Pediatric Partial and Intermediate Atrioventricular Septal Defects 

Updated: Jan 24, 2019
Author: M Silvana Horenstein, MD; Chief Editor: Syamasundar Rao Patnana, MD 

Overview

Background

Atrioventricular septal defects (AVSDs) refer to a broad spectrum of malformations characterized by a deficiency of the atrioventricular septum and abnormalities of the atrioventricular valves. 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 the image below). The most frequently encountered abnormality in patients with partial AVSD is the combination of primum ASD and cleft of the anterior mitral valve leaflet.

Partial atrioventricular septal defect (AVSD): The 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.

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 the image below).

Intermediate atrioventricular septal defect (AVSD) 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.

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.

Etiology

AVSDs are presumed to occur secondary to extracellular matrix abnormalities that produce faulty development of the endocardial cushions and the atrioventricular septum. It has been recently described that yet another structure, the dorsal mesenchymal protrusion, which derives from the second heart field, should also fully develop in order to have an intact 4-chambered heart; otherwise, an ASD or an AVSD occurs.[1]

More detailed scientific theories interpret the normal development of the human heart as an orderly coordination of transcriptional programs. Therefore, the variety and range of anatomic malformations in CHD are believed to be caused by a faulty mechanism that disrupts the above.

AVSDs are often associated with genetic syndromes such as trisomy 21 or Down syndrome; Holt-Oram syndrome, which results from mutations in the TBX5 gene; and heterotaxy syndromes, which result from mutations in genes such as PITX2, SHH, and NODAL. A newly described CRELD1 gene is likely to be an AVSD-susceptibility gene, and CRELD1 mutations may increase the risk of developing a heart defect[2] ; this mutation is believed to be associated with the 3p deletion syndrome[3] characterized by low birth weight, varying degrees of mental retardation, ptosis, and micrognathia.[4]

Genetic mutations may be also associated with nonsyndromic cardiac defects. For example, one of the most important factors for the differentiation of mesodermal progenitor cells is the homeobox protein Nkx-2.5. 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 AVSDs and VSDs.[5] Mutations in the GATA4 transcriptional factor may also cause AVSDs by disrupting its role during different stages in cardiogenesis.[6]

To date, approximately 100 CHD "risk genes" have been described. Of these, six subphenotypes have been shown to be linked to partial AVSDs. Of note, these genes have also been linked to aortic valve stenosis, subaortic stenosis, AVSDs associated with tetralogy of Fallot, tetralogy of Fallot, and truncus arteriosus.[7]

Epidemiology

United States data

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 data

International frequency of cardiovascular malformations is similar to US figures.

Prognosis

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.

Miller et al reviewed the long-term survival of infants with all types of atrioventricular septal defects with Down syndrome (n = 177) and without Down syndrome (n = 161). In this cohort, born from 1979-2003, overall survival probability through 2004 was 70% in those with Down syndrome and 69% in those without. Mortality was higher in children with a complex atrioventricular septal defect and in those with 2 or more major noncardiac malformations, but was lower in children born in 1992-2003.[8]

 

Presentation

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.

Note the following:

  • 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 Examination

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.

 

DDx

Diagnostic Considerations

Important considerations

Avoid delays in the diagnosis of these defects as they may lead to morbidity and mortality.

Special concerns

Seek genetic counseling for possible risk factors, especially in families with congenital heart disease (CHD).

Defects of the extracellular matrix have been associated with a higher incidence of extracardiac anomalies, such as gastrointestinal (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.

Other problems to be considered

When evaluating patients with suspected partial and intermediate AVSDs, also consider the following conditions:

  • Cleft mitral valve

  • Common atrium (usually associated with complex CHD)

Differential Diagnoses

 

Workup

Chest Radiography

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 and Doppler Studies

Echocardiography is the diagnostic method of choice.[9] Note the following:

  • Ostium primum defect is seen as an echo dropout in the lower portion of the septum at the crux of the heart, as shown below.

    Echocardiogram with subcostal view demonstrates an 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.
  • 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 (see the image below) reveals the tricuspid and mitral valve components at the same level without the normal apical displacement of the tricuspid valve.

    Echocardiogram of the apical 4-chamber view demons 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).
  • 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. See the images shown below.

    Color Doppler demonstrates left-to-right shunting Color Doppler demonstrates left-to-right shunting through the partial atrioventricular septal defect (AVSD) shown in the following images.
    Partial atrioventricular septal defect (AVSD): The 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.
    Intermediate atrioventricular septal defect (AVSD) 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.
  • 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. (Singh A, 2006)

  • It is also being used in centers to assess the dynamic morphology of the left-sided AV valve and LVOT anatomy after AVSD repair.

  • Intraoperative assessment with transesophageal echocardiography is an invaluable tool for the surgeons to assess adequacy of AV valve repair.[10]

Magnetic Resonance Imaging (MRI)

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.[11]

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, as depicted below.

    Left superior axis deviation in the frontal plane Left superior axis deviation in the frontal plane and rR' pattern 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.

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, electrocardiography (ECG), and echocardiography should be performed, if the physical examination warrants.

Consultations

Obtain consultations with the following specialists:

  • Pediatric cardiologist

  • Cardiovascular surgeon

  • Geneticist, if an abnormality is suspected (eg, Down syndrome)

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.[12]

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.[13, 14, 15]

While the conventional timing for repair of partial AV septal defects is between the ages of 4 and 5 years, the recent trend has been to repair them early, before the age of 18 months.[16, 17, 18] However, the mortality rates (5.9%) are higher in the infant group;[18] this may in part be due to higher prevalence of unfavorable anatomy (poor left AV valve morphology and abnormalities of the subvalvar apparatus). A recent editorial on this subject suggests that repair in infancy may increase the early risk without accruing long-term benefit[19] On the basis of these considerations, it may be wise to follow the conventional approach of repair between the ages of 4 and 5 years. If repair in infancy is required because of heart failure, technique of cleft augmentation with a patch of autologous pericardium (instead simple cleft closure or repair with prosthetic patch material) may be useful in preventing late re-operations.[20, 21]

Surgical morbidity

Severe MR develops in a significant number of patients after correction of ASD. In fact, MR is the most common residual defect[16] and therefore, it is the most frequent indication for reoperation in patients after repair of both partial and complete AVSD.[22, 23, 24]

LVOT obstruction may not be evident for years after the initial repair. LVOT obstruction is the second most common indication for reoperation in patients with partial AVSD.[25, 26]

Preoperative severe left-sided atrioventricular valve regurgitation and associated valve malformations are important risk factors for postoperative development of MR.[22, 27]

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.[13]

When the left-sided atrioventricular valve requires replacement because of unacceptable degrees of regurgitation, complete atrioventricular block (as well as higher mortality) are expected.[28]

Spontaneous regression of left-sided atrioventricular valve regurgitation after the immediate postoperative period has been described, thus avoiding the need for reoperation.[22]

Surgical mortality

Depending on the surgical series, early postoperative mortality rate is less than 3% in patients with mostly uncomplicated partial AVSD.[22, 29, 17] However, a multicenter study showed that the current survival rate from all types of AVSD repairs (in which 21.5% of patients had partial AVSDs and almost 12% had intermediate AVSDs) was 98-99%, of which 96-97% have no major complications.[30]

Poorer survival was seen in patients with major associated cardiac malformations and pulmonary hypertension, with an early postoperative mortality of 8%.[13] Poorer survival was also observed in patients who required reoperation, regardless of whether the procedure entailed AV valve repair or replacement.[26]

 

Medication

Medication Summary

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)

Class Summary

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.[31] 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.

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.

Lisinopril (Prinivil, Zestril)

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

Diuretics

Class Summary

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.

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.

Inotropic, Antiarrhythmic

Class Summary

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.