Pulmonary Atresia With Intact Ventricular Septum

INTRODUCTION

Background: Pulmonary atresia with intact ventricular septum (PAIVS) is a rare congenital cardiac lesion characterized by heterogeneous right ventricular development, imperforate pulmonary valve, and possible extensive ventriculocoronary connections. Prognosis and management depend on the degree of right ventricular hypoplasia and the dependency of the myocardial blood supply on abnormal communications between the right ventricle and coronary arteries. These 2 factors are the most important prognostic determinants.

 

Pathophysiology: The PAIVS spectrum ranges from a normal-sized or slightly hypoplastic right ventricle and a well-formed infundibulum and imperforate pulmonary valve with commissural fusion to a diminutive right ventricle, narrowed or atretic infundibulum, primitive pulmonary valve and ventriculocoronary artery connections (with or without stenoses). In PAIVS, the tricuspid valve rarely is normal and demonstrates a continuum of abnormalities, ranging from severe stenosis (often related to annular hypoplasia) to severe regurgitation. In addition, PAIVS has an obligatory right-to-left atrial-level shunt (through a patent foramen ovale or secundum atrial septal defect). Pulmonary blood flow usually depends on a patent ductus arteriosus; aortopulmonary collaterals originating from the descending thoracic aorta are rare.

 

Frequency:

  • In the US: Despite overall low prevalence, PAIVS is one of the cardiac etiologies of cyanotic congenital heart disease (CCHD) among neonates (along with transposition of the great arteries and pulmonary atresia with ventricular septal defect). PAIVS has no known genetic etiology, although rare familial cases have been described. PAIVS occurs in 7.1-8.1 per 100,000 live births and in 0.7-3.1% of patients with congenital heart disease (CHD).
  • Internationally: PAIVS occurs in 4.5 per 100,000 live births in the United Kingdom and Ireland.

Mortality/Morbidity: Early survival depends upon maintaining ductal patency until a palliative procedure can be performed to establish a reliable source of pulmonary blood flow. (Placement of a systemic-to-pulmonary artery shunt is the most common procedure.) In both the short- and long-term, patients are at risk for sudden death, angina, arrhythmias, and congestive heart failure (CHF), in addition to complications of prolonged cyanosis and hypoxemia. The overall probability of survival for patients with PAIVS is approximately 65-82% at age 1 year and 76% at age 5 years.

  • Sudden death, angina, and arrhythmias: PAIVS is associated with ventriculocoronary connections in approximately 45% of patients. Due to coronary artery stenoses in nearly 9% of patients, the coronary circulation is considered dependent on right ventricular systolic events. These patients are at particularly high risk for myocardial ischemia, angina, ventricular arrhythmias, and sudden death, as compared to patients with many other forms of CHD.
  • CHF: Depending upon the particular anatomic substrate, these patients may have an early predilection for heart failure due to both tricuspid regurgitation and left-to-right, ductal-dependent, pulmonary blood flow. Postoperatively, the risk of heart failure may continue, depending upon the ratio of pulmonary to systemic blood flow and on the degree of tricuspid and pulmonary regurgitation (following possible right ventricular outflow-tract reconstruction or pulmonary valvotomy).
  • Cyanosis: Long-term complications of cyanosis and hypoxemia include polycythemia and a hyperviscosity syndrome. These patients may develop headache, decreased exercise tolerance, and stroke. In addition, thrombocytopenia is a common finding that leads to bleeding complications in patients with CCHD.

Age: PAIVS is a cyanotic congenital heart lesion that presents in the newborn period coincident with closure of the patent ductus arteriosus.

CLINICAL

History:

  • Infants with PAIVS usually are born at term, and cyanosis is apparent within hours.
  • These babies develop progressively worsening cyanosis and tachypnea associated with closure of the patent ductus arteriosus.

Physical:

  • The most common finding on physical examination is central (perioral and periorbital) cyanosis. Following ductal closure, profound generalized cyanosis is present.
  • Apical left ventricular impulse may be pronounced.
  • The first and second heart sounds are single.
  • A pansystolic murmur often is heard at the left lower sternal border, consistent with tricuspid regurgitation. If severe, the murmur of tricuspid regurgitation may be associated with a thrill and a diastolic rumble.
  • A systolic ejection murmur of the patent ductus arteriosus may be heard at the left second or third intercostal space, particularly after initiating prostaglandin infusion.
  • Normal arterial pulses usually are present.
  • Hepatomegaly is uncommon unless the atrial septal defect is restrictive (rare).

Causes:

  • As with many forms of CHD, the genetic cause of PAIVS is unknown.
  • Kutsche and Van Mierop suggest that PAIVS probably occurs relatively late in cardiac morphogenesis after cardiac septation, in contrast to pulmonary atresia with ventricular septal defect. This may reflect a prenatal inflammatory or infectious condition; however, no histopathological evidence currently exists to support this view.
  • In rare familial cases, some researchers advocate a single gene theory.

DIFFERENTIALS

Ebstein Anomaly
Pulmonary Stenosis, Valvar
Tetralogy of Fallot With Pulmonary Atresia
Transposition of the Great Arteries
WORKUP

Lab Studies:

  • No laboratory blood tests exist to help confirm a specific diagnosis of PAIVS.
  • An arterial blood gas (ABG) study is likely to show hypoxemia and hypocarbia refractory to inspired oxygen concentration, consistent with CCHD.

Imaging Studies:

  • Echocardiography and Doppler
    • Two-dimensional echocardiography usually is diagnostic for PAIVS. A combination of subcostal and precordial views demonstrates anatomic pulmonary atresia in addition to tricuspid valve and right ventricular morphology and size. Echocardiography and angiography are the 2 most important studies in diagnosis of pulmonary atresia.
    • Absolute volume measurements of the right ventricle usually have limited value. Data from the Congenital Heart Surgeons Study showed that the diameter of the tricuspid valve normalized to body surface area (tricuspid valve z-value) and was highly correlated with size of the right ventricular cavity.
    • In addition, color flow and continuous wave Doppler interrogations demonstrate the degree of tricuspid regurgitation, allow estimation of right ventricular pressure, and detect restriction of the interatrial communication.
    • A combination of imaging and Doppler echocardiography demonstrates branch pulmonary artery size and configuration (usually within reference ranges), as well as ductal patency. Echocardiographic imaging has limited use for identifying ventriculocoronary connections.
  • Angiocardiography
    • A neonate's prognosis with PAIVS directly relates to the presence or absence of ventriculocoronary connections and right ventricular-dependent coronary circulation. Although echocardiography is diagnostic for PAIVS, angiocardiography is an important imaging modality for planning future intervention.
    • Right ventricular angiocardiography defines the presence or absence of ventriculocoronary connections and provides information about the size, morphology, and function of the tricuspid valve and right ventricle.
    • Balloon occlusion aortography images the proximal coronary arteries and demonstrates coronary arterial stenosis or interruption.
  • Radiography
    • Chest radiography usually demonstrates mild cardiomegaly and decreased or normal pulmonary vascular markings.
    • With severe tricuspid regurgitation (and a dysplastic tricuspid valve), profound cardiomegaly may exist because of right atrial enlargement.

Other Tests:

  • Electrocardiography
    • ECG often shows normal sinus rhythm, QRS axis +30° to +90°, decreased right ventricular forces, left ventricular dominance, and right atrial enlargement (proportional to the degree of tricuspid regurgitation).
    • In addition, ST-T wave abnormalities are common in patients with ventriculocoronary connections or coronary artery stenosis and are consistent with subendocardial ischemia.

Procedures:

  • Cardiac catheterization
    • Cardiac catheterization allows right ventricular pressure measurement, confirms anatomic pulmonary atresia, and evaluates right and left ventricular function.
    • Ventriculocoronary connections also can be delineated with cardiac catheterization, as can the morphology and size of the tricuspid valve and right ventricle.
    • In the rare instance of a restrictive atrial communication, a transcatheter balloon or blade atrial septostomy may help maintain adequate cardiac output. Recently, transcatheter wire puncture, laser, and radiofrequency-assisted balloon pulmonary valvotomy have been utilized as alternatives to surgical valvotomy in patients with PAIVS.
Histologic Findings: Patients with PAIVS can demonstrate a wide range of myocardial abnormalities including ischemia, fibrosis, infarction, rupture, fiber disarray, spongy myocardium, and endocardial fibroelastosis. The degree of endocardial fibroelastosis inversely relates to the degree of ventriculocoronary connections.

 

TREATMENT

Medical Care:

  • Initial treatment consists of maintaining ductal patency with continuous IV prostaglandin E1 infusion.
  • To correct metabolic acidosis in a sick neonate, replace fluids and administer sodium bicarbonate.
  • Mechanical ventilation may be necessary if acidosis persists.
  • Patients ultimately require surgical palliation or therapeutic catheterization prior to hospital discharge.

Surgical Care: Surgical algorithms for PAIVS depend upon the size and morphology of both the tricuspid valve and the right ventricle, as well as the presence of abnormal coronary artery anatomy.

  • Mild tricuspid valve and right ventricular hypoplasia without ventriculocoronary connections
    • Perform a surgical valvotomy or transannular patch, with or without a systemic-to-pulmonary artery shunt, or a transcatheter valvotomy, with or without stenting of the patent ductus arteriosus.

       

    • If the right ventricle and tricuspid valve grow, a 2-ventricle correction is probable in the future.
  • Moderate-to-severe tricuspid valve and right ventricular hypoplasia without ventriculocoronary connections
    • Perform a surgical valvotomy or transannular patch with a systemic-to-pulmonary artery shunt or a transcatheter valvotomy with stenting of the patent ductus arteriosus.

       

    • Future univentricular (Fontan) repair is likely.
  • Moderate-to-severe tricuspid valve and right ventricular hypoplasia with ventriculocoronary connections but no stenoses or interruption
    • Perform a surgical valvotomy or transannular patch with a systemic-to-pulmonary artery shunt or a transcatheter valvotomy with stenting of the patent ductus arteriosus.

       

    • Future univentricular (Fontan) repair is likely.
  • Moderate-to-severe tricuspid valve and right ventricular hypoplasia with ventriculocoronary connections and proximal stenoses or interruption
    • Perform a systemic-to-pulmonary artery shunt or stenting of the patent ductus arteriosus.

       

    • Future univentricular (Fontan) repair or heart transplant is likely.

Consultations:

  • Pediatric cardiology
  • Pediatric cardiothoracic surgery

Diet: Patients with PAIVS require increased caloric density during infancy to provide 120-130 kcal/kg/d for approximately 6 months.

Activity: No specific activity restrictions are necessary.

MEDICATION

No specific drug therapies address PAIVS. Following initial palliation and maintenance of ductal patency with alprostadil (PGE1), some patients may benefit from digoxin and diuretic therapy to improve left ventricular contractility and to avoid fluid retention. Patients with stents should receive low-dose aspirin therapy.

Drug Category: Inotropic agents -- Increases the contractility of cardiac muscle in a dose-dependent manner (ie, positive inotropic effect).
Drug Name
 Digoxin (Lanoxin) -- Frequently used cardiac glycoside that inhibits sarcolemmal Na-K adenosine triphosphatase, which leads to an increase in intracellular Ca concentration and increased myocardial contractility.
Adult Dose 0.125-0.5 mg PO qd
Pediatric Dose Preterm infant: 5-7.5 mcg/kg PO divided bid
Term infant: 6-10 mcg/kg PO divided bid
1 month to 2 years: 10-15 mcg/kg PO divided bid
2-5 years: 7.5-10 mcg/kg PO divided bid
5-10 years: 5-10 mcg/kg PO divided bid
>10 years: 2.5-5 mcg/kg PO qd
Contraindications Documented hypersensitivity; atrioventricular block, idiopathic hypertrophic subaortic stenosis, constrictive pericarditis, hypokalemia, or renal failure
Interactions Quinidine, quinine, verapamil, propafenone, diltiazem, erythromycin, itraconazole, indomethacin, and amiodarone increase plasma concentration, thus requiring dose adjustment; prokinetic agents (eg, cisapride, metoclopramide) may decrease absorption
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Monitor serum K levels; use cautiously with hypokalemia; monitor serum digoxin level due to narrow therapeutic index; reduce dose in renal dysfunction; CNS effects (eg, drowsiness) and GI effects (eg, nausea, vomiting) are among more common adverse reactions; administer at same time of day in relation to meals
Drug Category: Loop diuretics -- Inhibit electrolyte reabsorption in the thick ascending limb of the Henle loop in the kidney, thus promoting diuresis.
Drug Name
 Furosemide (Lasix) -- Commonly used loop diuretic; has moderate diuretic potency.
Adult Dose 20-80 mg/d PO/IV/IM in divided doses q6-12h
Pediatric Dose 1 mg/kg PO/IV qd; may increase dose up to tid
Contraindications Documented hypersensitivity; hypokalemia; renal failure
Interactions Increases nephrotoxicity of cephalosporins; ototoxicity may be increased when coadministered with aminoglycosides
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Closely monitor serum K levels; may produce intravascular dehydration, severe hypokalemia, and significant hypochloremic metabolic alkalosis; may cause hyperuricemia; may produce deafness due to ototoxicity; titrate dose to effect; administer PO dose with food or milk to decrease stomach upset
Drug Category: Prostaglandins -- PGE1 is used for treatment of ductal dependent cyanotic congenital heart disease, which is due to decreased pulmonary blood flow.
Drug Name
 Alprostadil (Prostin VR) -- 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 Initial dose: 0.05 mcg-0.1 mcg/kg/min IV into large vein or umbilical cord
Maintenance dose: 0.01-0.4 mcg/kg/min IV into large vein or umbilical cord
Contraindications Documented hypersensitivity; hyaline membrane disease or respiratory distress syndrome
Interactions Coadministration with heparin may increase aPTT
Pregnancy X - Contraindicated in pregnancy
Precautions Long-term infusions may cause cortical proliferation of the long bones in neonates; due to the inhibitory effects of prostaglandins in platelet aggregation, exercise caution when administering to neonates with bleeding tendencies

FOLLOW-UP

Further Inpatient Care:

  • Admit patient for future preoperative testing and surgical interventions.

Further Outpatient Care:

  • Carefully monitor medication doses and adverse effects.
  • Monitor adequacy of repair/palliation with periodic echocardiograms.

In/Out Patient Meds:

  • Possible discharge medications include digoxin, furosemide, and aspirin.

Transfer:

  • Transfer may be required for specialized diagnostic evaluation and surgical intervention.

Complications:

  • Congestive heart failure
  • Sudden death
  • Arrhythmia

Prognosis:

  • Prognosis depends upon the specific anatomy and type of intervention (univentricular or biventricular correction).
  • Overall survival is approximately 76% at age 5 years.

Patient Education:

  • Provide cardiopulmonary resuscitation (CPR) instruction to family members.
  • Educate family members about CHD.
  • Consider genetics counseling for future pregnancies.

MISCELLANEOUS

Medical/Legal Pitfalls:

  • Failure to consider the diagnosis, especially in a cyanotic newborn
  • Preoperative failure to evaluate for ventriculocoronary connections and coronary artery stenosis