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

Atrioventricular Septal Defect, Partial and Intermediate

M Silvana Horenstein, MD, Consultant, Pediatric and Fetal Cardiac Diagnostic, Diagnostico Gineco-Obstetrico, PC; Associate Medical Director, Legacy Department, Best Doctors, Inc
Michael A Portman, MD, Research Director, Department of Pediatrics, Division of Cardiology, Associate Professor, Childrens' Hospital

Updated: Oct 3, 2008

Introduction

Background

Atrioventricular septal defects (AVSDs) refer to a broad spectrum of malformations characterized by a deficiency of the atrioventricular septum. These malformations are presumed to result from abnormal or inadequate fusion of the superior and inferior endocardial cushions with the mid portion of the atrial septum and the muscular (trabecular) portion of the ventricular septum.

Several methods of classification and nomenclature are recognized, causing considerable confusion. The term partial AVSD (also called partial common atrioventricular canal) generally refers to endocardial cushion defects, which have an interatrial communication but lack an interventricular communication. In these types of defects the mitral and tricuspid annuli are separate. In addition, certain anatomic features should be present, alone or in combination: primum atrial septal defect (ASD), inlet ventricular septal defect (VSD), cleft of the anterior mitral valve leaflet, and wide anteroseptal tricuspid valve commissure or cleft septal tricuspid leaflet (see Media file 1). The most frequently encountered abnormality in patients with partial AVSD is the combination of primum ASD and cleft of the anterior mitral valve leaflet.

The term intermediate AVSD (also called transitional common atrioventricular canal) is variably defined; however, it most commonly refers to the combination of a partial AVSD with a small interventricular communication. This is an infrequent form of AVSD. A single valvar annulus is usually present where the anterior and posterior bridging leaflets fuse overlying the ventricular septum. Because of the leaflets' fusion, two distinct valvar components are observed (see Media file 2).

A thorough description of associated atrioventricular valve abnormalities should be included when classifying these defects.

This article considers AVSDs that demonstrate minimal or no shunting through an interventricular communication.

Pathophysiology

In the absence of obstruction of the right ventricular outflow tract, such as in pulmonary stenosis or pulmonary vascular obstructive disease, predominant left-to-right shunting occurs. The clinical presentation is determined by the degree of interatrial shunting, atrioventricular regurgitation, or both. The most inferior portion of the atrial septum is deficient. The resulting ostium primum defect varies in size and may occur in association with more superior ostium secundum–type ASDs. In some of the latter cases, only a small strand of the atrial septum remains, leading to the appearance of a common atrium. Some observers reserve the term common atrium for those cases with an additional sinus venosus deficiency.

The degree of left-to-right shunting through the atrial defect is determined by the size of the communication and the relative compliance of the 2 atria and ventricles. Ventricular compliance is affected by the level of pulmonary vascular resistance (PVR). In the newborn with a less compliant right ventricle (RV) and relatively high PVR, little left-to-right shunting occurs. If the defect is extremely large, obligatory mixing in a common, or near-common, atrium creates a component of right-to-left shunting. Left-to-right shunting increases with age as PVR decreases and RV compliance increases. This results in progressive RV enlargement and pulmonary vascular engorgement.

The atrioventricular valves are abnormal, even in a partial AVSD. Fusion failure of the endocardial cushions usually results in a separation or cleft in the anterior mitral valve leaflet. The degree of regurgitation through the cleft depends on its size and, occasionally, on the presence of left ventricular outflow tract (LVOT) obstruction or coarctation of the aorta. Typically, the cleft directs regurgitant blood through the atrial defect, creating an LV-to-RA (right atrium) shunt. RA enlargement, rather than left atrial (LA) enlargement, may occur. In addition, mitral regurgitation (MR) contributes to LA and LV enlargement.

Frequency

United States

Prevalence estimates of cardiovascular malformations in large cohorts vary from 4-8 cases per 1000 births. AVSD constitutes 5-8% of these defects. Incidence of AVSD in fetuses is 17%; however, occurrence of partial AVSD has not been separated from this general classification.

Studies report the incidence of congenital heart defect (CHD) in children with Down syndrome (trisomy 21) to be 42-48%. Of those CHDs, 45% are AVSDs.

In general, when not associated with heterotaxia syndrome, AVSDs commonly occur in Down syndrome.

Partial AVSD, as opposed to complete AVSD, of the ostium primum type is more common in patients without Down syndrome.

International

International frequency of cardiovascular malformations is similar to US figures.

Mortality/Morbidity

Left-to-right shunting through the atrial communication is generally well tolerated through the first decade of life. Patients are asymptomatic if MR is mild or absent. Symptoms of left-to-right shunting may develop in adolescence and are exacerbated by atrial arrhythmia. Sinus node dysfunction may occur and contributes to exercise intolerance if the defect is not repaired.

Moderate to severe MR may lead to morbidity in infancy and early childhood. Severe MR causes congestive heart failure (CHF) and failure to thrive in infants; it may result in death if left untreated.

A large left-to-right shunt from the LV to the RA through a cleft mitral valve causes volume overload in both ventricles, with CHF early in life.

Clinical

History

In the absence of moderate to severe mitral regurgitation (MR) and other associated congenital heart disease (CHD), partial atrioventricular septal defect (AVSD) is often discovered later in childhood when the patient is referred for evaluation of a heart murmur. Also, partial AVSD is less common in Down syndrome than in complete AVSD.

• The clinical presentation of patients with partial AVSD depends on the degree of MR and on the associated cardiac defects.
• Other cardiac anomalies that may be associated with partial AVSD include secundum atrial septal defect (ASD), persistent left superior vena cava draining to the coronary sinus, pulmonary stenosis, discrete subaortic stenosis, tricuspid stenosis, tricuspid atresia, coarctation of the aorta, patent ductus arteriosus (PDA), perimembranous ventricular septal defect (VSD), and hypoplastic left ventricle (LV).
• Children with atrioventricular valve competence usually exhibit no significant symptoms. They are usually referred to a pediatric cardiologist if a heart murmur is detected during routine examination.
• Substantial left-to-right shunting may exacerbate pulmonary disease and cause frequent lower respiratory infections in some patients. These patients may present with tachypnea, respiratory distress, and inadequate weight gain.
• Infants with severe MR often demonstrate poor feeding, tachypnea, and labored breathing. Rarely, respiratory distress may be so severe as to require mechanical ventilation.
• Progressive cardiac enlargement and LV dysfunction cause shocklike symptoms and eventually lead to mortality.
• Adolescents and young adults may note progressive exercise intolerance.
• Palpitations caused by atrial arrhythmia become more common in young adulthood, and sustained supraventricular tachycardia, atrial flutter, or atrial fibrillation may trigger the onset of congestive heart failure (CHF) in older patients with AVSD.
• Hypervolemia of pregnancy may trigger CHF symptoms and complicate pregnancy.

Physical

• General appearance
  • Most children with partial AVSD and minimal MR appear healthy. Patients who have Down syndrome exhibit features typical of the condition.
  • Patients with severe MR in infancy can manifest tachypnea, retractions, and diaphoresis, especially during and immediately after feeding. Poor caloric intake and excessive metabolic demands lead to growth failure. Older children and adolescents with severe MR may display a prominent left chest as well as a slim (asthenic) build.
• Pulmonary and cardiovascular examination
  • Palpation and auscultatory findings depend on the severity of the left-to-right shunt, the presence of MR, and associated defects (eg, LV outflow obstruction, PDA).
  • Fine rales or rhonchi, or both, may be heard in the lung fields of older patients with severe MR but are rare in infants.
  • The partial AVSD provides auscultatory findings that are indistinguishable from those created by any other large ASD. A prominent impulse along the right sternal border, consistent with a right ventricle (RV) lift, may be present. Alternatively, severe MR can cause a prominent apical impulse or thrill.
  • The classic auscultatory finding associated with an ASD is a constant or fixed splitting of the second heart sound (S₂), frequently accompanied by a pulmonary ejection murmur audible at the upper left sternal border.
  • A large AVSD with substantial left-to-right shunting creates a mid-diastolic rumbling murmur, audible along the lower left sternal border. This often occurs in association with a prominent third heart sound (S₃) in that location. These sounds are attributed to an abnormally high flow across the tricuspid component of the atrioventricular valve.
  • The apical murmur of MR occurs even with a small cleft in the atrioventricular valve. This murmur has a blowing quality and must be differentiated from the murmur caused by a VSD. However, when it occurs with a fixed split S₂, this murmur is helpful in differentiating a partial AVSD from a secundum ASD.
  • Severe MR can also cause a diastolic murmur audible over the apical area, which, in association with the systolic murmur, produces a to-and-fro quality.

Causes

For CHD, experimental and epidemiologic data suggest that a single mechanism may cause a range of anatomic malformations.

Specifically, AVSDs are presumed to occur secondary to extracellular matrix abnormalities that produce faulty development of the endocardial cushions and the atrioventricular septum.

Normal development of the human heart requires an orderly coordination of transcriptional programs. One of the most important factors for the differentiation of mesodermal progenitor cells is the homeobox protein Nkx-2.5. For example, the lack of Nkx-2.5 in mice arrests heart development prior to looping, which is lethal. In humans, 28 germline Nkx-2.5 mutations have been associated with CHD. Studies have shown that mutations in the gene Nkx-2.5 are associated specifically with AVSD and VSD.^{[1 ]}

Differential Diagnoses

Atrial Septal Defect, Coronary Sinus
Atrial Septal Defect, Ostium Secundum
Atrial Septal Defect, Sinus Venosus
Mitral Valve Insufficiency
Mitral Valve Prolapse
Partial Anomalous Pulmonary Venous Connection

Other Problems to Be Considered

Cleft mitral valve
Common atrium (usually associated with complex congestive heart disease [CHD])

Workup

Imaging Studies

• In patients with atrioventricular septal defects (AVSDs), chest roentgenography usually reveals the following:
  • Prominent pulmonary artery segment and abnormally dense pulmonary vascular markings
  • Cardiac enlargement, especially enlargement of the right atrium (RA) and right ventricle (RV)
• Echocardiography is the diagnostic method of choice.
  • Ostium primum defect is seen as an echo dropout in the lower portion of the septum at the crux of the heart.
  • Abnormal morphology of the atrioventricular valves can be studied in detail, including small inferior and mural leaflets, lack of coaptation of leaflets, and a cleft in the anterior mitral valve leaflet.
  • The attachments of the atrioventricular valves may extend into the left ventricular outflow tract (LVOT) and may create obstruction. Atrioventricular valve tissue may extend to the crest of the ventricular septum.
  • Apical 4-chamber view reveals the tricuspid and mitral valve components at the same level without the normal apical displacement of the tricuspid valve.
  • Anterior and superior displacement of the aorta, with elongation and narrowing of the LVOT, is seen in the long parasternal axis.
• Doppler and color Doppler studies are used for the following:
  • Demonstration of left-to-right shunting through the atrial septal defect (ASD) and detection of presence and severity of mitral regurgitation (MR); shunting from the left ventricle (LV) to the RA may also be identified.
  • If tricuspid regurgitation is present, RV pressure may be estimated. Care is needed to interrogate tricuspid regurgitation rather than the LV-to-RA jet; otherwise, a falsely high ventricular pressure estimate results.
  • LVOT obstruction may be identified and quantitated.
  • Three dimensional (3-D) echocardiography has been shown to provide excellent quality images of the atrioventricular valve morphology and relationships with the rest of the cardiac structures.
  • It is also being used in centers to assess the dynamic morphology of the left-sided AV valve and LVOT anatomy after AVSD repair.
• MRI is being more frequently used because more precise delineation of anatomy and evaluation of function may be obtained with this noninvasive method than with either echocardiography or angiography alone.
  • MRI can be used to help define morphologic abnormalities in AVSD as well as important anatomic variations.
  • MRI is particularly useful for evaluating shunt severity, expressed quantitatively as the ratio of pulmonary flow to systemic flow (Qp/Qs).

Other Tests

• Classic anatomic studies of the conduction tissue have shown that the atrioventricular node is usually displaced posteriorly, originating in the posterior wall of the RA.
• The bundle of His is posteriorly displaced and skirts the lower margin of the ventricular septal defect (VSD); the right bundle may give off several branches instead of continuing as a single trunk through the RV.
• This unusually long course and peculiar orientation of the conduction tissue creates a different advancing front of depolarization, resulting in the following characteristic electrocardiographic (ECG) features:
  • The superior-oriented, counterclockwise vector loop in the frontal plane occurs commonly in AVSD.
  • The mean QRS axis ranges from -30 º to -120 º (mostly between -30 º and -90 º).
  • On the standard 12-lead ECG, the small R wave is followed by a prominent S wave in lead aVF; in aVL, a small Q wave is followed by a prominent R wave. This pattern is caused by abnormal septal depolarization in AVSD, including PR-interval prolongation and RV hypertrophy, particularly an rSR' or RSR' pattern.
  • P-wave enlargement concordant with RA, left atrium (LA), or biatrial enlargement is seen in approximately half of patients with AVSDs.
  • Indications of LV hypertrophy occur with severe MR and include prominent R-wave voltage in left precordial leads and a deep S wave in right precordial leads.

Procedures

• Cardiac catheterization and angiography is no longer needed to confirm the diagnosis of partial AVSD.
• This procedure may be performed if echocardiography is not sufficient to delineate anatomy and if pulmonary hypertension is suspected. The shunt can be measured, and the response of the pulmonary arterial pressure and resistance to pulmonary vasodilators can be assessed.
• If present, LVOT obstruction can be quantified or other associated lesions can be evaluated.

Treatment

Medical Care

Treatment for congestive heart failure (CHF) is occasionally required if mitral regurgitation (MR) cannot be adequately surgically reduced.

Surgical Care

Management of partial atrioventricular septal defect (AVSD) is primarily surgical, and repair includes patch closure of the atrial septal defect (ASD), mitral valve annuloplasty, or cleft closure. Other defects (eg, left ventricular outflow tract [LVOT] obstruction, patent ductus arteriosus [PDA]) may require repair during the same operation.

Repair is usually electively performed in children aged 2-5 years, unless significant mitral regurgitation (MR) is present, in which case earlier repair is indicated. However, in the current era, repair of AVSD can be successfully performed in patients who weigh less than 5 kg.^{[2 ]}

• Surgical morbidity
  • Severe MR develops in a significant number of patients after correction of ASD. In fact, MR is the most common indication for reoperation in patients after repair of both partial and complete AVSD.^{[3 ]}
  • LVOT obstruction may not be evident for years after the initial repair. LVOT obstruction is the second most common indication for reoperation in these patients.^{[4 ]}
  • Preoperative severe left-sided atrioventricular valve regurgitation and associated valve malformations are important risk factors for postoperative development of MR.^{[5,3 ]}
  • According to another study, predictors for reoperation include postoperative MR, presence of major associated cardiac malformations, associated left atrioventricular valve malformations, partial or absent left atrioventricular valve cleft closure, and a weight of less than 5 kg.^{[2 ]}
  • When the left-sided atrioventricular valve requires replacement because of unacceptable degrees of regurgitation, higher mortality and complete atrioventricular block are expected.^{[6 ]}
  • Spontaneous regression of left-sided atrioventricular valve regurgitation after the immediate postoperative period has been described, thus avoiding the need for reoperation.^{[3 ]} 
• Surgical mortality
  • Depending on the surgical series, early postoperative mortality rate is less than 3% in patients with mostly uncomplicated partial AVSD.^{[7,3 ]}
  • However, poorer survival is seen in patients with major associated cardiac malformations and pulmonary hypertension, with an early postoperative mortality of 8%.^{[2 ]}

Consultations

• Pediatric cardiologist
• Cardiovascular surgeon
• Geneticist if an abnormality is suspected (eg, Down syndrome)

Medication

Medical treatment is indicated in patients with congestive heart failure (CHF) usually before surgical repair. However, it may also be needed in patients in whom mitral regurgitation (MR) persists postoperatively. The treatment outlined below is usually indicated for outpatient management.

Angiotensin-converting enzyme inhibitors (ACE inhibitors)

These medications are used to decrease the afterload to the left ventricle (LV) produced by the MR. This effect is achieved by producing peripheral vasodilatation, which, in turn, reduces systemic blood pressure (ie, reduces afterload). Reduction in systemic blood pressure decreases the amount of blood pumped by the LV with each systolic contraction (ie, stroke volume) and also reduces the pressure at which the blood is ejected. This, in turn, diminishes the amount of blood regurgitated by the mitral valve from the LV into the left atrium (LA) during systole, which decreases pulmonary venous pressure and, thus, decreases pulmonary congestion. By decreasing the afterload to the LV, ACE inhibitors reduce the left-to-right shunt through the atrioventricular septal defect (AVSD) or the atrial septal defect (ASD) in the case of partial AVSD.

A recently published observational study by Cooper et al reported that babies whose mothers had taken an ACE inhibitor during the first 3 months of pregnancy had an increased risk of birth defects compared with babies whose mothers had not taken any drugs for high blood pressure.^{[8 ]}At this time, based on this one observational study, the US Food and Drug Administration (FDA) did not change the pregnancy categories for ACE inhibitors. The current pregnancy categories assigned to ACE inhibitors are C for the first trimester and D for the second and third trimesters.

Enalapril (Vasotec)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
Helps control blood pressure and proteinuria. Decreases pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance. Has favorable clinical effect when administered over a long period. Helps prevent potassium loss in distal tubules. Body conserves potassium; thus, less oral potassium supplementation needed.
Patients who develop a cough, angioedema, bronchospasm, or other hypersensitivity reactions after starting ACE inhibitors should receive an angiotensin-receptor blocker.

Dosing

Adult

2.5-5 mg/d PO; increase prn
Dosing range: 10-40 mg/d PO qd or divided bid
Alternatively, 1.25 mg/dose IV over 5 min q6h

Pediatric

0.1-0.5 mg/kg/d PO qd or divided bid. Doses as high as 1 mg/kg/d have been reported to be well tolerated.

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 given 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

Pregnancy category D in second and third trimesters; caution in renal impairment, valvular stenosis, or severe CHF

Captopril (Capoten)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. Rapidly absorbed, but bioavailability is significantly reduced with food intake. It achieves a peak concentration in an hour and has a short half-life. The drug is cleared by the kidney. Impaired renal function requires reduction of dosage. Absorbed well PO. Give at least 1 h before meals. If added to water, use within 15 min. Can be started at low dose and titrated upward as needed and as patient tolerates.

Dosing

Adult

6.25-25 mg PO bid/tid; increase dose by 25 mg prn at 1- to 2-wk intervals; not to exceed 450 mg/d divided tid
ClCr 10-50 mL/min: give 75% of starting dose
ClCr <10 mL/min: give 50% of starting dose

Pediatric

Neonates: 0.05-0.1 mg/kg/dose PO q6-24h; titrate dose up to 0.5 mg/kg/dose prn
Infants: 0.15-0.3 mg/kg/dose PO q6-24h; titrate dose up; not to exceed 6 mg/kg/d in 2-4 divided doses prn
Children: 0.3-0.5 mg/kg/dose PO q6-24h; titrate dose up; not to exceed 6 mg/kg/d in 2-4 divided doses prn

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

Pregnancy category D in second and third trimesters; caution in renal impairment, valvular stenosis, or severe CHF

Lisinopril (Prinivil, Zestril)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Dosing

Adult

10 mg/d PO; increase 5-10 mg/d at 1-2 wk intervals; not to exceed 40 mg

Pediatric

Not established, data limited; 0.2 mg/kg PO qd initially; increase as BP and symptoms (eg, dizziness, light-headedness) allow

Interactions

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

Pregnancy category D in second and third trimesters; caution in renal impairment, valvular stenosis, or severe CHF

Diuretics

These agents help decrease pulmonary congestion.

Furosemide (Lasix)

Loop diuretic that increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending limb of loop of Henle and distal renal tubule. Increases renal blood flow without increasing filtration rate. Onset of action is generally within 1 h. Increases potassium, sodium, calcium, and magnesium excretion.
Dose must be individualized to patient. Depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after the previous dose, until desired diuresis occurs. When treating infants, titrate with 1 mg/kg/dose increments until a satisfactory effect is achieved.
Diuretics have major clinical uses in managing disorders involving abnormal fluid retention (edema) or in treating hypertension, in which their diuretic action causes decreased blood volume. Chronic use of furosemide can lead to hypercalcemia with renal damage and electrolyte disturbances.

Dosing

Adult

20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe edematous states

Pediatric

1-2 mg/kg/dose PO; not to exceed 6 mg/kg/dose; do not administer more frequently than q6h
Alternatively, 1 mg/kg IV/IM slowly under close supervision; not to exceed 6 mg/kg

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; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently with this medication; increased plasma lithium levels and toxicity are possible when taken concurrently with this medication

Contraindications

Documented hypersensitivity; hepatic coma, anuria, and 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

Perform frequent serum electrolyte, CO2, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter

Spironolactone (Aldactone)

For management of edema resulting from excessive aldosterone excretion. Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions. Therefore, it is generally used when concomitant chronic use of sodium-wasting diuretics such as furosemide is noted.

Dosing

Adult

25-200 mg/d PO in 1-2 divided doses

Pediatric

Maintenance: 1 mg/kg/dose PO up to qid

Interactions

May decrease effect of anticoagulants; potassium and potassium-sparing diuretics may increase toxicity of spironolactone

Contraindications

Documented hypersensitivity; anuria, renal failure or hyperkalemia

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 and hepatic impairment

Inotropic, Antiarrhythmic

It is used because of its direct inotropic effects in addition to indirect effects on the cardiovascular system.

Its indirect actions result in increased carotid sinus activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure. These effects help reduce the heart rate response to CHF, rendering a more effective stroke volume with each ventricular systole.

Digoxin (Lanoxin)

Enhances myocardial contractility by inhibition of Na+/K+ ATPase, a cell membrane enzyme that extrudes Na and brings K into the myocyte. Resulting increase in intracellular Na stimulates Na-Ca exchanger in the cell membrane, which extrudes Na and brings in Ca, leading to an increase in intracellular calcium in the sarcoplasmic reticulum of cardiac cells, therefore increasing contractility of myocyte (ie, positive inotropic effect). Has direct inotropic effects in addition to indirect effects on the cardiovascular system. Increases myocardial systolic contractions. It exerts vagomimetic action on sinus and AV nodes (slowing heart rate and conduction). Also, decreases degree of activation of sympathetic nervous system and renin-angiotensin system, which is referred to as the deactivating effect. May be given as a loading dose followed by a maintenance dose or simply as a maintenance regimen. Digitalis loading increases hazards of this drug. Therapeutic serum level range is 0.8-2 ng/mL.

Dosing

Adult

0.125-0.5 mg PO qd

Pediatric

Premature infants: 0.005-0.0075 mg/kg if tablet; 0.004-0.006 mg/kg if capsule, IV, or IM divided q12h
Full-term infants: 0.006-0.010 mg/kg if tablet; 0.005-0.008 if capsule, IV, or IM divided q12h
1-24 months: 0.010-0.015 mg/kg if tablet; 0.0075-0.012 mg/kg if capsule, IV, or IM divided q12h
2-5 years: 0.0075-0.010 mg/kg if tablet; 0.006-0.009 mg/kg if capsule, IV, or IM divided q12h
5-10 years: 0.005-0.010 mg/kg if tablet; 0.004-0.008 mg/kg if capsule, IV, or IM divided q12h
>10 years: 0.0025-0.005 mg/kg if tablet; 0.002-0.003 if capsule, IV, or IM qd or divided q12h

Interactions

IV calcium may produce arrhythmias in digitalized patients; 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, and 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; 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 A-V block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis; adjust dose in renal impairment; highly toxic (overdoses can be fatal)

Follow-up

Further Inpatient Care

• Follow-up in patients with atrioventricular septal defect (AVSD) is determined on an individual basis, and the frequency depends on the persistence and severity of atrioventricular valve regurgitation or other abnormalities.
• Chest radiography, ECG, and echocardiography should be performed, if the physical examination warrants.

Miscellaneous

Medicolegal Pitfalls

• Delay in diagnosis of these defects may lead to morbidity and mortality.

Special Concerns

• Genetic counseling for possible risk factors, especially in families with congenital heart disease (CHD), must be sought.
• Defects of the extracellular matrix have been associated with a higher incidence of extracardiac anomalies, such as GI (Hirschsprung disease, intestinal obstruction, annular pancreas, imperforate anus, biliary atresia) and facial (facial cleft).
• In patients with CHARGE association (colobomata, heart defects [in 50%], choanal atresia, retardation of growth or development, genital hypoplasia, ear anomalies), atrioventricular septal defect (AVSD) may be seen, as well as other CHDs.
• Patients with Ellis–van Creveld syndrome may have AVSD or a common atrium.

Multimedia

Media file 1: Partial atrioventricular septal defect (AVSD): The mitral and tricuspid annuli are separate. The cleft in the mitral leaflet is in the anterior position. This type of anatomy is usually associated with a primum atrial septal defect (ASD). Partial AVSD is more common than intermediate AVSD.

Media file 2: Intermediate atrioventricular septal defect (AVSD): A single valve annulus is present. The anterior and posterior bridging leaflets are fused (whereas in complete AVSD the anterior and posterior bridging leaflets are not fused). Therefore, the atrioventricular valve has a tricuspid and a mitral component. Intermediate AVSD is the least common type of AVSD.

Media file 3: Echocardiogram of the apical 4-chamber view demonstrating a partial atrioventricular septal defect (AVSD). Chambers are denoted by RA (right atrium), RV (right ventricle), and LV (left ventricle).

Media file 4: Echocardiogram with subcostal view demonstrates an atrioventricular septal defect (AVSD). A portion of the ostium secundum atrial septum is also missing, just superior to the ostium primum defect.

Media file 5: Color Doppler demonstrates left-to-right shunting through the partial atrioventricular septal defect (AVSD) shown in Media files 1-2.

Media file 6: Left superior axis deviation in the frontal plane and rR' pattern in right precordial leads.

References

1. Inga A, Reamon-Buettner SM, Borlak J, Resnick MA. Functional dissection of sequence-specific NKX2-5 DNA binding domain mutations associated with human heart septation defects using a yeast-based system. Hum Mol Genet. Jul 15 2005;14(14):1965-75. [Medline].

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Keywords

atrioventricular septal defect, AVSD, partial AVSD, partial atrioventricular septal defect, atrioventricular canal defect, mitral cleft, ostium primum defect, partial atrioventricular septal defect, partial common atrioventricular canal, endocardial cushion defects, intermediate atrioventricular septal defect, transitional common atrioventricular canal, ventricular septal defect, right ventricular outflow tract, pulmonary stenosis, pulmonary vascular obstructive disease, congenital heart defect, Down syndrome, mitral regurgitation, MR, congestive heart failure, failure to thrive, heart murmur, atrial septal defect, patent ductus arteriosus, tricuspid stenosis, tricuspid atresia, perimembranous ventricular septal defect, VSD, hypoplastic left ventricle, hypoplastic LV, respiratory distress, exercise intolerance

Contributor Information and Disclosures

Author

M Silvana Horenstein, MD, Consultant, Pediatric and Fetal Cardiac Diagnostic, Diagnostico Gineco-Obstetrico, PC; Associate Medical Director, Legacy Department, Best Doctors, Inc
M Silvana Horenstein, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Michael A Portman, MD, Research Director, Department of Pediatrics, Division of Cardiology, Associate Professor, Childrens' Hospital
Michael A Portman, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, American Physiological Society, and Society for Pediatric Research
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Medical Editor

Paul M Seib, MD, Associate Professor of Pediatrics, University of Arkansas for Medical Sciences; Medical Director, Cardiac Catheterization Laboratory, Co-Medical Director, Cardiovascular Intensive Care Unit, Arkansas Children's Hospital
Paul M Seib, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, Arkansas Medical Society, International Society for Heart and Lung Transplantation, and Society for Cardiac Angiography and Interventions
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Gilbert Herzberg, MD is a member of the following medical societies: American Academy of Pediatrics
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Steven R Neish, MD, SM, Director of Pediatric Cardiology Fellowship Program, Associate Professor, Department of Pediatrics, Baylor College of Medicine
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