonary valve abnormalities [20]. (See "Congenital rubella", section on 'Clinical features' and "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Pregnant females' and "Congenital heart disease: Prenatal screening, diagnosis, and management", section on 'Indications for echocardiography'.)

Additionally, fetal hemodynamic perturbations may occur in the setting of twin-twin transfusion syndrome and lead to critical pulmonary stenosis or PA [21]. This manifestation of pulmonary atresia with an intact ventricular septum may share common physiologic features with the more common congenital heart defect referred to as "PA/IVS," described here. (See "Twin-twin transfusion syndrome: Screening, prevalence, pathophysiology, and diagnosis".)

In contrast, PA with a ventricular septal defect (VSD) is thought to be an early gestational developmental lesion resulting from an abnormality in primary morphogenesis of the heart. (See "Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries (TOF/PA/MAPCAs)".)

ANATOMY — PA/IVS consists of a wide variety of anatomical cardiac defects that are associated with the primary lesion of PA (figure 1). In 2000, the Congenital Heart Surgery Nomenclature and Database Project established a unified reporting system for right ventricular outflow tract (RVOT) obstruction that defined PA/IVS as a duct-dependent congenital malformation with a spectrum of lesions, which include PA, variable degrees of hypoplasia of the RV and tricuspid valve (TV), and anomalies of the coronary circulation [22]. Because of the diversity of anatomic findings, there is not a standard universal interventional or surgical approach for PA/IVS. Interventions (ie, biventricular repair, univentricular palliation, or hybrid repair) are individualized based on the morphologic features of the RV, TV, and coronary artery circulations. (See 'Corrective repair or palliation' below.)

●Pulmonary valve atresia – In patients with PA/IVS, the underlying morphology of PA and RVOT obstruction is either valvar (membranous) or muscular.

•Valvar (membranous) PA – In most cases, the pulmonary valve is atretic with a small valve annulus and identifiable (but fused) valve leaflets, which form a thin, intact membrane causing total RVOT obstruction [7,23]. In these patients, the RV and infundibulum (the funnel-shaped muscular structure that forms the RVOT below the pulmonary valve, also referred to as the conus arteriosus) are usually well developed.

•Muscular PA – In approximately 20 to 25 percent of patients, there is obliteration of the muscular infundibulum, resulting in muscular PA [7]. Muscular PA is usually associated with severe RV hypoplasia, increased risk and severity of coronary artery abnormalities, and less favorable outcomes [5,24].

●RV – There is great variation in the morphology of the RV, ranging from a severely hypoplastic cavity with marked muscular hypertrophy to a large, dilated, thin-walled chamber. This variation is due to the degree of intracavitary muscular overgrowth. Normally, the RV is composed of three parts (tripartite): an inlet, a trabecular body, and an outlet. The majority of patients with PA/IVS will have a well-formed tripartite RV (59 to 83 percent); others will have a bipartite RV due to apical trabecular overgrowth, resulting in a small ventricle composed of an inlet and body but no discernible outlet (15 to 34 percent); and a small number of patients will have a unipartite RV due to both infundibular and apical trabecular overgrowth, resulting in a severely hypoplastic RV with only a detectable inlet (2 to 8 percent) [5,7].

Patients with a tripartite RV are more likely to be candidates for biventricular repair, as their RV may support a full cardiac output and normal pulmonary blood flow. (See 'Corrective repair or palliation' below.)

●TV – The size of the TV is highly variable, and the valve is often small and dysplastic with stenosis and/or regurgitation. The size of the TV annulus correlates with the size and morphology of the RV and the presence of coronary abnormalities (picture 1) and is a factor in deciding the optimal surgical intervention (biventricular repair versus univentricular palliation) [3]. The assessment of TV size using echocardiography is discussed below. (See 'Echocardiography' below.)

In a small minority of patients (4 to 10 percent), the TV may be inferiorly displaced in the RV. This is referred to as an Ebstein (or "Ebstenoid") anomaly of the TV [4,5,7]. (See "Ebstein anomaly: Clinical manifestations and diagnosis".)

●Coronary arteries – In the normal heart, the myocardium is predominantly perfused during diastolic flow from the aorta to the coronary arteries. In patients with PA/IVS, abnormal connections between the RV and the coronary arteries are common due to the high pressure in the dysplastic RV cavity (picture 1) [7,25-27]. Sinusoids, vascular pores within the ventricular myocardium that persist from fetal life, occur in approximately 70 percent of patients [5]. The reported incidence of fistulae in patients with PA/IVS, defined as a direct connection between a sinusoid and a coronary artery, ranges from 50 to 70 percent of patients [3,7,26,28]. Patients with a severely hypoplastic TV and a small, hypertensive RV are more likely to have fistulae [3,7,29,30]. Fistulae between the RV and the coronary arteries through histo-anatomical connections may lead to proximal coronary stenoses or interruptions. Other coronary abnormalities include complete absence (atresia) of the aortocoronary connection, stenosis of the normally branching coronary arteries, or abnormal connections between the right and left coronary system.

In approximately one-quarter of cases, there is an RV-dependent coronary circulation (RVDCC), defined as coronary blood flow that is at least partially dependent upon retrograde blood flow from the RV [5]. RVDCC occurs when a communicating RV fistula arises in the presence of an atretic or stenotic coronary artery connection proximal to the RV-coronary connection, which prevents or limits the antegrade myocardial perfusion from the aorta [3-5,7,28,31,32]. Recognition of this clinical scenario is critical because RV decompression (ie, interventional or surgical opening of the RVOT) may lead to coronary artery steal, ischemia, infarction, and/or sudden cardiac death when the RVOT obstruction is relieved and the RV pressure reduced [27,31]. In a study of 28 patients with PA/IVS and RVDCC, proximal coronary obstruction was associated with decreased transplant-free survival compared with distal obstruction, presumably because more myocardium is at risk for ischemia with proximal obstruction [33]. The coronary arteries also may receive blood flow only from the hypertensive RV, resulting in deoxygenated blood that delivers less oxygen to the myocardium compared with normal, fully oxygenated aortic blood flow. This may contribute to the long-term ventricular dysfunction that is associated with coronary abnormalities in patients with PA/IVS [5].

Because coronary artery abnormalities are common in patients with PA/IVS, most patients undergo angiography in the neonatal period to identify and define any coronary artery abnormalities, including which coronaries are affected and at what location (proximal versus distal), and to determine the potential impact on myocardial perfusion both pre- and post-intervention. This is discussed below. (See 'Cardiac catheterization' below.)

●Pulmonary circulation – The pulmonary circulation is usually supported with a normal, left-sided patent ductus arteriosus (PDA) connecting to confluent pulmonary arteries that exhibit a normal branching pattern from the main pulmonary trunk. Rarely, patients with PA/IVS have abnormal development of the pulmonary arteries and connections from the aorta to the pulmonary arteries called major aortopulmonary collateral arteries [34]. While gross anatomic abnormalities of the pulmonary arterial tree are uncommon, one histologic study of the pulmonary arteries in PA/IVS revealed significant medial and intimal abnormalities, possibly related to ductal-dependent pulmonary blood flow [35].

●Other anatomic features – Other less common anatomic defects may affect the left ventricle (LV), aortic valve, and right atrium.

•LV and aortic valve – The left heart may exhibit aortic stenosis or a bicuspid aortic valve. The morphology of the LV is usually normal, but LV function may be affected by coronary insufficiency, which can be exacerbated by chronic perfusion of deoxygenated blood from the RV leading to further coronary insufficiency [36]. A mild or moderate obstruction of the LV outflow tract by the hypertrophied interventricular septum has also been described in approximately 45 percent of patients [5]. These authors have presented theoretical connections between the presence of RV coronary sinusoids and LV noncompaction, but further studies are required to confirm this association [37].

•Right atrium – Due to tricuspid regurgitation, the right atrium may be enlarged, sometimes compressing the right lung. Usually a patent foramen ovale (PFO) or atrial septal defect exists to allow egress of blood from the right to the left atrium; a pressure-restrictive PFO is rare and most often leads to fetal demise.

PATHOPHYSIOLOGY — In PA/IVS, PA causes right ventricular outflow tract (RVOT) obstruction. With an IVS, there are only two paths for blood to exit the RV: via tricuspid regurgitation back into the right atrium, or through connections between the RV and the coronary artery circulation (ie, fistulae and sinusoids). Return of blood to the systemic circulation is primarily dependent on blood flow from the right atrium through the foramen ovale into the left atrium and, subsequently, the left ventricle (LV). In addition, blood passing out of the RV via sinusoids is returned to the systemic circulation through the coronary circulation.

The RV pressure is dependent on the extent of the RV egress. In cases with limited tricuspid regurgitation and coronary circulatory egress, the RV pressure may rise to suprasystemic levels (in some cases, as high as 200 mmHg). In contrast, in patients with free tricuspid regurgitation, the RV pressure may be nearly normal, with a significant amount of blood returned to the right atrium and then the left atrium via an atrial communication (ie, patent foramen ovale [PFO] and/or atrial septal defect).

In neonates with PA/IVS, the ductus arteriosus is small compared with healthy infants since normal fetal blood flow from the pulmonary artery through the ductus arteriosus to the descending aorta is nonexistent due to RVOT obstruction. However, after birth, a patent ductus arteriosus (PDA) is crucial for survival as it provides the sole source of pulmonary blood flow. (See 'Initial stabilization' below.)

CLINICAL PRESENTATION

Fetal presentation — Advances in ultrasound technology have enabled routine antenatal screening at 18 to 22 weeks gestation to establish an accurate fetal diagnosis. Features of critical pulmonary obstruction may be observed in some fetuses as early as 12 weeks gestation [38]. (See 'Fetal diagnosis' below.)

Postnatal presentation — Neonates with PA/IVS present with cyanosis due to an obligate right-to-left shunt at the atrial level [5]. Although infants may have mild tachypnea or hyperpnea, severe respiratory distress is uncommon and differentiates these patients from those with cyanosis due to a pulmonary cause (eg, neonatal respiratory distress syndrome). In addition, these infants generally have a benign fetal and birth history.

If untreated, PA/IVS is an almost uniformly fatal disease; approximately 50 percent of children will die within two weeks of birth and 85 percent by six months [39]. Because PA/IVS is a ductal-dependent lesion, closure of the patent ductus arteriosus (PDA) results in rapid clinical deterioration and life-threatening consequences, including severe hypoxemia and metabolic acidosis, seizures, cardiogenic shock, cardiac arrest, and death. Rarely, prolonged survival can occur with pulmonary blood flow maintained by a persistent PDA or systemic artery-to-pulmonary artery blood flow via one or more aortopulmonary collateral blood vessels [40]. (See 'Pathophysiology' above.)

Most patients undergo initial evaluation that includes physical examination, pulse oximetry, chest radiography, and electrocardiography (ECG). The findings on these tests may suggest cyanotic congenital heart disease (CHD), but, ultimately, echocardiography is required to make the diagnosis of PA/IVS, as discussed below. (See 'Echocardiography' below.)

●Physical findings – In addition to cyanosis, other physical findings may include:

•Single second heart sound due to a single semilunar valve (the aortic valve)

•Holosystolic murmur due to tricuspid regurgitation (the murmur is "S1 coincident," reflecting regurgitation immediately upon ventricular contraction, which is differentiated from a systolic ejection murmur)

•Right ventricular (RV) precordial impulse is not hyperdynamic, because of the small volume of blood entering the hypoplastic RV

•Less commonly, a continuous "machinery-type" murmur due to a PDA

●Pulse oximetry – The peripheral oxygen saturation (SpO₂) measured by pulse oximetry reveals hypoxemia consistent with the physical finding of cyanosis. The degree of hypoxemia depends on the amount of left-to-right shunt from the aorta to the pulmonary arteries via the PDA. (See "Newborn screening for critical congenital heart disease using pulse oximetry".)

●Chest radiography – The chest radiograph usually exhibits a normal or enlarged cardiac silhouette with normal pulmonary vascular markings in the neonate (image 1). If there is significant tricuspid regurgitation with an Ebstein-type tricuspid valve (TV), the chest radiograph may demonstrate marked right atrial and ventricular enlargement resulting in a large cardiac silhouette (cardiomegaly).

●ECG – The ECG reveals a QRS axis of 0 to +90, with decreased right-sided ventricular forces that correlate with increasing severity of RV hypoplasia (waveform 1). The normal right-axis deviation of a newborn is usually absent, and right atrial enlargement may be present. Therefore, relative left-axis deviation in a cyanotic newborn should prompt the clinician to consider PA/IVS in the differential diagnosis. Paradoxically, some children with PA/IVS may demonstrate normal or increased RV forces and RV hypertrophy; this is thought to be due to the thick, muscle-bound RV mass that results in a small RV cavity.

Other findings include tall P waves due to right atrial enlargement in the setting of significant tricuspid regurgitation, and abnormal ST segments and T waves may reflect subendocardial ischemia [41].

●Hyperoxia testing – With improved access to echocardiography, the hyperoxia test is usually not necessary for identifying infants with cyanotic CHD. When performed, hyperoxia testing in an infant with PA/IVS reveals a partial pressure of arterial oxygen (PaO₂) <100 mmHg. (See "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Hyperoxia test'.)

DIAGNOSIS

Fetal diagnosis — Improved detection of PA/IVS (and other conotruncal defects) by fetal ultrasound has resulted from standardized imaging of the great vessels and guidelines for fetal echocardiography when a cardiac defect is suspected [42-44]. Routine obstetric screening with ultrasound using a four-chamber view of the heart in the fetus can confirm a diagnosis of PA/IVS during the second trimester (18 to 22 weeks gestation) [45]. The characteristic findings of an atretic pulmonary valve and a hypoplastic tricuspid valve (TV) and right ventricle (RV) are key diagnostic features. In addition, fetal echocardiography may also note reversed ductal flow (from the aorta to pulmonary artery) with a "vertically oriented" ductus arteriosus (with an acute angle from the aorta). This contrasts with the normal ductal flow pattern: Venous blood from the RV is ejected through a horizontally-positioned ductus arteriosus to the descending aorta (with an obtuse aortic angle). Prenatal imaging of coronary artery abnormalities has also been described [46,47].

Findings on fetal echocardiography have been used to predict prognosis and assess the likelihood of achieving a biventricular repair after birth. Parameters commonly included in these prognostic models include [48-55]:

●Tricuspid valve Z-score

●Tricuspid regurgitation velocity

●Right and left ventricular length ratio

●Presence of ventriculo-coronary connections

A meta-analysis of eleven studies reporting on the prognostic accuracy of these parameters and various risk models found that overall, the models tended to overestimate the likelihood of biventricular repair [55]. Nine of the models had been externally validated. Among models that included multiparameter risk scores, the sensitivity ranged from 50 to 68 percent and specificity ranged from 92 to 100 percent. The overall accuracy for correctly predicting biventricular versus univentricular repair ranged from 78 to 93 percent. These findings highlight the difficulty in consistently identifying patients who will ultimately require univentricular palliation.

Efforts are ongoing to validate these risk models and to identify the most informative prognostic factors. Ultimately, it is hoped that this information may assist in parental counseling, education, and management decisions such as consideration of pregnancy termination, fetal intervention, and type of postnatal repair.

Establishing the diagnosis of PA/IVS with fetal echocardiography is an important part of prenatal management. For affected pregnant individuals who elect to continue pregnancy, arrangements should be made for planned delivery at a tertiary medical center with experience in managing complex congenital heart disease (CHD).

Additional details of prenatal screening and diagnosis of CHD are provided separately. (See "Congenital heart disease: Prenatal screening, diagnosis, and management".)

Postnatal diagnosis — Postnatal diagnosis of PA/IVS is generally confirmed by echocardiography. Echocardiography is performed based on a strong clinical suspicion for CHD because of signs and symptoms of cyanotic CHD (eg, cyanosis without marked respiratory distress) and physical findings suggestive of cardiac disease (eg, single second heart sound and/or pathologic cardiac murmur).

Further evaluation consists of additional echocardiographic imaging and cardiac catheterization to help inform decisions regarding intervention.

Echocardiography — The echocardiographic diagnosis is made by identifying the atretic pulmonary valve with pulse-wave Doppler sampling of the pulmonary valve to confirm the absence of RV outflow, thus differentiating between critical pulmonary stenosis and true PA (image 2).

In addition to confirming the diagnosis of PA/IVS, echocardiography provides information regarding the size and function of the RV and TV and evaluates the adequacy of intracardiac mixing and pulmonary blood flow.

The evaluation includes the following:

●Assess the RV size (area in cm²/m² of body surface area) and RV morphology (uni-, bi-, or tripartite).

●Measure the TV annulus size and compare with normal values using Z-scores, as discussed below. Careful analysis of not only the TV annulus but also the effective TV orifice is important as restriction of TV leaflets below the annulus may limit RV inflow.

●Assess the presence and degree of tricuspid regurgitation.

●Assess intracardiac mixing and pulmonary blood flow by qualitatively assessing blood flow through the patent foramen ovale (PFO) and ductus arteriosus.

●Assess left ventricular (LV) function, status of the aortic valve, and LV outflow tract.

●If possible, detection of coronary artery abnormalities, which are suggested by abnormal, continuous flow seen in the sinusoids or fistulae of the RV. Proximal coronary artery origins should be confirmed at the sinuses of Valsalva of the aorta, and assessment of intracoronary flow and velocity can suggest RV-dependent coronary circulation (RVDCC) [56]. However, angiography is needed to provide a more complete evaluation of the coronary system. (See 'Cardiac catheterization' below.)

The size of the TV annulus is compared with normal values and reported as a "Z-score," which represents the number of standard deviations from the normal mean valve annulus size in children of similar body size. Using this system, a Z-score of 0 signifies that the TV annulus is normal in size, whereas a Z-score of -2 indicates the annulus is two standard deviations below normal size. Usually, the TV Z-score correlates with RV size and morphology as follows:

●Z-score of -4 correlates with a unipartite ventricle

●Z-score of -2 to 0 correlates with a tripartite ventricle

●Z-scores of -4 to -2 are associated with variable degrees of RV hypoplasia

However, these correlations are not always reliable. Thus, it is important to evaluate both TV size and RV size since each one is a key factor in determining suitability for biventricular repair [4]. The Z-score of the TV annulus measurement can underestimate the degree of inlet obstruction to the RV since a small, effective orifice of the TV leaflets may significantly obstruct RV inflow. In addition, differences in the various available Z-score data sets may contribute to inconsistency with the correlation of this measurement as a reliable predictor of suitability for biventricular repair [57]. The TV annular size may be compared with the mitral valve (TV:mitral valve ratio), providing an additional measure to aid in decision-making [58,59].

Cardiac catheterization — Cardiac catheterization is performed in most neonates to identify RV coronary connections, assess for the presence of RVDCC, and perform initial interventions [25,28,31,60].

It is essential to identify coronary abnormalities, because these are important factors in the management of PA/IVS (image 3). Coronary sinusoids and fistulae are diagnosed by injection of contrast into the RV, and proximal coronary artery atresia and coronary stenoses are visualized by selective injection of the coronary artery origins from the aorta. It is important to determine whether arterial perfusion in two of the three main coronary arteries is dependent on circulation from the RV (ie, RVDCC), since decompression of the RV during surgery could lead to coronary artery steal, ischemia, infarction, cardiac arrest, and/or death [25,28,31,60]. One retrospective study suggested that quantification of antegrade coronary blood flow using a scoring system may provide additional predictive information on cardiac outcomes such as transplantation [61].

The RV size and morphology and TV size are also confirmed by angiography. Hemodynamic measurements may reveal a severely hypertensive RV in the smallest unipartite ventricles with little tricuspid regurgitation.

Cardiac catheterization also provides the opportunity for interventions such as pulmonary valve perforation with pulmonary valvuloplasty and ductus arteriosus stent placement. (See 'Biventricular repair' below and 'Univentricular palliation' below.)

Rarely, cardiac catheterization is not performed in the neonatal period, including any of the following situations:

●Patients with severely hypoplastic RVs (Z-scores between -3 and -5) and ductal anatomy unfavorable for a stent will require a surgical aorta-to-pulmonary shunt regardless of coronary artery anatomy (having confirmed normal aortocoronary origins by echocardiography).

●Extreme prematurity (or weight less <2 kg) may lead to deferral of the initial cardiac catheterization. In these cases, the coronary arteries are often assessed at future catheterizations (in preparation for stage II palliation of single-ventricle disease).

●The presence of other comorbidities may preclude cardiac catheterization before surgery.

CT angiography — Cardiac computed tomographic angiography (CTA) is emerging as a diagnostic tool for assessing coronary artery anatomy and RV dependence in infants with PA/IVS. While a specialized programmatic imaging approach (with meticulous CTA analysis) may preclude cardiac catheterization in some programs, other centers use CTA as an adjunct to planning for diagnostic and interventional cardiac catheterization (ie, ductal stenting) [62,63]. In a single-center case series of six neonates with PA/IVS who underwent both CTA and cardiac catheterization, CTA findings closely mirrored those of invasive cardiac catheterization and identified important morphological variations with considerably less radiation exposure [63]. However, diagnosis of RVDCC requires direct right ventricular angiography. Therefore, the potential benefits of CTA are to risk stratify, assist with procedural planning, and improve counseling for the parents/caregivers.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of PA/IVS includes other cyanotic cardiac conditions with right ventricular (RV) outlet obstruction, which typically have radiographic features of a normal to mildly enlarged heart and normal pulmonary vascular markings.

Echocardiography distinguishes PA/IVS from the following cardiac diseases:

●PA with ventricular septal defect (PA/VSD; also called tetralogy of Fallot [TOF]/PA)

●Critical pulmonary stenosis (see "Pulmonic stenosis in infants and children: Management and outcome")

●TOF (see "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis", section on 'Postnatal diagnosis')

●Tricuspid atresia (see "Tricuspid valve atresia")

MANAGEMENT — Patients with PA/IVS must be managed individually, given the heterogeneity of anatomic findings and physiologic consequences, especially the wide spectrum of abnormalities of the right ventricle (RV) and tricuspid valve (TV). There are limited long-term outcome data on patients with PA/IVS. Thus, there is uncertainty regarding the impact of interventions performed in infancy, particularly biventricular repair, on RV growth and cardiac function through childhood into adulthood.

Neonates with PA/IVS should be cared for at a tertiary medical center with experience in managing complex congenital heart disease (CHD). When an antenatal diagnosis is made, maternal transfer should be performed so that neonatal care can be provided immediately after birth. (See "Congenital heart disease: Prenatal screening, diagnosis, and management", section on 'Delivery planning'.)

Fetal intervention — Antenatal therapies to treat PA/IVS have been developed in centers that specialize in fetal cardiac intervention. Proponents of fetal intervention suggest that halting the development of PA would allow for continued growth of "upstream" cardiac structures, namely the RV and TV. However, current risk models are not sufficiently accurate to consistently identify univentricular circulation in the fetus [55]. Thus, fetal catheter-based intervention should be pursued only in fetuses with clear univentricular circulations.

A study from the International Fetal Cardiac Intervention Registry (IFCIR) reported outcomes of fetal pulmonary valvuloplasty procedures performed from 2001 to 2018 in 58 fetuses with PA/IVS [64]. The procedure was reported as being technically successful in 70 percent of cases, although there were fetal complications in 55 percent, including seven procedure-related fetal losses and two delayed fetal losses (total 16 percent). In successful cases, serial imaging demonstrated increasing TV size. Of the 48 liveborn infants, 43 (90 percent) were alive at discharge. Among the 31 surviving infants whose fetal intervention was technically successful, most (87 percent) underwent biventricular repair. Only 4 of the 10 surviving infants whose fetal intervention was not technically successful underwent biventricular repair.

Smaller case series from individual fetal intervention centers have also demonstrated that in utero dilation of the pulmonary valve is technically feasible [65-69]. These data suggest procedural and physiologic success in this cohort; however, lack of a control group in these studies precludes drawing firm conclusions about whether it was the procedure itself that resulted in the improvements in TV size and RV growth.

Initial stabilization — Initial management is focused on stabilizing and optimizing cardiac and pulmonary function and systemic oxygenation so that corrective repair or palliation can be performed.

Therapy is directed towards providing sufficient intercirculatory mixing by maintaining patency of the ductus arteriosus with prostaglandin E1 (alprostadil) infusion. Similarly, the cardiac output is dependent on blood shunting from the right to the left atrium. A severely restrictive atrial communication would likely result in spontaneous abortion and is rare in newborns with PA/IVS. Some centers perform balloon atrial septostomy to improve right-to-left atrial shunting, especially in patients who will eventually require an aortopulmonary shunt [7]. However, balloon septostomy was associated with increased mortality in one 30-year retrospective review of 89 patients [70]. (See "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Prostaglandin E1' and "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Cardiac catheterization'.)

Initial management also includes general cardiorespiratory support for infants with respiratory compromise, hypotension, poor perfusion, acidosis, and hypothermia. These measures include respiratory support (eg, supplemental oxygen and/or mechanical ventilation), inotropic agents, and correction of acidosis and metabolic derangements (eg, hypoglycemia). (See "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'General supportive care'.)

Corrective repair or palliation — The following are options for corrective repair or palliation for patients with PA/IVS. The choice of repair and implementation are best done under the direction of a multidisciplinary team of pediatric cardiologists and cardiothoracic surgeons since these repairs typically involve a series of both catheter-based and surgical procedures.

●Biventricular repair – Separates the pulmonary and systemic circulations with two pumping ventricles. (See 'Biventricular repair' below.)

●Hybrid (1.5-ventricle) repair – Separates the pulmonary and systemic circulations with two pumping ventricles, but the RV does not completely support the pulmonary circulation. (See 'Hybrid (1.5-ventricle) approach' below.)

●Univentricular palliation – Separates the pulmonary and systemic circulations with only one pumping ventricle (ie, the left ventricle [LV]). (See 'Univentricular palliation' below.)

●Primary cardiac transplantation – Patients with aortocoronary atresia have a mortality rate approaching 100 percent, even with palliative surgery, leading many centers to offer these patients primary cardiac transplantation [60]. One case report of one patient with aortocoronary atresia treated with an aortic-to-RV shunt (to provide coronary blood flow) successfully avoided primary transplantation [71].

Key considerations — A central issue in surgical decision-making is determining the suitability and feasibility of biventricular repair, which depends on the morphologic features of the individual patient [3,4,72,73]. The following general questions are useful in determining the feasibility of biventricular repair:

●Are coronary artery abnormalities present, and can the RV be decompressed during repair? In other words, does this patient have RV-dependent coronary circulation (RVDCC), and could decompression of the RV result in ischemic "coronary steal" and, potentially, cardiac death [31]?

●Can the RV be rehabilitated so that it can fully support the pulmonary circulation [74]? In other words, can the RV receive a full cardiac output from the venous system and then pump a full cardiac output to the pulmonary arteries?

●Is there a tripartite RV with membranous atresia of the pulmonary valve?

Often, it is challenging to answer all of these questions accurately because of the complexity and heterogeneity of this lesion, leading to variability among different centers regarding the choice of intervention. In order to provide accurate answers based on measurable morphologic findings, several studies have reviewed outcome data to identify factors that predict the success of biventricular repair. The factors associated with success include the following [3-5,31,72,73,75-78]:

●TV size – TV Z-score ≥-2 is associated with greater likelihood of successful biventricular repair. In addition, the ratio of the tricuspid to mitral valve annulus has been reported, with ratios ≥0.8, suggesting favorable biventricular circulation [58,59].

●RV size (area) and morphology – A tripartite or near-normal-size RV is associated with greater likelihood of successful biventricular repair.

●Coronary circulation – Absence of RVDCC is associated with greater likelihood of successful biventricular repair.

●Degree of tricuspid regurgitation – Moderate or greater tricuspid regurgitation is associated with greater likelihood of successful biventricular repair.

In a review of 13 studies reporting surgical outcomes of nearly 1400 patients with PA/IVS, 30 percent achieved biventricular repair [57]. None of the studies included in the review reported a mean TV Z-score <-2.8 in biventricular repair patients. However, one study of catheter-based pulmonary valve perforation suggests encouraging results for patients with PA/IVS even when there is moderate RV hypoplasia [59]. Additionally, a study of 81 patients has identified echocardiographic parameters associated with a biventricular circulation and RV growth [79]; the largest increase in RV area was found in those with smaller baseline measurements of RV area, more than moderate baseline tricuspid regurgitation, and a larger baseline TV Z-score. After intervention, RV growth was associated with larger TV Z-scores, more than moderate baseline tricuspid regurgitation, and more than moderate post-intervention pulmonary regurgitation.

In addition, definitive diagnosis of RVDCC can be challenging and dependent on specific coronary perfusion distributions in a given patient. In patients with "borderline RVDCC," some centers have shown promising results with pursuit of RV decompression accompanied by surgical ligation of the coronary fistulae [80]. Some centers also incorporate interval assessment and intervention of sinusoidal communications to the right ventricle [81].

Our approach — At our institution, the management of newborns with PA/IVS is a collaborative medical and surgical effort. Decision-making is based on anatomical and physiologic data of the lesion for each individual patient to determine whether biventricular repair is feasible.

At our center, we base the choice of intervention on factors that are most predictive of successful biventricular repair (ie, absence of RVDCC, RV size/area and morphology [uni-, bi-, or tri-partite], TV Z-score, and degree of tricuspid regurgitation), as discussed above. (See 'Key considerations' above.)

●Patients with favorable anatomy for biventricular repair – For patients with anatomy that is favorable for biventricular repair, biventricular repair is the long-term goal. This typically includes patients who meet all of the following criteria:

•Bi- or tripartite RV

•RV area ≥6 cm²/m²

•TV Z-score ≥-3

•Moderate or greater tricuspid regurgitation

•No RVDCC

Details of the biventricular repair are provided below. (See 'Biventricular repair' below.)

●Patients with borderline anatomy – Patients with the following characteristics may undergo a hybrid (1.5-ventricle) repair [5,82-86]:

•Borderline-sized RV

•TV Z-score ≥-4 and <-2

•No RVDCC

Details of the hybrid approach are provided below. (See 'Hybrid (1.5-ventricle) approach' below.)

●Patients with unfavorable anatomy for biventricular repair – Factors that are unfavorable for biventricular repair include:

•Unipartite RV

•RV area <6 cm²/m²

•TV Z-score <-3

•Less than moderate tricuspid regurgitation

•Presence of RVDCC

Patients with any of these unfavorable findings typically undergo univentricular palliation, as described below. (See 'Univentricular palliation' below.)

Types of repair/palliation

Biventricular repair

●Initial step: RVOT decompression – The initial step to biventricular repair is decompression of the RV by reconstructing the RV outflow tract (RVOT). The goal of RVOT decompression is to promote RV and TV growth so that the right side of the heart will eventually be able to pump a full cardiac output to the lungs [87]. RVOT decompression can be accomplished by catheter-based or surgical intervention [3,88-90]:

•Radiofrequency perforation of the plate-like pulmonary valve and subsequent balloon dilation of the pulmonary valve is performed during cardiac catheterization [58,91-93]. In one report, the use of echocardiographic guidance improved the safety of catheter-based pulmonary valve perforation, although this additional imaging is not currently the standard of care [94].

•Alternatively, the RVOT may be opened surgically with a patch across the pulmonary valve annulus ("transannular patch") and/or pulmonary valvotomy.

●Subsequent monitoring and RV growth – After RVOT decompression, patients often require prostaglandin E1 (alprostadil) infusion to maintain ductal patency to provide an additional source of pulmonary blood flow. Over a period of four to six weeks, multiple trials of prostaglandin E1 discontinuation can help determine the ability of the RV to provide adequate pulmonary blood flow. If the RV is not adequate after the initial four- to six-week period, a hybrid approach may be necessary to provide adequate pulmonary blood flow and oxygenation until RV growth is adequate [88,91,92,95-97]. In this setting, the hybrid approach includes either catheter-based stenting of the ductus arteriosus or surgical creation of an aorta-to-pulmonary shunt (ie, modified Blalock-Thomas-Taussig shunt, as shown in panel B of the figure (figure 2)).

Performing multiple trials on and off prostaglandin E1 tests the RV to determine whether it can accommodate more flow, which informs decisions about the suitability and timing of repair. The main disadvantage of this approach is that these trials can take several weeks, and the patient must remain hospitalized in the intensive care unit for the duration. An alternative approach is to perform ductal stenting early on. While this provides a source of pulmonary blood flow, it doesn't allow for testing of the RV over time and, thus, it may be more challenging to determine if the patient is a suitable candidate for biventricular repair.

In a multicenter retrospective study of 99 neonates who underwent catheter-based RVOT decompression, 42 percent subsequently required reintervention to provide a secondary source of pulmonary blood flow [76]. In this study, elevated RV end-diastolic pressure and mild or no tricuspid regurgitation were predictors of need for additional pulmonary blood flow. In addition, 43 percent of patients required reintervention on the RVOT. Despite the high rate of reintervention in these patients, most (85 percent) were able to maintain a two-ventricle circulation. Patients who are most likely to achieve successful biventricular repair with this approach and who are unlikely to require subsequent reintervention are those with larger TVs (based on Z-score) and tripartite RVs [97].

●Completing the biventricular repair – Once prostaglandin E1 is successfully discontinued (with or without establishing an additional source of pulmonary blood flow) and there has been time for RV growth, cardiac catheterization is performed to assess RV adequacy. If the RV is adequate as the sole source of pulmonary blood flow and the right atrial pressure is not significantly elevated, the patent foramen ovale (PFO)/atrial septal defect and aorta-to-pulmonary shunt may be closed using catheter-delivered occlusion devices, thereby completing the biventricular repair [98].

●Pulmonary valve implantation – With the advent of catheter-deployed pulmonary valve replacement, patients with favorable biventricular anatomy may have complete catheter-based intervention for PA/IVS. Following successful neonatal radiofrequency perforation of the pulmonary valve, suitable patients are closely followed and subsequently have catheter-based pulmonary valve implantation at approximately 5 years of age [99].

Hybrid (1.5-ventricle) approach — The hybrid (1.5-ventricle) approach is a surgical palliation that consists of opening the RVOT, partially closing the PFO, and creating a bidirectional superior cavopulmonary anastomosis (Glenn shunt). The bidirectional Glenn shunt provides a direct source of pulmonary blood flow from the superior vena cava, while blood flow from the inferior vena cava is pumped through the RV and reconstructed pulmonary valve [100]. In this way, a borderline-sized RV can accommodate approximately one-half of the systemic venous return (ie, only blood return from the inferior vena cava). Often, a small atrial communication is left as a "pop off" for blood to exit the right atrium in the setting of a noncompliant RV. Hemodynamic catheterization is then repeated at one to three years to determine if the RV is adequate for complete closure of the PFO/atrial septal defect or if a single-ventricle palliation via the Fontan procedure is required.

Data from small studies suggest that flow through the TV stimulates growth of right heart structures if the outflow obstruction to the pulmonary artery is relieved [74].

Univentricular palliation — Univentricular palliation involves staged procedures towards a Fontan circulation (typically with an extracardiac Fontan, as shown in panel C of the figure (figure 3)). The first stage is performed in the neonatal period and consists of establishing a reliable source of pulmonary blood flow, which can be accomplished surgically or by catheter-based intervention:

●A surgical aortopulmonary shunt is often used as the method to provide pulmonary blood flow (ie, modified Blalock-Thomas-Taussig shunt, as shown in panel B of the figure (figure 2)).

●Alternatively, pulmonary blood flow can be provided by stenting the ductus arteriosus during cardiac catheterization. In the available case series reporting on ductal stenting in infants with PA/IVS, the procedure appears to be safe and achieves similar outcomes and perhaps better pulmonary artery growth compared with surgical shunt placement [101-105].

In patients with RVDCC, surgical management also includes specific intraoperative techniques to maintain adequate coronary perfusion and postoperative care also focuses on avoiding cardiac ischemia [106,107]. Of note, successful single-ventricle palliation (rather than primary cardiac transplantation) has been reported in a patient with left coronary artery atresia in PA/IVS [108].

Additional details regarding staged surgical palliation for single-ventricle physiology and management of children who have undergone Fontan palliation are provided separately. (See "Hypoplastic left heart syndrome: Management and outcome", section on 'Surgical management' and "Overview of the management and prognosis of patients with Fontan circulation".)

Primary cardiac transplantation — Primary cardiac transplant is an acceptable approach in infants with severe forms of PA/IVS since they are at high risk of mortality. However, waitlist mortality is also high. In a study analyzing data from a large pediatric transplant registry, among the 300 infants with PA/IVS listed for cardiac transplant from 1993 through 2018, 63 percent were transplanted by six months and 21 percent died while waiting [109]. Waitlist mortality for infants with PA/IVS was similar to that of infants with other single-ventricle diagnoses (for whom waitlist mortality was 23 percent at six months). Both groups had considerably higher waitlist mortality compared with patients without single-ventricle diagnoses (eg, for patients with cardiomyopathy, waitlist mortality was 16 percent at six months). Risk factors for waitlist mortality among patients with PA/IVS included requiring mechanical ventilation at time of listing, receiving extracorporeal membrane oxygenation support at time of listing, and not undergoing surgical shunt or ductal stenting prior to listing. Among patients who survived and underwent cardiac transplantation, post-transplant survival was better for infants with PA/IVS compared with other single-ventricle diagnoses (estimated ten-year survival 76 versus 66 percent, respectively).

OUTCOMES — Although PA/IVS continues to be challenging to treat, outcomes have improved as surgeons and cardiologists have gained experience with the spectrum of anatomic findings.

Periprocedural mortality and morbidity — In a registry study that included 268 infants with PA/IVS managed at 19 different centers in the United States from 2009 to 2019, in-hospital mortality following catheter-based or surgical intervention was 8.2 percent [110]. In this study, 20 percent of patients experienced at least one major adverse event during the hospitalization, including need for cardiopulmonary resuscitation (13 percent), need for extracorporeal membrane oxygenation support (9 percent), or stroke (6 percent). Independent risk factors for experiencing major morbidities included low birth weight and the presence of two major coronary artery stenoses.

Mortality rates according to the type of intervention performed were as follows [110]:

●Surgical shunt or transcatheter ductal stenting only – 11 percent

●Right ventricular outflow tract (RVOT) decompression only (surgically or transcatheter) – 6 percent

●RVOT decompression with surgical shunt or ductal stenting – 0 percent

Type of repair/palliation achieved — In two large multicenter cohort studies including a total of 728 infants with PA/IVS followed for an average of 5 to 15 years, the end-states achieved were as follows [111,112]:

●Underwent biventricular repair and survived to last follow-up – 26 percent

●Underwent hybrid (1.5 ventricle) repair and survived to last follow-up – 5 percent

●Underwent univentricular palliation (ie, Fontan circulation) and survived to last follow-up – 20 percent

●Underwent other shunt palliation (ie, continued to have mixed circulation but had not undergone Fontan at time of last follow-up) – 15 percent

●Underwent cardiac transplantation and survived to last follow-up – 5 percent

●Did not survive – 30 percent

Long-term survival — In the available studies reporting outcomes for children with PA/IVS, rates of long-term survival have varied considerably, ranging from approximately 60 percent at 10 years in some studies to as high as 90 percent at 5 to 10 years in others [3,4,7,113-115]. This variability is likely accounted for by differences in the era in which the studies were performed, differences in the individual morphologic characteristics of the patients included in the reports, and differences in the management approach. In most studies, lower tricuspid valve (TV) Z-score, smaller right ventricle (RV) size, and presence of RV-dependent coronary circulation (RVDCC) correlated with increased risk of mortality.

Survival rates vary depending on the type of repair or palliation:

●Biventricular repair – Long-term survival approaches 90 percent in studies using a selective management approach, which results in fewer patients receiving biventricular repair [60,74,90,112,116-118]. However, most patients require reintervention [76,118].

●Hybrid repair – For patients repaired with a hybrid (1.5-ventricle) approach, five-year survival is approximately 90 percent; 95 percent of survivors are classified as New York Heart Association class I or II [83,84,100]. However, ongoing concerns regarding restrictive RV physiology and diastolic dysfunction warrant long-term hemodynamic surveillance [119].

●Univentricular palliation – Patients who undergo univentricular palliation with the Fontan procedure have a reported survival of approximately 80 percent at 5- to 15-year follow-up [120-122], a rate that is comparable with patients who undergo single-ventricle palliation for other complex congenital heart defects. However, patients with abnormal coronary arteries, particularly RVDCC, may be at increased risk for morbidity and mortality following the Fontan procedure [120,123-126]. Coronary ischemia can also present late after univentricular palliation in patients with PA/IVS [127]. In a study of 120 patients who underwent Fontan palliation for PA/IVS, 10-year survival in patients with RVDCC was 77 percent, compared with 96 percent for those without RVDCC [125]. The prognosis after Fontan palliation is discussed in greater detail separately. (See "Overview of the management and prognosis of patients with Fontan circulation", section on 'Prognosis after Fontan procedure'.)

●Primary cardiac transplantation – Ten-year survival after primary cardiac transplantation for PA/IVS is approximately 75 percent, which is superior to that of other single-ventricle diagnoses [109].

Long-term morbidity

●Cardiac morbidity – For adult survivors, there is a high incidence of arrhythmias and need for reintervention, particularly pulmonary valve reintervention [124,128]. This was illustrated by a case series of 20 adult patients from the Mayo Clinic, which included patients with a wide range of anatomy and surgical palliation [124]. In this cohort, arrhythmias were common, including atrial arrhythmias in 80 percent and ventricular arrhythmias in 15 percent. All patients required reintervention in adulthood, underscoring the requirement for close cardiology follow-up after initial repair or palliation of this lesion [124].

Long-term complications in patients who undergo Fontan palliation are discussed in greater detail separately. (See "Management of complications in patients with Fontan circulation".)

●Functional status and exercise capacity – Long-term functional status for patients with PA/IVS was described in a study of 106 patients with PA/IVS who underwent repair or palliation (biventricular repair in 60 percent, univentricular palliation in 24 percent, hybrid [1.5 ventricle] repair in 12 percent, and transplant or other palliation in 5 percent) and were evaluated at a mean age of 15 years [112]. Scores on standardized questionnaires of functional status were lower than age- and sex-matched healthy controls in the domains of global health and physical functioning (mean scores of 81 and 85, respectively compared with 95 to 100 in the healthy population). However, scores were higher than controls in the social-emotional domain and other psychosocial domains. Most patients had evidence of reduced exercise capacity (approximately 70 to 80 percent of predicted capacity); patients who underwent univentricular palliation had greater limitations than those who underwent biventricular or hybrid repair.

Other studies have also reported reduced exercise capacity in patients with PA/IVS, especially those who undergo uni- or 1.5-ventricle repair [129-134]. In one study of 42 children with PA/IVS who were evaluated at median age of 8.5 years, 78 percent had no limitations of physical activity (ie, New York Heart Association [NYHA] class I (table 1)), 16 percent had NYHA class II symptoms, and 5 percent had NYHA class III symptoms [135].

●Quality of life (QOL) – In a study of 42 children with PA/IVS who were surveyed about QOL at a median age of 8.5 years, overall ratings of QOL by patients with PA/IVS and their parents were similar to those of a reference group of age-matched healthy children [135]. In another study of 64 patients with PA/IVS who were evaluated at mean age of 15 years, health-related QOL scores were similar for patients with PA/IVS as compared with healthy controls for the psychosocial domain, but physical health QOL scores were lower [112].

●Neurodevelopmental outcomes – Although there are limited data on neurodevelopmental outcomes specifically for patients with PA/IVS, it is well accepted that children with complex congenital heart disease who undergo cardiac surgery in infancy are at increased risk of developmental delays [136-138]. The risk is particularly high in patients with single-ventricle physiology [137]. Infants and children with PA/IVS require close neurodevelopmental surveillance; referral for early intervention is appropriate in most cases [139]. (See "Developmental-behavioral surveillance and screening in primary care".)

Long-term neurodevelopmental outcomes following Fontan palliation are discussed in greater detail separately. (See "Management of complications in patients with Fontan circulation", section on 'Neurologic complications'.)

LONG-TERM FOLLOW-UP CARE — As for all patients with repaired or palliated congenital heart disease (CHD), long-term health care maintenance is a collaborative effort between primary care and pediatric cardiology clinicians.

Follow-up visits — At each health maintenance visit, patients should be evaluated for the following:

●History:

•Symptoms of fatigue or dyspnea may be suggestive of heart failure

•Symptoms of palpitation or syncope may be suggestive of cardiac arrhythmias

●Physical examination:

•Vital signs should include measurement of peripheral oxygen saturation (SpO₂) by pulse oximetry. This is especially important in patients with uni- or 1.5-ventricle repair who have intracardiac shunts to ensure adequate oxygenation (SpO₂ should be >90 percent).

•Evidence of right-sided heart failure (eg, hepatomegaly or peripheral edema).

•Cardiac auscultation, particularly murmurs that suggest tricuspid regurgitation and/or pulmonary stenosis and/or regurgitation.

●Electrocardiography (ECG) to detect any evidence of arrhythmias, ischemic changes, or right atrial hypertrophy

●Chest radiography to assess right-sided anatomy, particularly evidence of right ventricular (RV) dilatation

●Echocardiography:

•In patients with biventricular repair, assess RV size and function as well as size and function of the tricuspid and pulmonary valves

•In patients with univentricular palliation, detect any evidence of atrial obstruction or thrombus and evaluate the status of intracardiac shunts

●Other studies may be indicated including cardiac catheterization, magnetic resonance imaging, and nuclear scintigraphy for further delineation of the hemodynamic status of the heart and intracardiac shunts, coronary artery anatomy, and cardiac perfusion

Long-term health concerns differ depending on the type of repair/palliation:

●Biventricular repair – Patients with biventricular repair may have residual pulmonary stenosis and tricuspid and/or pulmonary regurgitation [74,116,117]. In addition, atrial arrhythmias may occur in patients with right atrial dilatation due to tricuspid and/or pulmonary regurgitation.

●Univentricular (Fontan) palliation – Long-term complications following the Fontan procedure may include atrial arrhythmias, cyanosis, right atrial thrombosis, ischemia, and heart failure. These are discussed separately. (See "Management of complications in patients with Fontan circulation".)

Activity — The 2015 scientific statement of the American Heart Association and American College of Cardiology provides competitive athletic participation guidelines for patients with CHD [140]. These guidelines do not provide specific recommendations for patients with PA/IVS; however, activity recommendations can be inferred from those of similar CHD lesions following either repair or palliation.

●Before participating in sports, patients with PA/IVS should undergo evaluation, including clinical assessment, ECG, imaging assessment of ventricular function (with echocardiogram or magnetic resonance imaging), and exercise testing.

●Patients who have undergone biventricular repair with minimal residual effects can participate in all sports if they have normal ventricular function, a normal exercise test, and no arrhythmias (similar to recommendations for patients with repaired tetralogy of Fallot [TOF] or D-transposition of the great arteries). (See "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Sports participation'.)

●Recommendations for patients who have undergone Fontan palliation (univentricular palliation) are discussed separately. (See "Overview of the management and prognosis of patients with Fontan circulation", section on 'Exercise'.)

●Patients with congenital coronary artery anomalies are allowed to participate in all sports following successful operation if the patient does not have ischemia, ventricular tachyarrhythmias, or dysfunction. However, patients with persistent coronary anomalies or ischemia should be restricted from participating in competitive sports. (See "Congenital and pediatric coronary artery abnormalities".)

Physical activity and exercise in patients with CHD are discussed in greater detail separately. (See "Physical activity and exercise in patients with congenital heart disease".)

Endocarditis prophylaxis — Patients with PA/IVS may require antibiotic prophylaxis before certain dental procedures to reduce the risk of infective endocarditis. Antibiotic prophylaxis is recommended during the first six months after complete repair and beyond that for patients who have repairs that include the use of prosthetic material, those with a prior episode of endocarditis, and those with a residual intracardiac shunt who remain cyanotic or have patch leaks. The approach to determining the need for prophylaxis is summarized in the figure (algorithm 1) and discussed in detail separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

Vaccination — Patients with PA/IVS should receive all routine childhood vaccinations, including pneumococcal vaccine, yearly influenza vaccine, COVID-19 vaccine, and respiratory syncytial virus (RSV) immunoprophylaxis for eligible infants. (See "Standard immunizations for children and adolescents: Overview" and "Pneumococcal vaccination in children" and "Seasonal influenza in children: Prevention with vaccines" and "COVID-19: Vaccines", section on 'Children' and "Respiratory syncytial virus infection: Prevention in infants and children".)

Vaccinations are usually administered six weeks after major cardiac procedures or surgery.

Pregnancy — Successful pregnancies have been reported in patients who have achieved biventricular repair [141]. A preconception comprehensive cardiovascular evaluation by an adult congenital heart disease specialist is recommended prior to pregnancy to confirm that there are no cardiovascular features that would be best treated before a pregnancy or to suggest that a pregnancy would be high-risk and thus not advised.

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: Congenital heart disease in infants and children".)

SUMMARY AND RECOMMENDATIONS

●Anatomy and pathophysiology – Pulmonary atresia with intact ventricular septum (PA/IVS) is characterized by complete obstruction to the right ventricular outflow tract (RVOT) with varying degrees of RV and tricuspid valve (TV) hypoplasia (picture 1). In most cases, there are abnormal connections between the RV and coronary arteries. Because the ventricular septum is intact, blood can only exit the RV either by regurgitating into the right atrium or through connections between the RV and the coronary artery circulation (ie, fistulae and sinusoids). Blood is returned to the systemic circulation from the right to left atrium through the patent foramen ovale (PFO) and through the coronary connections. (See 'Anatomy' above and 'Pathophysiology' above.)

●Incidence and pathogenesis – PA/IVS accounts for 1 to 3 percent of all congenital heart defects, with a reported incidence between 4 and 8 per 100,000 live births. The pathogenesis of PA/IVS is unknown. It has been proposed that PA/IVS is an acquired lesion due to perturbation of fetal blood flow rather than a primary morphogenetic lesion. (See 'Epidemiology' above and 'Pathogenesis' above.)

●Presentation – Patients with PA/IVS present as neonates with cyanosis accompanied with mild tachypnea or hyperpnea. Because PA/IVS is a ductal-dependent lesion, closure of the patent ductus arteriosus (PDA) generally results in rapid clinical deterioration and life-threatening consequences (eg, cardiogenic shock and cardiac arrest). If untreated, PA/IVS is an almost always fatal. (See 'Postnatal presentation' above.)

Initial evaluation demonstrates hypoxemia on pulse oximetry screening, unremarkable chest radiograph (image 1), and an electrocardiograph (ECG) with characteristic findings of a QRS axis between 0 to +90 degrees and decreased right-sided ventricular forces (waveform 1). (See 'Clinical presentation' above.)

●Diagnosis – PA/IVS is diagnosed by echocardiography with the identification of an atretic PA and IVS (image 2). In addition, echocardiography should evaluate the size and function of the RV and TV and assess intracardiac mixing through the PFO and pulmonary blood flow through the PDA. (See 'Diagnosis' above.)

Cardiac catheterization is essential to identify coronary abnormalities, which are important factors in the choice of intervention (image 3). (See 'Cardiac catheterization' above.)

●Management – Neonates with PA/IVS should be managed in a medical center with experience in managing complex congenital heart disease (CHD).

Initial stabilization includes general cardiorespiratory support and administration of prostaglandin E1 (alprostadil) to maintain patency of the ductus arteriosus. (See 'Initial stabilization' above and "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Prostaglandin E1'.)

The treatment algorithm for PA/IVS is complex and requires careful consideration of anatomic and physiologic findings in each individual patient. After the initial stabilization, our general approach to choosing subsequent interventions is based on assessing the feasibility of biventricular repair, which depends on the morphologic features of the individual patient (eg, RV and TV size and function and coronary artery circulation):

•For most patients with favorable anatomy for biventricular repair (bi- or tripartite RV, RV area ≥6 cm²/m², TV Z-score ≥-3, moderate or greater tricuspid regurgitation, and no RV-dependent coronary circulation [RVDCC]), we suggest biventricular repair (Grade 2C). The goal of biventricular repair is to have separate pulmonary and systemic circulations with two pumping ventricles. Additional details of biventricular repair are provided above. (See 'Biventricular repair' above.)

•For most patients with intermediate or borderline characteristics (borderline-sized RV, TV Z-score ≥-4 and <-2, and no RVDCC), we suggest a hybrid (1.5 ventricle) repair (Grade 2C). The hybrid approach results in separate pulmonary and systemic circulations with two pumping ventricles, but with one source of pulmonary blood flow from the superior vena cava. Additional details of the hybrid approach are provided above. (See 'Hybrid (1.5-ventricle) approach' above.)

•For most patients with characteristics that are unfavorable for biventricular repair (unipartite RV, RV area <6 cm²/m², TV Z-score <-3, less than moderate tricuspid regurgitation, or presence of RVDCC), we suggest univentricular palliation (Grade 2C). Many centers initiate treatment with interventional catheterization and ductal stenting for the first stage of palliation in this setting. Staged surgical palliation for single-ventricle physiology is summarized above and discussed in greater detail separately. (See 'Univentricular palliation' above and "Hypoplastic left heart syndrome: Management and outcome", section on 'Surgical management'.)

●Outcome – Without intervention, PA/IVS is almost always a fatal condition. For patients who undergo repair/palliation, short-term periprocedural mortality is approximately 8 percent. For surviving infants, long-term survival varies according to the type of repair/palliation achieved. For patients with biventricular repair, five- to ten-year survival is >90 percent. For patients with univentricular palliation, five- to ten-year survival is approximately 80 percent. (See 'Outcomes' above.)

●Long-term follow-up – Providing health care maintenance is a collaborative effort between primary care and pediatric cardiology clinicians. Follow-up care consists of routine visits that include history, physical examination, and cardiac testing (ECG and echocardiography). Follow-up care focuses on identifying complications following repair such as heart failure and arrhythmias, and in patients with univentricular palliation, identifying evidence of increasing cyanosis or cardiac ischemia. (See 'Long-term follow-up care' above and "Overview of the management and prognosis of patients with Fontan circulation" and "Management of complications in patients with Fontan circulation".)