eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Cardiology

Double Outlet Right Ventricle, Normally Related Great Arteries

Rod Tarrago, MD, Pediatric Intensivist, Department of Pediatric Critical Care, Children's Hospitals and Clinics of Minnesota
Steven R Neish, MD, SM, Director of Pediatric Cardiology Fellowship Program, Associate Professor, Department of Pediatrics, Baylor College of Medicine

Updated: Oct 6, 2008

Introduction

Background

Double outlet right ventricle (DORV) was first pathologically described in the late 19th century as partial transposition. In 1957, Witham first used the term double outlet right ventricle to describe a partial transposition of the great arteries.¹ He described 4 hearts with 2 varieties of "complete aortic transposition with the pulmonary artery in normal position."

Double outlet right ventricle is defined as a form of ventriculoarterial connection in which both great arteries arise completely or predominantly from the morphologic right ventricle. This definition is still controversial. For example, some researchers require that the aorta and the pulmonary artery arise entirely from the right ventricle. Others require that 90% of the great vessels arise from the morphologic right ventricle. Alternatively, the 50% rule states that more than one half of both arterial trunks must arise from the morphologic right ventricle. Some require only the presence of fibrous discontinuity between the mitral and semilunar valves. This is present in most specimens and is referred to as subpulmonic and subaortic conus.

Pathophysiology

Double outlet right ventricle, with a large variability in anatomy, represents a continuum of congenital heart defects (CHDs) that includes ventricular septal defect (VSD) with significant override of the aorta, origin of both great arteries from the right ventricle, and transposition of the great arteries with pulmonary override of the VSD. A common arterial trunk may also arise completely from the right ventricle. This is actually a type of truncus arteriosus.

Pathophysiologic description and classification is accomplished by relating the location of the VSD to the arrangement of the great vessels. Each combination results in a physiologic behavior similar to that of other CHDs. The VSD in double outlet right ventricle can be subaortic, subpulmonary, noncommitted, or doubly committed. Most VSDs are nonrestrictive, but as many as 17% of patients may require VSD enlargement during repair to allow unrestricted systemic blood flow.

The most common type of VSD found in double outlet right ventricle is a subaortic type. The aortic orifice is usually posterior and to the right of the pulmonary orifice, with a spiral arterial relationship. Because the great arteries are normally related, the left ventricular outflow is directed toward the aorta, resulting in aortic oxygen saturations that exceed pulmonary saturations. Associated pulmonary stenosis is present in as many as 50% of patients with double outlet right ventricle. The resulting physiology is similar to tetralogy of Fallot, in which the aorta completely overrides the right ventricle.

Systolic pressures are equal in both ventricles and in the aorta. In the absence of pulmonary stenosis, the physiology resembles that of a large isolated VSD, in which the ratio of pulmonary to systemic blood flow is determined by the pulmonary vascular resistance. Systemic and pulmonary saturations are also affected by the degree of mixing in the right ventricle. This anatomy may result in congestive heart failure (CHF) and pulmonary vascular disease.

In double outlet right ventricle with subpulmonary VSD (Taussig-Bing anomaly), the left ventricular outflow is directed toward the pulmonary artery. This preferential streaming results in pulmonary artery saturations greater than aortic saturations. The aortic and pulmonary orifices are usually positioned side by side but are described as transposed or malposed. The rare presence of pulmonary stenosis results in physiology similar to tetralogy of Fallot. However, in the absence of pulmonary obstruction or stenosis, patients with double outlet right ventricle and subpulmonary VSD have physiology similar to transposition of the great arteries and VSD. In this case, pulmonary vascular resistance (PVR) determines pulmonary blood flow. Early-onset pulmonary obstructive vascular disease commonly develops because of increased pulmonary blood flow and pressures, yet cyanosis may be absent with high pulmonary blood flow. This type of double outlet right ventricle is frequently associated with subaortic stenosis and arch obstruction.

Double outlet right ventricle with noncommitted or remote VSD has anatomy and physiology similar to that of an isolated VSD or atrioventricular canal defect. To meet the criteria for double outlet right ventricle with noncommitted VSD, some have suggested that the distance between the VSD and the aortic and pulmonary outflow tracts should be at least equal to the aortic valve diameter. Most commonly, the great arteries are normally related in this type of double outlet right ventricle. Pulmonary and systemic blood flow and saturations are determined by the ratio of pulmonary to systemic vascular resistance and by the degree of right ventricular mixing.

Finally, double outlet right ventricle with doubly committed VSD displays physiology in which the left ventricular outflow is equally shared by the aorta and pulmonary artery. The systemic and pulmonary vascular resistances determine the ratio of pulmonary-to-systemic blood flow. This is a relatively rare form of double outlet right ventricle that typically has normally related great arteries. Right ventricular mixing affects oxygen saturations.

Because double outlet right ventricle is the only defect in less than 50% of patients with double outlet right ventricle, classification and description may also take into consideration obstruction of the systemic circulation, ventricular anomalies, coronary artery anomalies, and conduction system abnormalities. Upon further investigation, findings of additional VSDs, anomalies of ventricular rotation, and anomalies of insertion of the subvalvar apparatus of atrioventricular valves are not uncommon.

Systemic circulation may be obstructed at the aortic valve or the obstruction may be subaortic; subaortic obstruction develops in approximately 10% of patients. Aortic valve anomalies are usually associated with mitral valve anomalies that may also be present in the form of a restrictive VSD. Coarctation of the aorta is the most common associated lesion, and interrupted aortic arch may also be present.

Patients with double outlet right ventricle can have coexisting ventricular anomalies. Left ventricular inflow anomalies are less frequent yet can be severe. Mitral stenosis or atresia is often associated with a hypoplastic left ventricle and intact ventricular septum. Left ventricular hypoplasia is present if decreased pulmonary venous return, restrictive VSD, and large atrial septal defect (ASD) are present. Misalignment of atrioventricular valves is also visible. This is very important for surgical correction and must be investigated. Finally, straddling of the atrioventricular valve annuli or straddling of the chordae may be present. Right ventricular abnormalities including tricuspid regurgitation, tricuspid stenosis, and Ebstein malformation may develop.

Coronary artery abnormalities are related to the relationship of the great arteries with several variations, including anomalous origin of the right coronary artery (RCA) from the left main coronary artery (LMCA), duplication of left anterior descending coronary artery (LAD), anomalous origin of LAD from RCA (associated with a subaortic VSD and pulmonary stenosis), anterior origin of LAD, RCA immediately beneath pulmonary annulus (seen with L-malposed aorta), and RCA from the posterior sinus of Valsalva/LMCA from the left sinus, which is seen with an anterior aorta and subpulmonary VSD and is similar to transposition of the great arteries.

Conduction system abnormalities develop because of alterations in anatomy. Anatomy of the atrioventricular node and His-Purkinje system is similar to that in an isolated perimembranous VSD. In subaortic, subpulmonary, and doubly committed VSD, conduction tissues are displaced from the superior margin of the VSD.

Other abnormalities and associations are rare and can include dextrocardia and atrioventricular discordance, superior and inferior ventricles, and single atrioventricular valve connection.

Frequency

United States

Double outlet right ventricle accounts for 1-1.5% of all CHDs, with an incidence of 1 per 10,000 live births.

International

Incidence is the same internationally as in the United States.

Mortality/Morbidity

One review found early in-hospital mortality after operation to be 4.8%.² The rate was significantly higher in patients with complex lesions. Late mortality was 3.2% with a mean follow-up time of 5.3 years. Overall 15-year survival ranged from 89.5-95.8%, with more complex lesions exhibiting higher mortality rates. Reoperation was required in 11.2% of surviving patients. This occurred a mean of 4.1 years after the original definitive repair. The most likely cause of reoperation was right ventricular outflow tract obstruction. Fifteen-year freedom from reoperation rates in surviving patients ranged from 72-100%. The reoperation rate was higher in patients with subpulmonary VSDs.

Race

No race predilection has been reported.

Sex

No sex predilection has been reported.

Age

Most cases of double outlet right ventricle are diagnosed in the first month of life.

Clinical

History

History of double outlet right ventricle (DORV) varies based on type of anatomy.

• Subaortic or subpulmonary ventricular septal defect (VSD) with pulmonary stenosis
  • These children present with histories similar to those of children with tetralogy of Fallot.
  • If pulmonary oligemia is present, severe cyanosis is seen in the newborn period, and the condition is recognized early.
  • Beyond the newborn period, cyanosis may be accompanied by hypercyanotic spells, polycythemia, and failure to thrive.
  • These children are less likely to develop pulmonary obstructive vascular disease due to limitation of blood flow and pressure by pulmonary stenosis.
• Subaortic VSD without pulmonary stenosis
  • These children present with histories similar to those of children with a large VSD and pulmonary hypertension.
  • Oxygenation is relatively normal, and patients usually present with congestive heart failure (CHF) and failure to thrive.
  • Referral usually occurs later unless associated left heart lesions are present.
  • These children may have associated chromosomal abnormalities such as trisomy 13 or 18.
  • These children are likely to acquire pulmonary obstructive vascular disease without surgical repair, especially if the VSD is large.
• Subpulmonary VSD without pulmonary stenosis
  • These children present with histories similar to those of children with transposition of the great arteries.
  • Cyanosis varies, with oxygen saturations ranging from 40-80%.
  • If associated coarctation or interruption of the aorta is present, earlier onset of CHF can be expected to result in earlier referral.

Physical

Physical examination findings vary with the anatomy.

• Subaortic or subpulmonary VSD with pulmonary stenosis: Physical examination reveals prominent right ventricular impulse, systolic thrill at left upper sternal border, harsh systolic murmur, and a single second heart sound.
• Subaortic VSD without pulmonary stenosis
  • Physical examination reveals hyperdynamic precordial impulse, a grade III-IV/VI holosystolic murmur, a loud pulmonary component of the second heart sound, an apical diastolic rumble, and, sometimes, a palpable thrill.
  • Once these children acquire pulmonary obstructive vascular disease, they exhibit decreased pulmonary blood flow with subsequent loss of the diastolic rumble and attenuation of systolic murmur. They may also develop a loud second heart sound and a diastolic decrescendo murmur of pulmonary insufficiency.
• Subpulmonary VSD without pulmonary stenosis
  • Physical examination reveals cyanosis, tachypnea, grunting, and signs of CHF.
  • Examination also reveals a loud pulmonary component of the second heart sound, a III/VI systolic murmur, and an apical diastolic rumble.
  • If coarctation of aorta is present, the examination also reveals diminished femoral pulses.

Causes

As with other conotruncal heart defects, the cause of double outlet right ventricle may be of neural crest origin.³ The neural crest is involved in the development of the cardiac septum. Studies indicate removal of the neural crest during development results in outflow tract malformations, and total removal of cardiac neural crest usually results in truncus arteriosus abnormality. Deletions of smaller parts of the cardiac neural crest result in malformations such as double outlet right ventricle, tetralogy of Fallot, and Eisenmenger complex. Interestingly, neural crest ablation rarely results in transposition of the great arteries. Most changes in heart morphology occur while the heart is still in the looped tube stage.

In addition to formation of cardiac structures, this area of neural crest cells participates in formation of the thymus and the thyroid and parathyroid glands, serving as the basis for association of congenital heart diseases (CHDs) with DiGeorge syndrome. The combination of velocardiofacial syndrome, DiGeorge syndrome (facial anomalies and parathyroid/thymus aplasia or hypoplasia), and a chromosome band 22q11 deletion is known as CATCH 22.^4,5,6

The most common types of CHD associated with the band 22q11 deletion include tetralogy of Fallot, truncus arteriosus, VSDs, and aortic arch abnormalities.^4,5,6 Research has shown that 22q11 deletions are rare in double outlet right ventricle. In one study, only 1 in 20 patients with double outlet right ventricle had the deletion; double outlet right ventricle was defined only by lack of fibrous continuity between mitral and aortic valves and an aorta that arises more than 50% above the right ventricle.⁶ However, because double outlet right ventricle encompasses such a large spectrum of anomalies, recommendations are to continue to test patients for the 22q11 deletion, especially when they display other features of velocardiofacial syndrome.

Differential Diagnoses

Transposition of the Great Arteries
Truncus Arteriosus
Ventricular Septal Defect, General Concepts

Workup

Laboratory Studies

• Routine laboratory studies are not required for the initial diagnosis and management in children with double outlet right ventricle (DORV).
• Assess hemoglobin and hematocrit if children are thought to have polycythemia.
• Monitor serum electrolyte levels after treating children with diuretics, glycosides, and afterload-reducing agents.

Imaging Studies

• Chest radiography
  • Chest radiography findings usually correlate with clinical presentation.
  • Chest radiographs cannot be used to differentiate double outlet right ventricle from other forms of congenital heart disease (CHD).
  • Presence or absence of pulmonary stenosis and pulmonary vascular resistance determines if cardiomegaly and increased pulmonary vascularity are present.
  • Patients with subaortic ventricular septal defect (VSD) and severe pulmonary stenosis demonstrate diminished pulmonary vascularity and concave left heart border (similar to appearance associated with tetralogy of Fallot).
  • If pulmonary obstructive vascular disease is present, peripheral pulmonary vascularity may be reduced and proximal pulmonary arteries may be dilated.
  • The appearance in patients with subpulmonary VSD is similar to that in patients with transposition of the great arteries, revealing increased pulmonary vascularity and cardiomegaly.
  • In patients in whom the aorta is anterior and to the left, radiography may reveal the leftward position of the aorta.
• Echocardiography
  • Echocardiography is the imaging technique most often used to diagnose double outlet right ventricle.
  • The principle diagnostic feature is appearance of both great arteries primarily committed to the right ventricle. Parasternal long-axis and short-axis views reveal the degree of commitment to the right ventricle.
  • Subcostal and apical 4-chamber views reveal the separation between semilunar and atrioventricular valves (ventriculoinfundibular fold).
  • Use multiple views to determine the relationship between the ventricular septum and the outlet septum.
  • Features that must be established with echocardiography include the primary commitment of both great arteries to the right ventricle, the spatial relationship of both great arteries, the location of the VSD and its relationship to semilunar valves, and the presence of associated anomalies such as coarctation, the straddle/override of atrioventricular valve in relation to the VSD, and the presence of restrictive VSD.
  • In addition, fetal echocardiography has been used to prenatally diagnose cases of double outlet right ventricle. This imaging modality can also reveal other congenital cardiac anomalies that may be present in addition to double outlet right ventricle. Prenatal quantification of left ventricular size is important. One study noted that, in patients with double outlet right ventricle and borderline left ventricular size, only 33% of pregnancies proceeded to live birth.⁷ Of those patients, only 25% successfully underwent biventricular repair. Patients with double outlet right ventricle may demonstrate other abnormalities on fetal ultrasonography. However, even in patients with isolated double outlet right ventricle, diagnosis is possible based solely on limited fetal echocardiography, provided a long-axis view is included.⁸  
• MRI
  • MRI can help clarify ambiguities that remain after echocardiography.
  • MRI reveals the relationship between the great arteries, the anatomy of the outlet septum relative to the ventricular septum, and the relationship of the VSD to the great arteries.
  • One study reported that, in patients with doubly committed or noncommitted VSDs, MRI more reliably predicted the feasibility of a biventricular repair than did echocardiography.⁹
  • Limitations include the need for prolonged evaluation, deeper sedation, and incomplete atrioventricular valve definition. MRI may also fail to reveal the presence of aberrant chordae tendineae.

Other Tests

• Abnormalities are often present on electrocardiography (ECG) but are not diagnostic of double outlet right ventricle.
• If obtained after the newborn period, ECG reveals right ventricular hypertrophy.
• Left ventricular hypertrophy may develop in the presence of a restrictive VSD that leads to left ventricular pressure overload or an increased pulmonary venous return that leads to left ventricular volume overload.
• Right atrial enlargement is common.
• Left atrial enlargement may be present if pulmonary venous return or mitral stenosis/atresia is increased.
• Usually, left axis deviation of the frontal plane QRS is present because of displacement of the bundle of His posterior to VSD.

Procedures

• Cardiac catheterization may delineate anatomy and hemodynamics. Objectives of catheterization include the following:
  • Evaluation of right and left ventricular volumes
  • Evaluation for possible gradient across VSD and pulmonary vascular resistance (PVR)
  • Evaluation of relationship between VSD and great arteries
  • Evaluation of coronary artery and aortic arch anatomy
  • Assessment of degree of mixing of the 2 circulations
• If a restrictive atrial septal defect (ASD) is present, increased pulmonary blood flow with aortic saturations below 70%, or 10% less than pulmonary saturations, indicates the possibility of improvement with atrial septostomy (termed transposition physiology).
• Diagnostic angiographic features of double outlet right ventricle include the following:
  • Opacification of both great arteries following right ventriculography
  • Similarity of aortic and pulmonary valve horizontal planes
  • Frequent anterior malposition of the aorta
  • Presence of a filling defect dividing the 2 outflow tracts

Histologic Findings

• Findings vary depending on the clinical presentation; various physiologic effects determine histology of cardiac structures.

Treatment

Medical Care

• Initial evaluation and treatment are usually performed in an outpatient setting. Treatment varies depending on the anatomy of the lesion. Direct medical treatment of infants with double outlet right ventricle (DORV) at control of congestive heart failure (CHF). Hospitalize children who present with severe heart failure and treat them with fluid restriction and reduction of physical stress. Monitor children to ensure adequate weight gain because CHF can decrease oral intake and increase caloric expenditure. Other therapies include the following:
  • Oxygen therapy may be required if pulmonary edema is present.
  • Use oxygen only to relieve hypoxemia because it is a pulmonary vasodilator and can exacerbate left-to-right shunt and CHF.
  • Promptly initiate diuretic therapy with furosemide.
  • Glycoside therapy with digoxin can be initiated in a maintenance dose if severe CHF is not present.
• Systemic afterload reduction is important in treating infants with CHF. ACE inhibitors (ie, captopril, enalapril) are the most commonly used afterload-reduction agents.

Surgical Care

In 1957, Kirkland reported the first surgical repair of double outlet right ventricle using an intraventricular tunnel to establish left ventricular-aortic continuity via subaortic ventricular septal defect (VSD). Surgical repair usually requires cardiopulmonary bypass with moderate hypothermia. Many double outlet right ventricles have been repaired with a period of circulatory arrest.

Most transpositions are repaired using a biventricular approach with placement of an intraventricular baffle; this is more difficult without 2 well-developed ventricles or if the anatomy precludes a biventricular repair. An alternative repair is a Fontan procedure, which deteriorates with time.

In general, procedures depend on the location of the VSD and the size of the left ventricle. A significant number of patients undergo palliative procedures prior to definitive repair, especially when the patients have borderline or hypoplastic left ventricles. These procedures include pulmonary artery banding, Blalock-Taussig shunt, coarctation repair, or a stage I Norwood procedure.

• Double outlet right ventricle with subaortic VSD is repaired by VSD closure to baffle the left ventricular outflow to the aorta. It is typically repaired in patients younger than 6 months to prevent pulmonary vascular disease. If severe pulmonary stenosis is present, the condition and repair are similar to those of tetralogy of Fallot. Pulmonary stenosis often occurs with hypoplasia of the pulmonary arteries and coronary artery anomalies, making repair more difficult. Historically, this condition often was treated with initial shunting and definitive repair in patients aged 4-5 years.
• Double outlet right ventricle with subpulmonary VSD can be repaired using the following 3 methods:
  • The first procedure involves construction of a left ventricle–to–subpulmonary outflow tract tunnel with a subsequent arterial switch. This is the preferred method when the aorta is malposed anteriorly. Coronary artery transfer is similar to that in transposition of the great arteries.
  • The second method consists of construction of a long intraventricular tunnel to establish continuity between the left ventricle and the aorta and between the right ventricle and pulmonary artery.
  • The third method involves closure of the VSD with baffling of the left ventricular outflow to the pulmonary artery with a subsequent atrial baffle (eg, Senning procedure, Mustard procedure). This method is associated with high operative and late mortality rates.
• Doubly committed or noncommitted VSDs often require a complex repair with a Fontan procedure and possibly reoperation for secondary subaortic stenosis. For example, a patient with double outlet right ventricle, complete atrioventricular septal defect (AVSD), and valvar pulmonary stenosis underwent repair involving patching the ventricular portion of the AVSD and translocating it into a subaortic position. A left ventricular–to–aortic tunnel was then created. Nine years after primary repair, the patient required right ventricle–to–pulmonary artery conduit replacement.
  • One case series studied 50 children with double outlet right ventricle and adequate left ventricular size.¹⁰ Eleven patients in the study had double outlet right ventricle with transposition of the great vessels. Biventricular repair was performed in 48 of the children, and the overall mortality rate was 6%. Actual surgical mortality rate in patients with biventricular repair was 4.3%.
  • In contrast, surgical and overall morbidity and mortality rates increase with more complex types of double outlet right ventricle. Takeuchi et al recently reported a case series of 96 patients with double outlet right ventricle and heterotaxy syndrome and/or complete atrioventricular canal defect.¹¹ Only 8 patients had biventricular repair. Nine of the 17 neonatal patients survived. Of the 79 patients older than 30 days, 71 survived. The overall mortality rate was 17% in all patients.

Consultations

• Refer patients with heart murmurs and physical findings suggestive of double outlet right ventricle to a pediatric cardiologist.
• Consult a pediatric cardiac surgeon for possible repair following diagnosis of double outlet right ventricle.
• Consult pediatric critical care personnel. Following surgical repair, postoperative care normally occurs in the pediatric ICU.
• Involve a geneticist in the care of patients diagnosed with double outlet right ventricle who may have associated genetic syndromes, including velocardiofacial syndrome and DiGeorge syndrome.

Diet

• Children with CHF due to double outlet right ventricle often require increased caloric intake supplemented by the addition of medium-chain triglyceride or carbohydrate preparations to conventional infant formulas.
• Some children may require overnight, bolus, or continuous feeds by nasogastric tubes.

Activity

• Activity is not limited for infants initially diagnosed with double outlet right ventricle, unless they have CHF. For patients with CHF, reduce physical stress until the heart failure can be controlled.
• Advance the activity of patients in the postoperative period as tolerated, until a normal level of activity is achieved.

Medication

The overall goal of medical therapy in patients with double outlet right ventricle (DORV) is to prevent or control congestive heart failure (CHF).

Diuretic agents

These agents promote excretion of water and electrolytes by the kidneys. They are used to treat heart failure or hepatic, renal, or pulmonary disease when sodium and water retention has resulted in edema or ascites. They are also used to reduce plasma volume and, thus, improve CHF.

Furosemide (Lasix)

Titrate treatment dose to produce initial diuresis and subsequently to control symptoms.
Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending Henle loop and distal renal tubule.

Dosing

Adult

20-80 mg/d PO/IV/IM in divided doses q6-12h; not to exceed 600 mg/d

Pediatric

1-6 mg/kg/d PO divided q6-12h
1-2 mg/kg/dose IV/IM q6-12h

Interactions

Metformin decreases furosemide concentrations; furosemide interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides and furosemide; varying degrees of hearing loss may develop; anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible

Contraindications

Documented hypersensitivity; hepatic coma, anuria, state of severe electrolyte depletion

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hepatic cirrhosis (rapid alterations in fluid/electrolytes may precipitate coma)

Inotropic agents

Positive inotropic agents increase the force of myocardial contraction and are used to treat acute and chronic CHF. Some agents may also increase or decrease the heart rate (ie, positive or negative chronotropic agents), provide vasodilatation, or improve myocardial relaxation. These additional properties influence the choice of drug for specific circumstances. Agents used predominantly for their inotropic effects include cardiac glycosides and phosphodiesterase inhibitors.

Digoxin (Lanoxin)

Used to increase contractility of the left ventricle. Inhibits Na/K-ATPase, which causes intracellular calcium in the sarcoplasmic reticulum of cardiac cells to increase. This leads to a sustained but modest positive inotropic effect on the heart. Some question the inotropic effect of these medications on immature myocardium, while others have demonstrated improved left ventricular contractility without symptomatic improvement.

Dosing

Adult

Total digitalizing dose (TDD):
0.75-1.5 mg PO
Divide TDD: Initially administer 50% and then administer the remaining two 25% portions at 6- to 12-h intervals (1/2, 1/4, 1/4)
Maintenance dose: 0.125-0.5 mg PO qd

Pediatric

TDD:
Preterm infants: 20-30 mcg/kg PO
Term infants: 25-35 mcg/kg PO
1 month to 2 years: 35-60 mcg/kg PO
2-5 years: 30-40 mcg/kg PO
5-10 years: 20-35 mcg/kg PO
>10 years: Administer as in adults
Divide TDD: Initially administer 50% and then administer the remaining two 25% portions at 6- to 12-h intervals (1/2, 1/4, 1/4)Maintenance dose:
Preterm infant: 5-7.5 mcg/kg/d PO divided bid
Term infant: 6-10 mcg/kg/d PO divided bid
1 mo-2 years: 10-15 mcg/kg/d PO divided bid
2-5 years: 7.5-10 mcg/kg/d PO divided bid
5-10 years: 5-10 mcg/kg/d PO divided bid
>10 years: Administer as in adults

Interactions

Medications that may increase digoxin levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, PO amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil
Medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, PO colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid

Contraindications

Documented hypersensitivity; beriberi heart disease, idiopathic hypertrophic subaortic stenosis, constrictive pericarditis, carotid sinus syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypokalemia may reduce positive inotropic effect of digitalis; IV calcium may produce arrhythmias in digitalized patients; hypercalcemia predisposes patient to digitalis toxicity, and hypocalcemia can make digoxin ineffective until serum calcium levels are normal; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete AV block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis

ACE inhibitors

These agents are used to reduce afterload and left-to-right shunting. ACE inhibitors are beneficial in all stages of chronic heart failure. Pharmacologic effects result in a decrease in systemic vascular resistance, reducing blood pressure, preload, and afterload. Dyspnea and exercise tolerance are improved.

Captopril (Capoten)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. Shown to increase systemic flow by reducing left-to-right shunting in patients with relatively low pulmonary vascular resistance.

Dosing

Adult

12.5-25 mg/dose PO q8-12h, increase by 25 mg/dose; not to exceed 450 mg/d

Pediatric

Infants: 0.15-0.3 mg/kg/dose PO, titrate upward; not to exceed 6 mg/kg qd or divided qid
Children: 0.3-0.5 mg/kg/dose PO, titrate upward; not to exceed 6 mg/kg/d divided bid/qid

Interactions

NSAIDs may reduce hypotensive effects of captopril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases captopril levels; probenecid may increase captopril levels; the hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics

Contraindications

Documented hypersensitivity; renal impairment

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal impairment, valvular stenosis, or severe CHF

Enalapril (Vasotec)

Decreases pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance. It has a favorable clinical effect when administered over a long period.

Dosing

Adult

2.5-5 mg/d PO; may gradually increase prn, not to exceed 40 mg/kg/d

Pediatric

Limited data available; suggested dose is 0.1 mg/kg PO qd or divided bid; increase prn over 2 wk; not to exceed 0.5 mg/kg/d

Interactions

NSAIDs may reduce hypotensive effects of enalapril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases enalapril levels; probenecid may increase enalapril levels; the hypotensive effects of ACE inhibitors may be enhanced when administered concurrently with diuretics

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use with caution and modify dosage with renal impairment (especially renal artery stenosis), hyponatremia, hypovolemia, severe CHF, or with coadministered diuretic therapy; severe hypotension may develop in patients who are sodium and/or volume depleted; initiate lower doses and monitor closely when starting therapy in these patients; experience in children is limited; use with caution in neonates

Phosphodiesterase Enzyme Inhibitor

This agent is used for short-term treatment of acute decompensated heart failure.

Milrinone (Primacor)

Positive inotropic agent and vasodilator. Selectively inhibits phosphodiesterase type III (PDE III) in cardiac and smooth vascular muscle, resulting in reduced afterload, reduced preload, and increased inotropy. Several studies that have compared milrinone with dobutamine demonstrated that milrinone showed greater improvements in preload and afterload and improvements in cardiac output, without significant increases in myocardial oxygen consumption.

Dosing

Adult

50 mcg/kg IV loading dose over 10 min, followed by continuous infusion at 0.25-1 mcg/kg/min; titrate to maintain adequate systolic blood pressure and cardiac output

Pediatric

Data limited; 50-75 mcg/kg IV loading dose over 15 minutes followed by continuous infusion of 0.25-0.7 mcg/kg/min; titrate dose to effect

Interactions

Milrinone precipitates in presence of furosemide

Contraindications

Documented hypersensitivity to milrinone, any component, or inamrinone

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor fluids, electrolyte changes, and renal function during therapy; excessive diuresis may increase potassium loss and predispose digitalized patients to arrhythmias; important to correct hypokalemia with potassium supplementation prior to treatment; patients who show excessive decreases in blood pressure should have infusion rates slowed or stopped; previous vigorous diuretic therapy has caused significant decreases in cardiac filling pressure (cautiously administer milrinone and monitor blood pressure, heart rate, and clinical symptomatology)

Follow-up

Further Inpatient Care

• Provide inpatient care if congestive heart failure (CHF) is severe. Treat patients initially with fluid restriction and alleviation of temperature and physical stress. Sedation may be required with opioids.
• Observe and manage ventricular function for patients in immediate postoperative period. Arrhythmias may develop after repair and may require medical intervention.

Further Outpatient Care

• After repair, children with double outlet right ventricle (DORV) are often treated with systemic afterload reduction using ACE inhibitors for several months to assist in cardiac remodeling.

Inpatient & Outpatient Medications

• Commonly used medications are listed above (see Medication), including furosemide, digoxin, captopril, and enalapril.

Transfer

• Transfer may be required for further diagnostic testing and medical/surgical treatment.

Complications

• If patients undergo surgery for repair at an older age, they often develop ventricular dysfunction and elevation of pulmonary artery pressures.
• Operative and postoperative complications depend on anatomy of lesion and type of repair.
  • Some patients develop restrictive ventricular septal defect (VSD) and require reoperation.
  • In patients with subaortic and subpulmonary VSD, the VSD diameter can decrease by 20% in the immediate postoperative period. These patients can sometimes develop subaortic obstruction.
  • Patients, especially those undergoing complex repair, can develop postoperative ventricular dysfunction associated with residual VSD, aortic insufficiency, atrioventricular valve insufficiency, and prolonged circulatory arrest at repair.
  • Some patients are at risk for late postoperative arrhythmias and sudden death.
  • Patients may develop persistent atrial tachycardia, complex ventricular ectopy, or syncope requiring electrophysiologic studies.

Prognosis

• The long-term survival rate for children who undergo repair for a subaortic VSD type of double outlet right ventricle is 80-95%.
• A retrospective study analyzed the pregnancy outcome of patients with previous biventricular repair of double outlet right ventricle. The study, which included 19 pregnancies, found a premature labor rate of 44% at a median of 32 weeks' gestation.¹²  Other complications included diminished fertility, menstrual disorders, and a higher than expected rate of neonates that were small for gestational age. However, despite these complications, 17 of the 19 pregnancies resulted in live births.

Patient Education

• Educate parents regarding anatomic defect, surgical repair, and postoperative course. Prior to repair, parents should learn about medical therapy and signs and symptoms of CHF.
• Institute a specific nutritional program to attain adequate weight gain.
• For excellent patient education resources, visit eMedicine's Heart Center. Also, see eMedicine's patient education article Tetralogy of Fallot.

Miscellaneous

Medicolegal Pitfalls

• Failure to make the correct diagnosis
• Failure to prepare for and treat surgical complications

Multimedia

Media file 1: Neonate with double outlet right ventricle. Chest radiograph shows a mildly enlarged heart with symmetrically slightly increased pulmonary vasculature.

Media file 2: Double outlet right ventricle with subaortic ventricular septal defect. Arrow shows flow of oxygenated blood from left ventricle to aorta.

Media file 3: Repair of double outlet right ventricle with subaortic ventricular septal defect.

Media file 4: Double outlet right ventricle with subpulmonary ventricular septal defect (Taussig-Bing anomaly).

Media file 5: Complex repair of double outlet right ventricle with subpulmonary ventricular septal defect.

Media file 6: Double outlet right ventricle with doubly committed ventricular septal defect.

Media file 7: Repair of double outlet right ventricle with doubly committed ventricular septal defect showing VSD patch and intraventricular baffle.

Media file 8: Double outlet right ventricle with noncommitted ventricular septal defect.

Media file 9: Repair of double outlet right ventricle with noncommitted ventricular septal defect using a long ventricular septal defect patch.

References

1. Witham AC. Double outlet right ventricle; a partial transposition complex. Am Heart J. Jun 1957;53(6):928-39. [Medline].

2. Brown JW, Ruzmetov M, Okada Y, et al. Surgical results in patients with double outlet right ventricle: a 20- year experience. Ann Thorac Surg. Nov 2001;72(5):1630-5. [Medline].

3. Kirby ML, Waldo KL. Role of neural crest in congenital heart disease. Circulation. Aug 1990;82(2):332-40. [Medline].

4. Goldmuntz E, Clark BJ, Mitchell LE, et al. Frequency of 22q11 deletions in patients with conotruncal defects. Journal of the American College of Cardiology. 1999;32:499-501. [Medline].

5. Khositseth A, Tocharoentanaphol C, Khowsathit P, Ruangdaraganon N. Chromosome 22q11 deletions in patients with conotruncal heart defects. Pediatr Cardiol. Sep-Oct 2005;26(5):570-3. [Medline].

6. Momma K, Kondo C, Matsuoka R, Takao A. Cardiac anomalies associated with a chromosome 22q11 deletion in patients with conotruncal anomaly face syndrome. American Journal of Cardiology. 1996;78:591-594. [Medline].

7. Pitkanen OM, Hornberger LK, Miner SE, et al. Borderline left ventricles in prenatally diagnosed atrioventricular septal defect or double outlet right ventricle: echocardiographic predictors of biventricular repair. Am Heart J. Jul 2006;152(1):163.e1-7. [Medline].

8. Tongsong T, Chanprapaph P, Sittiwangkul R, Khunamornpong S. Antenatal diagnosis of double outlet of right ventricle without extracardiac anomaly: a report of 4 cases. J Clin Ultrasound. May 2007;35(4):221-5. [Medline].

9. Beekmana RP, Roest AA, Helbing WA, et al. Spin echo MRI in the evaluation of hearts with a double outlet right ventricle: usefulness and limitations. Magn Reson Imaging. Apr 2000;18(3):245-53. [Medline].

10. Artrip JH, Sauer H, Campbell DN, et al. Biventricular repair in double outlet right ventricle: surgical results based on the STS-EACTS International Nomenclature classification. Eur J Cardiothorac Surg. Apr 2006;29(4):545-50. [Medline].

11. Takeuchi K, McGowan FX, Bacha EA, et al. Analysis of surgical outcome in complex double-outlet right ventricle with heterotaxy syndrome or complete atrioventricular canal defect. Ann Thorac Surg. Jul 2006;82(1):146-52. [Medline].

12. Drenthen W, Pieper PG, van der Tuuk K, et al. Fertility, pregnancy and delivery in women after biventricular repair for double outlet right ventricle. Cardiology. 2008;109(2):105-9. [Medline].

13. Bartelings MM, Gittenberger-de Groot AC. Morphogenetic considerations on congenital malformations of the outflow tract. Part 2: Complete transposition of the great arteries and double outlet right. International Journal of Cardiology. 1991;33:5-26. [Medline].

14. Battistessa S, Soto B. Double outlet right ventricle with discordant atrioventricular connexion: an angiographic analysis of 19 cases. International Journal of Cardiology. 1990;27:253-267. [Medline].

15. Belli E, Serraf A, Lacour-Gayet F, et al. Biventricular repair for double-outlet right ventricle. Results and long-term follow-up. Circulation. 1998;98 (19 supplement):360-367. [Medline].

16. Belli E, Serraf A, Lacour-Gayet F, et al. Double-outlet right ventricle with non-committed ventricular septal defect. Eur J Cardiothorac Surg. Jun 1999;15(6):747-52. [Medline].

17. Manner J, Seidl W, Steding G. Embryological observations on the morphogenesis of double-outlet right ventricle with subaortic ventricular septal defect and normal arrangement of the great arteries. Thorac Cardiovasc Surg. Dec 1995;43(6):307-12. [Medline].

18. Oppido G, Napoleone CP, Loforte A, et al. Complex double-outlet right ventricle repair in a neonate with complete tracheal agenesis. J Thorac Cardiovasc Surg. Jan 2004;127(1):283-5. [Medline].

19. Patel CR, Steele MA, Stewart JW. Double-outlet right ventricle with partial anomalous pulmonary venous connection:prenatal diagnosis. J Ultrasound Med. Jun 2005;24(6):861-4. [Medline].

20. Silka MJ. Double-outlet ventricles. In: The Science and Practice of Pediatric Cardiology. 2^nd ed. 1997:1132, 1505-23.

21. Takeuchi K, McGowan FX Jr, Moran AM, et al. Surgical outcome of double-outlet right ventricle with subpulmonary VSD. Ann Thorac Surg. Jan 2001;71(1):49-52; discussion 52-3. [Medline].

22. Tchervenkov CI, Korkola SJ, Beland MJ. Single-stage anatomical repair of complete atrioventricular canal, double-outlet right ventricle, and cor triatriatum using ventricular septal defect translocation. Ann Thorac Surg. Apr 2002;73(4):1317-20. [Medline].

23. Walters HL, Mavroudis C, Tchervenkov CI, et al. Congenital Heart Surgery Nomenclature and Database Project: double outlet right ventricle. Ann Thorac Surg. Apr 2000;69(4 Suppl):S249-63. [Medline].

24. Wernovsky G, Hanley FL. Double outlet right ventricle. In: Pediatric Cardiac Intensive Care. ed. 1998:301-3.

Keywords

double outlet right ventricle, normally related great arteries, DORV, both great arteries originating from the right ventricle, partial transposition complex of the great arteries, transposition of the aorta and levoposition of the pulmonary artery, congenital heart defect, CHD, ventricular septal defect, VSD, Taussig-Bing anomaly, tetralogy of Fallot, DiGeorge syndrome, DiGeorge's syndrome, neural crest, congestive heart failure, subaortic stenosis, arch obstruction, atrioventricular canal defect, mitral stenosis, coarctation of the aorta, interrupted aortic arch, mitral atresia, atrial septal defect, ASD, tricuspid regurgitation, Ebstein malformation, transposition of the great arteries, hypercyanotic spells, polycythemia, failure to thrive

Contributor Information and Disclosures

Author

Rod Tarrago, MD, Pediatric Intensivist, Department of Pediatric Critical Care, Children's Hospitals and Clinics of Minnesota
Rod Tarrago, MD is a member of the following medical societies: Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Steven R Neish, MD, SM, Director of Pediatric Cardiology Fellowship Program, Associate Professor, Department of Pediatrics, Baylor College of Medicine
Steven R Neish, MD, SM is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, and American Heart Association
Disclosure: Nothing to disclose.

Medical Editor

Juan Carlos Alejos, MD, Associate Clinical Professor, Department of Pediatrics, Division of Cardiology, University of California at Los Angeles
Juan Carlos Alejos, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, American Medical Association, and International Society for Heart and Lung Transplantation
Disclosure: Actelion Honoraria Speaking and teaching

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Julian M Stewart, MD, PhD, Associate Chairman of Pediatrics, Director, Center for Hypotension, Westchester Medical Center; Professor of Pediatrics and Physiology, New York Medical College
Julian M Stewart, MD, PhD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

CME Editor

Gilbert Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College
Gilbert Herzberg, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Chief Editor

Stuart Berger, MD, Professor of Pediatrics, Division of Cardiology, Medical College of Wisconsin; Chief of Pediatric Cardiology, Medical Director of Pediatric Heart Transplant Program, Medical Director of The Heart Center, Children's Hospital of Wisconsin
Stuart Berger, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American College of Chest Physicians, American Heart Association, and Society for Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

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