WORKUP

Lab Studies:

• Laboratory evaluation usually is not helpful.

• Oximetry provides information of potential right-to-left shunting in borderline cyanotic lesions or in patients with anemia, but it does not identify the cause of the shunt (pulmonary, interatrial, interventricular, great arterial).

• Although arterial blood gas (ABG) analysis usually is not needed, one notable exception is the hyperoxia test in the newborn with cyanosis of undetermined origin.

• Administered 100% FIO2 generally does not increase the partial pressure of oxygen to levels much greater than 100 mmHg in patients with a cyanotic congenital heart defect (right-to-left intracardiac shunt).

Imaging Studies:

• Chest radiography

• Demonstrates a prominent main pulmonary artery segment but, usually, a normal heart size

• Pulmonary vascular markings are usually normal but may be decreased in severe pulmonary stenosis.

• Congestive heart failure appears as cardiomegaly with right ventricular and right atrial enlargement in severe valvar pulmonary stenosis, with or without tricuspid insufficiency.

• Echocardiography

• The sine qua non of diagnosis is 2-dimensional and Doppler echocardiography.

• A thickened pulmonary valve with restricted systolic motion (doming) in the parasternal short axis view is demonstrated.

• Multiple views are used to confirm the absence of coexistent congenital cardiac disease.

• Frequently, dilatation of the main pulmonary artery distal to the stenotic orifice occurs.

• Doppler studies can accurately determine the velocity of flow at single or multiple levels, which then can be converted to reproducible pressure gradients by means of the modified Bernoulli equation: pressure gradient (mmHg) = 4 x (velocity squared [m/s])

• Multiple views and measurements increases the accuracy of the predicted peak systolic pressure gradient.

• Severe pulmonary stenosis with gradients greater than 50 mm Hg, as diagnosed by using a continuous wave Doppler recording through the pulmonary valve, requires balloon valvuloplasty or surgery.

• Most children with pulmonary stenosis do not require further evaluation beyond echocardiography.

Other Tests:

• Electrocardiography

• Results usually are normal in mild pulmonary stenosis.

• Right axis deviation and right ventricular hypertrophy occur in moderate valvar pulmonary stenosis.

• The degree of right ventricular hypertrophy correlates well with the severity of pulmonary stenosis.

• Right atrial hypertrophy and right ventricular hypertrophy with strain pattern are observed when pulmonary stenosis is severe.

• Superior QRS axis (left axis deviation) is seen with dysplastic pulmonary valve and Noonan syndrome.

Procedures:

• Cardiac catheterization

• Catheterization is not indicated for mild pulmonary stenosis but is essential in severe stenosis.

• This procedure is used to assess the morphology of the right ventricle, the pulmonary outflow tract, and the pulmonary arteries.

• Patients with echocardiographic evidence of significant pulmonary stenosis (50-60 mmHg) should undergo diagnostic and therapeutic cardiac catheterization with preparation for balloon dilatation of the pulmonary valve.

• Angioplasty of a branch of the pulmonary artery stenosis has been accomplished but carries a significantly higher risk than valvar pulmonary stenosis.

• Infundibular and supravalvar pulmonary stenosis, if severe, require operative and invasive surgical intervention.

TREATMENT

Medical Care:

• Prehospital care: Collect essential information from the vital signs, including pulse, respiratory rate and work of breathing, blood pressure (upper and lower extremities), and presence or absence of cyanosis.

• Presence of associated congenital cardiac anomalies should be anticipated until proven otherwise.

   

• If the patient has a known large left-to-right shunt, such as PDA or ventriculoseptal defect (VSD) and is in respiratory distress, diuresis should be attempted and is effective in reducing the cyanosis secondary to pulmonary edema.

   

• Use of oxygen may reduce pulmonary artery pressure in patients with a reactive pulmonary vasculature, thereby increasing pulmonary blood flow.

• Administer oxygen in any cyanotic patient with respiratory distress.

• Emergency department care

• Limited diagnostics are needed after the structural diagnosis is made.

• Frequently, the workup performed for the cyanotic infant with respiratory distress and hypotension or shock is the same as that performed in a septic patient.

Surgical Care:

• Cardiac catheterization with balloon valvuloplasty is the preferred therapy for severe or critical valvar pulmonary stenosis. In neonates with critical valvar pulmonary stenosis, balloon dilatation mortality is lower than surgery mortality and is the treatment of choice.

• Patients are referred for this procedure when the echocardiography gradient is in the moderate or severe range.

• A balloon catheter is placed over a wire in an antegrade fashion through the femoral vein, inferior vena cava, right atrium, right ventricle, and across the valve.

• The balloon, with diameter 120% of the annulus diameter, is inflated and deflated while straddling the valve. This usually results in a significant gradient reduction. Some pulmonary insufficiency may develop but is well tolerated.

• Temporary subvalvar dynamic obstruction may occur and usually resolves over several days. The procedure usually is well tolerated but is more risky in infants younger than six months, especially neonates with critical stenosis.

• Surgery may be necessary in a variety of conditions associated with pulmonary valve dysplasia.

• Balloon valvuloplasty may not be able to open a dysplastic pulmonary valve.

• Severe right ventricular hypoplasia may be associated with critical pulmonary stenosis requiring univentricular palliation, which is a staged repair ultimately requiring a Fontan (right atrial to pulmonary artery) modification.

Consultations: Pediatric cardiology consultation precedes consultation with a cardiothoracic surgeon.

• Pulmonary valve atresia or critical pulmonary stenosis with an inadequate right ventricle requires a shunt (usually modified Blalock-Taussig or central shunt) after the ductus arteriosus is kept patent pharmacologically with prostaglandin E1.

• Definitive repair may not be possible if the right ventricle is hypoplastic, requiring a single ventricular palliation, such as the Fontan procedure, or variation, such as a direct right atrial appendage to main pulmonary artery anastomosis.

Activity: A prudent philosophy is to allow patients to limit their own activity according to personal tolerance.

MEDICATION

No medications are useful in isolated valvar pulmonary stenosis. Patients with CHF may benefit from anticongestive therapy. Cyanotic patients may benefit from oxygen and prostaglandin E1. Patients with cyanosis from a large right-to-left shunt require a definitive surgical procedure.

Drug Category: Prostaglandins -- Alprostadil (Prostaglandin E1, PGE1) is used for treatment of ductal-dependent cyanotic congenital heart disease, which is caused by decreased pulmonary blood flow. It acts as a smooth muscle relaxer and maintains patency of the ductus arteriosus when a cyanotic lesion (ie, critical pulmonary stenosis or atresia) or an interrupted aortic arch presents in a newborn. It is more effective in premature infants than in mature infants.

Drug Name	Alprostadil (Prostin VR) -- First-line medication used as palliative therapy to temporarily maintain patency of the ductus arteriosus before surgery. Produces vasodilation and increases cardiac output. Also inhibits platelet aggregation and stimulates intestinal and uterine smooth muscle. Used for suspected critical pulmonary stenosis when presentation includes cyanosis, and with a ductal-dependent lesion (eg, pulmonary atresia variants, coarctation of the aorta, interrupted aortic arch). Each 1-mL ampule contains 500 mcg/mL.
Pediatric Dose	0.01 mcg/kg/min; up to 0.4 mcg/kg/min IV
Contraindications	Documented hypersensitivity; hyaline membrane disease, respiratory distress syndrome
Interactions	Limited data exist; caution with concurrent use of antiplatelet drugs or anticoagulants
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Adverse effects and toxicity include apnea, seizures, fever, hypotension, leukocytosis, fever and pulmonary overcirculation; neonates usually are intubated prophylactically because of potential risk of apnea (10-12%); prolonged use occasionally is necessary (in hypoplastic left heart syndrome transplant candidates) and may be associated with third spacing of fluid; monitor blood oxygenation and arterial pressure

Drug Category: Antibiotics, prophylactic -- Antibiotic prophylaxis is given to patients before undergoing 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 6 h after initial dose
Pediatric Dose	50 mg/kg 1 h PO before procedure; not to exceed 2 g/dose
Contraindications	Documented hypersensitivity
Interactions	Reduces the 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 gastrointestinal or genitourinary procedures.
Adult Dose	2 g IV/IM 30 min before procedure High-risk patients: 2 g ampicillin IV/IM plus 1.5 mg/kg gentamicin 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 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 ampicillin 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 of clindamycin; antidiarrheals may delay absorption of clindamycin
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 1-2 g ampicillin 30 min before procedure; not to exceed 80 mg
Pediatric Dose	2 mg/kg IV; not to exceed 120 mg/dose, 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; aminoglycosides enhance effects of neuromuscular blocking agents (thus, 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 CrCl to adjust dose in patients with renal impairment. Used in conjunction with gentamicin for prophylaxis in penicillin-allergic patients undergoing gastrointestinal 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 more than that in 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 caused by too rapid IV infusion (dose given over a few min) but rarely occurs when dose given as 2-h administration or as PO or 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 of cefazolin; coadministration with aminoglycosides, may increase renal toxicity; may yield false-positive urine dipstick test result 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 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; not to administer 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 with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in elderly patients and in patients who are hospitalized or debilitated

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; clarithromycin 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, and HMG CoA-reductase inhibitors; cardiac arrhythmias may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase 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 is 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:

• Patients with mild valvar pulmonary stenosis (<25 mmHg) do not experience an increase in gradient, nor do they require any treatment.

• Choice of management of patients with gradients of 40-49 mmHg remains a matter of debate.

• Patients with a gradient greater than or equal to 50 mm Hg should have valvotomy or valvuloplasty. If valvotomy or valvuloplasty is required in a child, reoperation rarely is necessary.

• The neonate with critical pulmonary stenosis requires special consideration. Critical pulmonary stenosis may present with near pulmonary atresia (cyanotic lesion) with a small and often inadequate right ventricle. These patients survive because of a patent ductus arteriosus.

• Patients with severe or symptomatic infundibular or supravalvar pulmonary stenosis require surgical intervention.

• Pulmonary valve atresia or critical pulmonary stenosis with an inadequate right ventricle may require a shunt (usually a modified Blalock-Taussig or central shunt) if it is deemed impossible to "puncture" the pulmonary valve and balloon dilate. Throughout the procedure, the ductus arteriosus is kept patent pharmacologically with prostaglandin E1.

• Definitive repair may not be possible if the right ventricle is hypoplastic, requiring a single ventricular palliation, such as the Fontan procedure, or a variation of this. The Fontan procedure is a direct right atrial appendage to main pulmonary artery anastomosis.

• Frequently, the main and branch pulmonary arteries require augmentation prior to a Fontan, especially if a prior systemic to pulmonary artery shunt was performed (modified Blalock-Taussig shunt). This is not performed for pure valvar pulmonary stenosis.

• Balloon valvuloplasty has become an accepted alternative to surgery for valvar stenosis.

• Balloon dilation avoids a potentially painful operation and a long postoperative recovery, and at the same time offers substantial cost savings. However, such advantages are meaningless if the safety of the interventional procedure does not match or surpass the results of conventional surgery.

Further Outpatient Care:

• Physical activity should be normal.

• Most patients with PS are given subacute bacterial endocarditis (SBE) prophylaxis.

• Opinions differ as to the need for SBE prophylaxis recommendations for valvar pulmonary stenosis because of the extremely low incidence of pulmonary valve endocarditis in this relatively large subpopulation.

Transfer:

• Transfer patients with symptomatic pulmonary stenosis to a tertiary care center offering pediatric cardiology and pediatric cardiothoracic surgery.

Complications:

• One complication with the acute palliation for severe pulmonary stenosis involves the hypercontractile residual obstructing muscular hypertrophy in the infundibulum.

• This phenomenon of infundibular obstruction after valvar stenosis repair by surgery or valvuloplasty has led to the designation of a "suicide right ventricle." Beta-blockers and volume replacement are used to treat this condition, which occurs more frequently in older patients with long-standing pulmonary stenosis.

• Late atrial arrhythmias

• Persistent repolarization abnormalities

Prognosis:

• Mild valvar pulmonary stenosis usually does not progress, but the moderate-to-severe disease does tend to progress.

• After relief of the stenosis, the condition does not recur, and right ventricular hypertrophy regresses.

• Following balloon or surgical valvulotomy, the outcome generally is excellent. Probability of survival is similar to that of the general population, and the vast majority of patients are asymptomatic.

Patient Education:

• Reassure patients and parents of those with mild valvar pulmonary stenosis that this condition is not related to, or associated with, coronary artery disease, dysrhythmia, or sudden death.

• Insurability may become a factor in obtaining further care. Patients are no more at risk for disastrous health consequences than the usual population.

• Provided the patient is asymptomatic, acyanotic, and has mild valvar pulmonary stenosis by initial Doppler echocardiography, a yearly screening examination and electrocardiography would be prudent follow-up care.

• If no significant change in the evaluation is present a few years after the initial evaluation, the patient can be reasonably discharged for follow-up care over extended periods of 3-5 years.

MISCELLANEOUS

Medical/Legal Pitfalls:

• Failure to exclude associated congenital anomalies and detect the presence of cyanosis or a ductal-dependent lesion is a major error.

• Failure to diagnose a more serious congenital heart defect, such as tetralogy of Fallot, could yield disastrous consequences.

• Acyanotic patients with tetralogy of Fallot and mild right ventricular outflow tract obstruction may have a similar presentation and physical examination.

• Tetralogy of Fallot is a lesion that is surgically correctable and can be corrected safely, even in the neonatal period.

• A "tet spell," or hypercyanotic spell, is potentially lethal, frequently aborted with simple skills, and can occur in previously pink tets.

• Echocardiography can reliably confirm the precise diagnosis and differentiate between valvar pulmonary stenosis and tetralogy of Fallot.

• Echocardiography should not be withheld if any suspicion of a more complex anatomy exists.