Version July 2025
INTRODUCTION —
Heterotaxy, also referred to as isomerism of the atrial appendages, is defined as an abnormal assembly of the thoracic and abdominal organs from the normal arrangement known as "situs solitus." It is caused by disruption of left-right axis orientation during early embryonic development. Cardiac malformations are a major component of heterotaxy syndrome and are associated with considerable morbidity and mortality. Abnormal cardiac development typically leads to atrial appendage isomerism, resulting in either bilateral paired right atria (right atrial isomerism) or paired left atria (left atrial isomerism).
This topic will review the management and outcome of patients with heterotaxy (isomerism). The anatomical variation, clinical features, and diagnosis of heterotaxy (isomerism) are presented separately. (See "Heterotaxy (isomerism of the atrial appendages): Anatomy, clinical features, and diagnosis".)
TERMINOLOGY —
The following sections briefly summarize the anatomic abnormalities in heterotaxy syndrome. Additional details are provided separately. (See "Heterotaxy (isomerism of the atrial appendages): Anatomy, clinical features, and diagnosis", section on 'Embryology and anatomy'.)
●Heterotaxy – Heterotaxy, derived from Greek (hetero, meaning "different," and taxy, meaning "arrangement"), is defined as an abnormal arrangement of the internal thoracic-abdominal organs across the left-right axis of the body. Patients with heterotaxy have been historically stratified into either the subsets of asplenia syndrome or polysplenia syndrome [1-3]. However, this classification is not useful in describing the cardiac malformations associated with heterotaxy. (See "Heterotaxy (isomerism of the atrial appendages): Anatomy, clinical features, and diagnosis", section on 'Embryology and anatomy'.)
●Right atrial isomerism (RAI) - RAI, also referred to as right atrial appendage isomerism, results in bilateral morphologic right atria and atrial appendages and an absence of left-sided structures (eg, coronary sinus). These patients usually have pulmonary venous anomalies, such as anomalous pulmonary venous connections or small pulmonary veins. Most patients with RAI have single ventricle physiology. These patients also typically have asplenia, as the spleen is a left-side abdominal organ.
●Left atrial isomerism (LAI) – LAI, also referred to as left atrial appendage isomerism, results in bilateral morphologic left atria and atrial appendages. In these cases, systemic venous abnormalities, such as interruption of the inferior vena cava, are common. The cardiac anatomy is more variable in LAI than in RAI. Polysplenia also occurs more often, as left-sided organs are more frequently duplicated in patients with LAI.
●Other thoracic and abdominal organs – Patients with heterotaxy display right- or left-sidedness of other thoracic and abdominal organs (table 1), which may be discordant from atrial isomerism, including:
•Bronchial and lung abnormalities that encompass symmetrical tri- or bilobed lungs, or bilateral eparterial or hyparterial bronchus (figure 1 and figure 2) (see "Heterotaxy (isomerism of the atrial appendages): Anatomy, clinical features, and diagnosis", section on 'Bronchial tree and lung')
•Asplenia or polysplenia (see "Heterotaxy (isomerism of the atrial appendages): Anatomy, clinical features, and diagnosis", section on 'Spleen')
•Biliary atresia is present in approximately 10 percent of patients with LAI (see "Heterotaxy (isomerism of the atrial appendages): Anatomy, clinical features, and diagnosis", section on 'Liver')
•Malrotation of the intestines and possible intestinal obstruction occur in both RAI and LAI (see "Heterotaxy (isomerism of the atrial appendages): Anatomy, clinical features, and diagnosis", section on 'Stomach and intestinal tract')
The bronchial tree anomalies do not usually have any clinical significance; however, the abdominal abnormalities (ie, asplenia, biliary atresia, and gut malrotation resulting in intestinal obstruction) have a major impact on morbidity and mortality in patients with heterotaxy.
SETTING OF CARE —
Because cardiac lesions are the predominant cause of early mortality and morbidity, neonates should be cared for at a tertiary medical center with experience in managing complex congenital heart disease (CHD). When an antenatal diagnosis is made, delivery should be planned at a facility with the appropriate level of care for the neonate (ie, a facility with a level III neonatal intensive care unit and pediatric cardiology expertise). If this is not feasible, transport arrangements should be established in advance of the delivery. (See "Congenital heart disease: Prenatal screening, diagnosis, and management", section on 'Delivery planning'.)
The management of patients with heterotaxy syndrome is challenging given the wide spectrum of both cardiac and noncardiac anatomical anomalies. The approach to management, including both medical and surgical interventions, depends on the specific anatomy of both cardiac and noncardiac defects.
CARDIAC MANAGEMENT —
Cardiac management is dependent on the severity of the cardiac lesions. It includes:
●Initial medical management to maintain adequate tissue perfusion and oxygenation in patients
●Subsequent management focused on palliative and corrective surgical procedures based on ventricular physiology (ie, single versus biventricular function)
Those with right atrial isomerism (RAI) usually have more severe heart defects, often precluding them from a biventricular repair and necessitating neonatal palliative interventions leading to the single ventricle pathway. As the lesions in left atrial isomerism (LAI) are often less severe, biventricular repair is more often attained.
Medical management — Cardiac medical management is focused on stabilization of cardiac and pulmonary function ensuring adequate pulmonary blood flow and systemic oxygenation in severely affected neonates. In addition, patients with LAI are at risk for complete heart block and sinus node dysfunction.
●Pulmonary arterial outflow obstruction and cyanosis – Patients with RAI typically have right-to-left shunting due to pulmonary outflow obstruction, which rarely occurs in LAI. In severely affected neonates, there is inadequate pulmonary blood flow and survival is dependent on maintaining a patent ductus arteriosus (PDA) to ensure adequate pulmonary blood flow. In these patients, administration of prostaglandin E1 (PGE1, also known as alprostadil) is needed to ensure pulmonary blood flow until a definitive pulmonary blood supply is attained, either by surgery or interventional catheterization techniques.
In cases that are also accompanied by obstructed pulmonary venous return resulting in severe hypoxemia and metabolic acidosis, PGE1 is usually unhelpful. Maintaining patency may in fact be detrimental in neonates who have already undergone the physiologic decline in pulmonary vascular resistance (PVR) by causing an increase in pulmonary edema due to pulmonary venous obstruction in the face of increased flow to the lungs through the PDA. In contrast, a patent ductus may provide a pop-off for pulmonary blood flow in neonates who continue to have a high PVR, resulting in increasing cyanosis due to the right-to-left shunting [4-6]. In these settings, standard intensive care stabilization techniques are employed, and surgery should be performed as soon as possible. (See "Cyanotic congenital heart disease (CHD) in the newborn: Causes, evaluation, and initial management", section on 'Initial management'.)
●Pulmonary venous congestion and heart failure – Some patients with atrial isomerism may present in the neonatal period with heart failure and metabolic acidosis related to left heart obstruction with or without pulmonary overcirculation. In these patients, medical management includes supportive nonpharmacologic intervention (eg, oxygen administration, positive pressure support, and mechanical ventilation), and pharmacologic therapy (eg, angiotensin-converting enzyme [ACE] inhibitor, inotropic therapy, and loop diuretic). (See "Heart failure in children: Management".)
●Complete atrioventricular (AV) block and sinus node dysfunction – Patients with LAI are at risk for complete AV block causing ventricular bradycardia. In one case series, 40 of 116 fetal cases of AV block were associated with LAI [7]. The principal therapeutic decision after the immediate perinatal period is whether a pacemaker should be inserted. In addition, because of the increased risk of sinus node dysfunction, some experts in the field have proposed prophylactic pacemaker placement in the adult with LAI [8]. (See "Atrial arrhythmias (including AV block) in congenital heart disease".)
Surgical management — Surgical treatment of patients with atrial isomerism is complex, and the surgical planning must be tailored to the individual anatomy. Although primary repair is preferred, in cases in which a two-ventricle repair is not feasible (eg, one of the ventricles is hypoplastic), surgical palliation is performed using interventions developed for other single ventricular morphologic conditions, such as hypoplastic left heart syndrome.
In general, biventricular repair is not suitable for patients with RAI, as they usually have single ventricle morphology [9]. Although biventricular repair is more likely in patients with LAI, single ventricle palliation still appears to be more appropriate in at least 50 to 70 percent of LAI cases.
Single ventricle palliation — Similar to other univentricular conditions, palliative management beginning in the neonate generally consists of a series of staged procedures, which vary with the underlying lesions. These procedures are discussed in greater detail elsewhere. (See "Hypoplastic left heart syndrome: Management and outcome", section on 'Surgical management'.)
Right atrial isomerism — The following steps are the typical staged palliative approach in the management of patients with RAI:
●Because patients with RAI generally have pulmonary outflow obstruction, the initial palliative procedure is usually a systemic-pulmonary shunt that provides a reliable conduit for pulmonary blood flow. Risk factors for mortality include the need for an initial palliation at a younger age and the presence of total anomalous venous return, especially if there is obstruction to the anomalous venous connection [4,10].
●The second procedure is bidirectional cavopulmonary anastomosis. This procedure is generally performed soon after the initial palliative procedure since most patients with RAI have significant regurgitation through a malformed AV valve, which is often worsened by placement of the initial palliative systemic-pulmonary shunt. The presence of anomalous pulmonary venous connection has not been shown to be a risk factor for morbidity and mortality in patients undergoing bidirectional cavopulmonary anastomosis [11].
●The final stage is completion of the Fontan operation. Although this procedure is similar to that performed in other patients with single ventricle anatomy (figure 3), reports have shown a higher mortality and morbidity rate for patients with RAI compared with patients with non-isometric single ventricle physiology [12,13]. The increased risk of poor outcome was thought to be due to the presence of a common AV valve, right ventricular morphology, and anomalous venous connections. In a subsequent case series of patients undergoing Fontan procedure from 1996 to 2005, survival and reoperation rates for patients with heterotaxy substantially improved, approaching similar rates to patients without heterotaxy [13]. The improved outcome was attributed to superior surgical techniques utilizing extracardiac conduits and creating baffle fenestrations, and improved postsurgical intensive care. However, patients with heterotaxy still had an increased risk of post-Fontan arrhythmias and AV valve regurgitation.
In a multicenter cross-section study of 546 survivors of the Fontan procedure, patients with heterotaxy (n = 42) compared with patients without isomerism were more likely to undergo Fontan procedure at a later age (median age 3.9 versus 2.8 years), have previous pulmonary vein surgery (21 versus 0.4 percent), have atrial arrhythmia post-Fontan (19 versus 8 percent), and have a greater degree of AV valve regurgitation [14].
Left atrial isomerism — As noted above, 50 to 70 percent of patients will LAI undergo single ventricle palliation. The following are the typical steps in the staged palliative management of patients with LAI:
●The initial palliative step for LAI can include any of the following:
•A systemic-pulmonary shunt (if there is obstruction of pulmonary outflow obstruction).
•A Norwood-type procedure for obstructive left-sided lesions that result in left ventricular hypoplasia. (See "Hypoplastic left heart syndrome: Management and outcome", section on 'Stage I with mBTTS (classic Norwood)'.)
•Banding of the main pulmonary artery in those with single ventricle physiology and unobstructed pulmonary blood flow is needed. If the pulmonary bed is left unprotected (unbanded), early cardiac failure will ensue in any infant with a large left-to-right shunt with severe pulmonary overcirculation, which will cause systemic hypoperfusion resulting in metabolic acidosis.
●Because many patients with LAI have an interrupted inferior vena cava with azygos continuation, the second stage of palliation of a total cavopulmonary shunt is often a unique procedure (Kawashima procedure) from that performed in patients with other forms of univentricular physiology [15]. It entails end-to-side anastomosis between the superior vena cava and the confluent pulmonary artery, division or ligation of the pulmonary artery trunk to eliminate competitive antegrade pulmonary flow, and repair of the common AV valve when regurgitation is present. As a result, all the venous return, apart from the hepatic veins that drain directly into the atria, will flow to the pulmonary bed. Although the Kawashima operation was initially thought to be the final palliative procedure needed for patients with LAI, patients subsequently developed progressive oxygen desaturation due to pulmonary arteriovenous malformations. Thus, it is prudent to follow patients who have undergone a Kawashima procedure closely for the development of pulmonary arteriovenous malformations both by pulse oximetry and by contrast echocardiography [16].
●In patients who develop significant pulmonary arteriovenous malformations resulting in severe cyanosis, redirection of the hepatic venous return (Fontan completion) to the pulmonary circulation results in regression of the pulmonary arteriovenous malformations and a concomitant improvement in oxygen saturation [17-19]. It appears that at least one-half or more of patients with LAI will require hepatic vein redirection following Kawashima procedure [20].
Biventricular repair — Biventricular repair in patients with heterotaxy is primarily performed in patients with LAI. In general, 40 to 50 percent of patients with LAI have two good-sized ventricles with concordant ventriculoarterial connection and normal outflow tracts and are amenable to biventricular repair. Repair typically encompasses septation of a common AV valve, ventricular septal defect closure, and mitral valve cleft repair along with appropriate baffling of anomalous systemic or pulmonary venous return. A frequent cause of reoperation following biventricular repair is progressive AV valvar regurgitation of the left-sided AV valve. Recurrent subaortic stenosis has also been described [21-23].
Biventricular repair is uncommon in patients with RAI, as most of these patients do not have two adequate-sized ventricles. Patients with RAI who undergo biventricular repair have similar long-term morbidities (such as arrhythmias) to those with a palliative Fontan [24,25]. In addition to the general risk factors for mortality in those with LAI (biliary atresia, low birth weight, complete AV block, coarctation of the aorta), single ventricle physiology has been shown to be an independent risk factor.
The relative frequency of biventricular repair for RAI and LAI was illustrated in a large case series of 371 patients with heterotaxy cared for in a tertiary center in the United States between 1990 and 2007 [25]. In this cohort, of the 91 patients who underwent biventricular repair (median age at repair 6.8 months), 66 had LAI, 9 had RAI, and 16 had indeterminate atrial anatomy.
Cardiac transplantation — A subset of patients with isomerism will eventually need cardiac transplantation. These patients are usually those who have undergone single ventricle palliation and have untreatable severe AV valve regurgitation accompanied by severe ventricular dysfunction [26]. Successful transplantation is achievable in this group of patients; however, there is an increase in post-transplant pulmonary venous obstruction [27].
Another issue for any patient with complex congenital heart disease is the multiple exposures to blood products while undergoing previous palliative procedures. This exposure may result in the development of HLA-directed antibodies, which raises the risk of hyperacute rejection, and requires specific pre- and post-transplant immunomodulation [28,29]. The surgical techniques in transplantation have evolved so that the surgical outcome of complex patients is very similar to that obtained in the pediatric population with situs solitus and should not be withheld from patients with heterotaxy [30-32].
MANAGEMENT OF NONCARDIAC DEFECTS —
Noncardiac-associated lesions are common in atrial isomerism and are a source of morbidity. Management issues include:
●Prevention of infections in patients with impaired splenic function
●Monitoring for and managing intestinal obstruction in patients with intestinal malrotation
●Identification and care of a patient with biliary atresia
Prevention of infections in patients with impaired splenic function — Patients with heterotaxy who have asplenia or reduced splenic function are at risk of acquiring serious and potentially life-threatening infections. The risk is highest for infection with encapsulated bacteria (Streptococcus pneumoniae and Haemophilus influenzae), although gram-negative bacteria have also been implicated, especially during the first six months of life [33].
Patients and parents/caregivers should be informed about this risk and should be instructed to seek medical attention early when fevers develop so that blood cultures can be obtained and empirical antibiotic therapy administered pending culture results. (See "Clinical features, evaluation, and management of fever in patients with impaired splenic function", section on 'Evaluation and management'.)
Other measures to prevent sepsis in patients with asplenia include immunization and the use of prophylactic antibiotics, which are reviewed separately. (See "Prevention of infection in patients with impaired splenic function".)
Monitoring for and managing intestinal obstruction
●Symptomatic patients – Patients who develop symptoms consistent with intestinal obstruction (eg, vomiting, feeding intolerance) should be evaluated with an upper gastrointestinal contrast study to delineate the foregut and midgut anatomy. If a malrotation with a volvulus is detected, surgical repair (Ladd procedure) should be performed. Surgical management of malrotation is discussed in greater detail separately. (See "Intestinal malrotation in children", section on 'Surgical treatment'.)
●Asymptomatic patients – In asymptomatic patients, the available evidence suggests that benefits of prophylactic surgery are outweighed by the risks of the procedure in this population [34-42]. In our practice, we screen patients for malrotation and manage asymptomatic patients conservatively. We do not perform prophylactic surgery in asymptomatic patients, because of the high risk of complications in patients with heterotaxy and because the benefit of preemptive surgery in asymptomatic patients has not been established.
Identifying and treating biliary atresia — Neonates with heterotaxy, especially those with left atrial isomerism, who present with clinically significant jaundice, should be evaluated for biliary atresia. If the diagnosis of biliary atresia is confirmed, management consists of surgical hepatoportoenterostomy (Kasai procedure), which should be performed promptly. Evaluation and management of biliary atresia are discussed in detail separately. (See "Biliary atresia".)
FOLLOW-UP CARE —
Because cases of heterotaxy are rare and have a wide range of clinical variability, follow-up care and timing of subsequent surgical procedures need to be individualized. It should be conducted in a center with expertise in congenital heart disease, and it is imperative for clinicians caring for these patients to know the risk and management of issues following either palliative interventions or biventricular repair. For patients undergoing palliation, the care is based on the clinical status of the patient following each intervention.
Palliative interventions: Follow-up and timing — Follow-up care is dependent on the stage of palliation and the clinical status of the patient. (See 'Single ventricle palliation' above.)
●Initial neonatal shunting – Follow-up visits are frequent for neonates who undergo palliative shunting to secure either pulmonary blood flow or systemic blood flow. At each visit, the clinical status is evaluated with a focus on the adequacy of oxygen saturation and somatic growth. As many of these single ventricle patients have ventricular overload and abnormal atrioventricular (AV) valves, surveillance echocardiograms are performed on a monthly basis to monitor for the development of AV insufficiency.
●Bidirectional cavopulmonary anastomosis is typically performed at three to four months as the patient begins to outgrow his or her original shunt, and becomes progressively more cyanotic. Prior to bidirectional cavopulmonary anastomosis, a cardiac catheterization is performed to assess for suitability for passive pulmonary blood flow.
However, if there is interruption of the inferior vena cava with azygos continuation (typically seen in left atrial isomerism [LAI] cases), we delay performing this procedure because in these patients, connection of the superior vena cava means that all of the systemic venous return, apart from the hepatic veins (which drains directly into an atrium), will be rerouted passively to the pulmonary arteries. As this might not be accommodated easily at three to four months, we usually wait until eight to nine months of age to perform this procedure.
●Once a more stable circulation is obtained following the bidirectional cavopulmonary anastomosis, follow-up care may be performed at three- to four-month intervals until the third stage of palliation (total cavopulmonary anastomosis [ie, Fontan completion]) occurs. A cardiac catheterization is also performed prior to the Fontan completion to assess hemodynamic suitability and to see whether any interventions such as occlusion of collaterals or stenting of pulmonary arteries are needed.
●The decision of when to perform a Fontan completion varies among institutions but can be performed as early as two years of age. Fontan completion is typically performed when patients begin to outgrow (ie, become more cyanotic) their bidirectional cavopulmonary anastomosis.
●Following a Fontan completion, patients need monitoring for conduction defects and arrhythmias. An electrocardiogram is obtained at all scheduled visits and yearly Holter testing is performed. Ongoing assessment of ventricular function is also required with imaging by echocardiogram and, in older patients, cardiac magnetic resonance imaging (MRI).
Health care visits — For all patients, follow-up health care visits are conducted with a focused history and physical examination, and testing.
The history and physical examination concentrates on the cardiac status of the patients.
●Episodes of palpations, dizziness, or syncope are suggestive of an underlying arrhythmia
●Dyspnea or decreased exercise tolerance is suggestive of ventricular dysfunction
●Irregular pulse may suggest an underlying arrhythmia
●Murmurs detected by cardiac auscultation may be suggestive of AV valvar regurgitation
●Signs of heart failure include pulmonary congestion, peripheral edema, and hepatomegaly
●Comparison of oxygen saturation to previous levels
The following tests are performed on a routine basis: pulse oximetry, blood pressure monitoring (upper and lower limbs if there is a history of aortic arch abnormalities), and electrocardiogram. Monitoring of ventricular function is performed by echocardiogram and, in some older patients, cardiac MRI and cardiopulmonary testing.
All patients with heterotaxy have a risk for developing conduction defects and/or arrhythmias and need lifelong electrocardiac surveillance, especially those with LAI or following Fontan completion (as noted above). An electrocardiogram is obtained at all scheduled visits and yearly Holter testing is performed.
PROGNOSIS —
Heterotaxy represents a heterogeneous group of cardiac and noncardiac abnormalities, and the prognosis depends on the severity of the specific lesion(s). Many affected patients are diagnosed prenatally, and counselling the expecting parents about the prognosis of this heterogenous group of patients is challenging. (See "Heterotaxy (isomerism of the atrial appendages): Anatomy, clinical features, and diagnosis", section on 'Antenatal presentation'.)
Patients who present with severe cyanosis in the neonatal period have a high risk of mortality. Among infants with prenatally diagnosed heterotaxy who undergo surgery in early infancy, approximately one-quarter die in the perioperative or postoperative period [43]. By contrast, patients with only mild lesions may experience little or no impact on life expectancy or quality of life.
Data on long-term survival in patients with heterotaxy are limited [9,44-52]. In a meta-analysis of three observational studies that provided data on survival in patients with heterotaxy managed in the modern era (after 2000), survival to age 3 years was 78 percent, falling to 70 percent by age 13 years [45]. In a report of 254 patients with heterotaxy syndrome managed at a single center from 1985 to 2014, overall mortality was 40 percent over a median follow-up of 10 years [52]. In this study, there did not appear to be a meaningful improvement in outcomes over the 30-year period.
Factors that impact the risk of mortality include the following [9,52-55]:
●Isomerism subtype – Survival appears to be higher in patients with left atrial isomerism (LAI) compared with right atrial isomerism (RAI) [45]. In a meta-analysis that included both modern and older studies, five-year survival for patients with LAI and RAI were 94 and 76 percent, respectively; 10-year survival was 83 and 64 percent, respectively.
●Type of repair – Survival is better for patients who achieve a biventricular repair, though most require subsequent intervention [25,52].
●Arrhythmias – Arrhythmias are common in patients with heterotaxy. Bradyarrhythmias, including complete heart block (CHB), are associated with LAI. Tachyarrhythmias seem to correlate more with hemodynamic and anatomic factors than isomerism subtype. One report found that tachyarrhythmias, but not bradyarrhythmias, were associated with increased risk of mortality or need for transplant [56]. In other reports, CHB has been an independent predictor of early mortality [9,53,55].
●Pulmonary venous obstruction (PVO) – PVO is a particularly strong predictor of mortality [44,52,57]. In one study, the mortality rate in patients with PVO was 95 percent [57].
●Other cardiovascular lesions – Patients with associated total anomalous pulmonary venous connection, pulmonary outflow obstruction, coarctation, or atrioventricular valve regurgitation appear to have an increased risk of mortality compared with patients without these associated lesions.
●Extracardiac manifestations – Extracardiac manifestations of heterotaxy also have an important impact on survival (eg, biliary atresia, asplenia, and risk of sepsis) [52,55,58].
SUMMARY AND RECOMMENDATIONS
●Definitions and anatomy – Heterotaxy, also referred to as isomerism of the atrial appendages, is defined as an abnormal arrangement of the internal thoracic-abdominal organs across the left-right axis of the body (table 1). Cardiac malformations are a major component of heterotaxy syndrome and are associated with considerable morbidity and mortality. Right atrial isomerism (RAI) results in bilateral morphologic right atria and absence of left-sided structures (eg, coronary sinus). Patients with RAI usually have pulmonary venous anomalies, such as anomalous pulmonary venous connections or small pulmonary veins; most have single ventricle physiology. Left atrial isomerism (LAI) results in bilateral morphologic left atria and atrial appendages. Patients with LAI commonly have systemic venous abnormalities (eg, interruption of the inferior vena cava). The cardiac anatomy is more variable in LAI than in RAI. (See 'Terminology' above and "Heterotaxy (isomerism of the atrial appendages): Anatomy, clinical features, and diagnosis", section on 'Embryology and anatomy'.)
●Management – The management of patients with atrial isomerism is challenging, given the wide spectrum of both cardiac and noncardiac anatomical anomalies. Because cardiac lesions are the predominant cause of mortality and morbidity, neonates should be cared for at a tertiary medical center with experience in managing complex congenital heart disease (CHD). When an antenatal diagnosis is made, delivery should be planned at a facility with the appropriate level of care for the neonate. If this is not feasible, transport arrangements should be established in advance of the delivery. (See 'Setting of care' above.)
•Cardiac management – Cardiac management is dependent on the severity of the cardiac lesions. It includes:
-Medical management – Initial medical management focuses on stabilization of cardiac function and pulmonary blood flow in the most severely affected neonates. (See 'Medical management' above.)
In patients with severe cyanosis caused by right-to-left shunting due to pulmonary outflow obstruction, survival is dependent on maintaining a patent ductus arteriosus with the administration of prostaglandin E1 (alprostadil). (See "Cyanotic congenital heart disease (CHD) in the newborn: Causes, evaluation, and initial management", section on 'Prostaglandin E1'.)
Patients with significant pulmonary venous obstruction may develop pulmonary congestion and heart failure. Management of these patients includes supportive care and pharmacologic therapy (eg, angiotensin-converting enzyme [ACE] inhibitors, inotropic therapy, and loop diuretic). (See "Heart failure in children: Management".)
Patients with LAI are at risk for arrhythmias and complete heart block and may be candidates for pacemaker placement.
-Surgical management – Surgical decision making is complex in patients with atrial isomerism. Although primary repair is preferred, in cases in which a two-ventricle repair is not feasible (eg, one of the ventricles is hypoplastic), staged surgical palliation is performed using interventions developed for other single ventricular morphologic conditions, such as hypoplastic left heart syndrome. (See 'Surgical management' above and "Hypoplastic left heart syndrome: Management and outcome", section on 'Surgical management'.)
•Management of noncardiac abnormalities – Management issues for noncardiac defects include (see 'Management of noncardiac defects' above):
-Prevention of infections in patients with impaired splenic function – Patients with heterotaxy who have asplenia or reduced splenic function are at risk of acquiring serious and potentially life-threatening infections. Patients and parents/caregivers should be counseled to seek prompt medical attention when fever develops so that blood cultures can be obtained and empiric antibiotics started. Preventive measures include immunization and prophylactic antibiotic therapy. These measures are discussed separately. (See "Prevention of infection in patients with impaired splenic function".)
-Management of intestinal malrotation – Patients who develop signs of intestinal obstruction (eg, vomiting, feeding intolerance) should undergo evaluation for intestinal malrotation and volvulus followed by surgical repair (Ladd procedure) if the diagnosis is confirmed. Surgical management of malrotation is discussed separately. (See "Intestinal malrotation in children", section on 'Surgical treatment'.)
For asymptomatic patients, we suggest against performing prophylactic Ladd procedure (Grade 2C) because of the high risk of complications in patients with heterotaxy and because the benefit of preemptive surgery in asymptomatic patients has not been established. (See 'Monitoring for and managing intestinal obstruction' above.)
-Management of biliary atresia – Neonates with heterotaxy, especially those with LAI, who present with clinically significant jaundice, should be evaluated for biliary atresia. If the diagnosis is confirmed, management consists of surgical hepatoportoenterostomy (Kasai procedure), which should be performed promptly, as discussed separately. (See "Biliary atresia", section on 'Kasai procedure'.)
●Follow-up care – All patients with atrial isomerism require lifelong follow-up with a cardiologist with expertise in CHD. Follow-up care depends upon the clinical status of the patient, type of intervention (single-ventricle palliation versus biventricular repair), and proximity of surgery. All patients should undergo lifelong electrocardiac surveillance as they are at risk for developing life-threatening conduction defects and arrhythmias. (See 'Follow-up care' above.)
●Prognosis – Heterotaxy represents a heterogeneous group of cardiac and noncardiac abnormalities, and the prognosis depends on the severity of the specific lesion(s). (See 'Prognosis' above.)
