WORKUP

Lab Studies:

• Hyperoxia test (for cyanotic congenital heart disease)

• In a patient with arterial hypoxemia, an arterial blood gas measurement is obtained on 100% oxygen for 10 minutes.

• Pulmonary disease (not cyanotic congenital heart disease) is suspected if the partial pressure of oxygen increases to greater than 150 mm Hg with oxygen.

Imaging Studies:

• Chest radiography

• The chest radiograph may appear normal in newborns with TGA and intact ventricular septum but may demonstrate the classic "egg on a string" appearance in approximately one third of patients.

• With a ventricular septal defect, cardiomegaly usually occurs with increased pulmonary arterial vascular markings.

• Echocardiography

• Echocardiographic images should be diagnostic of TGA by demonstrating the bifurcating pulmonary artery arising posteriorly from the left ventricle in the parasternal long-axis view.

• The parasternal short-axis view shows the relationship of the great arteries to one another. The aorta is usually anterior and rightward of the pulmonary artery in cross-section.

• Most associated anatomic lesions, including atrial septal defects, ventricular septal defects, and patent ductus arteriosus, are also diagnosed readily by echocardiography.

• The coronary artery anatomy needs to be ascertained and may be abnormal in nearly one third of patients. The coronary artery origins and branching pattern are often delineated by echocardiogram.

Procedures:

• Cardiac catheterization

• Diagnostic cardiac catheterization usually is reserved for the subgroup of patients for whom the echocardiogram does not adequately delineate the anatomy. Suspected coronary artery abnormalities and additional ventricular septal defects may be confirmed or better delineated by cardiac catheterization with angiography. In addition, cardiac catheterization may be necessary to improve left-to-right shunting.

• Postcatheterization precautions include hemorrhage, vascular disruption after balloon dilation, pain, nausea and vomiting, and arterial or venous obstruction from thrombosis or spasm.

• Complications may include rupture of blood vessel, tachyarrhythmias, bradyarrhythmias, and vascular occlusion.

TREATMENT

Medical Care:

• Initial treatment consists of maintaining ductal patency with continuous IV prostaglandin E₁ infusion to promote pulmonary blood flow, increase left atrial pressure, and promote left-to-right intercirculatory mixing at the atrial level. This is particularly important in patients with severe left ventricular outflow tract stenosis or atresia. Prostaglandin therapy may or may not benefit the patient with simple TGA and an intact ventricular septum without left ventricular outflow tract obstruction.

• Cardiac catheterization, depending on the degree of restriction at the atrial septum and the timing of operative repair, is indicated for a balloon atrial septostomy in severely hypoxemic patients with an inadequate atrial level communication and insufficient mixing. The balloon atrial septostomy is used to increase the atrial level shunt and to improve mixing.

• For the ill neonate, metabolic acidosis should be corrected with fluid replacement and bicarbonate administration.

• Mechanical ventilation may be necessary if pulmonary edema develops in concert with severe hypoxemia.

• Ultimately, the patient requires surgical repair or palliation early in life.

Surgical Care:

• Surgical approach depends on the age of the patient at presentation, the presence of associated congenital cardiac lesions, and the experience of the cardiothoracic surgeon with a given surgical technique. Most full-term neonates with uncomplicated TGA can undergo an arterial switch procedure in one operation, with minimal mortality.

• TGA with intact ventricular septum

• The ideal operation is an arterial switch procedure.
  • It represents an anatomic repair and establishes ventriculoarterial concordance.

     

  • This procedure should be performed when the infant is younger than 4 weeks, as the left ventricle may not be able to handle systemic pressure postoperatively if left too long in the low-pressure, low-resistance pulmonary circuit.

   

• Rarely, however, depending on the particular coronary artery anatomy (eg, intramural coronary artery), coronary artery translocation may not be feasible, and an arterial switch is not recommended. In this subgroup, an atrial level switch (Senning or Mustard procedure) has lower surgical and short-term morbidity and mortality.

• TGA with ventricular septal defect

• The preferred operation is an arterial switch procedure with ventricular septal defect closure.

   

• If the ventricular septal defect is large and nonrestrictive and coronary artery anatomy makes an arterial switch operation inadvisable, a Rastelli-type intracardiac repair may be feasible.

   

• With the Rastelli-type procedure, it may be preferable to wait until the infant is older and larger because of the need for a right ventricle–pulmonary artery conduit in the Rastelli operation.

   

• If the infant has excessive congestive heart failure (with growth failure), it may be advisable to either proceed with reparative surgery or, if not feasible, band/ligate the main pulmonary artery and place an aortopulmonary shunt during the newborn period to restrict pulmonary blood flow.

• TGA with ventricular septal defect and left ventricular outflow tract obstruction

• An arterial switch operation may not be feasible due to pulmonary (left ventricular outflow tract) stenosis or atresia.

   

• If the ventricular septal defect is nonrestrictive and not too remote from the aorta, a Rastelli intracardiac repair could be possible.

• Since the Rastelli procedure necessitates a conduit from the right ventricle to the pulmonary artery, it may be preferable to delay repair until the infant is older and larger. In this case, it could be necessary to place an aortopulmonary shunt during the newborn period to establish adequate pulmonary blood flow while waiting.

• TGA with ventricular septal defect and pulmonary vascular obstructive disease

• These patients might not be appropriate surgical candidates because of the progressive increase in pulmonary vascular resistance.

   

• This is a small subgroup of patients whose conditions are not often diagnosed until after a palliative or reparative procedure is performed.

Consultations:

• Pediatric cardiologist

• Pediatric cardiothoracic surgeon

Diet:

• Patients with TGA and a large ventricular septal defect who have not undergone repair may require increased caloric density during infancy (120-130 kcal/kg/d), particularly if they have significant congestive heart failure and poor weight gain.

• Following definitive repair, most patients do not need a special diet.

Activity:

• No specific activity requirements are necessary.

MEDICATION

TGA has no specific or recommended drug therapies. Newborn infants with TGA (particularly those with severe left ventricular outflow tract obstruction) may derive some initial benefit from alprostadil (ie, prostaglandin E₁) therapy. Patients with TGA and ventricular septal defect who have not undergone surgical repair, and some patients following complete repair, might potentially benefit from digoxin and diuretic therapy to improve systemic ventricular function and avoid fluid retention. All patients require antibiotic prophylaxis prior to dental and indicated surgical procedures in order to reduce the risk of subacute bacterial endocarditis.

Drug Category: Inotropic agents -- These drugs increase the contractility of cardiac muscle in a dose-dependent manner (ie, positive inotropic effect).

Drug Name	Digoxin (Lanoxin) -- Frequently used cardiac glycoside that inhibits the sarcolemmal sodium-potassium adenosine triphosphatase, which leads to an increase in intracellular calcium concentration and increased myocardial contractility.
Adult Dose	0.125-0.5 mg PO qd
Pediatric Dose	Preterm infant: 5-7.5 mcg/kg/d PO divided bid Term infant: 6-10 mcg/kg/d PO divided bid 1 month to 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: 2.5-5 mcg/kg PO qd
Contraindications	Documented hypersensitivity, atrioventricular block, idiopathic hypertrophic subaortic stenosis, constrictive pericarditis, hypokalemia, renal failure
Interactions	Quinidine, quinine, verapamil, propafenone, diltiazem, erythromycin, itraconazole, indomethacin, and amiodarone increase plasma concentration of digoxin, which requires dose adjustment; prokinetic agents (eg, cisapride, metoclopramide) may decrease absorption
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Monitor serum potassium levels and use cautiously with hypokalemia; monitor serum digoxin level due to narrow therapeutic index; reduce dose in renal dysfunction; CNS effects, such as drowsiness, and GI effects, such as nausea and vomiting, are some of the more common adverse drug reactions; digoxin can cause cardiac arrhythmias; patients are predisposed to digoxin toxicity with hypokalemia, hypomagnesemia, hypercalcemia, and hypermagnesemia; digoxin should be administered at the same time of day in relation to meals

Drug Category: Loop diuretics -- These drugs inhibit electrolyte reabsorption in the thick ascending limb of the loop of Henle, thus promoting diuresis.

Drug Name	Furosemide (Lasix) -- This is a commonly utilized loop diuretic with moderate diuretic potency. Increases excretion of water by interfering with chloride-binding co-transport system which in turn inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule.
Adult Dose	20-80 mg/d PO/IV/IM divided q6-12h
Pediatric Dose	1 mg/kg/dose PO/IV qd; may increase up to tid
Contraindications	Documented hypersensitivity; hypokalemia; renal failure
Interactions	Nephrotoxicity of cephalosporins is increased by furosemide; ototoxicity can be increased with concomitant administration of aminoglycoside
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Monitor serum potassium levels closely; may produce intravascular dehydration, severe hypokalemia, and significant hypochloremic metabolic alkalosis; may cause hyperuricemia; may produce deafness due to ototoxicity; dose should be titrated to effect; administer oral dose with food or milk to decrease stomach upset

Drug Category: Prostaglandins -- Temporary maintenance of patency of ductus arteriosus in neonates with ductal-dependent congenital heart disease.

Drug Name	Alprostadil (Prostin VR) -- Temporary maintenance of patency of ductus arteriosus in neonates with ductal-dependent congenital heart disease. Relaxes smooth muscle of the ductus arteriosus. Beneficial in infants with congenital defects that restrict pulmonary or systemic blood flow and who in order to get adequate oxygenation and lower body perfusion, depend on a patent ductus arteriosus.
Pediatric Dose	Neonates and infants: 0.01-0.1 mcg/kg/min IV continuous infusion depending on the therapeutic response; with ductal patency, rate may be reduced to lowest effective dosage
Contraindications	Respiratory distress syndrome or persistent fetal circulation
Interactions	Coadministration with heparin may increase PTT
Pregnancy	X - Contraindicated in pregnancy
Precautions	Apnea occurs in 10-12% of neonates with congenital heart defects; use cautiously in neonates with bleeding tendencies (inhibits platelet aggregation); may cause systemic hypotension, flushing, bradycardia, rhythm disturbances, fever, or seizure-like activity; long-term infusions associated with cortical proliferation of long bones and gastric outlet obstruction

Drug Category: Antibiotics, prophylactic -- Antibiotic prophylaxis is given to patients before performing procedures that may cause bacteremia.

Drug Name	Amoxicillin (Amoxil, Trimox) -- Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. Used as prophylaxis in minor procedures.
Adult Dose	2 g PO 1 h before procedure Alternatively, 3 g PO 1 h before procedure, followed by 1.5 g PO 6 h after initial dose
Pediatric Dose	50 mg/kg PO 1 h before procedure; not to exceed 2 g/dose
Contraindications	Documented hypersensitivity
Interactions	Reduces efficacy of oral contraceptives
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment

Drug Name	Ampicillin (Marcillin, Omnipen) -- For prophylaxis in patients undergoing dental, oral, or respiratory tract procedures. Coadministered with gentamicin for prophylaxis in GI or genitourinary procedures.
Adult Dose	2 g IV/IM 30 min before procedure High-risk patients: 2 g ampicillin IV/IM plus gentamicin 1.5 mg/kg IV 30 min before procedure, followed 6 h later by 1 g ampicillin IV/IM or 1 g amoxicillin PO
Pediatric Dose	50 mg/kg IV/IM 30 min before procedure; not to exceed 2 g/dose High-risk patients: 50 mg/kg IV/IM ampicillin plus gentamicin 1.5 mg/kg IV 30 min before procedure, followed 6 h later by ampicillin 25 mg/kg IV/IM or amoxicillin 25 mg/kg PO
Contraindications	Documented hypersensitivity
Interactions	Probenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Drug Name	Clindamycin (Cleocin) -- Used in penicillin-allergic patients undergoing dental, oral, or respiratory tract procedures. Useful for treatment against streptococcal and most staphylococcal infections.
Adult Dose	600 mg PO/IV 1 h before procedure and 150 mg PO/IV 6 h after first dose
Pediatric Dose	20 mg/kg PO 1 h or 20 mg/kg IV 30 min before procedure; not to exceed 600 mg/dose
Contraindications	Documented hypersensitivity; regional enteritis, ulcerative colitis, hepatic impairment, antibiotic-associated colitis
Interactions	Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis

Drug Name	Gentamicin (Garamycin) -- Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Used in conjunction with ampicillin or vancomycin for prophylaxis in GI or genitourinary procedures.
Adult Dose	1.5 mg/kg IV; not to exceed 120 mg/dose; administer with ampicillin 2 g IV 30 min before procedure
Pediatric Dose	1.5 mg/kg IV; not to exceed 120 mg/dose; administer with ampicillin (50 mg/kg IV; not to exceed 2 g/dose) 30 min before procedure
Contraindications	Documented hypersensitivity; non–dialysis-dependent renal insufficiency
Interactions	Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; because aminoglycosides enhance effects of neuromuscular blocking agents, prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Drug Name	Vancomycin (Vancocin) -- Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in the treatment of septicemia and skin structure infections. Indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or have infections with resistant staphylococci. Use creatinine clearance to adjust dose in renal impairment. Used in conjunction with gentamicin for prophylaxis in penicillin-allergic patients undergoing GI or genitourinary procedures.
Adult Dose	Dental, oral, or upper respiratory tract surgery: 1 g IV, infused over 1 h, 1 h before procedure GI/GU procedures: 1 g IV plus gentamicin 1.5 mg/kg IV, infused over 1 h, 1 h before surgery
Pediatric Dose	Dental, oral, or upper respiratory tract surgery: 20 mg/kg IV, infused over 1 h, 1 h before procedure
Contraindications	Documented hypersensitivity
Interactions	Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal failure, neutropenia; red man syndrome is caused by too rapid IV infusion (dose given over a few minutes) but rarely happens when dose given IV over 2 h or as PO/IP administration; red man syndrome is not an allergic reaction

Drug Name	Cefazolin (Ancef) -- First-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including Staphylococcus aureus.
Adult Dose	1 g IV/IM within 30 min before procedure
Pediatric Dose	25 mg/kg IV/IM within 30 min before procedure; not to exceed 1 g/dose
Contraindications	Documented hypersensitivity
Interactions	Probenecid prolongs effect; coadministration with aminoglycosides may increase renal toxicity; may yield false-positive urine-dip test results for glucose
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy

Drug Name	Cephalexin (Keflex) -- First-generation cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Primary activity against skin flora and used for skin infections or prophylaxis in minor procedures.
Adult Dose	2 g PO 1 h before procedure
Pediatric Dose	50 mg/kg PO 1 h before procedure; not to exceed 2 g/dose
Contraindications	Documented hypersensitivity
Interactions	Coadministration with aminoglycosides increase nephrotoxic potential
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment

Drug Name	Cefadroxil (Duricef) -- First-generation cephalosporin arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Primary activity against skin flora and used for skin infections or prophylaxis in minor procedures.
Adult Dose	2 g PO 1 h before procedure
Pediatric Dose	50 mg/kg PO 1 h before procedure; not to exceed 2 g/dose
Contraindications	Documented hypersensitivity
Interactions	Coadministration with furosemide or aminoglycosides may increase nephrotoxicity; probenecid prolongs effects
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy

Drug Name	Azithromycin (Zithromax) -- Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Adult Dose	500 mg PO 1 h before procedure
Pediatric Dose	15 mg/kg PO 1 h before procedure; not to exceed 500 mg/dose
Contraindications	Documented hypersensitivity; hepatic impairment; administration with pimozide
Interactions	May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Bacterial or fungal overgrowth may result from prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients

Drug Name	Clarithromycin (Biaxin) -- Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Adult Dose	500 mg PO 1 h before procedure
Pediatric Dose	15 mg/kg PO 1 h before procedure; not to exceed 500 mg/dose
Contraindications	Documented hypersensitivity; coadministration of pimozide
Interactions	Toxicity increases with coadministration of fluconazole, astemizole, and pimozide; effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, HMG CoA-reductase inhibitors; cardiac arrhythmias may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increases in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Coadministration with ranitidine or bismuth citrate not recommended with CrCl <25 mL/min; give half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies

FOLLOW-UP

Further Inpatient Care:

• Admit for preoperative testing and surgical interventions.

• Carefully monitor medication doses and side effects.

• Monitor adequacy of repair and palliation with periodic physical examinations and possibly echocardiograms.

• Periodic electrocardiograms and/or 24-hour Holter monitoring to monitor for atrial arrhythmias should be employed, particularly following atrial-level switch operation (ie, Senning or Mustard procedure).

• Controversy exists about whether patients should undergo cardiac catheterization every few years following arterial switch operation because of the possible increased risk for coronary artery stenosis following surgical translocation. No specific recommendations for routine cardiac catheterization will exist until more information is available.

In/Out Patient Meds:

• Many patients do not require any specific medications. Possible discharge medications might include digoxin and/or furosemide.

• All preoperative and postoperative patients require antibiotic prophylaxis for dental or other invasive procedures to decrease the risk for bacterial endocarditis.

Transfer:

• Transfer may be required for specialized diagnostic, therapeutic, and surgical interventions.

Complications:

• Congestive heart failure

• Arrhythmia

• Eisenmenger syndrome (irreversible and progressive pulmonary vascular obstructive disease)

Prognosis:

• Prognosis depends on the specific anatomic substrate and type of surgical therapy employed (arterial switch operation, atrial switch operation, or Rastelli procedure).

• The overall survival rate following arterial switch operation is 90%.

• The overall mortality rate following an atrial level switch is low; however, long-term morbidity associated with systemic (right) ventricular dilatation and failure, systemic atrioventricular (tricuspid) valve regurgitation, and atrial bradyarrhythmias and tachyarrhythmias is significant.

Patient Education:

• Family members should learn cardiopulmonary resuscitation (CPR).

• Educate family members about congenital heart disease.

• Obtain genetics counseling for future pregnancy, despite the relatively low risk of recurrence.

MISCELLANEOUS

Medical/Legal Pitfalls:

• Failure to consider the diagnosis, particularly in a cyanotic newborn

• Failure to adequately delineate coronary artery anatomy preoperatively

• Failure to appropriately interpret diagnostic information, including echocardiography, x-rays, and oxygenation studies

• Complications of surgery, including death

PICTURES

Caption: Picture 1. This 2-dimensional echocardiogram (parasternal long-axis view) shows a patient with transposition of the great arteries and ventricular septal defect. The pulmonary artery arises from the posterior (left) ventricular, dives posteriorly, and bifurcates immediately into left and right branch pulmonary arteries. A large ventricular septal defect is present in the outlet septum.

Picture Type: ECG

Caption: Picture 2. This 2-dimensional echocardiogram (apical 4-chamber view) shows a patient with transposition of the great arteries and ventricular septal defect. The anterior aorta arises from the right-sided right ventricle.

Picture Type: ECG

Caption: Picture 3. This right ventricular angiogram shows a patient with transposition of the great arteries. The aorta arises directly from the right-sided anterior right ventricle (10° left anterior oblique [LAO]).

Picture Type: X-RAY

Caption: Picture 4. This right ventricular angiogram shows a patient with transposition of the great arteries. The aorta arises directly from the right-sided anterior right ventricle (70° left anterior oblique [LAO]).

Picture Type: X-RAY

Caption: Picture 5. This left ventricular angiogram shows a patient with transposition of the great arteries. The pulmonary artery arises directly from the left-sided posterior left ventricle (30° right anterior oblique [RAO]).

Picture Type: X-RAY

Caption: Picture 6. This left ventricular angiogram shows a patient with transposition of the great arteries. The pulmonary artery arises directly from the left-sided posterior left ventricle (20° cranial).

Picture Type: X-RAY