INTRODUCTION — Partial anomalous pulmonary venous return (PAPVR; also known as partial anomalous pulmonary venous connection [PAPVC]), encompasses a spectrum of congenital cardiovascular anomalies. Blood from one or more pulmonary veins returns abnormally to the right atrium, either directly or indirectly through a variety of systemic venous pathways that connect with the anomalous pulmonary vein.
The anatomic abnormalities that result in PAPVR and the diagnosis and management of PAPVR will be reviewed here. Total anomalous pulmonary venous connection (TAPVC) is discussed separately. (See "Total anomalous pulmonary venous connection".)
EPIDEMIOLOGY — The overall incidence of PAPVR is estimated to be 0.7 percent of the population [1]. However, as this rate is based upon autopsy data, the true prevalence of PAPVR may actually be higher [2-5]. Multiple case series report PAPVR as an incidental finding without associated symptoms.
Although PAPVR can present as an isolated structural abnormality, it commonly occurs with other cardiac abnormalities, most often an atrial septal defect (ASD). In addition, patients with Turner syndrome are at increased risk for PAPVR [6,7]. (See "Clinical manifestations and diagnosis of Turner syndrome".)
PULMONARY VEIN ANATOMIC VARIANTS
Terminology — For congenital anomalies of the pulmonary vein, the terms "anomalous venous return," "anomalous venous connection," and "anomalous venous drainage" are often used synonymously and reflect the same physiology. (See 'Physiology' below.)
However, in the purest anatomic sense, the term "anomalous venous return" is the more general description, while "anomalous venous connection" and "anomalous venous drainage" are distinct from one another. (See 'Partial anomalous pulmonary venous connections' below and 'Partial anomalous pulmonary venous drainage' below.)
Normal variants — Normal variants return blood from the pulmonary circulation directly to the left atrium:
●The most common arrangement involves two left and two right pulmonary veins that form separate orifices and connect directly to the posterior wall of the left atrium.
●In the second most common variant, pulmonary veins from the entire right or left lung form a single confluent vessel before it connects into the left atrium, thereby forming a single orifice for an entire lung.
●In less common variants, there can be a total of five or more pulmonary vein connections, each draining a correspondingly smaller proportion of the lung but all connecting normally to the left atrium.
These variations have no clinical impact.
Total versus partial anomalous pulmonary venous return — There is a wide range of congenital pulmonary vein arrangements that result in anomalous return of blood from the lung to the heart.
●Total anomalous pulmonary venous connection (TAPVC) – TAPVC (also known as total anomalous pulmonary venous return [TAPVR]) is a cyanotic congenital defect in which all four pulmonary veins fail to make their normal connection to the left atrium. This results in drainage of all pulmonary veins into the systemic venous circulation. There are four variants of TAPVCs based upon the location of the anomalous connection: supracardiac (typically a vertical vein connecting to the innominate vein), cardiac (to the right atrium or coronary sinus), infracardiac, or mixed connection(s) at two or more levels. TAPVC is reviewed in detail separately. (See "Total anomalous pulmonary venous connection".)
●Partial anomalous pulmonary venous return (PAPVR) – PAPVR occurs when one or more, but not all, of the pulmonary veins return directly to the right atrium or indirectly through a variety of venous connections from a pulmonary vein to a systemic vein.
PAPVR consists of two distinct anatomic subtypes with similar physiology, as discussed in the following sections [8]:
•Partial anomalous pulmonary venous connections
•Partial anomalous pulmonary venous drainage
Partial anomalous pulmonary venous connections — In these defects, the anomalous vein connects with a systemic vein, resulting in the mixing of oxygenated blood from the pulmonary circulation with the systemic venous blood before returning to the right side of the heart.
Common variants — In the most common form of partial anomalous venous connection, the left upper pulmonary vein connects to the left innominate vein, which, in turn, drains into the superior vena cava (SVC) (movie 1).
In another variant, small segments of the right upper lobe connect directly to the SVC, usually at or above the level of the azygous vein. Because of the more superior location of the pulmonary vein connection, this anatomy is different from that of sinus venosus defects. (See 'Sinus venosus defects' below.)
Other less common forms include anomalous pulmonary vein connections to the coronary sinus, azygous vein, or the inferior vena cava (IVC).
A secundum atrial septal defect (ASD) is typically present in most of these defects.
Scimitar syndrome — Scimitar syndrome is a variant partial anomalous venous connection in which part or even the entire right lung is drained by right pulmonary veins that connect anomalously to the IVC (image 1 and movie 2). The affected lung and its associated airways, which are drained by the scimitar vein, are often hypoplastic or have unusual bronchial or vascular distribution patterns. Sequestration as well as aortopulmonary collateral vessels may also involve the affected lung. (See "Bronchopulmonary sequestration".)
Other cardiac defects are commonly seen and often include hypoplasia of the left heart or aorta [9]. Left-sided scimitar syndrome has also been described, in which some or all of the left pulmonary veins connect to the right-sided IVC [10].
A chest radiograph may show the shadow of these veins as they course and coalesce towards the diaphragm and the IVC, giving the characteristic "scimitar" appearance (image 2).
Symptomatic infants with this diagnosis tend to present with more severe disease and have a poorer prognosis than patients who present as adults or children [9]. At the time of diagnosis, most affected infants have pulmonary hypertension. (See 'Presentation of scimitar syndrome' below.)
Partial anomalous pulmonary venous drainage — In partial anomalous pulmonary venous drainage, the involved pulmonary vein(s) connect directly to the left atrium in an anatomically appropriate location (ie, directly to the morphologic left atrium). However, due to an additional intracardiac defect such as a sinus venosus defect or malposition of the septum primum, oxygenated blood from the anomalous vein is delivered to only the right atrium or to both the left and right atria simultaneously. In both cases, there is return of oxygenated blood to the right side of the heart, which mixes with the systemic venous blood.
Sinus venosus defects — Normally, the right upper pulmonary vein courses behind the SVC and part of the right atrium before connecting to the left atrium. A sinus venosus defect occurs when there is an absence or unroofing of the wall that normally separates the right upper pulmonary vein from the SVC (movie 3 and movie 4) [11]. This anomaly results in the right pulmonary vein draining into the SVC or in the right and left atria. In some affected individuals, additional pulmonary veins may connect anomalously to the SVC.
Inferior sinus venosus defects are an uncommon form of interatrial communications that can lead to the impression of anomalously draining right pulmonary vein(s) [12].
Malposition of the septum primum — Anomalous drainage of one or more normally connecting pulmonary veins results from leftward malposition of the septum primum [13]. In this rare condition, the posterior and/or superior attachments of the atrial septum primum are shifted so far leftward that the pulmonary veins from the right lung drain into the right atrium rather than to the left atrium. This anomaly is associated with complex congenital heart conditions, such as hypoplastic left heart syndrome, heterotaxy syndrome, and polysplenia [13].
PHYSIOLOGY — PAPVR results in recirculation of already oxygenated pulmonary venous blood through the pulmonary vasculature (left-to-right shunting). (See "Pathophysiology of left-to-right shunts".)
In patients with isolated PAPVR (no other associated cardiac anomaly), the magnitude of the shunt is dependent upon the proportion of anomalous draining blood compared with the total pulmonary venous return. This is usually dependent upon the following factors [14]:
●Number and size of anomalous pulmonary veins involved – Shunting from PAPVR involving a single pulmonary vein is usually hemodynamically insignificant, and affected patients are generally asymptomatic and lack evidence of chamber enlargement on echocardiogram. Patients with two or more anomalous connecting veins may have more significant shunting and may have enlargement of the right atrium, right ventricle, and pulmonary arteries.
●Pulmonary segment or lobes from which the anomalous veins originate because of differences in the distribution of blood flow to each lung segment/lobe.
●Relative resistance of the normal and abnormal pulmonary veins and compliance of the respective receiving chambers [14].
CLINICAL MANIFESTATIONS — The severity of clinical signs and symptoms is related to the degree of left-to-right shunting and the presence of other associated cardiac and pulmonary defects.
Associated cardiac and pulmonary defects
Atrial septal defect — In most patients with PAPVR, there is an associated cardiac defect, which is usually an atrial septal defect (ASD). In these patients, the clinical findings are like those seen in individuals with ASD and correspond to the combined shunting from both the ASD and PAPVR. (See "Isolated atrial septal defects (ASDs) in children: Classification, clinical features, and diagnosis", section on 'Clinical features'.)
●Patients with a small degree of shunting are usually asymptomatic and are often identified incidentally by a murmur detected on physical examination.
●Although patients with moderate to large shunts may be asymptomatic in childhood, left-to-right shunting increases with age and symptoms may appear generally during early adulthood before 40 years of age. Symptoms start with dyspnea and fatigue and may progress to heart failure depending upon the degree of shunting.
●In symptomatic patients, the severity of findings is dependent upon the degree of shunting and the presence of pulmonary hypertension or other cardiac anomalies. Clinical findings include dyspnea on exertion, recurrent pneumonia, and heart failure.
Presentation of scimitar syndrome — The presentation of scimitar syndrome varies depending upon the age of diagnosis. Patients who present as infants have more severe symptoms related to heart failure and other cardiac and pulmonary conditions [15,16]. Symptoms in infants with scimitar syndrome include tachypnea, poor feeding, failure to thrive, cyanosis, and lethargy.
Approximately one-half of older patients who are diagnosed after the first year of life remain asymptomatic and are typically identified by an incidental finding on chest radiograph. In other patients, there is a range of symptoms that includes fatigue, dyspnea, and recurrent pneumonia [15].
Other associated anomalies are common in patients with scimitar syndrome and include ASD, pulmonary sequestration, hypoplastic lung, dextrocardia, pulmonary vein stenosis, and other cardiac anomalies (eg, coarctation of the aorta, ventricular septal defect, and patent ductus arteriosus) [15].
Children with scimitar syndrome have a high rate of respiratory complications. In a study of 81 patients, 38 percent of the group had pulmonary infections and 43 percent reported a wheezing episode during the last 12 months of follow-up [17].
Isolated PAPVR — In patients with isolated PAPVR, hemodynamic abnormalities generally do not develop unless a sizable amount of pulmonary blood flow (ie, more than one-half) is recirculated back to the pulmonary vasculature [18]. Thus, individuals with a single anomalous pulmonary vein usually remain asymptomatic.
In patients with isolated PAPVR involving multiple pulmonary veins, signs and symptoms are dependent upon the degree of left-to-right shunting and are similar to those seen in patients with an uncomplicated ASD or in cases of PAPVR that are associated with an ASD. (See 'Atrial septal defect' above.)
Physical examination — The physical findings are directly related to the degree of left-to-right shunting and are similar to those seen in patients with an ASD. (See "Isolated atrial septal defects (ASDs) in children: Classification, clinical features, and diagnosis", section on 'Physical examination'.)
The following findings may be detected:
●A precordial bulge due to right atrial and ventricular enlargement.
●The aortic and pulmonary components of the second heart sound are generally widely split and fixed. In PAPVR without an ASD, the time interval between the aortic and pulmonary components may not be as prominent and can sometimes sound normal.
●A systolic ejection murmur is often heard along the left sternal border due to the increased amount of blood crossing the pulmonary valve in patients with moderate to large left-to-right shunting.
●A low-pitch diastolic rumble, representing flow across the tricuspid valve, may be heard at the left lower sternal border in patients with a large shunt.
Initial tests — Other tests that are usually performed in the evaluation for PAPVR include chest radiography and electrocardiogram (ECG). Although there may be findings that are suggestive of PAPVR, these are not diagnostic studies.
Chest radiography — The following radiographic findings are suggestive, but not diagnostic, of PAPVR:
●Cardiomegaly including right atrial prominence and right ventricular enlargement, which may be seen as retrosternal fullness on a lateral view, is suggestive of increased shunting.
●Increased pulmonary vascular markings provide evidence of significant left-to-right shunting.
●If the anomalous vein drains into the superior vena cava (SVC) or innominate vein, the superior mediastinal shadow may appear wide or the SVC shadow prominent.
In scimitar syndrome, the anomalous vein is often identifiable as it courses towards the diaphragm and the inferior vena cava (IVC), giving the characteristic "scimitar" appearance. (See 'Scimitar syndrome' above.)
Electrocardiogram — The ECG in patients with PAPVR may be normal or may demonstrate evidence of right heart enlargement and/or right ventricular hypertrophy. These changes may include:
●Right axis deviation of the frontal plane QRS complex
●Evidence of right atrial enlargement with an increased amplitude of the P wave (waveform 1)
●Right ventricular hypertrophy with tall R waves in the right precordial leads (V1, V2, V3R, and V4R) and deep S waves in the left precordial leads (V5 and V6) (waveform 2)
●qR pattern in the right precordial leads, which suggests volume-related right ventricular hypertrophy
In patients with sinus venosus defects, the P wave axis may be deviated leftward with a negative P wave in lead III [19]. (See "ECG tutorial: Chamber enlargement and hypertrophy".)
DIAGNOSIS — The initial diagnosis of PAPVR may be made by echocardiography. The diagnosis is typically confirmed by magnetic resonance imaging (MRI), computed tomography (CT), or cardiac catheterization. Other tests, including chest radiography and electrocardiogram (ECG), may provide supportive evidence for the diagnosis of PAPVR but are not diagnostic.
Echocardiography — Echocardiography is the most frequently used method for an initial diagnosis of PAPVR. PAPVR should be considered when the echocardiogram demonstrates unexpected or unexplained right atrial or right ventricular enlargement (ie, not explained by another structural abnormality such as a secundum atrial septal defect [ASD]). In cases with right heart enlargement, PAPVR is inferred if there are fewer than four pulmonary veins connecting to the left atrium, although one must consider the possibility of a single pulmonary vein draining an entire lung.
In addition, PAPVR should be considered if the superior vena cava (SVC), innominate vein, or inferior vena cava (IVC) appears dilated and no other clear explanations are present. In these cases, the anomalous pulmonary vein may connect directly to the dilated structures.
Color flow mapping and other Doppler techniques may aid the identification of anomalous connections to the innominate vein, SVC and IVC, or right atrium (movie 3) [20]. Transesophageal echocardiography (TEE) is more sensitive than transthoracic echocardiography (TTE) in detecting PAPVR (movie 3 and movie 4) and heart chamber enlargement [21,22]. However, the superior-most aspect of the SVC and the innominate veins are better evaluated with TTE.
A potential limitation of echocardiography is the availability of acoustic windows. Vessels that cross behind large airways such as the mainstem bronchi are masked due to attenuation of the ultrasound beams. In some patients, especially those with chronic lung disease, the anterior and medial margins of the lungs can mask the areas of interest. Distinguishing between a secundum ASD and a sinus venosus defect, with or without anomalous pulmonary vein connections, is sometimes challenging. While TEE can circumvent some of the issues with poor acoustic windows, it also can be subject to the same problems as TTE when the airways obscure areas of interest.
Prenatal diagnosis of PAPVR by fetal echocardiography is feasible and has been reported in a large tertiary care center [23,24], although its predictive value remains to be fully defined. (See "Congenital heart disease: Prenatal screening, diagnosis, and management", section on 'Advanced fetal cardiac evaluation'.)
Magnetic resonance imaging — Cardiovascular MRI (CMR) is becoming widely available as a cardiovascular diagnostic technique used to diagnose and characterize congenital heart disease, including PAPVR [25,26]. (See "Clinical utility of cardiovascular magnetic resonance imaging".)
The optimal use of CMR is in cooperative patients who can lie still and hold their breath on command. CMR imaging in young children or anxious patients often requires conscious sedation or even general anesthesia. (See "Procedural sedation in children outside of the operating room".)
When echocardiography is equivocal or imaging quality is limited (eg, due to poor windows), CMR can provide additional information, including quantitation of heart chamber volumes, ventricular mass, and blood flow through the great vessels [27,28].
There are several CMR techniques that are particularly useful in the diagnosis of PAPVR:
●Magnetic resonance angiography typically uses gadolinium-based intravenous contrast agents and provides enhanced visualization of the pulmonary vasculature, including the anomalous pulmonary vein(s) (image 1). In patients with renal failure, CMR is capable of viewing vascular structures without intravenous contrast, though the diagnostic accuracy may be suboptimal.
●Phase-contrast velocity mapping is a CMR technique that is used to noninvasively measure blood flow. It can derive the ratio of pulmonary to systemic blood flow, also known as shunt volume or Qp:Qs, which reflects the degree of left-to-right shunting [29,30]. (See 'Physiology' above.)
Computed tomography — Cardiac CT (CCT) can be used to diagnose or confirm PAPVR [31]. CCT has several advantages over other diagnostic modalities. It provides more detailed anatomic information than echocardiography and, like CMR, is not limited by narrow acoustic windows. CCT is more readily available than CMR. It can be performed in a shorter period of time than CMR and, as a result, may eliminate the need for anesthesia or sedation in younger patients. If necessary, contrast can be given after noncontrast images have been obtained to provide additional anatomic detail, including enhanced visualization of the pulmonary vasculature. However, the benefits of CCT must be balanced with the known long-term risks of exposure to ionizing radiation, especially in small children [32-34].
Cardiac catheterization — Although cardiac catheterization can establish a definitive diagnosis of PAPVR, its role as a diagnostic tool for this condition has largely been replaced by other less invasive diagnostic modalities (ie, echocardiography, MRI, and CT). For patients with PAPVR, catherization is most commonly used if the patient requires therapeutic intervention (eg, occlusion of small anomalous connections). In addition, cardiac catheterization is used to obtain additional hemodynamic information, such as pulmonary vascular resistance, cardiac output, and ventricular pressures. Shunt volume can be calculated by oximetry, but some authors have questioned its reliability in PAPVR [35] since mixed venous saturation can be difficult to measure, especially if the anomalous vein drains directly into the SVC.
MANAGEMENT — Asymptomatic patients with small PAPVR-related left-to-right shunts without evidence of right heart volume overload generally do not require intervention, as the defect has no significant clinical impact and life expectancy without correction appears to be normal [14].
For symptomatic patients and those with clinically significant left-to-right shunts, surgery is the definitive treatment. Transcatheter occlusion may be used to reduce the shunting in selected cases. Surgical treatment is considered in the following circumstances [14]:
●Hemodynamically significant left-to-right shunt – We define this as either of the following:
•Signs and symptoms attributable to right ventricular volume overload (see 'Clinical manifestations' above), or
•Ratio of pulmonary to systemic blood flow (Qp:Qs) greater than 2:1. The American Heart Association 2018 adult congenital heart disease management guidelines use a somewhat lower threshold (Qp:Qs >1.5:1) [36].
●Patients with scimitar syndrome who have recurrent pulmonary infections in the setting of pulmonary sequestration, as discussed separately. (See "Bronchopulmonary sequestration", section on 'Management'.)
●During surgical repair of other major cardiac lesions, depending upon the surgical risk of repair and level and degree of shunting.
The surgical technique varies depending upon the anatomy (including other associated cardiac anomalies) and local expertise and practice preferences. The likelihood of a successful procedure and its potential benefit must be weighed against the risks of the intervention itself. For example, surgical correction in infants and toddlers is more technically challenging than in larger patients.
OUTCOME — The outcome depends upon the underlying anatomy and the presence of associated conditions, such as pulmonary hypertension, sequestration, or hypoplasia.
Scimitar syndrome — Patients with scimitar syndrome who present as infants have historically had poor outcomes, with considerable morbidity and mortality.
●In one Italian case series of 68 patients (mean age at surgery 1.4 years) with a mean follow-up of 4.8 years, there were six deaths (9 percent), including two late deaths due to severe pulmonary arterial hypertension [37]. Four patients required intervention for restenosis, and the remainder were asymptomatic at follow-up without evidence of scimitar drainage stenosis.
●In a second case series of 80 patients from a tertiary center in the United States, patients presenting at earlier than one year of age had a higher incidence of aortopulmonary collaterals, coexisting congenital heart disease, extracardiac anomalies, and pulmonary hypertension [38]. Sixty-one (76 percent) survived at a median follow-up of 6.2 years. Scimitar vein surgery was performed in 33 of these 61 patients, of whom 18 had postoperative pulmonary vein obstruction, which was more common in infants. Patients who did not undergo surgery generally did not have evidence of pulmonary hypertension. Overall, 19 patients died and multivariate risk factors for death included systolic pulmonary hypertension and left pulmonary vein stenosis.
Other causes — Patients with other causes of PAPVR generally have an excellent outcome, including those who undergo surgical correction [39,40]. In a case series of 306 children who underwent surgery for PAPVR, follow-up at 15 years demonstrated no deaths and limited significant morbidity [39]. In this cohort, scimitar vein stenosis did not occur in 85 percent of patients at 10-year follow-up.
SUMMARY AND RECOMMENDATIONS
●Anatomy – Partial anomalous pulmonary venous return (PAPVR) encompasses a heterogenous group of congenital cardiac anomalies that are caused by the abnormal return of one or more, but not all, of the pulmonary veins to the right side of the heart. (See 'Pulmonary vein anatomic variants' above.)
●Physiology – PAPVR results in recirculation of pulmonary venous blood through the pulmonary vasculature (left-to-right shunting). The amount of shunted pulmonary blood flow is dependent upon the number and size of anomalous pulmonary veins involved. Significant shunting is associated with two or more anomalous connecting veins, which may result in enlargement of the right atrium and ventricle as well as dilation of the pulmonary artery. (See 'Physiology' above.)
●Presentation – The clinical presentation of PAPVR is related to the degree of left-to-right shunting and the presence of other associated cardiac and pulmonary defects. Most patients with PAPVR have an associated atrial septal defect (ASD). (See 'Clinical manifestations' above.)
•Patients with hemodynamically insignificant shunting are generally asymptomatic and are identified incidentally by echocardiography performed for other indications.
•Patients with greater degrees of shunting may present with dyspnea and fatigue that may progress to heart failure as left-to-right shunting increases with age.
•Infants with scimitar syndrome, a variant of PAPVR in which part or even the entire right lung is drained by right pulmonary veins that connect anomalously to the inferior vena cava (IVC) (image 1 and movie 2), tend to have earlier and more severe symptoms (heart failure, recurrent pulmonary infections, pulmonary hypertension, and pulmonary and cardiac anomalies). (See 'Scimitar syndrome' above and 'Presentation of scimitar syndrome' above.)
●Diagnosis – The initial diagnosis of PAPVR may be made by echocardiography. The diagnosis is typically confirmed with magnetic resonance imaging (MRI; including angiography), computed tomography (CT), or cardiac catheterization. (See 'Diagnosis' above.)
●Management – Surgery is the definitive treatment for PAPVR, though transcatheter occlusion may be used to reduce the shunting in selected cases. The need for intervention is determined by the degree of left-to-right shunting (ie, the ratio of pulmonary to systemic blood flow [Qp:Qs]), presence or absence of symptoms, and associated anatomic abnormalities (see 'Management' above):
•Asymptomatic patients with small left-to-right shunts do not require intervention, as the defect has no significant clinical impact.
•For patients with hemodynamically significant left-to-right shunting (ie, Qp:Qs >2:1) and/or signs and symptoms attributable to right ventricular volume overload, we suggest surgical intervention (Grade 2C). The surgical technique varies depending upon the anatomy as well as local expertise and practice preferences.
•In addition, surgical intervention may be required in patients with scimitar syndrome who have recurrent pulmonary infections in the setting of pulmonary sequestration, as discussed separately. (See "Bronchopulmonary sequestration", section on 'Management'.)
•Patients who are undergoing surgery for repair of an associated major cardiac lesion may have PAPVR addressed as part of surgery, depending upon the anatomy, level and degree of shunting, and surgical risk.
●Outcome – With the exception of infants with scimitar syndrome, the outcome for patients with PAPVR generally is excellent, including those who undergo surgical correction. Patients with scimitar syndrome who present as infants have historically had poor outcomes, with considerable morbidity and mortality. This is likely related to the higher incidence of coexisting congenital heart disease, extracardiac anomalies, and pulmonary hypertension in scimitar syndrome compared with other forms of PAPVR. (See 'Outcome' above.)
